TY - DATA
AB - Graph matching problems as described in "Active Graph Matching for Automatic Joint Segmentation and Annotation of C. Elegans." by Kainmueller, Dagmar and Jug, Florian and Rother, Carsten and Myers, Gene, MICCAI 2014. Problems are in OpenGM2 hdf5 format (see http://hciweb2.iwr.uni-heidelberg.de/opengm/) and a custom text format used by the feature matching solver described in "Feature Correspondence via Graph Matching: Models and Global Optimization." by Lorenzo Torresani, Vladimir Kolmogorov and Carsten Rother, ECCV 2008, code at http://pub.ist.ac.at/~vnk/software/GraphMatching-v1.02.src.zip.
AU - Kainmueller, Dagmar
AU - Jug, Florian
AU - Rother, Carsten
AU - Meyers, Gene
ID - 5561
KW - graph matching
KW - feature matching
KW - QAP
KW - MAP-inference
TI - Graph matching problems for annotating C. Elegans
ER -
TY - DATA
AB - This data was collected as part of the study [1]. It consists of preprocessed multi-electrode array recording from 160 salamander retinal ganglion cells responding to 297 repeats of a 19 s natural movie. The data is available in two formats: (1) a .mat file containing an array with dimensions “number of repeats” x “number of neurons” x “time in a repeat”; (2) a zipped .txt file containing the same data represented as an array with dimensions “number of neurons” x “number of samples”, where the number of samples is equal to the product of the number of repeats and timebins within a repeat. The time dimension is divided into 20 ms time windows, and the array is binary indicating whether a given cell elicited at least one spike in a given time window during a particular repeat. See the reference below for details regarding collection and preprocessing:
[1] Tkačik G, Marre O, Amodei D, Schneidman E, Bialek W, Berry MJ II. Searching for Collective Behavior in a Large Network of Sensory Neurons. PLoS Comput Biol. 2014;10(1):e1003408.
AU - Marre, Olivier
AU - Tkacik, Gasper
AU - Amodei, Dario
AU - Schneidman, Elad
AU - Bialek, William
AU - Berry, Michael
ID - 5562
KW - multi-electrode recording
KW - retinal ganglion cells
TI - Multi-electrode array recording from salamander retinal ganglion cells
ER -
TY - DATA
AB - MATLAB code and processed datasets available for reproducing the results in:
Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast.
*equal contributions
AU - Lukacisin, Martin
ID - 5563
TI - MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'
ER -
TY - DATA
AB - Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). Information on this data collection is available in the Methods Section of the primary publication.
AU - Steinrück, Magdalena
AU - Guet, Calin C
ID - 5564
TI - Fastq files for "Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection"
ER -
TY - DATA
AB - One of the key questions in understanding plant development is how single cells behave in a larger context of the tissue. Therefore, it requires the observation of the whole organ with a high spatial- as well as temporal resolution over prolonged periods of time, which may cause photo-toxic effects. This protocol shows a plant sample preparation method for light-sheet microscopy, which is characterized by mounting the plant vertically on the surface of a gel. The plant is mounted in such a way that the roots are submerged in a liquid medium while the leaves remain in the air. In order to ensure photosynthetic activity of the plant, a custom-made lighting system illuminates the leaves. To keep the roots in darkness the water surface is covered with sheets of black plastic foil. This method allows long-term imaging of plant organ development in standardized conditions.
The Video is licensed under a CC BY NC ND license.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Friml, Jirí
ID - 5565
TI - Light Sheet Fluorescence microscopy of plant roots growing on the surface of a gel
ER -
TY - DATA
AB - Current minimal version of TipTracker
AU - Hauschild, Robert
ID - 5566
KW - tool
KW - tracking
KW - confocal microscopy
TI - Live tracking of moving samples in confocal microscopy for vertically grown roots
ER -
TY - DATA
AB - Immunological synapse DC-Tcells
AU - Leithner, Alexander F
ID - 5567
KW - Immunological synapse
TI - Immunological synapse DC-Tcells
ER -
TY - DATA
AB - Includes source codes, test cases, and example data used in the thesis Brittle Fracture Simulation with Boundary Elements for Computer Graphics. Also includes pre-built binaries of the HyENA library, but not sources - please contact the HyENA authors to obtain these sources if required (https://mech.tugraz.at/hyena)
AU - Hahn, David
ID - 5568
KW - Boundary elements
KW - brittle fracture
KW - computer graphics
KW - fracture simulation
TI - Source codes: Brittle fracture simulation with boundary elements for computer graphics
ER -
TY - JOUR
AB - PURPOSE. Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. METHODS. Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by expression of the tdTomato reporter. Immunostaining was used to localize tdTomato expression in select cell types. RESULTS. Successful transduction of RGCs was achieved at all time points after ONC using AAV2 expressing Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an increase in the transduction of cell types in the inner nuclear layer, including Müller cells and rod bipolar neurons. There was minimal evidence of transduction of amacrine cells and astrocytes in the inner retina or optic nerve. CONCLUSIONS. Damaged RGCs can be transduced and at least some endogenous genes can be subsequently activated. Optic nerve damage may change retinal architecture to allow greater penetration of an AAV2 virus to transduce several additional cell types in the inner nuclear layer.
AU - Nickells, Robert
AU - Schmitt, Heather
AU - Maes, Margaret E
AU - Schlamp, Cassandra
ID - 557
IS - 14
JF - Investigative Ophthalmology and Visual Science
SN - 01460404
TI - AAV2 mediated transduction of the mouse retina after optic nerve injury
VL - 58
ER -
TY - DATA
AB - Matlab script to calculate the forward migration indexes (/) from TrackMate spot-statistics files.
AU - Hauschild, Robert
ID - 5570
KW - Cell migration
KW - tracking
KW - forward migration index
KW - FMI
TI - Forward migration indexes
ER -
TY - DATA
AB - This folder contains all the data used in each of the main figures of "The genomic characterization of the t-haplotype, a mouse meiotic driver, highlights its complex history and specialized biology" (Kelemen, R., Vicoso, B.), as well as in the supplementary figures.
AU - Vicoso, Beatriz
ID - 5571
TI - Data for "The genomic characterization of the t-haplotype, a mouse meiotic driver, highlights its complex history and specialized biology"
ER -
TY - DATA
AB - Code described in the Supplementary Methods of "The genomic characterization of the t-haplotype, a mouse meiotic driver, highlights its complex history and specialized biology" (Kelemen, R., Vicoso, B.)
AU - Vicoso, Beatriz
ID - 5572
TI - Code for "The genomic characterization of the t-haplotype, a mouse meiotic driver, highlights its complex history and specialized biology"
ER -
TY - JOUR
AB - Immune specificity is the degree to which a host’s immune system discriminates among various pathogens or antigenic variants. Vertebrate immune memory is highly specific due to antibody responses. On the other hand, some invertebrates show immune priming, i.e. improved survival after secondary exposure to a previously encountered pathogen. Until now, specificity of priming has only been demonstrated via the septic infection route or when live pathogens were used for priming. Therefore, we tested for specificity in the oral priming route in the red flour beetle, Tribolium castaneum. For priming, we used pathogen-free supernatants derived from three different strains of the entomopathogen, Bacillus thuringiensis, which express different Cry toxin variants known for their toxicity against this beetle. Subsequent exposure to the infective spores showed that oral priming was specific for two naturally occurring strains, while a third engineered strain did not induce any priming effect. Our data demonstrate that oral immune priming with a non-infectious bacterial agent can be specific, but the priming effect is not universal across all bacterial strains.
AU - Futo, Momir
AU - Sell, Marie
AU - Kutzer, Megan
AU - Kurtz, Joachim
ID - 558
IS - 12
JF - Biology Letters
SN - 17449561
TI - Specificity of oral immune priming in the red flour beetle Tribolium castaneum
VL - 13
ER -
TY - CONF
AB - Proofs of space (PoS) were suggested as more ecological and economical alternative to proofs of work, which are currently used in blockchain designs like Bitcoin. The existing PoS are based on rather sophisticated graph pebbling lower bounds. Much simpler and in several aspects more efficient schemes based on inverting random functions have been suggested, but they don’t give meaningful security guarantees due to existing time-memory trade-offs. In particular, Hellman showed that any permutation over a domain of size N can be inverted in time T by an algorithm that is given S bits of auxiliary information whenever (Formula presented). For functions Hellman gives a weaker attack with S2· T≈ N2 (e.g., S= T≈ N2/3). To prove lower bounds, one considers an adversary who has access to an oracle f: [ N] → [N] and can make T oracle queries. The best known lower bound is S· T∈ Ω(N) and holds for random functions and permutations. We construct functions that provably require more time and/or space to invert. Specifically, for any constant k we construct a function [N] → [N] that cannot be inverted unless Sk· T∈ Ω(Nk) (in particular, S= T≈ (Formula presented). Our construction does not contradict Hellman’s time-memory trade-off, because it cannot be efficiently evaluated in forward direction. However, its entire function table can be computed in time quasilinear in N, which is sufficient for the PoS application. Our simplest construction is built from a random function oracle g: [N] × [N] → [ N] and a random permutation oracle f: [N] → N] and is defined as h(x) = g(x, x′) where f(x) = π(f(x′)) with π being any involution without a fixed point, e.g. flipping all the bits. For this function we prove that any adversary who gets S bits of auxiliary information, makes at most T oracle queries, and inverts h on an ϵ fraction of outputs must satisfy S2· T∈ Ω(ϵ2N2).
AU - Abusalah, Hamza M
AU - Alwen, Joel F
AU - Cohen, Bram
AU - Khilko, Danylo
AU - Pietrzak, Krzysztof Z
AU - Reyzin, Leonid
ID - 559
SN - 978-331970696-2
TI - Beyond Hellman’s time-memory trade-offs with applications to proofs of space
VL - 10625
ER -
TY - JOUR
AB - In a recent article (Jentzen et al. 2016 Commun. Math. Sci. 14, 1477–1500 (doi:10.4310/CMS.2016.v14. n6.a1)), it has been established that, for every arbitrarily slow convergence speed and every natural number d ? {4, 5, . . .}, there exist d-dimensional stochastic differential equations with infinitely often differentiable and globally bounded coefficients such that no approximation method based on finitely many observations of the driving Brownian motion can converge in absolute mean to the solution faster than the given speed of convergence. In this paper, we strengthen the above result by proving that this slow convergence phenomenon also arises in two (d = 2) and three (d = 3) space dimensions.
