TY - JOUR
AB - The yeast Rab5 homologue, Vps21p, is known to be involved both in the vacuolar protein sorting (VPS) pathway from the trans-Golgi network to the vacuole, and in the endocytic pathway from the plasma membrane to the vacuole. However, the intracellular location at which these two pathways converge remains unclear. In addition, the endocytic pathway is not completely blocked in yeast cells lacking all Rab5 genes, suggesting the existence of an unidentified route that bypasses the Rab5-dependent endocytic pathway. Here we show that convergence of the endocytic and VPS pathways occurs upstream of the requirement for Vps21p in these pathways. We also identify a previously unidentified endocytic pathway mediated by the AP-3 complex. Importantly, the AP-3-mediated pathway appears mostly intact in Rab5-disrupted cells, and thus works as an alternative route to the vacuole/lysosome. We propose that the endocytic traffic branches into two routes to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3-mediated pathway.
AU - Toshima, Junko
AU - Nishinoaki, Show
AU - Sato, Yoshifumi
AU - Yamamoto, Wataru
AU - Furukawa, Daiki
AU - Siekhaus, Daria E
AU - Sawaguchi, Akira
AU - Toshima, Jiro
ID - 2024
JF - Nature Communications
TI - Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole
VL - 5
ER -
TY - CONF
AB - We present a tool for translating LTL formulae into deterministic ω-automata. It is the first tool that covers the whole LTL that does not use Safra’s determinization or any of its variants. This leads to smaller automata. There are several outputs of the tool: firstly, deterministic Rabin automata, which are the standard input for probabilistic model checking, e.g. for the probabilistic model-checker PRISM; secondly, deterministic generalized Rabin automata, which can also be used for probabilistic model checking and are sometimes by orders of magnitude smaller. We also link our tool to PRISM and show that this leads to a significant speed-up of probabilistic LTL model checking, especially with the generalized Rabin automata.
AU - Komárková, Zuzana
AU - Kretinsky, Jan
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 2026
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Rabinizer 3: Safraless translation of ltl to small deterministic automata
VL - 8837
ER -
TY - CONF
AB - We present a general framework for applying machine-learning algorithms to the verification of Markov decision processes (MDPs). The primary goal of these techniques is to improve performance by avoiding an exhaustive exploration of the state space. Our framework focuses on probabilistic reachability, which is a core property for verification, and is illustrated through two distinct instantiations. The first assumes that full knowledge of the MDP is available, and performs a heuristic-driven partial exploration of the model, yielding precise lower and upper bounds on the required probability. The second tackles the case where we may only sample the MDP, and yields probabilistic guarantees, again in terms of both the lower and upper bounds, which provides efficient stopping criteria for the approximation. The latter is the first extension of statistical model checking for unbounded properties inMDPs. In contrast with other related techniques, our approach is not restricted to time-bounded (finite-horizon) or discounted properties, nor does it assume any particular properties of the MDP. We also show how our methods extend to LTL objectives. We present experimental results showing the performance of our framework on several examples.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Forejt, Vojtěch
AU - Kretinsky, Jan
AU - Kwiatkowska, Marta
AU - Parker, David
AU - Ujma, Mateusz
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 2027
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Verification of markov decision processes using learning algorithms
VL - 8837
ER -
TY - JOUR
AB - We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses) and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses.
AU - Rubio, Maía
AU - Fukazawa, Yugo
AU - Kamasawa, Naomi
AU - Clarkson, Cheryl
AU - Molnár, Elek
AU - Shigemoto, Ryuichi
ID - 2064
IS - 18
JF - Journal of Comparative Neurology
TI - Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus
VL - 522
ER -
TY - CONF
AB - Spinning tops and yo-yos have long fascinated cultures around the world with their unexpected, graceful motions that seemingly elude gravity. We present an algorithm to generate designs for spinning objects by optimizing rotational dynamics properties. As input, the user provides a solid 3D model and a desired axis of rotation. Our approach then modifies the mass distribution such that the principal directions of the moment of inertia align with the target rotation frame. We augment the model by creating voids inside its volume, with interior fill represented by an adaptive multi-resolution vox-elization. The discrete voxel fill values are optimized using a continuous, nonlinear formulation. Further, we optimize for rotational stability by maximizing the dominant principal moment. We extend our technique to incorporate deformation and multiple materials for cases where internal voids alone are insufficient. Our method is well-suited for a variety of 3D printed models, ranging from characters to abstract shapes. We demonstrate tops and yo-yos that spin surprisingly stably despite their asymmetric appearance.
AU - Bac̈her, Moritz
AU - Whiting, Emily
AU - Bernd Bickel
AU - Sorkine-Hornung, Olga
ID - 2080
IS - 4
TI - Spin-It: Optimizing moment of inertia for spinnable objects
VL - 33
ER -
TY - CONF
AB - We propose an interactive, optimization-in-the-loop tool for designing inflatable structures. Given a target shape, the user draws a network of seams defining desired segment boundaries in 3D. Our method computes optimally-shaped flat panels for the segments, such that the inflated structure is as close as possible to the target while satisfying the desired seam positions. Our approach is underpinned by physics-based pattern optimization, accurate coarse-scale simulation using tension field theory, and a specialized constraint-optimization method. Our system is fast enough to warrant interactive exploration of different seam layouts, including internal connections, and their effects on the inflated shape. We demonstrate the resulting design process on a varied set of simulation examples, some of which we have fabricated, demonstrating excellent agreement with the design intent.
AU - Skouras, Mélina
AU - Thomaszewski, Bernhard
AU - Kaufmann, Peter
AU - Garg, Akash
AU - Bickel, Bernd
AU - Grinspun, Eitan
AU - Gross, Markus
ID - 2081
IS - 4
TI - Designing inflatable structures
VL - 33
ER -
TY - JOUR
AB - Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen - Nosema ceranae (Microsporidia) - on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed.
