TY - JOUR
AB - A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release.
AU - Arai, Itaru
AU - Jonas, Peter M
ID - 2031
JF - eLife
TI - Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse
VL - 3
ER -
TY - JOUR
AB - As light-based control of fundamental signaling pathways is becoming a reality, the field of optogenetics is rapidly moving beyond neuroscience. We have recently developed receptor tyrosine kinases that are activated by light and control cell proliferation, epithelial–mesenchymal transition, and angiogenic sprouting—cell behaviors central to cancer progression.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Schelch, Karin
AU - Janovjak, Harald L
AU - Grusch, Michael
ID - 2032
IS - 4
JF - Molecular and Cellular Oncology
TI - The optogenetic promise for oncology: Episode I
VL - 1
ER -
TY - CONF
AB - The learning with privileged information setting has recently attracted a lot of attention within the machine learning community, as it allows the integration of additional knowledge into the training process of a classifier, even when this comes in the form of a data modality that is not available at test time. Here, we show that privileged information can naturally be treated as noise in the latent function of a Gaussian process classifier (GPC). That is, in contrast to the standard GPC setting, the latent function is not just a nuisance but a feature: it becomes a natural measure of confidence about the training data by modulating the slope of the GPC probit likelihood function. Extensive experiments on public datasets show that the proposed GPC method using privileged noise, called GPC+, improves over a standard GPC without privileged knowledge, and also over the current state-of-the-art SVM-based method, SVM+. Moreover, we show that advanced neural networks and deep learning methods can be compressed as privileged information.
AU - Hernandez Lobato, Daniel
AU - Sharmanska, Viktoriia
AU - Kersting, Kristian
AU - Lampert, Christoph
AU - Quadrianto, Novi
ID - 2033
IS - January
T2 - Advances in Neural Information Processing Systems
TI - Mind the nuisance: Gaussian process classification using privileged noise
VL - 1
ER -
TY - JOUR
AB - In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.
AU - Lagator, Mato
AU - Colegrave, Nick
AU - Neve, Paul
ID - 2036
IS - 1794
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses
VL - 281
ER -
TY - JOUR
AB - Recently, there has been an effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions. At the heart of quantitative objectives lies the accumulation of values along a computation. It is often the accumulated sum, as with energy objectives, or the accumulated average, as with mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric (or Boolean) variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point in time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire infinite computation. We study the border of decidability for such quantitative extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities with both prefix-accumulation assertions, or extending LTL with both path-accumulation assertions, results in temporal logics whose model-checking problem is decidable. Moreover, the prefix-accumulation assertions may be generalized with "controlled accumulation," allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that this branching-time logic is, in a sense, the maximal logic with one or both of the prefix-accumulation assertions that permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, such as CTL or LTL, makes the problem undecidable.
AU - Boker, Udi
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Kupferman, Orna
ID - 2038
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
TI - Temporal specifications with accumulative values
VL - 15
ER -
TY - JOUR
AB - A fundamental question in biology is the following: what is the time scale that is needed for evolutionary innovations? There are many results that characterize single steps in terms of the fixation time of new mutants arising in populations of certain size and structure. But here we ask a different question, which is concerned with the much longer time scale of evolutionary trajectories: how long does it take for a population exploring a fitness landscape to find target sequences that encode new biological functions? Our key variable is the length, (Formula presented.) of the genetic sequence that undergoes adaptation. In computer science there is a crucial distinction between problems that require algorithms which take polynomial or exponential time. The latter are considered to be intractable. Here we develop a theoretical approach that allows us to estimate the time of evolution as function of (Formula presented.) We show that adaptation on many fitness landscapes takes time that is exponential in (Formula presented.) even if there are broad selection gradients and many targets uniformly distributed in sequence space. These negative results lead us to search for specific mechanisms that allow evolution to work on polynomial time scales. We study a regeneration process and show that it enables evolution to work in polynomial time.