AU - Gerencser, Mate
AU - Jentzen, Arnulf
AU - Salimova, Diyora
ID - 560
IS - 2207
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
SN - 13645021
TI - On stochastic differential equations with arbitrarily slow convergence rates for strong approximation in two space dimensions
VL - 473
ER -
TY - JOUR
AB - Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape.
AU - Pleska, Maros
AU - Guet, Calin C
ID - 561
IS - 12
JF - Biology Letters
SN - 17449561
TI - Effects of mutations in phage restriction sites during escape from restriction–modification
VL - 13
ER -
TY - BOOK
AB - This book is a concise and self-contained introduction of recent techniques to prove local spectral universality for large random matrices. Random matrix theory is a fast expanding research area, and this book mainly focuses on the methods that the authors participated in developing over the past few years. Many other interesting topics are not included, and neither are several new developments within the framework of these methods. The authors have chosen instead to present key concepts that they believe are the core of these methods and should be relevant for future applications. They keep technicalities to a minimum to make the book accessible to graduate students. With this in mind, they include in this book the basic notions and tools for high-dimensional analysis, such as large deviation, entropy, Dirichlet form, and the logarithmic Sobolev inequality.
AU - Erdös, László
AU - Yau, Horng
ID - 567
SN - 9781470436483
TI - A dynamical approach to random matrix theory
VL - 28
ER -
TY - JOUR
AB - We study robust properties of zero sets of continuous maps f: X → ℝn. Formally, we analyze the family Z< r(f) := (g-1(0): ||g - f|| < r) of all zero sets of all continuous maps g closer to f than r in the max-norm. All of these sets are outside A := (x: |f(x)| ≥ r) and we claim that Z< r(f) is fully determined by A and an element of a certain cohomotopy group which (by a recent result) is computable whenever the dimension of X is at most 2n - 3. By considering all r > 0 simultaneously, the pointed cohomotopy groups form a persistence module-a structure leading to persistence diagrams as in the case of persistent homology or well groups. Eventually, we get a descriptor of persistent robust properties of zero sets that has better descriptive power (Theorem A) and better computability status (Theorem B) than the established well diagrams. Moreover, if we endow every point of each zero set with gradients of the perturbation, the robust description of the zero sets by elements of cohomotopy groups is in some sense the best possible (Theorem C).
AU - Franek, Peter
AU - Krcál, Marek
ID - 568
IS - 2
JF - Homology, Homotopy and Applications
SN - 15320073
TI - Persistence of zero sets
VL - 19
ER -
TY - JOUR
AB - The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.
AU - Spira, Felix
AU - Cuylen Haering, Sara
AU - Mehta, Shalin
AU - Samwer, Matthias
AU - Reversat, Anne
AU - Verma, Amitabh
AU - Oldenbourg, Rudolf
AU - Sixt, Michael K
AU - Gerlich, Daniel
ID - 569
JF - eLife
SN - 2050084X
TI - Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments
VL - 6
ER -
TY - JOUR
AB - Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.
AU - Lagator, Mato
AU - Sarikas, Srdjan
AU - Acar, Hande
AU - Bollback, Jonathan P
AU - Guet, Calin C
ID - 570
JF - eLife
SN - 2050084X
TI - Regulatory network structure determines patterns of intermolecular epistasis
VL - 6
ER -
TY - JOUR
AB - Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface.
AU - Gärtner, Florian R
AU - Ahmad, Zerkah
AU - Rosenberger, Gerhild
AU - Fan, Shuxia
AU - Nicolai, Leo
AU - Busch, Benjamin
AU - Yavuz, Gökce
AU - Luckner, Manja
AU - Ishikawa Ankerhold, Hellen
AU - Hennel, Roman
AU - Benechet, Alexandre
AU - Lorenz, Michael
AU - Chandraratne, Sue
AU - Schubert, Irene
AU - Helmer, Sebastian
AU - Striednig, Bianca
AU - Stark, Konstantin
AU - Janko, Marek
AU - Böttcher, Ralph
AU - Verschoor, Admar
AU - Leon, Catherine
AU - Gachet, Christian
AU - Gudermann, Thomas
AU - Mederos Y Schnitzler, Michael
AU - Pincus, Zachary
AU - Iannacone, Matteo
AU - Haas, Rainer
AU - Wanner, Gerhard
AU - Lauber, Kirsten
AU - Sixt, Michael K
AU - Massberg, Steffen
ID - 571
IS - 6
JF - Cell Press
SN - 00928674
TI - Migrating platelets are mechano scavengers that collect and bundle bacteria
VL - 171
ER -
TY - JOUR
AB - In this review, we summarize the different biosynthesis-related pathways that contribute to the regulation of endogenous auxin in plants. We demonstrate that all known genes involved in auxin biosynthesis also have a role in root formation, from the initiation of a root meristem during embryogenesis to the generation of a functional root system with a primary root, secondary lateral root branches and adventitious roots. Furthermore, the versatile adaptation of root development in response to environmental challenges is mediated by both local and distant control of auxin biosynthesis. In conclusion, auxin homeostasis mediated by spatial and temporal regulation of auxin biosynthesis plays a central role in determining root architecture.
AU - Olatunji, Damilola
AU - Geelen, Danny
AU - Verstraeten, Inge
ID - 572
IS - 12
JF - International Journal of Molecular Sciences
TI - Control of endogenous auxin levels in plant root development
VL - 18
ER -
TY - JOUR
AB - The first hundred attoseconds of the electron dynamics during strong field tunneling ionization are investigated. We quantify theoretically how the electron’s classical trajectories in the continuum emerge from the tunneling process and test the results with those achieved in parallel from attoclock measurements. An especially high sensitivity on the tunneling barrier is accomplished here by comparing the momentum distributions of two atomic species of slightly deviating atomic potentials (argon and krypton) being ionized under absolutely identical conditions with near-infrared laser pulses (1300 nm). The agreement between experiment and theory provides clear evidence for a nonzero tunneling time delay and a nonvanishing longitudinal momentum of the electron at the “tunnel exit.”
AU - Camus, Nicolas
AU - Yakaboylu, Enderalp
AU - Fechner, Lutz
AU - Klaiber, Michael
AU - Laux, Martin
AU - Mi, Yonghao
AU - Hatsagortsyan, Karen Z.
AU - Pfeifer, Thomas
AU - Keitel, Christoph H.
AU - Moshammer, Robert
ID - 6013
IS - 2
JF - Physical Review Letters
SN - 0031-9007
TI - Experimental evidence for quantum tunneling time
VL - 119
ER -
TY - CHAP
AB - In several settings of physics and chemistry one has to deal with molecules interacting with some kind of an external environment, be it a gas, a solution, or a crystal surface. Understanding molecular processes in the presence of such a many-particle bath is inherently challenging, and usually requires large-scale numerical computations. Here, we present an alternative approach to the problem, based on the notion of the angulon quasiparticle. We show that molecules rotating inside superfluid helium nanodroplets and Bose–Einstein condensates form angulons, and therefore can be described by straightforward solutions of a simple microscopic Hamiltonian. Casting the problem in the language of angulons allows us not only to greatly simplify it, but also to gain insights into the origins of the observed phenomena and to make predictions for future experimental studies.
AU - Lemeshko, Mikhail
AU - Schmidt, Richard
ED - Dulieu, Oliver
ED - Osterwalder, Andreas
ID - 604
SN - 20413181
T2 - Cold Chemistry: Molecular Scattering and Reactivity Near Absolute Zero
TI - Molecular impurities interacting with a many-particle environment: From ultracold gases to helium nanodroplets
VL - 11
ER -
TY - CONF
AB - Position based cryptography (PBC), proposed in the seminal work of Chandran, Goyal, Moriarty, and Ostrovsky (SIAM J. Computing, 2014), aims at constructing cryptographic schemes in which the identity of the user is his geographic position. Chandran et al. construct PBC schemes for secure positioning and position-based key agreement in the bounded-storage model (Maurer, J. Cryptology, 1992). Apart from bounded memory, their security proofs need a strong additional restriction on the power of the adversary: he cannot compute joint functions of his inputs. Removing this assumption is left as an open problem. We show that an answer to this question would resolve a long standing open problem in multiparty communication complexity: finding a function that is hard to compute with low communication complexity in the simultaneous message model, but easy to compute in the fully adaptive model. On a more positive side: we also show some implications in the other direction, i.e.: we prove that lower bounds on the communication complexity of certain multiparty problems imply existence of PBC primitives. Using this result we then show two attractive ways to “bypass” our hardness result: the first uses the random oracle model, the second weakens the locality requirement in the bounded-storage model to online computability. The random oracle construction is arguably one of the simplest proposed so far in this area. Our results indicate that constructing improved provably secure protocols for PBC requires a better understanding of multiparty communication complexity. This is yet another example where negative results in one area (in our case: lower bounds in multiparty communication complexity) can be used to construct secure cryptographic schemes.
AU - Brody, Joshua
AU - Dziembowski, Stefan
AU - Faust, Sebastian
AU - Pietrzak, Krzysztof Z
ED - Kalai, Yael
ED - Reyzin, Leonid
ID - 605
SN - 978-331970499-9
TI - Position based cryptography and multiparty communication complexity
VL - 10677
ER -
TY - CONF
AB - Several cryptographic schemes and applications are based on functions that are both reasonably efficient to compute and moderately hard to invert, including client puzzles for Denial-of-Service protection, password protection via salted hashes, or recent proof-of-work blockchain systems. Despite their wide use, a definition of this concept has not yet been distilled and formalized explicitly. Instead, either the applications are proven directly based on the assumptions underlying the function, or some property of the function is proven, but the security of the application is argued only informally. The goal of this work is to provide a (universal) definition that decouples the efforts of designing new moderately hard functions and of building protocols based on them, serving as an interface between the two. On a technical level, beyond the mentioned definitions, we instantiate the model for four different notions of hardness. We extend the work of Alwen and Serbinenko (STOC 2015) by providing a general tool for proving security for the first notion of memory-hard functions that allows for provably secure applications. The tool allows us to recover all of the graph-theoretic techniques developed for proving security under the older, non-composable, notion of security used by Alwen and Serbinenko. As an application of our definition of moderately hard functions, we prove the security of two different schemes for proofs of effort (PoE). We also formalize and instantiate the concept of a non-interactive proof of effort (niPoE), in which the proof is not bound to a particular communication context but rather any bit-string chosen by the prover.