AU - Wolf, Stephan
AU - Mcmahon, Dino
AU - Lim, Ka
AU - Pull, Christopher
AU - Clark, Suzanne
AU - Paxton, Robert
AU - Osborne, Juliet
ID - 2086
IS - 8
JF - PLoS One
TI - So near and yet so far: Harmonic radar reveals reduced homing ability of Nosema infected honeybees
VL - 9
ER -
TY - JOUR
AB - Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.
AU - Lagator, Mato
AU - Morgan, Andrew
AU - Neve, Paul
AU - Colegrave, Nick
ID - 2083
IS - 8
JF - Evolution
TI - Role of sex and migration in adaptation to sink environments
VL - 68
ER -
TY - JOUR
AB - The facial performance of an individual is inherently rich in subtle deformation and timing details. Although these subtleties make the performance realistic and compelling, they often elude both motion capture and hand animation. We present a technique for adding fine-scale details and expressiveness to low-resolution art-directed facial performances, such as those created manually using a rig, via marker-based capture, by fitting a morphable model to a video, or through Kinect reconstruction using recent faceshift technology. We employ a high-resolution facial performance capture system to acquire a representative performance of an individual in which he or she explores the full range of facial expressiveness. From the captured data, our system extracts an expressiveness model that encodes subtle spatial and temporal deformation details specific to that particular individual. Once this model has been built, these details can be transferred to low-resolution art-directed performances. We demonstrate results on various forms of input; after our enhancement, the resulting animations exhibit the same nuances and fine spatial details as the captured performance, with optional temporal enhancement to match the dynamics of the actor. Finally, we show that our technique outperforms the current state-of-the-art in example-based facial animation.
AU - Bermano, Amit H
AU - Bradley, Derek J
AU - Beeler, Thabo
AU - Zund, Fabio
AU - Nowrouzezahrai, Derek
AU - Baran, Ilya
AU - Sorkine-Hornung, Olga
AU - Pfister, Hanspeter
AU - Sumner, Robert W
AU - Bernd Bickel
AU - Groß, Markus S
ID - 2115
IS - 2
JF - ACM Transactions on Graphics
TI - Facial performance enhancement using dynamic shape space analysis
VL - 33
ER -
TY - JOUR
AB - We study approximations to a class of vector-valued equations of Burgers type driven by a multiplicative space-time white noise. A solution theory for this class of equations has been developed recently in Probability Theory Related Fields by Hairer and Weber. The key idea was to use the theory of controlled rough paths to give definitions of weak/mild solutions and to set up a Picard iteration argument. In this article the limiting behavior of a rather large class of (spatial) approximations to these equations is studied. These approximations are shown to converge and convergence rates are given, but the limit may depend on the particular choice of approximation. This effect is a spatial analogue to the Itô-Stratonovich correction in the theory of stochastic ordinary differential equations, where it is well known that different approximation schemes may converge to different solutions.
AU - Hairer, Martin M
AU - Jan Maas
AU - Weber, Hendrik
ID - 2131
IS - 5
JF - Communications on Pure and Applied Mathematics
TI - Approximating Rough Stochastic PDEs
VL - 67
ER -
TY - JOUR
AB - We consider discrete porous medium equations of the form ∂tρt=Δϕ(ρt), where Δ is the generator of a reversible continuous time Markov chain on a finite set χ, and ϕ is an increasing function. We show that these equations arise as gradient flows of certain entropy functionals with respect to suitable non-local transportation metrics. This may be seen as a discrete analogue of the Wasserstein gradient flow structure for porous medium equations in ℝn discovered by Otto. We present a one-dimensional counterexample to geodesic convexity and discuss Gromov-Hausdorff convergence to the Wasserstein metric.
AU - Erbar, Matthias
AU - Jan Maas
ID - 2132
IS - 4
JF - Discrete and Continuous Dynamical Systems- Series A
TI - Gradient flow structures for discrete porous medium equations
VL - 34
ER -
TY - JOUR
AB - Let ℭ denote the Clifford algebra over ℝ𝑛, which is the von Neumann algebra generated by n self-adjoint operators Q j , j = 1,…,n satisfying the canonical anticommutation relations, Q i Q j + Q j Q i = 2δ ij I, and let τ denote the normalized trace on ℭ. This algebra arises in quantum mechanics as the algebra of observables generated by n fermionic degrees of freedom. Let 𝔓 denote the set of all positive operators 𝜌∈ℭ such that τ(ρ) = 1; these are the non-commutative analogs of probability densities in the non-commutative probability space (ℭ,𝜏). The fermionic Fokker–Planck equation is a quantum-mechanical analog of the classical Fokker–Planck equation with which it has much in common, such as the same optimal hypercontractivity properties. In this paper we construct a Riemannian metric on 𝔓 that we show to be a natural analog of the classical 2-Wasserstein metric, and we show that, in analogy with the classical case, the fermionic Fokker–Planck equation is gradient flow in this metric for the relative entropy with respect to the ground state. We derive a number of consequences of this, such as a sharp Talagrand inequality for this metric, and we prove a number of results pertaining to this metric. Several open problems are raised.
AU - Carlen, Eric
AU - Maas, Jan
ID - 2133
IS - 3
JF - Communications in Mathematical Physics
TI - An analog of the 2-Wasserstein metric in non-commutative probability under which the fermionic Fokker-Planck equation is gradient flow for the entropy
VL - 331
ER -
TY - JOUR
AB - We propose a technique for engineering momentum-dependent dissipation in Bose-Einstein condensates with non-local interactions. The scheme relies on the use of momentum-dependent dark-states in close analogy to velocity-selective coherent population trapping. During the short-time dissipative dynamics, the system is driven into a particular finite-momentum phonon mode, which in real space corresponds to an ordered structure with non-local density-density correlations. Dissipation-induced ordering can be observed and studied in present-day experiments using cold atoms with dipole-dipole or off-resonant Rydberg interactions. Due to its dissipative nature, the ordering does not require artificial breaking of translational symmetry by an opticallattice or harmonic trap. This opens up a perspective of direct cooling of quantum gases into strongly-interacting phases.