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Adlam, Ben
AU - Nowak, Martin
ID - 2039
IS - 9
JF - PLoS Computational Biology
TI - The time scale of evolutionary innovation
VL - 10
ER -
TY - JOUR
AB - Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand.
AU - Kicheva, Anna
AU - Bollenbach, Mark Tobias
AU - Ribeiro, Ana
AU - Pérez Valle, Helena
AU - Lovell Badge, Robin
AU - Episkopou, Vasso
AU - Briscoe, James
ID - 2040
IS - 6204
JF - Science
TI - Coordination of progenitor specification and growth in mouse and chick spinal cord
VL - 345
ER -
TY - JOUR
AB - The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time.
AU - Jonas, Peter M
AU - Lisman, John
ID - 2041
JF - Frontiers in Neural Circuits
TI - Structure, function and plasticity of hippocampal dentate gyrus microcircuits
VL - 8
ER -
TY - JOUR
AB - Background: CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.Results: To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.Conclusions: The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.
AU - Kupczok, Anne
AU - Bollback, Jonathan P
ID - 2042
IS - 1
JF - BMC Genomics
TI - Motif depletion in bacteriophages infecting hosts with CRISPR systems
VL - 15
ER -
TY - CONF
AB - Persistent homology is a popular and powerful tool for capturing topological features of data. Advances in algorithms for computing persistent homology have reduced the computation time drastically – as long as the algorithm does not exhaust the available memory. Following up on a recently presented parallel method for persistence computation on shared memory systems [1], we demonstrate that a simple adaption of the standard reduction algorithm leads to a variant for distributed systems. Our algorithmic design ensures that the data is distributed over the nodes without redundancy; this permits the computation of much larger instances than on a single machine. Moreover, we observe that the parallelism at least compensates for the overhead caused by communication between nodes, and often even speeds up the computation compared to sequential and even parallel shared memory algorithms. In our experiments, we were able to compute the persistent homology of filtrations with more than a billion (109) elements within seconds on a cluster with 32 nodes using less than 6GB of memory per node.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
ED - McGeoch, Catherine
ED - Meyer, Ulrich
ID - 2043
T2 - Proceedings of the Workshop on Algorithm Engineering and Experiments
TI - Distributed computation of persistent homology
ER -
TY - CHAP
AB - We present a parallel algorithm for computing the persistent homology of a filtered chain complex. Our approach differs from the commonly used reduction algorithm by first computing persistence pairs within local chunks, then simplifying the unpaired columns, and finally applying standard reduction on the simplified matrix. The approach generalizes a technique by Günther et al., which uses discrete Morse Theory to compute persistence; we derive the same worst-case complexity bound in a more general context. The algorithm employs several practical optimization techniques, which are of independent interest. Our sequential implementation of the algorithm is competitive with state-of-the-art methods, and we further improve the performance through parallel computation.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
ED - Bremer, Peer-Timo
ED - Hotz, Ingrid
ED - Pascucci, Valerio
ED - Peikert, Ronald
ID - 2044
T2 - Topological Methods in Data Analysis and Visualization III
TI - Clear and Compress: Computing Persistent Homology in Chunks
ER -
TY - CONF
AB - We introduce and study a new notion of enhanced chosen-ciphertext security (ECCA) for public-key encryption. Loosely speaking, in the ECCA security experiment, the decryption oracle provided to the adversary is augmented to return not only the output of the decryption algorithm on a queried ciphertext but also of a randomness-recovery algorithm associated to the scheme. Our results mainly concern the case where the randomness-recovery algorithm is efficient. We provide constructions of ECCA-secure encryption from adaptive trapdoor functions as defined by Kiltz et al. (EUROCRYPT 2010), resulting in ECCA encryption from standard number-theoretic assumptions. We then give two applications of ECCA-secure encryption: (1) We use it as a unifying concept in showing equivalence of adaptive trapdoor functions and tag-based adaptive trapdoor functions, resolving an open question of Kiltz et al. (2) We show that ECCA-secure encryption can be used to securely realize an approach to public-key encryption with non-interactive opening (PKENO) originally suggested by Damgård and Thorbek (EUROCRYPT 2007), resulting in new and practical PKENO schemes quite different from those in prior work. Our results demonstrate that ECCA security is of both practical and theoretical interest.