AU - Alwen, Joel F
AU - Tackmann, Björn
ED - Kalai, Yael
ED - Reyzin, Leonid
ID - 609
SN - 978-331970499-9
TI - Moderately hard functions: Definition, instantiations, and applications
VL - 10677
ER -
TY - JOUR
AB - The fact that the complete graph K5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph Kn embeds in a closed surface M (other than the Klein bottle) if and only if (n−3)(n−4) ≤ 6b1(M), where b1(M) is the first Z2-Betti number of M. On the other hand, van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of Kn+1) embeds in R2k if and only if n ≤ 2k + 1. Two decades ago, Kühnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k − 1)-connected 2k-manifold with kth Z2-Betti number bk only if the following generalized Heawood inequality holds: (k+1 n−k−1) ≤ (k+1 2k+1)bk. This is a common generalization of the case of graphs on surfaces as well as the van Kampen–Flores theorem. In the spirit of Kühnel’s conjecture, we prove that if the k-skeleton of the n-simplex embeds in a compact 2k-manifold with kth Z2-Betti number bk, then n ≤ 2bk(k 2k+2)+2k+4. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k−1)-connected. Our results generalize to maps without q-covered points, in the spirit of Tverberg’s theorem, for q a prime power. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.
AU - Goaoc, Xavier
AU - Mabillard, Isaac
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 610
IS - 2
JF - Israel Journal of Mathematics
TI - On generalized Heawood inequalities for manifolds: A van Kampen–Flores type nonembeddability result
VL - 222
ER -
TY - JOUR
AB - Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.
AU - Bradley, Desmond
AU - Xu, Ping
AU - Mohorianu, Irina
AU - Whibley, Annabel
AU - Field, David
AU - Tavares, Hugo
AU - Couchman, Matthew
AU - Copsey, Lucy
AU - Carpenter, Rosemary
AU - Li, Miaomiao
AU - Li, Qun
AU - Xue, Yongbiao
AU - Dalmay, Tamas
AU - Coen, Enrico
ID - 611
IS - 6365
JF - Science
SN - 00368075
TI - Evolution of flower color pattern through selection on regulatory small RNAs
VL - 358
ER -
TY - JOUR
AB - Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.
AU - Chait, Remy P
AU - Ruess, Jakob
AU - Bergmiller, Tobias
AU - Tkacik, Gasper
AU - Guet, Calin C
ID - 613
IS - 1
JF - Nature Communications
SN - 20411723
TI - Shaping bacterial population behavior through computer interfaced control of individual cells
VL - 8
ER -
TY - JOUR
AB - Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes.
AU - Fraisse, Christelle
AU - Picard, Marion A
AU - Vicoso, Beatriz
ID - 614
IS - 1
JF - Nature Communications
SN - 20411723
TI - The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W
VL - 8
ER -
TY - JOUR
AB - We show that the Dyson Brownian Motion exhibits local universality after a very short time assuming that local rigidity and level repulsion of the eigenvalues hold. These conditions are verified, hence bulk spectral universality is proven, for a large class of Wigner-like matrices, including deformed Wigner ensembles and ensembles with non-stochastic variance matrices whose limiting densities differ from Wigner's semicircle law.
AU - Erdös, László
AU - Schnelli, Kevin
ID - 615
IS - 4
JF - Annales de l'institut Henri Poincare (B) Probability and Statistics
SN - 02460203
TI - Universality for random matrix flows with time dependent density
VL - 53
ER -
TY - JOUR
AB - PMAC is a simple and parallel block-cipher mode of operation, which was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a (pseudo)random permutation over n-bit strings, PMAC constitutes a provably secure variable input-length (pseudo)random function. For adversaries making q queries, each of length at most l (in n-bit blocks), and of total length σ ≤ ql, the original paper proves an upper bound on the distinguishing advantage of Ο(σ2/2n), while the currently best bound is Ο (qσ/2n).In this work we show that this bound is tight by giving an attack with advantage Ω (q2l/2n). In the PMAC construction one initially XORs a mask to every message block, where the mask for the ith block is computed as τi := γi·L, where L is a (secret) random value, and γi is the i-th codeword of the Gray code. Our attack applies more generally to any sequence of γi’s which contains a large coset of a subgroup of GF(2n). We then investigate if the security of PMAC can be further improved by using τi’s that are k-wise independent, for k > 1 (the original distribution is only 1-wise independent). We observe that the security of PMAC will not increase in general, even if the masks are chosen from a 2-wise independent distribution, and then prove that the security increases to O(q<2/2n), if the τi are 4-wise independent. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether 3-wise independence is already sufficient to get this level of security is left as an open problem.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Rybar, Michal
ID - 6196
IS - 2
JF - IACR Transactions on Symmetric Cryptology
TI - The exact security of PMAC
VL - 2016
ER -
TY - JOUR
AB - The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non-cell-autonomous or community effects in regulating RGP proliferation behavior and lineage progression.
AU - Beattie, Robert J
AU - Hippenmeyer, Simon
ID - 621
IS - 24
JF - FEBS letters
SN - 00145793
TI - Mechanisms of radial glia progenitor cell lineage progression
VL - 591
ER -
TY - CHAP
AB - Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology.
AU - Hill Yardin, Elisa
AU - Mckeown, Sonja
AU - Novarino, Gaia
AU - Grabrucker, Andreas
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 623
SN - 03015556
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Extracerebral dysfunction in animal models of autism spectrum disorder
VL - 224
ER -
TY - JOUR
AB - Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.
AU - Nikolic, Nela
AU - Didara, Zrinka
AU - Moll, Isabella
ID - 624
IS - 9
JF - PeerJ
SN - 21678359
TI - MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations
VL - 2017
ER -
TY - CHAP
AB - In the analysis of reactive systems a quantitative objective assigns a real value to every trace of the system. The value decision problem for a quantitative objective requires a trace whose value is at least a given threshold, and the exact value decision problem requires a trace whose value is exactly the threshold. We compare the computational complexity of the value and exact value decision problems for classical quantitative objectives, such as sum, discounted sum, energy, and mean-payoff for two standard models of reactive systems, namely, graphs and graph games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ED - Aceto, Luca
ED - Bacci, Giorgio
ED - Ingólfsdóttir, Anna
ED - Legay, Axel
ED - Mardare, Radu
ID - 625
SN - 03029743
T2 - Models, Algorithms, Logics and Tools
TI - The cost of exactness in quantitative reachability
VL - 10460
ER -
TY - JOUR
AB - Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Véber, Amandine
ID - 626
JF - Theoretical Population Biology
SN - 00405809
TI - The infinitesimal model: Definition derivation and implications
VL - 118
ER -
TY - JOUR
AB - Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases.
AU - Jiang, Changyu
AU - Zhai, Ming-Zhu
AU - Yan, Dong
AU - Li, Da
AU - Li, Chen
AU - Zhang, Yonghong
AU - Xiao, Lizu
AU - Xiong, Donglin
AU - Deng, Qiwen
AU - Sun, Wuping
ID - 627
IS - 43
JF - Oncotarget
SN - 19492553
TI - Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity
VL - 8
ER -
TY - CONF
AB - We consider the problem of developing automated techniques for solving recurrence relations to aid the expected-runtime analysis of programs. The motivation is that several classical textbook algorithms have quite efficient expected-runtime complexity, whereas the corresponding worst-case bounds are either inefficient (e.g., Quick-Sort), or completely ineffective (e.g., Coupon-Collector). Since the main focus of expected-runtime analysis is to obtain efficient bounds, we consider bounds that are either logarithmic, linear or almost-linear (O(log n), O(n), O(n · log n), respectively, where n represents the input size). Our main contribution is an efficient (simple linear-time algorithm) sound approach for deriving such expected-runtime bounds for the analysis of recurrence relations induced by randomized algorithms. The experimental results show that our approach can efficiently derive asymptotically optimal expected-runtime bounds for recurrences of classical randomized algorithms, including Randomized-Search, Quick-Sort, Quick-Select, Coupon-Collector, where the worst-case bounds are either inefficient (such as linear as compared to logarithmic expected-runtime complexity, or quadratic as compared to linear or almost-linear expected-runtime complexity), or ineffective.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Murhekar, Aniket
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 628
SN - 978-331963386-2
TI - Automated recurrence analysis for almost linear expected runtime bounds
VL - 10426
ER -
TY - THES
AB - The main objects considered in the present work are simplicial and CW-complexes with vertices forming a random point cloud. In particular, we consider a Poisson point process in R^n and study Delaunay and Voronoi complexes of the first and higher orders and weighted Delaunay complexes obtained as sections of Delaunay complexes, as well as the Čech complex. Further, we examine theDelaunay complex of a Poisson point process on the sphere S^n, as well as of a uniform point cloud, which is equivalent to the convex hull, providing a connection to the theory of random polytopes. Each of the complexes in question can be endowed with a radius function, which maps its cells to the radii of appropriately chosen circumspheres, called the radius of the cell. Applying and developing discrete Morse theory for these functions, joining it together with probabilistic and sometimes analytic machinery, and developing several integral geometric tools, we aim at getting the distributions of circumradii of typical cells. For all considered complexes, we are able to generalize and obtain up to constants the distribution of radii of typical intervals of all types. In low dimensions the constants can be computed explicitly, thus providing the explicit expressions for the expected numbers of cells. In particular, it allows to find the expected density of simplices of every dimension for a Poisson point process in R^4, whereas the result for R^3 was known already in 1970's.
AU - Nikitenko, Anton
ID - 6287
TI - Discrete Morse theory for random complexes
ER -
TY - CHAP
AB - Even simple cells like bacteria have precisely regulated cellular anatomies, which allow them to grow, divide and to respond to internal or external cues with high fidelity. How spatial and temporal intracellular organization in prokaryotic cells is achieved and maintained on the basis of locally interacting proteins still remains largely a mystery. Bulk biochemical assays with purified components and in vivo experiments help us to approach key cellular processes from two opposite ends, in terms of minimal and maximal complexity. However, to understand how cellular phenomena emerge, that are more than the sum of their parts, we have to assemble cellular subsystems step by step from the bottom up. Here, we review recent in vitro reconstitution experiments with proteins of the bacterial cell division machinery and illustrate how they help to shed light on fundamental cellular mechanisms that constitute spatiotemporal order and regulate cell division.