AU - Otterbach, Johannes
AU - Lemeshko, Mikhail
ID - 2140
IS - 7
JF - Physical Review Letters
TI - Dissipative preparation of spatial order in Rydberg-dressed Bose-Einstein condensates
VL - 113
ER -
TY - CONF
AB - We define a simple, explicit map sending a morphism f : M → N of pointwise finite dimensional persistence modules to a matching between the barcodes of M and N. Our main result is that, in a precise sense, the quality of this matching is tightly controlled by the lengths of the longest intervals in the barcodes of ker f and coker f . As an immediate corollary, we obtain a new proof of the algebraic stability theorem for persistence barcodes [5, 9], a fundamental result in the theory of persistent homology. In contrast to previous proofs, ours shows explicitly how a δ-interleaving morphism between two persistence modules induces a δ-matching between the barcodes of the two modules. Our main result also specializes to a structure theorem for submodules and quotients of persistence modules. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Lesnick, Michael
ID - 2153
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Induced matchings of barcodes and the algebraic stability of persistence
ER -
TY - JOUR
AB - A result of Boros and Füredi (d = 2) and of Bárány (arbitrary d) asserts that for every d there exists cd > 0 such that for every n-point set P ⊂ ℝd, some point of ℝd is covered by at least (Formula presented.) of the d-simplices spanned by the points of P. The largest possible value of cd has been the subject of ongoing research. Recently Gromov improved the existing lower bounds considerably by introducing a new, topological proof method. We provide an exposition of the combinatorial component of Gromov's approach, in terms accessible to combinatorialists and discrete geometers, and we investigate the limits of his method. In particular, we give tighter bounds on the cofilling profiles for the (n - 1)-simplex. These bounds yield a minor improvement over Gromov's lower bounds on cd for large d, but they also show that the room for further improvement through the cofilling profiles alone is quite small. We also prove a slightly better lower bound for c3 by an approach using an additional structure besides the cofilling profiles. We formulate a combinatorial extremal problem whose solution might perhaps lead to a tight lower bound for cd.
AU - Matoušek, Jiří
AU - Wagner, Uli
ID - 2154
IS - 1
JF - Discrete & Computational Geometry
TI - On Gromov's method of selecting heavily covered points
VL - 52
ER -
TY - CONF
AB - Given a finite set of points in Rn and a positive radius, we study the Čech, Delaunay-Čech, alpha, and wrap complexes as instances of a generalized discrete Morse theory. We prove that the latter three complexes are simple-homotopy equivalent. Our results have applications in topological data analysis and in the reconstruction of shapes from sampled data. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 2155
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - The morse theory of Čech and Delaunay filtrations
ER -
TY - CONF
AB - We propose a metric for Reeb graphs, called the functional distortion distance. Under this distance, the Reeb graph is stable against small changes of input functions. At the same time, it remains discriminative at differentiating input functions. In particular, the main result is that the functional distortion distance between two Reeb graphs is bounded from below by the bottleneck distance between both the ordinary and extended persistence diagrams for appropriate dimensions. As an application of our results, we analyze a natural simplification scheme for Reeb graphs, and show that persistent features in Reeb graph remains persistent under simplification. Understanding the stability of important features of the Reeb graph under simplification is an interesting problem on its own right, and critical to the practical usage of Reeb graphs. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Ge, Xiaoyin
AU - Wang, Yusu
ID - 2156
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Measuring distance between Reeb graphs
ER -
TY - CONF
AB - Motivated by topological Tverberg-type problems, we consider multiple (double, triple, and higher multiplicity) selfintersection points of maps from finite simplicial complexes (compact polyhedra) into ℝd and study conditions under which such multiple points can be eliminated. The most classical case is that of embeddings (i.e., maps without double points) of a κ-dimensional complex K into ℝ2κ. For this problem, the work of van Kampen, Shapiro, and Wu provides an efficiently testable necessary condition for embeddability (namely, vanishing of the van Kampen ob-struction). For κ ≥ 3, the condition is also sufficient, and yields a polynomial-time algorithm for deciding embeddability: One starts with an arbitrary map f : K→ℝ2κ, which generically has finitely many double points; if k ≥ 3 and if the obstruction vanishes then one can successively remove these double points by local modifications of the map f. One of the main tools is the famous Whitney trick that permits eliminating pairs of double points of opposite intersection sign. We are interested in generalizing this approach to intersection points of higher multiplicity. We call a point y 2 ℝd an r-fold Tverberg point of a map f : Kκ →ℝd if y lies in the intersection f(σ1)∩. ∩f(σr) of the images of r pairwise disjoint simplices of K. The analogue of (non-)embeddability that we study is the problem Tverbergκ r→d: Given a κ-dimensional complex K, does it satisfy a Tverberg-type theorem with parameters r and d, i.e., does every map f : K κ → ℝd have an r-fold Tverberg point? Here, we show that for fixed r, κ and d of the form d = rm and k = (r-1)m, m ≥ 3, there is a polynomial-time algorithm for deciding this (based on the vanishing of a cohomological obstruction, as in the case of embeddings). Our main tool is an r-fold analogue of the Whitney trick: Given r pairwise disjoint simplices of K such that the intersection of their images contains two r-fold Tverberg points y+ and y- of opposite intersection sign, we can eliminate y+ and y- by a local isotopy of f. In a subsequent paper, we plan to develop this further and present a generalization of the classical Haeiger-Weber Theorem (which yields a necessary and sufficient condition for embeddability of κ-complexes into ℝd for a wider range of dimensions) to intersection points of higher multiplicity.
