TY - JOUR
AB - We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of sequences produced under a non-preemptive scheduler. We guarantee that our synthesis does not introduce deadlocks and that the synchronization inserted is optimal w.r.t. a given objective function. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and generation of a set of global constraints over synchronization placements. Each model of the global constraints set corresponds to a correctness-ensuring synchronization placement. The placement that is optimal w.r.t. the given objective function is chosen as the synchronization solution. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient. The implicit specification helped us find one concurrency bug previously missed when model-checking using an explicit, user-provided specification. We implemented objective functions for coarse-grained and fine-grained locking and observed that different synchronization placements are produced for our experiments, favoring a minimal number of synchronization operations or maximum concurrency, respectively.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1338
IS - 2-3
JF - Formal Methods in System Design
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 50
ER -
TY - JOUR
AB - The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.
AU - Giacobbe, Mirco
AU - Guet, Calin C
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Paixao, Tiago
AU - Petrov, Tatjana
ID - 1351
IS - 8
JF - Acta Informatica
SN - 00015903
TI - Model checking the evolution of gene regulatory networks
VL - 54
ER -
TY - JOUR
AB - One of the major challenges in physically based modelling is making simulations efficient. Adaptive models provide an essential solution to these efficiency goals. These models are able to self-adapt in space and time, attempting to provide the best possible compromise between accuracy and speed. This survey reviews the adaptive solutions proposed so far in computer graphics. Models are classified according to the strategy they use for adaptation, from time-stepping and freezing techniques to geometric adaptivity in the form of structured grids, meshes and particles. Applications range from fluids, through deformable bodies, to articulated solids.
AU - Manteaux, Pierre
AU - Wojtan, Christopher J
AU - Narain, Rahul
AU - Redon, Stéphane
AU - Faure, François
AU - Cani, Marie
ID - 1367
IS - 6
JF - Computer Graphics Forum
SN - 01677055
TI - Adaptive physically based models in computer graphics
VL - 36
ER -
TY - JOUR
AB - We consider the problem of computing the set of initial states of a dynamical system such that there exists a control strategy to ensure that the trajectories satisfy a temporal logic specification with probability 1 (almost-surely). We focus on discrete-time, stochastic linear dynamics and specifications given as formulas of the Generalized Reactivity(1) fragment of Linear Temporal Logic over linear predicates in the states of the system. We propose a solution based on iterative abstraction-refinement, and turn-based 2-player probabilistic games. While the theoretical guarantee of our algorithm after any finite number of iterations is only a partial solution, we show that if our algorithm terminates, then the result is the set of all satisfying initial states. Moreover, for any (partial) solution our algorithm synthesizes witness control strategies to ensure almost-sure satisfaction of the temporal logic specification. While the proposed algorithm guarantees progress and soundness in every iteration, it is computationally demanding. We offer an alternative, more efficient solution for the reachability properties that decomposes the problem into a series of smaller problems of the same type. All algorithms are demonstrated on an illustrative case study.
AU - Svoreňová, Mária
AU - Kretinsky, Jan
AU - Chmelik, Martin
AU - Chatterjee, Krishnendu
AU - Cěrná, Ivana
AU - Belta, Cǎlin
ID - 1407
IS - 2
JF - Nonlinear Analysis: Hybrid Systems
TI - Temporal logic control for stochastic linear systems using abstraction refinement of probabilistic games
VL - 23
ER -
TY - JOUR
AB - Phat is an open-source C. ++ library for the computation of persistent homology by matrix reduction, targeted towards developers of software for topological data analysis. We aim for a simple generic design that decouples algorithms from data structures without sacrificing efficiency or user-friendliness. We provide numerous different reduction strategies as well as data types to store and manipulate the boundary matrix. We compare the different combinations through extensive experimental evaluation and identify optimization techniques that work well in practical situations. We also compare our software with various other publicly available libraries for persistent homology.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
AU - Wagner, Hubert
ID - 1433
JF - Journal of Symbolic Computation
SN - 07477171
TI - Phat - Persistent homology algorithms toolbox
VL - 78
ER -
TY - JOUR
AB - We consider N×N Hermitian random matrices H consisting of blocks of size M≥N6/7. The matrix elements are i.i.d. within the blocks, close to a Gaussian in the four moment matching sense, but their distribution varies from block to block to form a block-band structure, with an essential band width M. We show that the entries of the Green’s function G(z)=(H−z)−1 satisfy the local semicircle law with spectral parameter z=E+iη down to the real axis for any η≫N−1, using a combination of the supersymmetry method inspired by Shcherbina (J Stat Phys 155(3): 466–499, 2014) and the Green’s function comparison strategy. Previous estimates were valid only for η≫M−1. The new estimate also implies that the eigenvectors in the middle of the spectrum are fully delocalized.