AU - Loose, Martin
AU - Zieske, Katja
AU - Schwille, Petra
ID - 629
T2 - Prokaryotic Cytoskeletons
TI - Reconstitution of protein dynamics involved in bacterial cell division
VL - 84
ER -
TY - CONF
AB - Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.
AU - Sauermann, Stefan
AU - David, Veronika
AU - Schlögl, Alois
AU - Egelkraut, Reinhard
AU - Frohner, Matthias
AU - Pohn, Birgit
AU - Urbauer, Philipp
AU - Mense, Alexander
ID - 630
SN - 978-161499758-0
TI - Biosignals standards and FHIR: The way to go
VL - 236
ER -
TY - CONF
AB - Template polyhedra generalize intervals and octagons to polyhedra whose facets are orthogonal to a given set of arbitrary directions. They have been employed in the abstract interpretation of programs and, with particular success, in the reachability analysis of hybrid automata. While previously, the choice of directions has been left to the user or a heuristic, we present a method for the automatic discovery of directions that generalize and eliminate spurious counterexamples. We show that for the class of convex hybrid automata, i.e., hybrid automata with (possibly nonlinear) convex constraints on derivatives, such directions always exist and can be found using convex optimization. We embed our method inside a CEGAR loop, thus enabling the time-unbounded reachability analysis of an important and richer class of hybrid automata than was previously possible. We evaluate our method on several benchmarks, demonstrating also its superior efficiency for the special case of linear hybrid automata.
AU - Bogomolov, Sergiy
AU - Frehse, Goran
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
ID - 631
SN - 978-366254576-8
TI - Counterexample guided refinement of template polyhedra
VL - 10205
ER -
TY - JOUR
AB - We consider a 2D quantum system of N bosons in a trapping potential |x|s, interacting via a pair potential of the form N2β−1 w(Nβ x). We show that for all 0 < β < (s + 1)/(s + 2), the leading order behavior of ground states of the many-body system is described in the large N limit by the corresponding cubic nonlinear Schrödinger energy functional. Our result covers the focusing case (w < 0) where even the stability of the many-body system is not obvious. This answers an open question mentioned by X. Chen and J. Holmer for harmonic traps (s = 2). Together with the BBGKY hierarchy approach used by these authors, our result implies the convergence of the many-body quantum dynamics to the focusing NLS equation with harmonic trap for all 0 < β < 3/4.
AU - Lewin, Mathieu
AU - Nam, Phan
AU - Rougerie, Nicolas
ID - 632
IS - 6
JF - Proceedings of the American Mathematical Society
TI - A note on 2D focusing many boson systems
VL - 145
ER -
TY - CONF
AB - A Rapidly-exploring Random Tree (RRT) is an algorithm which can search a non-convex region of space by incrementally building a space-filling tree. The tree is constructed from random points drawn from system’s state space and is biased to grow towards large unexplored areas in the system. RRT can provide better coverage of a system’s possible behaviors compared with random simulations, but is more lightweight than full reachability analysis. In this paper, we explore some of the design decisions encountered while implementing a hybrid extension of the RRT algorithm, which have not been elaborated on before. In particular, we focus on handling non-determinism, which arises due to discrete transitions. We introduce the notion of important points to account for this phenomena. We showcase our ideas using heater and navigation benchmarks.
AU - Bak, Stanley
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Kumar, Aviral
ED - Abate, Alessandro
ED - Bodo, Sylvie
ID - 633
SN - 978-331963500-2
TI - Challenges and tool implementation of hybrid rapidly exploring random trees
VL - 10381
ER -
TY - CHAP
AB - As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.
AU - Schroeder, Jan
AU - Deliu, Elena
AU - Novarino, Gaia
AU - Schmeisser, Michael
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 634
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder
VL - 224
ER -
TY - CONF
AB - Memory-hard functions (MHFs) are hash algorithms whose evaluation cost is dominated by memory cost. As memory, unlike computation, costs about the same across different platforms, MHFs cannot be evaluated at significantly lower cost on dedicated hardware like ASICs. MHFs have found widespread applications including password hashing, key derivation, and proofs-of-work. This paper focuses on scrypt, a simple candidate MHF designed by Percival, and described in RFC 7914. It has been used within a number of cryptocurrencies (e.g., Litecoin and Dogecoin) and has been an inspiration for Argon2d, one of the winners of the recent password-hashing competition. Despite its popularity, no rigorous lower bounds on its memory complexity are known. We prove that scrypt is optimally memory-hard, i.e., its cumulative memory complexity (cmc) in the parallel random oracle model is Ω(n2w), where w and n are the output length and number of invocations of the underlying hash function, respectively. High cmc is a strong security target for MHFs introduced by Alwen and Serbinenko (STOC’15) which implies high memory cost even for adversaries who can amortize the cost over many evaluations and evaluate the underlying hash functions many times in parallel. Our proof is the first showing optimal memory-hardness for any MHF. Our result improves both quantitatively and qualitatively upon the recent work by Alwen et al. (EUROCRYPT’16) who proved a weaker lower bound of Ω(n2w/ log2 n) for a restricted class of adversaries.
AU - Alwen, Joel F
AU - Chen, Binchi
AU - Pietrzak, Krzysztof Z
AU - Reyzin, Leonid
AU - Tessaro, Stefano
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 635
SN - 978-331956616-0
TI - Scrypt is maximally memory hard
VL - 10212
ER -
TY - CONF
AB - Signal regular expressions can specify sequential properties of real-valued signals based on threshold conditions, regular operations, and duration constraints. In this paper we endow them with a quantitative semantics which indicates how robustly a signal matches or does not match a given expression. First, we show that this semantics is a safe approximation of a distance between the signal and the language defined by the expression. Then, we consider the robust matching problem, that is, computing the quantitative semantics of every segment of a given signal relative to an expression. We present an algorithm that solves this problem for piecewise-constant and piecewise-linear signals and show that for such signals the robustness map is a piecewise-linear function. The availability of an indicator describing how robustly a signal segment matches some regular pattern provides a general framework for quantitative monitoring of cyber-physical systems.
AU - Bakhirkin, Alexey
AU - Ferrere, Thomas
AU - Maler, Oded
AU - Ulus, Dogan
ED - Abate, Alessandro
ED - Geeraerts, Gilles
ID - 636
SN - 978-331965764-6
TI - On the quantitative semantics of regular expressions over real-valued signals
VL - 10419
ER -
TY - CONF
AB - For many cryptographic primitives, it is relatively easy to achieve selective security (where the adversary commits a-priori to some of the choices to be made later in the attack) but appears difficult to achieve the more natural notion of adaptive security (where the adversary can make all choices on the go as the attack progresses). A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption (Panjwani, TCC ’07 and Fuchsbauer et al., CRYPTO ’15), constrained PRFs (Fuchsbauer et al., ASIACRYPT ’14), and Yao garbled circuits (Jafargholi and Wichs, TCC ’16b). Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework that connects all of these works and allows us to present them in a unified and simplified fashion. Moreover, we use the framework to derive a new result for adaptively secure secret sharing over access structures defined via monotone circuits. We envision that further applications will follow in the future. Underlying our framework is the following simple idea. It is well known that selective security, where the adversary commits to n-bits of information about his future choices, automatically implies adaptive security at the cost of amplifying the adversary’s advantage by a factor of up to 2n. However, in some cases the proof of selective security proceeds via a sequence of hybrids, where each pair of adjacent hybrids locally only requires some smaller partial information consisting of m ≪ n bits. The partial information needed might be completely different between different pairs of hybrids, and if we look across all the hybrids we might rely on the entire n-bit commitment. Nevertheless, the above is sufficient to prove adaptive security, at the cost of amplifying the adversary’s advantage by a factor of only 2m ≪ 2n. In all of our examples using the above framework, the different hybrids are captured by some sort of a graph pebbling game and the amount of information that the adversary needs to commit to in each pair of hybrids is bounded by the maximum number of pebbles in play at any point in time. Therefore, coming up with better strategies for proving adaptive security translates to various pebbling strategies for different types of graphs.
AU - Jafargholi, Zahra
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Komargodski, Ilan
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Katz, Jonathan
ED - Shacham, Hovav
ID - 637
SN - 978-331963687-0
TI - Be adaptive avoid overcommitting
VL - 10401
ER -
TY - GEN
ED - Bogomolov, Sergiy
ED - Martel, Matthieu
ED - Prabhakar, Pavithra
ID - 638
TI - Numerical Software Verification
VL - 10152
ER -
TY - CONF
AB - Data-independent Memory Hard Functions (iMHFS) are finding a growing number of applications in security; especially in the domain of password hashing. An important property of a concrete iMHF is specified by fixing a directed acyclic graph (DAG) Gn on n nodes. The quality of that iMHF is then captured by the following two pebbling complexities of Gn: – The parallel cumulative pebbling complexity Π∥cc(Gn) must be as high as possible (to ensure that the amortized cost of computing the function on dedicated hardware is dominated by the cost of memory). – The sequential space-time pebbling complexity Πst(Gn) should be as close as possible to Π∥cc(Gn) (to ensure that using many cores in parallel and amortizing over many instances does not give much of an advantage). In this paper we construct a family of DAGs with best possible parameters in an asymptotic sense, i.e., where Π∥cc(Gn) = Ω(n2/ log(n)) (which matches a known upper bound) and Πst(Gn) is within a constant factor of Π∥cc(Gn). Our analysis relies on a new connection between the pebbling complexity of a DAG and its depth-robustness (DR) – a well studied combinatorial property. We show that high DR is sufficient for high Π∥cc. Alwen and Blocki (CRYPTO’16) showed that high DR is necessary and so, together, these results fully characterize DAGs with high Π∥cc in terms of DR. Complementing these results, we provide new upper and lower bounds on the Π∥cc of several important candidate iMHFs from the literature. We give the first lower bounds on the memory hardness of the Catena and Balloon Hashing functions in a parallel model of computation and we give the first lower bounds of any kind for (a version) of Argon2i. Finally we describe a new class of pebbling attacks improving on those of Alwen and Blocki (CRYPTO’16). By instantiating these attacks we upperbound the Π∥cc of the Password Hashing Competition winner Argon2i and one of the Balloon Hashing functions by O (n1.71). We also show an upper bound of O(n1.625) for the Catena functions and the two remaining Balloon Hashing functions.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Pietrzak, Krzysztof Z
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 640
SN - 978-331956616-0
TI - Depth-robust graphs and their cumulative memory complexity
VL - 10212
ER -
TY - CONF
AB - We introduce two novel methods for learning parameters of graphical models for image labelling. The following two tasks underline both methods: (i) perturb model parameters based on given features and ground truth labelings, so as to exactly reproduce these labelings as optima of the local polytope relaxation of the labelling problem; (ii) train a predictor for the perturbed model parameters so that improved model parameters can be applied to the labelling of novel data. Our first method implements task (i) by inverse linear programming and task (ii) using a regressor e.g. a Gaussian process. Our second approach simultaneously solves tasks (i) and (ii) in a joint manner, while being restricted to linearly parameterised predictors. Experiments demonstrate the merits of both approaches.