AU - Mabillard, Isaac
AU - Wagner, Uli
ID - 2159
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Eliminating Tverberg points, I. An analogue of the Whitney trick
ER -
TY - CONF
AB - Transfer learning has received a lot of attention in the machine learning community over the last years, and several effective algorithms have been developed. However, relatively little is known about their theoretical properties, especially in the setting of lifelong learning, where the goal is to transfer information to tasks for which no data have been observed so far. In this work we study lifelong learning from a theoretical perspective. Our main result is a PAC-Bayesian generalization bound that offers a unified view on existing paradigms for transfer learning, such as the transfer of parameters or the transfer of low-dimensional representations. We also use the bound to derive two principled lifelong learning algorithms, and we show that these yield results comparable with existing methods.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ED - Xing, Eric
ED - Jebara, Tony
ID - 2160
TI - A PAC-Bayesian bound for Lifelong Learning
VL - 32
ER -
TY - JOUR
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 - 2161
IS - 10
JF - Behavioral Ecology and Sociobiology
TI - Increased grooming after repeated brood care provides sanitary benefits in a clonal ant
VL - 68
ER -
TY - JOUR
AB - Directional guidance of migrating cells is relatively well explored in the reductionist setting of cell culture experiments. Here spatial gradients of chemical cues as well as gradients of mechanical substrate characteristics prove sufficient to attract single cells as well as their collectives. How such gradients present and act in the context of an organism is far less clear. Here we review recent advances in understanding how guidance cues emerge and operate in the physiological context.
AU - Majumdar, Ritankar
AU - Sixt, Michael K
AU - Parent, Carole
ID - 2158
IS - 1
JF - Current Opinion in Cell Biology
TI - New paradigms in the establishment and maintenance of gradients during directed cell migration
VL - 30
ER -
TY - JOUR
AB - Many species have an essentially continuous distribution in space, in which there are no natural divisions between randomly mating subpopulations. Yet, the standard approach to modelling these populations is to impose an arbitrary grid of demes, adjusting deme sizes and migration rates in an attempt to capture the important features of the population. Such indirect methods are required because of the failure of the classical models of isolation by distance, which have been shown to have major technical flaws. A recently introduced model of extinction and recolonisation in two dimensions solves these technical problems, and provides a rigorous technical foundation for the study of populations evolving in a spatial continuum. The coalescent process for this model is simply stated, but direct simulation is very inefficient for large neighbourhood sizes. We present efficient and exact algorithms to simulate this coalescent process for arbitrary sample sizes and numbers of loci, and analyse these algorithms in detail.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Barton, Nicholas H
ID - 2168
JF - Theoretical Population Biology
TI - Coalescent simulation in continuous space: Algorithms for large neighbourhood size
VL - 95
ER -
TY - JOUR
AU - Barton, Nicholas H
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 2169
IS - 29
JF - PNAS
TI - Diverse forms of selection in evolution and computer science
VL - 111
ER -
TY - JOUR
AB - Short-read sequencing technologies have in principle made it feasible to draw detailed inferences about the recent history of any organism. In practice, however, this remains challenging due to the difficulty of genome assembly in most organisms and the lack of statistical methods powerful enough to discriminate between recent, nonequilibrium histories. We address both the assembly and inference challenges. We develop a bioinformatic pipeline for generating outgroup-rooted alignments of orthologous sequence blocks from de novo low-coverage short-read data for a small number of genomes, and show how such sequence blocks can be used to fit explicit models of population divergence and admixture in a likelihood framework. To illustrate our approach, we reconstruct the Pleistocene history of an oak-feeding insect (the oak gallwasp Biorhiza pallida), which, in common with many other taxa, was restricted during Pleistocene ice ages to a longitudinal series of southern refugia spanning the Western Palaearctic. Our analysis of sequence blocks sampled from a single genome from each of three major glacial refugia reveals support for an unexpected history dominated by recent admixture. Despite the fact that 80% of the genome is affected by admixture during the last glacial cycle, we are able to infer the deeper divergence history of these populations. These inferences are robust to variation in block length, mutation model and the sampling location of individual genomes within refugia. This combination of de novo assembly and numerical likelihood calculation provides a powerful framework for estimating recent population history that can be applied to any organism without the need for prior genetic resources.
AU - Hearn, Jack
AU - Stone, Graham
AU - Bunnefeld, Lynsey
AU - Nicholls, James
AU - Barton, Nicholas H
AU - Lohse, Konrad
ID - 2170
IS - 1
JF - Molecular Ecology
TI - Likelihood-based inference of population history from low-coverage de novo genome assemblies
VL - 23
ER -
TY - CONF
AB - We present LS-CRF, a new method for training cyclic Conditional Random Fields (CRFs) from large datasets that is inspired by classical closed-form expressions for the maximum likelihood parameters of a generative graphical model with tree topology. Training a CRF with LS-CRF requires only solving a set of independent regression problems, each of which can be solved efficiently in closed form or by an iterative solver. This makes LS-CRF orders of magnitude faster than classical CRF training based on probabilistic inference, and at the same time more flexible and easier to implement than other approximate techniques, such as pseudolikelihood or piecewise training. We apply LS-CRF to the task of semantic image segmentation, showing that it achieves on par accuracy to other training techniques at higher speed, thereby allowing efficient CRF training from very large training sets. For example, training a linearly parameterized pairwise CRF on 150,000 images requires less than one hour on a modern workstation.