AU - Bao, Zhigang
AU - Erdös, László
ID - 1528
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Delocalization for a class of random block band matrices
VL - 167
ER -
TY - CONF
AB - We study probabilistic models of natural images and extend the autoregressive family of PixelCNN models by incorporating latent variables. Subsequently, we describe two new generative image models that exploit different image transformations as latent variables: a quantized grayscale view of the image or a multi-resolution image pyramid. The proposed models tackle two known shortcomings of existing PixelCNN models: 1) their tendency to focus on low-level image details, while largely ignoring high-level image information, such as object shapes, and 2) their computationally costly procedure for image sampling. We experimentally demonstrate benefits of our LatentPixelCNN models, in particular showing that they produce much more realistically looking image samples than previous state-of-the-art probabilistic models.
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 1000
SN - 978-151085514-4
TI - PixelCNN models with auxiliary variables for natural image modeling
VL - 70
ER -
TY - CONF
AB - We present a computational approach for designing CurveUps, curvy shells that form from an initially flat state. They consist of small rigid tiles that are tightly held together by two pre-stretched elastic sheets attached to them. Our method allows the realization of smooth, doubly curved surfaces that can be fabricated as a flat piece. Once released, the restoring forces of the pre-stretched sheets support the object to take shape in 3D. CurveUps are structurally stable in their target configuration. The design process starts with a target surface. Our method generates a tile layout in 2D and optimizes the distribution, shape, and attachment areas of the tiles to obtain a configuration that is fabricable and in which the curved up state closely matches the target. Our approach is based on an efficient approximate model and a local optimization strategy for an otherwise intractable nonlinear optimization problem. We demonstrate the effectiveness of our approach for a wide range of shapes, all realized as physical prototypes.
AU - Guseinov, Ruslan
AU - Miguel, Eder
AU - Bickel, Bernd
ID - 1001
IS - 4
TI - CurveUps: Shaping objects from flat plates with tension-actuated curvature
VL - 36
ER -
TY - CONF
AB - We present an interactive design system to create functional mechanical objects. Our computational approach allows novice users to retarget an existing mechanical template to a user-specified input shape. Our proposed representation for a mechanical template encodes a parameterized mechanism, mechanical constraints that ensure a physically valid configuration, spatial relationships of mechanical parts to the user-provided shape, and functional constraints that specify an intended functionality. We provide an intuitive interface and optimization-in-the-loop approach for finding a valid configuration of the mechanism and the shape to ensure that higher-level functional goals are met. Our algorithm interactively optimizes the mechanism while the user manipulates the placement of mechanical components and the shape. Our system allows users to efficiently explore various design choices and to synthesize customized mechanical objects that can be fabricated with rapid prototyping technologies. We demonstrate the efficacy of our approach by retargeting various mechanical templates to different shapes and fabricating the resulting functional mechanical objects.