AU - Trajkovska, Vera
AU - Swoboda, Paul
AU - Åström, Freddie
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 641
SN - 978-331958770-7
TI - Graphical model parameter learning by inverse linear programming
VL - 10302
ER -
TY - JOUR
AB - Cauchy problems with SPDEs on the whole space are localized to Cauchy problems on a ball of radius R. This localization reduces various kinds of spatial approximation schemes to finite dimensional problems. The error is shown to be exponentially small. As an application, a numerical scheme is presented which combines the localization and the space and time discretization, and thus is fully implementable.
AU - Gerencser, Mate
AU - Gyöngy, István
ID - 642
IS - 307
JF - Mathematics of Computation
SN - 00255718
TI - Localization errors in solving stochastic partial differential equations in the whole space
VL - 86
ER -
TY - GEN
AB - Synchronous programs are easy to specify because the side effects of an operation are finished by the time the invocation of the operation returns to the caller. Asynchronous programs, on the other hand, are difficult to specify because there are side effects due to pending computation scheduled as a result of the invocation of an operation. They are also difficult to verify because of the large number of possible interleavings of concurrent asynchronous computation threads. We show that specifications and correctness proofs for asynchronous programs can be structured by introducing the fiction, for proof purposes, that intermediate, non-quiescent states of asynchronous operations can be ignored. Then, the task of specification becomes relatively simple and the task of verification can be naturally decomposed into smaller sub-tasks. The sub-tasks iteratively summarize, guided by the structure of an asynchronous program, the atomic effect of non-atomic operations and the synchronous effect of asynchronous operations. This structuring of specifications and proofs corresponds to the introduction of multiple layers of stepwise refinement for asynchronous programs. We present the first proof rule, called synchronization, to reduce asynchronous invocations on a lower layer to synchronous invocations on a higher layer. We implemented our proof method in CIVL and evaluated it on a collection of benchmark programs.
AU - Henzinger, Thomas A
AU - Kragl, Bernhard
AU - Qadeer, Shaz
ID - 6426
SN - 2664-1690
TI - Synchronizing the asynchronous
ER -
TY - JOUR
AB - It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT) were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H2O2 levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.
AU - Sun, Wuping
AU - Zhai, Ming-Zhu
AU - Zhou, Qian
AU - Qian, Chengrui
AU - Jiang, Changyu
ID - 643
IS - 4
JF - Chinese Journal of Physiology
SN - 03044920
TI - Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats
VL - 60
ER -
TY - JOUR
AB - An instance of the valued constraint satisfaction problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P 6= NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in f0;1g corresponds to ordinary CSPs, where one deals only with the feasibility issue, and there is no optimization. This case is the subject of the algebraic CSP dichotomy conjecture predicting for which constraint languages CSPs are tractable (i.e., solvable in polynomial time) and for which they are NP-hard. The case when all allowed functions take only finite values corresponds to a finitevalued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Živný. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e., the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 644
IS - 3
JF - SIAM Journal on Computing
TI - The complexity of general-valued CSPs
VL - 46
ER -
TY - CONF
AB - Markov decision processes (MDPs) are standard models for probabilistic systems with non-deterministic behaviours. Long-run average rewards provide a mathematically elegant formalism for expressing long term performance. Value iteration (VI) is one of the simplest and most efficient algorithmic approaches to MDPs with other properties, such as reachability objectives. Unfortunately, a naive extension of VI does not work for MDPs with long-run average rewards, as there is no known stopping criterion. In this work our contributions are threefold. (1) We refute a conjecture related to stopping criteria for MDPs with long-run average rewards. (2) We present two practical algorithms for MDPs with long-run average rewards based on VI. First, we show that a combination of applying VI locally for each maximal end-component (MEC) and VI for reachability objectives can provide approximation guarantees. Second, extending the above approach with a simulation-guided on-demand variant of VI, we present an anytime algorithm that is able to deal with very large models. (3) Finally, we present experimental results showing that our methods significantly outperform the standard approaches on several benchmarks.
AU - Ashok, Pranav
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Kretinsky, Jan
AU - Meggendorfer, Tobias
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 645
SN - 978-331963386-2
TI - Value iteration for long run average reward in markov decision processes
VL - 10426
ER -
TY - CONF
AB - We present a novel convex relaxation and a corresponding inference algorithm for the non-binary discrete tomography problem, that is, reconstructing discrete-valued images from few linear measurements. In contrast to state of the art approaches that split the problem into a continuous reconstruction problem for the linear measurement constraints and a discrete labeling problem to enforce discrete-valued reconstructions, we propose a joint formulation that addresses both problems simultaneously, resulting in a tighter convex relaxation. For this purpose a constrained graphical model is set up and evaluated using a novel relaxation optimized by dual decomposition. We evaluate our approach experimentally and show superior solutions both mathematically (tighter relaxation) and experimentally in comparison to previously proposed relaxations.
AU - Kuske, Jan
AU - Swoboda, Paul
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 646
SN - 978-331958770-7
TI - A novel convex relaxation for non binary discrete tomography
VL - 10302
ER -
TY - CONF
AB - Despite researchers’ efforts in the last couple of decades, reachability analysis is still a challenging problem even for linear hybrid systems. Among the existing approaches, the most practical ones are mainly based on bounded-time reachable set over-approximations. For the purpose of unbounded-time analysis, one important strategy is to abstract the original system and find an invariant for the abstraction. In this paper, we propose an approach to constructing a new kind of abstraction called conic abstraction for affine hybrid systems, and to computing reachable sets based on this abstraction. The essential feature of a conic abstraction is that it partitions the state space of a system into a set of convex polyhedral cones which is derived from a uniform conic partition of the derivative space. Such a set of polyhedral cones is able to cut all trajectories of the system into almost straight segments so that every segment of a reach pipe in a polyhedral cone tends to be straight as well, and hence can be over-approximated tightly by polyhedra using similar techniques as HyTech or PHAVer. In particular, for diagonalizable affine systems, our approach can guarantee to find an invariant for unbounded reachable sets, which is beyond the capability of bounded-time reachability analysis tools. We implemented the approach in a tool and experiments on benchmarks show that our approach is more powerful than SpaceEx and PHAVer in dealing with diagonalizable systems.
AU - Bogomolov, Sergiy
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
AU - Kong, Hui
ID - 647
SN - 978-331965764-6
TI - Conic abstractions for hybrid systems
VL - 10419
ER -
TY - CONF
AB - Pseudoentropy has found a lot of important applications to cryptography and complexity theory. In this paper we focus on the foundational problem that has not been investigated so far, namely by how much pseudoentropy (the amount seen by computationally bounded attackers) diﬀers from its information-theoretic counterpart (seen by unbounded observers), given certain limits on attacker’s computational power? We provide the following answer for HILL pseudoentropy, which exhibits a threshold behavior around the size exponential in the entropy amount:– If the attacker size (s) and advantage () satisfy s (formula presented) where k is the claimed amount of pseudoentropy, then the pseudoentropy boils down to the information-theoretic smooth entropy. – If s (formula presented) then pseudoentropy could be arbitrarily bigger than the information-theoretic smooth entropy. Besides answering the posted question, we show an elegant application of our result to the complexity theory, namely that it implies the clas-sical result on the existence of functions hard to approximate (due to Pippenger). In our approach we utilize non-constructive techniques: the duality of linear programming and the probabilistic method.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 648
SN - 978-331955910-0
TI - On the complexity of breaking pseudoentropy
VL - 10185
ER -
TY - CHAP
AB - We give a short overview on a recently developed notion of Ricci curvature for discrete spaces. This notion relies on geodesic convexity properties of the relative entropy along geodesics in the space of probability densities, for a metric which is similar to (but different from) the 2-Wasserstein metric. The theory can be considered as a discrete counterpart to the theory of Ricci curvature for geodesic measure spaces developed by Lott–Sturm–Villani.
AU - Maas, Jan
ED - Najman, Laurent
ED - Romon, Pascal
ID - 649
T2 - Modern Approaches to Discrete Curvature
TI - Entropic Ricci curvature for discrete spaces
VL - 2184
ER -
TY - CONF
AB - In this work we present a short and unified proof for the Strong and Weak Regularity Lemma, based on the cryptographic tech-nique called low-complexity approximations. In short, both problems reduce to a task of finding constructively an approximation for a certain target function under a class of distinguishers (test functions), where dis-tinguishers are combinations of simple rectangle-indicators. In our case these approximations can be learned by a simple iterative procedure, which yields a unified and simple proof, achieving for any graph with density d and any approximation parameter the partition size. The novelty in our proof is: (a) a simple approach which yields both strong and weaker variant, and (b) improvements when d = o(1). At an abstract level, our proof can be seen a refinement and simplification of the “analytic” proof given by Lovasz and Szegedy.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 650
SN - 03029743
TI - A cryptographic view of regularity lemmas: Simpler unified proofs and refined bounds
VL - 10185
ER -
TY - JOUR
AB - Superhydrophobic surfaces reduce the frictional drag between water and solid materials, but this effect is often temporary. The realization of sustained drag reduction has applications for water vehicles and pipeline flows.
AU - Hof, Björn
ID - 651
IS - 7636
JF - Nature
SN - 00280836
TI - Fluid dynamics: Water flows out of touch
VL - 541
ER -
TY - CONF
AB - A (possibly degenerate) drawing of a graph G in the plane is approximable by an embedding if it can be turned into an embedding by an arbitrarily small perturbation. We show that testing, whether a drawing of a planar graph G in the plane is approximable by an embedding, can be carried out in polynomial time, if a desired embedding of G belongs to a fixed isotopy class, i.e., the rotation system (or equivalently the faces) of the embedding of G and the choice of outer face are fixed. In other words, we show that c-planarity with embedded pipes is tractable for graphs with fixed embeddings. To the best of our knowledge an analogous result was previously known essentially only when G is a cycle.