AU - Kolesnikov, Alexander
AU - Guillaumin, Matthieu
AU - Ferrari, Vittorio
AU - Lampert, Christoph
ED - Fleet, David
ED - Pajdla, Tomas
ED - Schiele, Bernt
ED - Tuytelaars, Tinne
ID - 2171
IS - PART 3
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Closed-form approximate CRF training for scalable image segmentation
VL - 8691
ER -
TY - CONF
AB - Fisher Kernels and Deep Learning were two developments with significant impact on large-scale object categorization in the last years. Both approaches were shown to achieve state-of-the-art results on large-scale object categorization datasets, such as ImageNet. Conceptually, however, they are perceived as very different and it is not uncommon for heated debates to spring up when advocates of both paradigms meet at conferences or workshops. In this work, we emphasize the similarities between both architectures rather than their differences and we argue that such a unified view allows us to transfer ideas from one domain to the other. As a concrete example we introduce a method for learning a support vector machine classifier with Fisher kernel at the same time as a task-specific data representation. We reinterpret the setting as a multi-layer feed forward network. Its final layer is the classifier, parameterized by a weight vector, and the two previous layers compute Fisher vectors, parameterized by the coefficients of a Gaussian mixture model. We introduce a gradient descent based learning algorithm that, in contrast to other feature learning techniques, is not just derived from intuition or biological analogy, but has a theoretical justification in the framework of statistical learning theory. Our experiments show that the new training procedure leads to significant improvements in classification accuracy while preserving the modularity and geometric interpretability of a support vector machine setup.
AU - Sydorov, Vladyslav
AU - Sakurada, Mayu
AU - Lampert, Christoph
ID - 2172
T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition
TI - Deep Fisher Kernels – End to end learning of the Fisher Kernel GMM parameters
ER -
TY - CONF
AB - In this work we introduce a new approach to co-classification, i.e. the task of jointly classifying multiple, otherwise independent, data samples. The method we present, named CoConut, is based on the idea of adding a regularizer in the label space to encode certain priors on the resulting labelings. A regularizer that encourages labelings that are smooth across the test set, for instance, can be seen as a test-time variant of the cluster assumption, which has been proven useful at training time in semi-supervised learning. A regularizer that introduces a preference for certain class proportions can be regarded as a prior distribution on the class labels. CoConut can build on existing classifiers without making any assumptions on how they were obtained and without the need to re-train them. The use of a regularizer adds a new level of flexibility. It allows the integration of potentially new information at test time, even in other modalities than what the classifiers were trained on. We evaluate our framework on six datasets, reporting a clear performance gain in classification accuracy compared to the standard classification setup that predicts labels for each test sample separately.
AU - Khamis, Sameh
AU - Lampert, Christoph
ID - 2173
T2 - Proceedings of the British Machine Vision Conference 2014
TI - CoConut: Co-classification with output space regularization
ER -
TY - JOUR
AB - When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are equivalent. Furthermore, the genetic variance that is maintained by mutation-selection balance is 2μ/S per locus, where μ is the mutation rate and S the strength of stabilizing selection. In reality, alleles vary in their effects, making the fitness landscape asymmetric and complicating analysis of the equilibria. We show that that the resulting genetic variance depends on the fraction of alleles near fixation, which contribute by 2μ/S, and on the total mutational effects of alleles that are at intermediate frequency. The inpplayfi between stabilizing selection and mutation leads to a sharp transition: alleles with effects smaller than a threshold value of 2 remain polymorphic, whereas those with larger effects are fixed. The genetic load in equilibrium is less than for traits of equal effects, and the fitness equilibria are more similar. We find p the optimum is displaced, alleles with effects close to the threshold value sweep first, and their rate of increase is bounded by Long-term response leads in general to well-adapted traits, unlike the case of equal effects that often end up at a suboptimal fitness peak. However, the particular peaks to which the populations converge are extremely sensitive to the initial states and to the speed of the shift of the optimum trait value.
AU - De Vladar, Harold
AU - Barton, Nicholas H
ID - 2174
IS - 2
JF - Genetics
TI - Stability and response of polygenic traits to stabilizing selection and mutation
VL - 197
ER -
TY - JOUR
AB - The cerebral cortex, the seat of our cognitive abilities, is composed of an intricate network of billions of excitatory projection and inhibitory interneurons. Postmitotic cortical neurons are generated by a diverse set of neural stem cell progenitors within dedicated zones and defined periods of neurogenesis during embryonic development. Disruptions in neurogenesis can lead to alterations in the neuronal cytoarchitecture, which is thought to represent a major underlying cause for several neurological disorders, including microcephaly, autism and epilepsy. Although a number of signaling pathways regulating neurogenesis have been described, the precise cellular and molecular mechanisms regulating the functional neural stem cell properties in cortical neurogenesis remain unclear. Here, we discuss the most up-to-date strategies to monitor the fundamental mechanistic parameters of neuronal progenitor proliferation, and recent advances deciphering the logic and dynamics of neurogenesis.
AU - Postiglione, Maria P
AU - Hippenmeyer, Simon
ID - 2175
IS - 3
JF - Future Neurology
TI - Monitoring neurogenesis in the cerebral cortex: an update
VL - 9
ER -
TY - JOUR
AB - Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.
AU - Studer, Daniel
AU - Zhao, Shanting
AU - Chai, Xuejun
AU - Jonas, Peter M
AU - Graber, Werner
AU - Nestel, Sigrun
AU - Frotscher, Michael
ID - 2176
IS - 6
JF - Nature Protocols
TI - Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue
VL - 9
ER -
TY - CONF
AB - We give evidence for the difficulty of computing Betti numbers of simplicial complexes over a finite field. We do this by reducing the rank computation for sparse matrices with to non-zero entries to computing Betti numbers of simplicial complexes consisting of at most a constant times to simplices. Together with the known reduction in the other direction, this implies that the two problems have the same computational complexity.