AU - Dachman Soled, Dana
AU - Fuchsbauer, Georg
AU - Mohassel, Payman
AU - O’Neill, Adam
ED - Krawczyk, Hugo
ID - 2045
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Enhanced chosen-ciphertext security and applications
VL - 8383
ER -
TY - CONF
AB - We introduce policy-based signatures (PBS), where a signer can only sign messages conforming to some authority-specified policy. The main requirements are unforgeability and privacy, the latter meaning that signatures not reveal the policy. PBS offers value along two fronts: (1) On the practical side, they allow a corporation to control what messages its employees can sign under the corporate key. (2) On the theoretical side, they unify existing work, capturing other forms of signatures as special cases or allowing them to be easily built. Our work focuses on definitions of PBS, proofs that this challenging primitive is realizable for arbitrary policies, efficient constructions for specific policies, and a few representative applications.
AU - Bellare, Mihir
AU - Fuchsbauer, Georg
ED - Krawczyk, Hugo
ID - 2046
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Policy-based signatures
VL - 8383
ER -
TY - CONF
AB - Following the publication of an attack on genome-wide association studies (GWAS) data proposed by Homer et al., considerable attention has been given to developing methods for releasing GWAS data in a privacy-preserving way. Here, we develop an end-to-end differentially private method for solving regression problems with convex penalty functions and selecting the penalty parameters by cross-validation. In particular, we focus on penalized logistic regression with elastic-net regularization, a method widely used to in GWAS analyses to identify disease-causing genes. We show how a differentially private procedure for penalized logistic regression with elastic-net regularization can be applied to the analysis of GWAS data and evaluate our method’s performance.
AU - Yu, Fei
AU - Rybar, Michal
AU - Uhler, Caroline
AU - Fienberg, Stephen
ED - Domingo Ferrer, Josep
ID - 2047
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Differentially-private logistic regression for detecting multiple-SNP association in GWAS databases
VL - 8744
ER -
TY - JOUR
AB - The flow instability and further transition to turbulence in a toroidal pipe (torus) with curvature ratio (tube-to-coiling diameter) 0.049 is investigated experimentally. The flow inside the toroidal pipe is driven by a steel sphere fitted to the inner pipe diameter. The sphere is moved with constant azimuthal velocity from outside the torus by a moving magnet. The experiment is designed to investigate curved pipe flow by optical measurement techniques. Using stereoscopic particle image velocimetry, laser Doppler velocimetry and pressure drop measurements, the flow is measured for Reynolds numbers ranging from 1000 to 15 000. Time- and space-resolved velocity fields are obtained and analysed. The steady axisymmetric basic flow is strongly influenced by centrifugal effects. On an increase of the Reynolds number we find a sequence of bifurcations. For Re=4075±2% a supercritical bifurcation to an oscillatory flow is found in which waves travel in the streamwise direction with a phase velocity slightly faster than the mean flow. The oscillatory flow is superseded by a presumably quasi-periodic flow at a further increase of the Reynolds number before turbulence sets in. The results are found to be compatible, in general, with earlier experimental and numerical investigations on transition to turbulence in helical and curved pipes. However, important aspects of the bifurcation scenario differ considerably.