AU - Fulek, Radoslav
ID - 6517
TI - Embedding graphs into embedded graphs
VL - 92
ER -
TY - CONF
AB - Graph games with omega-regular winning conditions provide a mathematical framework to analyze a wide range of problems in the analysis of reactive systems and programs (such as the synthesis of reactive systems, program repair, and the verification of branching time properties). Parity conditions are canonical forms to specify omega-regular winning conditions. Graph games with parity conditions are equivalent to mu-calculus model checking, and thus a very important algorithmic problem. Symbolic algorithms are of great significance because they provide scalable algorithms for the analysis of large finite-state systems, as well as algorithms for the analysis of infinite-state systems with finite quotient. A set-based symbolic algorithm uses the basic set operations and the one-step predecessor operators. We consider graph games with n vertices and parity conditions with c priorities (equivalently, a mu-calculus formula with c alternations of least and greatest fixed points). While many explicit algorithms exist for graph games with parity conditions, for set-based symbolic algorithms there are only two algorithms (notice that we use space to refer to the number of sets stored by a symbolic algorithm): (a) the basic algorithm that requires O(n^c) symbolic operations and linear space; and (b) an improved algorithm that requires O(n^{c/2+1}) symbolic operations but also O(n^{c/2+1}) space (i.e., exponential space). In this work we present two set-based symbolic algorithms for parity games: (a) our first algorithm requires O(n^{c/2+1}) symbolic operations and only requires linear space; and (b) developing on our first algorithm, we present an algorithm that requires O(n^{c/3+1}) symbolic operations and only linear space. We also present the first linear space set-based symbolic algorithm for parity games that requires at most a sub-exponential number of symbolic operations.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika
AU - Loitzenbauer, Veronika
ID - 6519
TI - Improved set-based symbolic algorithms for parity games
VL - 82
ER -
TY - CONF
AB - We present an approach that enables robots to self-organize their sensorimotor behavior from scratch without providing specific information about neither the robot nor its environment. This is achieved by a simple neural control law that increases the consistency between external sensor dynamics and internal neural dynamics of the utterly simple controller. In this way, the embodiment and the agent-environment coupling are the only source of individual development. We show how an anthropomorphic tendon driven arm-shoulder system develops different behaviors depending on that coupling. For instance: Given a bottle half-filled with water, the arm starts to shake it, driven by the physical response of the water. When attaching a brush, the arm can be manipulated into wiping a table, and when connected to a revolvable wheel it finds out how to rotate it. Thus, the robot may be said to discover the affordances of the world. When allowing two (simulated) humanoid robots to interact physically, they engage into a joint behavior development leading to, for instance, spontaneous cooperation. More social effects are observed if the robots can visually perceive each other. Although, as an observer, it is tempting to attribute an apparent intentionality, there is nothing of the kind put in. As a conclusion, we argue that emergent behavior may be much less rooted in explicit intentions, internal motivations, or specific reward systems than is commonly believed.
AU - Der, Ralf
AU - Martius, Georg S
ID - 652
SN - 978-150905069-7
TI - Dynamical self consistency leads to behavioral development and emergent social interactions in robots
ER -
TY - CONF
AB - This paper studies the complexity of estimating Rényi divergences of discrete distributions: p observed from samples and the baseline distribution q known a priori. Extending the results of Acharya et al. (SODA'15) on estimating Rényi entropy, we present improved estimation techniques together with upper and lower bounds on the sample complexity. We show that, contrarily to estimating Rényi entropy where a sublinear (in the alphabet size) number of samples suffices, the sample complexity is heavily dependent on events occurring unlikely in q, and is unbounded in general (no matter what an estimation technique is used). For any divergence of integer order bigger than 1, we provide upper and lower bounds on the number of samples dependent on probabilities of p and q (the lower bounds hold for non-integer orders as well). We conclude that the worst-case sample complexity is polynomial in the alphabet size if and only if the probabilities of q are non-negligible. This gives theoretical insights into heuristics used in the applied literature to handle numerical instability, which occurs for small probabilities of q. Our result shows that they should be handled with care not only because of numerical issues, but also because of a blow up in the sample complexity.
AU - Skórski, Maciej
ID - 6526
SN - 9781509040964
T2 - 2017 IEEE International Symposium on Information Theory (ISIT)
TI - On the complexity of estimating Rènyi divergences
ER -
TY - CONF
AB - A memory-hard function (MHF) ƒn with parameter n can be computed in sequential time and space n. Simultaneously, a high amortized parallel area-time complexity (aAT) is incurred per evaluation. In practice, MHFs are used to limit the rate at which an adversary (using a custom computational device) can evaluate a security sensitive function that still occasionally needs to be evaluated by honest users (using an off-the-shelf general purpose device). The most prevalent examples of such sensitive functions are Key Derivation Functions (KDFs) and password hashing algorithms where rate limits help mitigate off-line dictionary attacks. As the honest users' inputs to these functions are often (low-entropy) passwords special attention is given to a class of side-channel resistant MHFs called iMHFs.
Essentially all iMHFs can be viewed as some mode of operation (making n calls to some round function) given by a directed acyclic graph (DAG) with very low indegree. Recently, a combinatorial property of a DAG has been identified (called "depth-robustness") which results in good provable security for an iMHF based on that DAG. Depth-robust DAGs have also proven useful in other cryptographic applications. Unfortunately, up till now, all known very depth-robust DAGs are impractically complicated and little is known about their exact (i.e. non-asymptotic) depth-robustness both in theory and in practice.
In this work we build and analyze (both formally and empirically) several exceedingly simple and efficient to navigate practical DAGs for use in iMHFs and other applications. For each DAG we:
*Prove that their depth-robustness is asymptotically maximal.
*Prove bounds of at least 3 orders of magnitude better on their exact depth-robustness compared to known bounds for other practical iMHF.
*Implement and empirically evaluate their depth-robustness and aAT against a variety of state-of-the art (and several new) depth-reduction and low aAT attacks.
We find that, against all attacks, the new DAGs perform significantly better in practice than Argon2i, the most widely deployed iMHF in practice.
Along the way we also improve the best known empirical attacks on the aAT of Argon2i by implementing and testing several heuristic versions of a (hitherto purely theoretical) depth-reduction attack. Finally, we demonstrate practicality of our constructions by modifying the Argon2i code base to use one of the new high aAT DAGs. Experimental benchmarks on a standard off-the-shelf CPU show that the new modifications do not adversely affect the impressive throughput of Argon2i (despite seemingly enjoying significantly higher aAT).
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Harsha, Ben
ID - 6527
SN - 9781450349468
T2 - Proceedings of the 2017 ACM SIGSAC Conference on Computer and Communications Security
TI - Practical graphs for optimal side-channel resistant memory-hard functions
ER -
TY - JOUR
AB - The extent of heterogeneity among driver gene mutations present in naturally occurring metastases - that is, treatment-naive metastatic disease - is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.
AU - Makohon Moore, Alvin
AU - Zhang, Ming
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Kundu, Deepanjan
AU - Chatterjee, Krishnendu
AU - Wong, Fay
AU - Jiao, Yuchen
AU - Kohutek, Zachary
AU - Hong, Jungeui
AU - Attiyeh, Marc
AU - Javier, Breanna
AU - Wood, Laura
AU - Hruban, Ralph
AU - Nowak, Martin
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth
AU - Vogelstein, Bert
AU - Iacobuzio Donahue, Christine
ID - 653
IS - 3
JF - Nature Genetics
SN - 10614036
TI - Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
VL - 49
ER -
TY - JOUR
AB - In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.
AU - Kicheva, Anna
AU - Rivron, Nicolas
ID - 654
IS - 5
JF - Development
SN - 09501991
TI - Creating to understand – developmental biology meets engineering in Paris
VL - 144
ER -
TY - JOUR
AB - The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.
AU - Renault, Thibaud
AU - Abraham, Anthony
AU - Bergmiller, Tobias
AU - Paradis, Guillaume
AU - Rainville, Simon
AU - Charpentier, Emmanuelle
AU - Guet, Calin C
AU - Tu, Yuhai
AU - Namba, Keiichi
AU - Keener, James
AU - Minamino, Tohru
AU - Erhardt, Marc
ID - 655
JF - eLife
SN - 2050084X
TI - Bacterial flagella grow through an injection diffusion mechanism
VL - 6
ER -
TY - JOUR
AB - Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.
AU - Novarino, Gaia
ID - 656
IS - 381
JF - Science Translational Medicine
SN - 19466234
TI - Modeling Alzheimer's disease in mice with human neurons
VL - 9
ER -
TY - JOUR
AB - Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a well-established gene network revolving around the key regulator SHORT-ROOT (SHR). In contrast, it is completely unknown how ground tissue identity is first specified from totipotent precursor cells in the embryo. The plant signaling molecule auxin, acting through AUXIN RESPONSE FACTOR (ARF) transcription factors, is critical for embryo patterning. The auxin effector ARF5/MONOPTEROS (MP) acts both cell-autonomously and noncell-autonomously to control embryonic vascular tissue formation and root initiation, respectively. Here we show that auxin response and ARF activity cell-autonomously control the asymmetric division of the first ground tissue cells. By identifying embryonic target genes, we show that MP transcriptionally initiates the ground tissue lineage and acts upstream of the regulatory network that controls ground tissue patterning and maintenance. Strikingly, whereas the SHR network depends on MP, this MP function is, at least in part, SHR independent. Our study therefore identifies auxin response as a regulator of ground tissue specification in the embryonic root, and reveals that ground tissue initiation and maintenance use different regulators and mechanisms. Moreover, our data provide a framework for the simultaneous formation of multiple cell types by the same transcriptional regulator.