AU - Edelsbrunner, Herbert
AU - Parsa, Salman
ID - 2177
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - On the computational complexity of betti numbers reductions from matrix rank
ER -
TY - JOUR
AB - We consider the three-state toric homogeneous Markov chain model (THMC) without loops and initial parameters. At time T, the size of the design matrix is 6 × 3 · 2T-1 and the convex hull of its columns is the model polytope. We study the behavior of this polytope for T ≥ 3 and we show that it is defined by 24 facets for all T ≥ 5. Moreover, we give a complete description of these facets. From this, we deduce that the toric ideal associated with the design matrix is generated by binomials of degree at most 6. Our proof is based on a result due to Sturmfels, who gave a bound on the degree of the generators of a toric ideal, provided the normality of the corresponding toric variety. In our setting, we established the normality of the toric variety associated to the THMC model by studying the geometric properties of the model polytope.
AU - Haws, David
AU - Martin Del Campo Sanchez, Abraham
AU - Takemura, Akimichi
AU - Yoshida, Ruriko
ID - 2178
IS - 1
JF - Beitrage zur Algebra und Geometrie
TI - Markov degree of the three-state toric homogeneous Markov chain model
VL - 55
ER -
TY - JOUR
AB - We extend the proof of the local semicircle law for generalized Wigner matrices given in MR3068390 to the case when the matrix of variances has an eigenvalue -1. In particular, this result provides a short proof of the optimal local Marchenko-Pastur law at the hard edge (i.e. around zero) for sample covariance matrices X*X, where the variances of the entries of X may vary.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 2179
JF - Electronic Communications in Probability
TI - Local semicircle law with imprimitive variance matrix
VL - 19
ER -
TY - JOUR
AB - Weighted majority votes allow one to combine the output of several classifiers or voters. MinCq is a recent algorithm for optimizing the weight of each voter based on the minimization of a theoretical bound over the risk of the vote with elegant PAC-Bayesian generalization guarantees. However, while it has demonstrated good performance when combining weak classifiers, MinCq cannot make use of the useful a priori knowledge that one may have when using a mixture of weak and strong voters. In this paper, we propose P-MinCq, an extension of MinCq that can incorporate such knowledge in the form of a constraint over the distribution of the weights, along with general proofs of convergence that stand in the sample compression setting for data-dependent voters. The approach is applied to a vote of k-NN classifiers with a specific modeling of the voters' performance. P-MinCq significantly outperforms the classic k-NN classifier, a symmetric NN and MinCq using the same voters. We show that it is also competitive with LMNN, a popular metric learning algorithm, and that combining both approaches further reduces the error.
AU - Bellet, Aurélien
AU - Habrard, Amaury
AU - Morvant, Emilie
AU - Sebban, Marc
ID - 2180
IS - 1-2
JF - Machine Learning
TI - Learning a priori constrained weighted majority votes
VL - 97
ER -
TY - JOUR
AB - We describe a simple adaptive network of coupled chaotic maps. The network reaches a stationary state (frozen topology) for all values of the coupling parameter, although the dynamics of the maps at the nodes of the network can be nontrivial. The structure of the network shows interesting hierarchical properties and in certain parameter regions the dynamics is polysynchronous: Nodes can be divided in differently synchronized classes but, contrary to cluster synchronization, nodes in the same class need not be connected to each other. These complicated synchrony patterns have been conjectured to play roles in systems biology and circuits. The adaptive system we study describes ways whereby this behavior can evolve from undifferentiated nodes.
AU - Botella Soler, Vicente
AU - Glendinning, Paul
ID - 2183
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Hierarchy and polysynchrony in an adaptive network
VL - 89
ER -
TY - JOUR
AB - Given topological spaces X,Y, a fundamental problem of algebraic topology is understanding the structure of all continuous maps X→ Y. We consider a computational version, where X,Y are given as finite simplicial complexes, and the goal is to compute [X,Y], that is, all homotopy classes of suchmaps.We solve this problem in the stable range, where for some d ≥ 2, we have dim X ≤ 2d-2 and Y is (d-1)-connected; in particular, Y can be the d-dimensional sphere Sd. The algorithm combines classical tools and ideas from homotopy theory (obstruction theory, Postnikov systems, and simplicial sets) with algorithmic tools from effective algebraic topology (locally effective simplicial sets and objects with effective homology). In contrast, [X,Y] is known to be uncomputable for general X,Y, since for X = S1 it includes a well known undecidable problem: testing triviality of the fundamental group of Y. In follow-up papers, the algorithm is shown to run in polynomial time for d fixed, and extended to other problems, such as the extension problem, where we are given a subspace A ⊂ X and a map A→ Y and ask whether it extends to a map X → Y, or computing the Z2-index-everything in the stable range. Outside the stable range, the extension problem is undecidable.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Sergeraert, Francis
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2184
IS - 3
JF - Journal of the ACM
TI - Computing all maps into a sphere
VL - 61
ER -
TY - CONF