AU - Kühnen, Jakob
AU - Holzner, Markus
AU - Hof, Björn
AU - Kuhlmann, Hendrik
ID - 2050
JF - Journal of Fluid Mechanics
TI - Experimental investigation of transitional flow in a toroidal pipe
VL - 738
ER -
TY - CONF
AB - We show that the usual score function for conditional Markov networks can be written as the expectation over the scores of their spanning trees. We also show that a small random sample of these output trees can attain a significant fraction of the margin obtained by the complete graph and we provide conditions under which we can perform tractable inference. The experimental results confirm that practical learning is scalable to realistic datasets using this approach.
AU - Marchand, Mario
AU - Hongyu, Su
AU - Emilie Morvant
AU - Rousu, Juho
AU - Shawe-Taylor, John
ID - 2051
TI - Multilabel structured output learning with random spanning trees of max-margin Markov networks
ER -
TY - CONF
AB - In contrast to the usual understanding of probabilistic systems as stochastic processes, recently these systems have also been regarded as transformers of probabilities. In this paper, we give a natural definition of strong bisimulation for probabilistic systems corresponding to this view that treats probability distributions as first-class citizens. Our definition applies in the same way to discrete systems as well as to systems with uncountable state and action spaces. Several examples demonstrate that our definition refines the understanding of behavioural equivalences of probabilistic systems. In particular, it solves a longstanding open problem concerning the representation of memoryless continuous time by memoryfull continuous time. Finally, we give algorithms for computing this bisimulation not only for finite but also for classes of uncountably infinite systems.
AU - Hermanns, Holger
AU - Krčál, Jan
AU - Kretinsky, Jan
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2053
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Probabilistic bisimulation: Naturally on distributions
VL - 8704
ER -
TY - JOUR
AB - We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.
AU - Ganguly, Arnab
AU - Petrov, Tatjana
AU - Koeppl, Heinz
ID - 2056
IS - 3
JF - Journal of Mathematical Biology
TI - Markov chain aggregation and its applications to combinatorial reaction networks
VL - 69
ER -
TY - CONF
AB - In the past few years, a lot of attention has been devoted to multimedia indexing by fusing multimodal informations. Two kinds of fusion schemes are generally considered: The early fusion and the late fusion. We focus on late classifier fusion, where one combines the scores of each modality at the decision level. To tackle this problem, we investigate a recent and elegant well-founded quadratic program named MinCq coming from the machine learning PAC-Bayesian theory. MinCq looks for the weighted combination, over a set of real-valued functions seen as voters, leading to the lowest misclassification rate, while maximizing the voters’ diversity. We propose an extension of MinCq tailored to multimedia indexing. Our method is based on an order-preserving pairwise loss adapted to ranking that allows us to improve Mean Averaged Precision measure while taking into account the diversity of the voters that we want to fuse. We provide evidence that this method is naturally adapted to late fusion procedures and confirm the good behavior of our approach on the challenging PASCAL VOC’07 benchmark.
AU - Morvant, Emilie
AU - Habrard, Amaury
AU - Ayache, Stéphane
ID - 2057
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Majority vote of diverse classifiers for late fusion
VL - 8621
ER -
TY - CONF
AB - We present a method for smoothly blending between existing liquid animations. We introduce a semi-automatic method for matching two existing liquid animations, which we use to create new fluid motion that plausibly interpolates the input. Our contributions include a new space-time non-rigid iterative closest point algorithm that incorporates user guidance, a subsampling technique for efficient registration of meshes with millions of vertices, and a fast surface extraction algorithm that produces 3D triangle meshes from a 4D space-time surface. Our technique can be used to instantly create hundreds of new simulations, or to interactively explore complex parameter spaces. Our method is guaranteed to produce output that does not deviate from the input animations, and it generalizes to multiple dimensions. Because our method runs at interactive rates after the initial precomputation step, it has potential applications in games and training simulations.
AU - Raveendran, Karthik
AU - Wojtan, Christopher J
AU - Thuerey, Nils
AU - Türk, Greg
ID - 2058
IS - 4
T2 - ACM Transactions on Graphics
TI - Blending liquids
VL - 33
ER -