AU - Möller, Barbara
AU - Ten Hove, Colette
AU - Xiang, Daoquan
AU - Williams, Nerys
AU - López, Lorena
AU - Yoshida, Saiko
AU - Smit, Margot
AU - Datla, Raju
AU - Weijers, Dolf
ID - 657
IS - 12
JF - PNAS
SN - 00278424
TI - Auxin response cell autonomously controls ground tissue initiation in the early arabidopsis embryo
VL - 114
ER -
TY - JOUR
AB - With the accelerated development of robot technologies, control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of specific objectives for the task at hand. While very successful in many applications, self-organized control schemes seem to be favored in large complex systems with unknown dynamics or which are difficult to model. Reasons are the expected scalability, robustness, and resilience of self-organizing systems. The paper presents a self-learning neurocontroller based on extrinsic differential plasticity introduced recently, applying it to an anthropomorphic musculoskeletal robot arm with attached objects of unknown physical dynamics. The central finding of the paper is the following effect: by the mere feedback through the internal dynamics of the object, the robot is learning to relate each of the objects with a very specific sensorimotor pattern. Specifically, an attached pendulum pilots the arm into a circular motion, a half-filled bottle produces axis oriented shaking behavior, a wheel is getting rotated, and wiping patterns emerge automatically in a table-plus-brush setting. By these object-specific dynamical patterns, the robot may be said to recognize the object's identity, or in other words, it discovers dynamical affordances of objects. Furthermore, when including hand coordinates obtained from a camera, a dedicated hand-eye coordination self-organizes spontaneously. These phenomena are discussed from a specific dynamical system perspective. Central is the dedicated working regime at the border to instability with its potentially infinite reservoir of (limit cycle) attractors "waiting" to be excited. Besides converging toward one of these attractors, variate behavior is also arising from a self-induced attractor morphing driven by the learning rule. We claim that experimental investigations with this anthropomorphic, self-learning robot not only generate interesting and potentially useful behaviors, but may also help to better understand what subjective human muscle feelings are, how they can be rooted in sensorimotor patterns, and how these concepts may feed back on robotics.
AU - Der, Ralf
AU - Martius, Georg S
ID - 658
IS - MAR
JF - Frontiers in Neurorobotics
SN - 16625218
TI - Self organized behavior generation for musculoskeletal robots
VL - 11
ER -
TY - JOUR
AB - Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.
AU - Kage, Frieda
AU - Winterhoff, Moritz
AU - Dimchev, Vanessa
AU - Müller, Jan
AU - Thalheim, Tobias
AU - Freise, Anika
AU - Brühmann, Stefan
AU - Kollasser, Jana
AU - Block, Jennifer
AU - Dimchev, Georgi A
AU - Geyer, Matthias
AU - Schnittler, Hams
AU - Brakebusch, Cord
AU - Stradal, Theresia
AU - Carlier, Marie
AU - Sixt, Michael K
AU - Käs, Josef
AU - Faix, Jan
AU - Rottner, Klemens
ID - 659
JF - Nature Communications
SN - 20411723
TI - FMNL formins boost lamellipodial force generation
VL - 8
ER -
TY - JOUR
AB - Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steadystate growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.
AU - Rickman, Jamie
AU - Düllberg, Christian F
AU - Cade, Nicholas
AU - Griffin, Lewis
AU - Surrey, Thomas
ID - 660
IS - 13
JF - PNAS
SN - 00278424
TI - Steady state EB cap size fluctuations are determined by stochastic microtubule growth and maturation
VL - 114
ER -
TY - JOUR
AB - We report a direct-numerical-simulation study of the Taylor-Couette flow in the quasi-Keplerian regime at shear Reynolds numbers up to (105). Quasi-Keplerian rotating flow has been investigated for decades as a simplified model system to study the origin of turbulence in accretion disks that is not fully understood. The flow in this study is axially periodic and thus the experimental end-wall effects on the stability of the flow are avoided. Using optimal linear perturbations as initial conditions, our simulations find no sustained turbulence: the strong initial perturbations distort the velocity profile and trigger turbulence that eventually decays.
AU - Shi, Liang
AU - Hof, Björn
AU - Rampp, Markus
AU - Avila, Marc
ID - 662
IS - 4
JF - Physics of Fluids
SN - 10706631
TI - Hydrodynamic turbulence in quasi Keplerian rotating flows
VL - 29
ER -
TY - CONF
AB - In this paper, we propose an approach to automatically compute invariant clusters for nonlinear semialgebraic hybrid systems. An invariant cluster for an ordinary differential equation (ODE) is a multivariate polynomial invariant g(u→, x→) = 0, parametric in u→, which can yield an infinite number of concrete invariants by assigning different values to u→ so that every trajectory of the system can be overapproximated precisely by the intersection of a group of concrete invariants. For semialgebraic systems, which involve ODEs with multivariate polynomial right-hand sides, given a template multivariate polynomial g(u→, x→), an invariant cluster can be obtained by first computing the remainder of the Lie derivative of g(u→, x→) divided by g(u→, x→) and then solving the system of polynomial equations obtained from the coefficients of the remainder. Based on invariant clusters and sum-of-squares (SOS) programming, we present a new method for the safety verification of hybrid systems. Experiments on nonlinear benchmark systems from biology and control theory show that our approach is efficient.
AU - Kong, Hui
AU - Bogomolov, Sergiy
AU - Schilling, Christian
AU - Jiang, Yu
AU - Henzinger, Thomas A
ID - 663
SN - 978-145034590-3
T2 - Proceedings of the 20th International Conference on Hybrid Systems
TI - Safety verification of nonlinear hybrid systems based on invariant clusters
ER -
TY - JOUR
AB - The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.
AU - Bergmiller, Tobias
AU - Andersson, Anna M
AU - Tomasek, Kathrin
AU - Balleza, Enrique
AU - Kiviet, Daniel
AU - Hauschild, Robert
AU - Tkacik, Gasper
AU - Guet, Calin C
ID - 665
IS - 6335
JF - Science
SN - 00368075
TI - Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity
VL - 356
ER -
TY - JOUR
AB - Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to “cross-protect” bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors.
AU - Mitosch, Karin
AU - Rieckh, Georg
AU - Bollenbach, Tobias
ID - 666
IS - 4
JF - Cell Systems
SN - 24054712
TI - Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment
VL - 4
ER -
TY - JOUR
AB - Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.
AU - Novarino, Gaia
ID - 667
IS - 387
JF - Science Translational Medicine
SN - 19466234
TI - The antisocial side of antibiotics
VL - 9
ER -
TY - JOUR
AB - Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.
AU - Horsthemke, Markus
AU - Bachg, Anne
AU - Groll, Katharina
AU - Moyzio, Sven
AU - Müther, Barbara
AU - Hemkemeyer, Sandra
AU - Wedlich Söldner, Roland
AU - Sixt, Michael K
AU - Tacke, Sebastian
AU - Bähler, Martin
AU - Hanley, Peter
ID - 668
IS - 17
JF - Journal of Biological Chemistry
SN - 00219258
TI - Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion
VL - 292
ER -
TY - JOUR
AB - The exocyst, a eukaryotic tethering complex, coregulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis thaliana EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, EXO70C1, EXO70C2, EXO70F1, EXO70H3, EXO70H5, and EXO70H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited an enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollenspecific depletion of the closest paralog, EXO70C1, using artificial microRNA in the exo70C2 mutant background, resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP tagged and expressed under the control of their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. The expression of EXO70C2-GFP complemented the aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes.
AU - Synek, Lukáš
AU - Vukašinović, Nemanja
AU - Kulich, Ivan
AU - Hála, Michal
AU - Aldorfová, Klára
AU - Fendrych, Matyas
AU - Žárský, Viktor
ID - 669
IS - 1
JF - Plant Physiology
SN - 00320889
TI - EXO70C2 is a key regulatory factor for optimal tip growth of pollen
VL - 174
ER -
TY - JOUR
AB - We propose an efficient method to model paper tearing in the context of interactive modeling. The method uses geometrical information to automatically detect potential starting points of tears. We further introduce a new hybrid geometrical and physical-based method to compute the trajectory of tears while procedurally synthesizing high resolution details of the tearing path using a texture based approach. The results obtained are compared with real paper and with previous studies on the expected geometric paths of paper that tears.
AU - Schreck, Camille
AU - Rohmer, Damien
AU - Hahmann, Stefanie
ID - 670
IS - 2
JF - Computer Graphics Forum
SN - 01677055
TI - Interactive paper tearing
VL - 36
ER -
TY - JOUR
AB - Humans routinely use conditionally cooperative strategies when interacting in repeated social dilemmas. They are more likely to cooperate if others cooperated before, and are ready to retaliate if others defected. To capture the emergence of reciprocity, most previous models consider subjects who can only choose from a restricted set of representative strategies, or who react to the outcome of the very last round only. As players memorize more rounds, the dimension of the strategy space increases exponentially. This increasing computational complexity renders simulations for individuals with higher cognitive abilities infeasible, especially if multiplayer interactions are taken into account. Here, we take an axiomatic approach instead. We propose several properties that a robust cooperative strategy for a repeated multiplayer dilemma should have. These properties naturally lead to a unique class of cooperative strategies, which contains the classical Win-Stay Lose-Shift rule as a special case. A comprehensive numerical analysis for the prisoner's dilemma and for the public goods game suggests that strategies of this class readily evolve across various memory-n spaces. Our results reveal that successful strategies depend not only on how cooperative others were in the past but also on the respective context of cooperation.
AU - Hilbe, Christian
AU - Martinez, Vaquero
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 671
IS - 18
JF - PNAS
SN - 00278424
TI - Memory-n strategies of direct reciprocity
VL - 114
ER -
TY - JOUR
AB - Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.
AU - Vaahtomeri, Kari
AU - Brown, Markus
AU - Hauschild, Robert
AU - De Vries, Ingrid
AU - Leithner, Alexander F
AU - Mehling, Matthias
AU - Kaufmann, Walter
AU - Sixt, Michael K
ID - 672
IS - 5
JF - Cell Reports
SN - 22111247
TI - Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia
VL - 19
ER -
TY - JOUR
AB - We present a numerical study of wavy supercritical cylindrical Couette flow between counter-rotating cylinders in which the wavy pattern propagates either prograde with the inner cylinder or retrograde opposite the rotation of the inner cylinder. The wave propagation reversals from prograde to retrograde and vice versa occur at distinct values of the inner cylinder Reynolds number when the associated frequency of the wavy instability vanishes. The reversal occurs for both twofold and threefold symmetric wavy vortices. Moreover, the wave propagation reversal only occurs for sufficiently strong counter-rotation. The flow pattern reversal appears to be intrinsic in the system as either periodic boundary conditions or fixed end wall boundary conditions for different system sizes always result in the wave propagation reversal. We present a detailed bifurcation sequence and parameter space diagram with respect to retrograde behavior of wavy flows. The retrograde propagation of the instability occurs when the inner Reynolds number is about two times the outer Reynolds number. The mechanism for the retrograde propagation is associated with the inviscidly unstable region near the inner cylinder and the direction of the global average azimuthal velocity. Flow dynamics, spatio-temporal behavior, global mean angular velocity, and torque of the flow with the wavy pattern are explored.