AB - We revisit the classical problem of converting an imperfect source of randomness into a usable cryptographic key. Assume that we have some cryptographic application P that expects a uniformly random m-bit key R and ensures that the best attack (in some complexity class) against P(R) has success probability at most δ. Our goal is to design a key-derivation function (KDF) h that converts any random source X of min-entropy k into a sufficiently "good" key h(X), guaranteeing that P(h(X)) has comparable security δ′ which is 'close' to δ. Seeded randomness extractors provide a generic way to solve this problem for all applications P, with resulting security δ′ = O(δ), provided that we start with entropy k ≥ m + 2 log (1/δ) - O(1). By a result of Radhakrishnan and Ta-Shma, this bound on k (called the "RT-bound") is also known to be tight in general. Unfortunately, in many situations the loss of 2 log (1/δ) bits of entropy is unacceptable. This motivates the study KDFs with less entropy waste by placing some restrictions on the source X or the application P. In this work we obtain the following new positive and negative results in this regard: - Efficient samplability of the source X does not help beat the RT-bound for general applications. This resolves the SRT (samplable RT) conjecture of Dachman-Soled et al. [DGKM12] in the affirmative, and also shows that the existence of computationally-secure extractors beating the RT-bound implies the existence of one-way functions. - We continue in the line of work initiated by Barak et al. [BDK+11] and construct new information-theoretic KDFs which beat the RT-bound for large but restricted classes of applications. Specifically, we design efficient KDFs that work for all unpredictability applications P (e.g., signatures, MACs, one-way functions, etc.) and can either: (1) extract all of the entropy k = m with a very modest security loss δ′ = O(δ·log (1/δ)), or alternatively, (2) achieve essentially optimal security δ′ = O(δ) with a very modest entropy loss k ≥ m + loglog (1/δ). In comparison, the best prior results from [BDK+11] for this class of applications would only guarantee δ′ = O(√δ) when k = m, and would need k ≥ m + log (1/δ) to get δ′ = O(δ). - The weaker bounds of [BDK+11] hold for a larger class of so-called "square- friendly" applications (which includes all unpredictability, but also some important indistinguishability, applications). Unfortunately, we show that these weaker bounds are tight for the larger class of applications. - We abstract out a clean, information-theoretic notion of (k,δ,δ′)- unpredictability extractors, which guarantee "induced" security δ′ for any δ-secure unpredictability application P, and characterize the parameters achievable for such unpredictability extractors. Of independent interest, we also relate this notion to the previously-known notion of (min-entropy) condensers, and improve the state-of-the-art parameters for such condensers.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Nguyen, Phong
ED - Oswald, Elisabeth
ID - 2185
TI - Key derivation without entropy waste
VL - 8441
ER -
TY - JOUR
AB - We prove the existence of scattering states for the defocusing cubic Gross-Pitaevskii (GP) hierarchy in ℝ3. Moreover, we show that an exponential energy growth condition commonly used in the well-posedness theory of the GP hierarchy is, in a specific sense, necessary. In fact, we prove that without the latter, there exist initial data for the focusing cubic GP hierarchy for which instantaneous blowup occurs.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 2186
IS - 7
JF - Letters in Mathematical Physics
TI - On the well-posedness and scattering for the Gross-Pitaevskii hierarchy via quantum de Finetti
VL - 104
ER -
TY - JOUR
AB - Systems should not only be correct but also robust in the sense that they behave reasonably in unexpected situations. This article addresses synthesis of robust reactive systems from temporal specifications. Existing methods allow arbitrary behavior if assumptions in the specification are violated. To overcome this, we define two robustness notions, combine them, and show how to enforce them in synthesis. The first notion applies to safety properties: If safety assumptions are violated temporarily, we require that the system recovers to normal operation with as few errors as possible. The second notion requires that, if liveness assumptions are violated, as many guarantees as possible should be fulfilled nevertheless. We present a synthesis procedure achieving this for the important class of GR(1) specifications, and establish complexity bounds. We also present an implementation of a special case of robustness, and show experimental results.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Hofferek, Georg
AU - Jobstmann, Barbara
AU - Könighofer, Bettina
AU - Könighofer, Robert
ID - 2187
IS - 3-4
JF - Acta Informatica
TI - Synthesizing robust systems
VL - 51
ER -
TY - JOUR
AB - Although plant and animal cells use a similar core mechanism to deliver proteins to the plasma membrane, their different lifestyle, body organization and specific cell structures resulted in the acquisition of regulatory mechanisms that vary in the two kingdoms. In particular, cell polarity regulators do not seem to be conserved, because genes encoding key components are absent in plant genomes. In plants, the broad knowledge on polarity derives from the study of auxin transporters, the PIN-FORMED proteins, in the model plant Arabidopsis thaliana. In animals, much information is provided from the study of polarity in epithelial cells that exhibit basolateral and luminal apical polarities, separated by tight junctions. In this review, we summarize the similarities and differences of the polarization mechanisms between plants and animals and survey the main genetic approaches that have been used to characterize new genes involved in polarity establishment in plants, including the frequently used forward and reverse genetics screens as well as a novel chemical genetics approach that is expected to overcome the limitation of classical genetics methods.
AU - Kania, Urszula
AU - Fendrych, Matyas
AU - Friml, Jiřĺ
ID - 2188
IS - APRIL
JF - Open Biology
TI - Polar delivery in plants; commonalities and differences to animal epithelial cells
VL - 4
ER -
TY - CONF
AB - En apprentissage automatique, nous parlons d'adaptation de domaine lorsque les données de test (cibles) et d'apprentissage (sources) sont générées selon différentes distributions. Nous devons donc développer des algorithmes de classification capables de s'adapter à une nouvelle distribution, pour laquelle aucune information sur les étiquettes n'est disponible. Nous attaquons cette problématique sous l'angle de l'approche PAC-Bayésienne qui se focalise sur l'apprentissage de modèles définis comme des votes de majorité sur un ensemble de fonctions. Dans ce contexte, nous introduisons PV-MinCq une version adaptative de l'algorithme (non adaptatif) MinCq. PV-MinCq suit le principe suivant. Nous transférons les étiquettes sources aux points cibles proches pour ensuite appliquer MinCq sur l'échantillon cible ``auto-étiqueté'' (justifié par une borne théorique). Plus précisément, nous définissons un auto-étiquetage non itératif qui se focalise dans les régions où les distributions marginales source et cible sont les plus similaires. Dans un second temps, nous étudions l'influence de notre auto-étiquetage pour en déduire une procédure de validation des hyperparamètres. Finalement, notre approche montre des résultats empiriques prometteurs.
AU - Morvant, Emilie
ID - 2189
TI - Adaptation de domaine de vote de majorité par auto-étiquetage non itératif
VL - 1
ER -
TY - CONF
AB - We present a new algorithm to construct a (generalized) deterministic Rabin automaton for an LTL formula φ. The automaton is the product of a master automaton and an array of slave automata, one for each G-subformula of φ. The slave automaton for G ψ is in charge of recognizing whether FG ψ holds. As opposed to standard determinization procedures, the states of all our automata have a clear logical structure, which allows for various optimizations. Our construction subsumes former algorithms for fragments of LTL. Experimental results show improvement in the sizes of the resulting automata compared to existing methods.
AU - Esparza, Javier
AU - Kretinsky, Jan
ID - 2190
TI - From LTL to deterministic automata: A safraless compositional approach
VL - 8559
ER -
TY - JOUR
AB - We propose to detect quadrupole interactions of neutral ultracold atoms via their induced mean-field shift. We consider a Mott insulator state of spin-polarized atoms in a two-dimensional optical square lattice. The quadrupole moments of the atoms are aligned by an external magnetic field. As the alignment angle is varied, the mean-field shift shows a characteristic angular dependence, which constitutes the defining signature of the quadrupole interaction. For the 3P2 states of Yb and Sr atoms, we find a frequency shift of the order of tens of Hertz, which can be realistically detected in experiment with current technology. We compare our results to the mean-field shift of a spin-polarized quasi-two-dimensional Fermi gas in continuum.
AU - Lahrz, Martin
AU - Lemeshko, Mikhail
AU - Sengstock, Klaus
AU - Becker, Christoph
AU - Mathey, Ludwig
ID - 2208
IS - 4
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Detecting quadrupole interactions in ultracold Fermi gases
VL - 89
ER -
TY - JOUR
AB - Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity.
AU - Chai, Xuejun
AU - Münzner, Gert
AU - Zhao, Shanting
AU - Tinnes, Stefanie
AU - Kowalski, Janina
AU - Häussler, Ute
AU - Young, Christina
AU - Haas, Carola
AU - Frotscher, Michael
ID - 2164
IS - 8
JF - Cerebral Cortex
TI - Epilepsy-induced motility of differentiated neurons
VL - 24
ER -
TY - JOUR
AB - In machine learning, the domain adaptation problem arrives when the test (tar-get) and the train (source) data are generated from different distributions. A key applied issue is thus the design of algorithms able to generalize on a new distribution, for which we have no label information. We focus on learning classification models defined as a weighted majority vote over a set of real-valued functions. In this context, Germain et al. (2013) have shown that a measure of disagreement between these functions is crucial to control. The core of this measure is a theoretical bound—the C-bound (Lacasse et al., 2007)—which involves the disagreement and leads to a well performing majority vote learn-ing algorithm in usual non-adaptative supervised setting: MinCq. In this work,we propose a framework to extend MinCq to a domain adaptation scenario.This procedure takes advantage of the recent perturbed variation divergence between distributions proposed by Harel and Mannor (2012). Justified by a theoretical bound on the target risk of the vote, we provide to MinCq a tar-get sample labeled thanks to a perturbed variation-based self-labeling focused on the regions where the source and target marginals appear similar. We also study the influence of our self-labeling, from which we deduce an original process for tuning the hyperparameters. Finally, our framework called PV-MinCq shows very promising results on a rotation and translation synthetic problem.
AU - Morvant, Emilie
ID - 2165
JF - Pattern Recognition Letters
TI - Domain Adaptation of Weighted Majority Votes via Perturbed Variation-Based Self-Labeling
VL - 51
ER -
TY - JOUR
AB - A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients.
AU - Stoler Barak, Liat
AU - Moussion, Christine
AU - Shezen, Elias
AU - Hatzav, Miki
AU - Sixt, Michael K
AU - Alon, Ronen
ID - 2214
IS - 1
JF - PLoS One
TI - Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects
VL - 9
ER -
TY - JOUR
AB - Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events.
AU - Renkawitz, Jörg
AU - Lademann, Claudio
AU - Jentsch, Stefan
ID - 2215
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - Mechanisms and principles of homology search during recombination
VL - 15
ER -
TY - CONF
AB - While fixing concurrency bugs, program repair algorithms may introduce new concurrency bugs. We present an algorithm that avoids such regressions. The solution space is given by a set of program transformations we consider in the repair process. These include reordering of instructions within a thread and inserting atomic sections. The new algorithm learns a constraint on the space of candidate solutions, from both positive examples (error-free traces) and counterexamples (error traces). From each counterexample, the algorithm learns a constraint necessary to remove the errors. From each positive examples, it learns a constraint that is necessary in order to prevent the repair from turning the trace into an error trace. We implemented the algorithm and evaluated it on simplified Linux device drivers with known bugs.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Tarrach, Thorsten
ID - 2218
SN - 978-331908866-2
TI - Regression-free synthesis for concurrency
VL - 8559
ER -
TY - CONF
AB - Recently, Döttling et al. (ASIACRYPT 2012) proposed the first chosen-ciphertext (IND-CCA) secure public-key encryption scheme from the learning parity with noise (LPN) assumption. In this work we give an alternative scheme which is conceptually simpler and more efficient. At the core of our construction is a trapdoor technique originally proposed for lattices by Micciancio and Peikert (EUROCRYPT 2012), which we adapt to the LPN setting. The main technical tool is a new double-trapdoor mechanism, together with a trapdoor switching lemma based on a computational variant of the leftover hash lemma.
AU - Kiltz, Eike
AU - Masny, Daniel
AU - Pietrzak, Krzysztof Z
ID - 2219
SN - 978-364254630-3
TI - Simple chosen-ciphertext security from low noise LPN
VL - 8383
ER -
TY - JOUR
AB - In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications.
AU - De Vos, Marjon
AU - Bollenbach, Mark Tobias
ID - 2220
IS - 4
JF - Chemistry and Biology
SN - 10745521
TI - Suppressive drug interactions between antifungals
VL - 21
ER -