AU - Altmeyer, Sebastian
AU - Lueptow, Richard
ID - 673
IS - 5
JF - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics
SN - 24700045
TI - Wave propagation reversal for wavy vortices in wide gap counter rotating cylindrical Couette flow
VL - 95
ER -
TY - JOUR
AB - Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.
AU - Schwarz, Jan
AU - Bierbaum, Veronika
AU - Vaahtomeri, Kari
AU - Hauschild, Robert
AU - Brown, Markus
AU - De Vries, Ingrid
AU - Leithner, Alexander F
AU - Reversat, Anne
AU - Merrin, Jack
AU - Tarrant, Teresa
AU - Bollenbach, Tobias
AU - Sixt, Michael K
ID - 674
IS - 9
JF - Current Biology
SN - 09609822
TI - Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6
VL - 27
ER -
TY - JOUR
AB - We report the enhancement of infrared absorption of chemisorbed carbon monoxide on platinum in the gap of plasmonic nanoantennas. Our method is based on the self-assembled formation of platinum nanoislands on nanoscopic dipole antenna arrays manufactured via electron beam lithography. We employ systematic variations of the plasmonic antenna resonance to precisely couple to the molecular stretch vibration of carbon monoxide adsorbed on the platinum nanoislands. Ultimately, we reach more than 1500-fold infrared absorption enhancements, allowing for an ultrasensitive detection of a monolayer of chemisorbed carbon monoxide. The developed procedure can be adapted to other metal adsorbents and molecular species and could be utilized for coverage sensing in surface catalytic reactions.
AU - Haase, Johannes
AU - Bagiante, Salvatore
AU - Sigg, Hans
AU - Van Bokhoven, Jeroen
ID - 675
IS - 10
JF - Optics Letters
TI - Surface enhanced infrared absorption of chemisorbed carbon monoxide using plasmonic nanoantennas
VL - 42
ER -
TY - JOUR
AB - The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR.
AU - Lademann, Claudio
AU - Renkawitz, Jörg
AU - Pfander, Boris
AU - Jentsch, Stefan
ID - 677
IS - 7
JF - Cell Reports
SN - 22111247
TI - The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination
VL - 19
ER -
TY - JOUR
AB - The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.
AU - Petridou, Nicoletta
AU - Spiro, Zoltan P
AU - Heisenberg, Carl-Philipp J
ID - 678
IS - 6
JF - Nature Cell Biology
SN - 14657392
TI - Multiscale force sensing in development
VL - 19
ER -
TY - JOUR
AB - Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection site. In the context of myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment protected mice against lethal soft tissue infection with Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other antiapoptotic B cell leukemia/ lymphoma 2 (Bcl2) family members. Higher Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections.
AU - Ebner, Florian
AU - Sedlyarov, Vitaly
AU - Tasciyan, Saren
AU - Ivin, Masa
AU - Kratochvill, Franz
AU - Gratz, Nina
AU - Kenner, Lukas
AU - Villunger, Andreas
AU - Sixt, Michael K
AU - Kovarik, Pavel
ID - 679
IS - 6
JF - The Journal of Clinical Investigation
SN - 00219738
TI - The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection
VL - 127
ER -
TY - JOUR
AB - In order to respond reliably to specific features of their environment, sensory neurons need to integrate multiple incoming noisy signals. Crucially, they also need to compete for the interpretation of those signals with other neurons representing similar features. The form that this competition should take depends critically on the noise corrupting these signals. In this study we show that for the type of noise commonly observed in sensory systems, whose variance scales with the mean signal, sensory neurons should selectively divide their input signals by their predictions, suppressing ambiguous cues while amplifying others. Any change in the stimulus context alters which inputs are suppressed, leading to a deep dynamic reshaping of neural receptive fields going far beyond simple surround suppression. Paradoxically, these highly variable receptive fields go alongside and are in fact required for an invariant representation of external sensory features. In addition to offering a normative account of context-dependent changes in sensory responses, perceptual inference in the presence of signal-dependent noise accounts for ubiquitous features of sensory neurons such as divisive normalization, gain control and contrast dependent temporal dynamics.
AU - Chalk, Matthew J
AU - Masset, Paul
AU - Gutkin, Boris
AU - Denève, Sophie
ID - 680
IS - 6
JF - PLoS Computational Biology
SN - 1553734X
TI - Sensory noise predicts divisive reshaping of receptive fields
VL - 13
ER -
TY - JOUR
AB - Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Filiot, Emmanuel
AU - Raskin, Jean
ID - 681
JF - Information and Computation
SN - 08905401
TI - Doomsday equilibria for omega-regular games
VL - 254
ER -
TY - CONF
AB - Given a triangulation of a point set in the plane, a flip deletes an edge e whose removal leaves a convex quadrilateral, and replaces e by the opposite diagonal of the quadrilateral. It is well known that any triangulation of a point set can be reconfigured to any other triangulation by some sequence of flips. We explore this question in the setting where each edge of a triangulation has a label, and a flip transfers the label of the removed edge to the new edge. It is not true that every labelled triangulation of a point set can be reconfigured to every other labelled triangulation via a sequence of flips, but we characterize when this is possible. There is an obvious necessary condition: for each label l, if edge e has label l in the first triangulation and edge f has label l in the second triangulation, then there must be some sequence of flips that moves label l from e to f, ignoring all other labels. Bose, Lubiw, Pathak and Verdonschot formulated the Orbit Conjecture, which states that this necessary condition is also sufficient, i.e. that all labels can be simultaneously mapped to their destination if and only if each label individually can be mapped to its destination. We prove this conjecture. Furthermore, we give a polynomial-time algorithm to find a sequence of flips to reconfigure one labelled triangulation to another, if such a sequence exists, and we prove an upper bound of O(n7) on the length of the flip sequence. Our proof uses the topological result that the sets of pairwise non-crossing edges on a planar point set form a simplicial complex that is homeomorphic to a high-dimensional ball (this follows from a result of Orden and Santos; we give a different proof based on a shelling argument). The dual cell complex of this simplicial ball, called the flip complex, has the usual flip graph as its 1-skeleton. We use properties of the 2-skeleton of the flip complex to prove the Orbit Conjecture.
AU - Lubiw, Anna
AU - Masárová, Zuzana
AU - Wagner, Uli
ID - 683
TI - A proof of the orbit conjecture for flipping edge labelled triangulations
VL - 77
ER -
TY - CONF
AB - In classical machine learning, regression is treated as a black box process of identifying a suitable function from a hypothesis set without attempting to gain insight into the mechanism connecting inputs and outputs. In the natural sciences, however, finding an interpretable function for a phenomenon is the prime goal as it allows to understand and generalize results. This paper proposes a novel type of function learning network, called equation learner (EQL), that can learn analytical expressions and is able to extrapolate to unseen domains. It is implemented as an end-to-end differentiable feed-forward network and allows for efficient gradient based training. Due to sparsity regularization concise interpretable expressions can be obtained. Often the true underlying source expression is identified.
AU - Martius, Georg S
AU - Lampert, Christoph
ID - 6841
T2 - 5th International Conference on Learning Representations, ICLR 2017 - Workshop Track Proceedings
TI - Extrapolation and learning equations
ER -
TY - JOUR
AB - By applying methods and principles from the physical sciences to biological problems, D'Arcy Thompson's On Growth and Form demonstrated how mathematical reasoning reveals elegant, simple explanations for seemingly complex processes. This has had a profound influence on subsequent generations of developmental biologists. We discuss how this influence can be traced through twentieth century morphologists, embryologists and theoreticians to current research that explores the molecular and cellular mechanisms of tissue growth and patterning, including our own studies of the vertebrate neural tube.
AU - Briscoe, James
AU - Kicheva, Anna
ID - 685
JF - Mechanisms of Development
SN - 09254773
TI - The physics of development 100 years after D'Arcy Thompson's “on growth and form”
VL - 145
ER -
TY - JOUR
AB - Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book ‘On Growth and Form’ has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology.
AU - Heisenberg, Carl-Philipp J
ID - 686
JF - Mechanisms of Development
SN - 09254773
TI - D'Arcy Thompson's ‘on growth and form’: From soap bubbles to tissue self organization
VL - 145
ER -
TY - JOUR
AB - Pursuing the similarity between the Kontsevich-Soibelman construction of the cohomological Hall algebra (CoHA) of BPS states and Lusztig's construction of canonical bases for quantum enveloping algebras, and the similarity between the integrality conjecture for motivic Donaldson-Thomas invariants and the PBW theorem for quantum enveloping algebras, we build a coproduct on the CoHA associated to a quiver with potential. We also prove a cohomological dimensional reduction theorem, further linking a special class of CoHAs with Yangians, and explaining how to connect the study of character varieties with the study of CoHAs.
AU - Davison, Ben
ID - 687
IS - 2
JF - Quarterly Journal of Mathematics
SN - 00335606
TI - The critical CoHA of a quiver with potential
VL - 68
ER -
TY - CONF
AB - We show that the framework of topological data analysis can be extended from metrics to general Bregman divergences, widening the scope of possible applications. Examples are the Kullback - Leibler divergence, which is commonly used for comparing text and images, and the Itakura - Saito divergence, popular for speech and sound. In particular, we prove that appropriately generalized čech and Delaunay (alpha) complexes capture the correct homotopy type, namely that of the corresponding union of Bregman balls. Consequently, their filtrations give the correct persistence diagram, namely the one generated by the uniformly growing Bregman balls. Moreover, we show that unlike the metric setting, the filtration of Vietoris-Rips complexes may fail to approximate the persistence diagram. We propose algorithms to compute the thus generalized čech, Vietoris-Rips and Delaunay complexes and experimentally test their efficiency. Lastly, we explain their surprisingly good performance by making a connection with discrete Morse theory.
AU - Edelsbrunner, Herbert
AU - Wagner, Hubert
ID - 688
SN - 18688969
TI - Topological data analysis with Bregman divergences
VL - 77
ER -