AU - Zhang, Ran
AU - Auzinger, Thomas
AU - Ceylan, Duygu
AU - Li, Wilmot
AU - Bickel, Bernd
ID - 1002
IS - 4
SN - 07300301
TI - Functionality-aware retargeting of mechanisms to 3D shapes
VL - 36
ER -
TY - CONF
AB - Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an overapproximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. Our experimental results demonstrate the efficiency of the methodology.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 1003
SN - 10450823
TI - An abstraction-refinement methodology for reasoning about network games
ER -
TY - JOUR
AB - The fundamental tasks of the root system are, besides anchoring, mediating interactions between plant and soil and providing the plant with water and nutrients. The architecture of the root system is controlled by endogenous mechanisms that constantly integrate environmental signals, such as availability of nutrients and water. Extremely important for efficient soil exploitation and survival under less favorable conditions is the developmental flexibility of the root system that is largely determined by its postembryonic branching capacity. Modulation of initiation and outgrowth of lateral roots provides roots with an exceptional plasticity, allows optimal adjustment to underground heterogeneity, and enables effective soil exploitation and use of resources. Here we discuss recent advances in understanding the molecular mechanisms that shape the plant root system and integrate external cues to adapt to the changing environment.
AU - Ötvös, Krisztina
AU - Benková, Eva
ID - 1004
JF - Current Opinion in Genetics & Development
SN - 0959437X
TI - Spatiotemporal mechanisms of root branching
VL - 45
ER -
TY - JOUR
AB - Background: The phenomenon of immune priming, i.e. enhanced protection following a secondary exposure to a pathogen, has now been demonstrated in a wide range of invertebrate species. Despite accumulating phenotypic evidence, knowledge of its mechanistic underpinnings is currently very limited. Here we used the system of the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus thuringiensis (Bt) to further our molecular understanding of the oral immune priming phenomenon. We addressed how ingestion of bacterial cues (derived from spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects gene expression upon later challenge exposure, using a whole-transcriptome sequencing approach. Results: Whereas gene expression of individuals primed with the orally non-pathogenic strain showed minor changes to controls, we found that priming with the pathogenic strain induced regulation of a large set of distinct genes, many of which are known immune candidates. Intriguingly, the immune repertoire activated upon priming and subsequent challenge qualitatively differed from the one mounted upon infection with Bt without previous priming. Moreover, a large subset of priming-specific genes showed an inverse regulation compared to their regulation upon challenge only. Conclusions: Our data demonstrate that gene expression upon infection is strongly affected by previous immune priming. We hypothesise that this shift in gene expression indicates activation of a more targeted and efficient response towards a previously encountered pathogen, in anticipation of potential secondary encounter.
AU - Greenwood, Jenny
AU - Milutinovic, Barbara
AU - Peuß, Robert
AU - Behrens, Sarah
AU - Essar, Daniela
AU - Rosenstiel, Philip
AU - Schulenburg, Hinrich
AU - Kurtz, Joachim
ID - 1006
IS - 1
JF - BMC Genomics
SN - 14712164
TI - Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae
VL - 18
ER -
TY - JOUR
AB - A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.
AU - Lang, Moritz
AU - Sontag, Eduardo
ID - 1007
JF - Automatica
SN - 00051098
TI - Zeros of nonlinear systems with input invariances
VL - 81C
ER -
TY - CONF
AB - A standard objective in partially-observable Markov decision processes (POMDPs) is to find a policy that maximizes the expected discounted-sum payoff. However, such policies may still permit unlikely but highly undesirable outcomes, which is problematic especially in safety-critical applications. Recently, there has been a surge of interest in POMDPs where the goal is to maximize the probability to ensure that the payoff is at least a given threshold, but these approaches do not consider any optimization beyond satisfying this threshold constraint. In this work we go beyond both the “expectation” and “threshold” approaches and consider a “guaranteed payoff optimization (GPO)” problem for POMDPs, where we are given a threshold t and the objective is to find a policy σ such that a) each possible outcome of σ yields a discounted-sum payoff of at least t, and b) the expected discounted-sum payoff of σ is optimal (or near-optimal) among all policies satisfying a). We present a practical approach to tackle the GPO problem and evaluate it on standard POMDP benchmarks.
AU - Chatterjee, Krishnendu
AU - Novotny, Petr
AU - Pérez, Guillermo
AU - Raskin, Jean
AU - Zikelic, Djordje
ID - 1009
T2 - Proceedings of the 31st AAAI Conference on Artificial Intelligence
TI - Optimizing expectation with guarantees in POMDPs
VL - 5
ER -
TY - JOUR
AB - We prove a local law in the bulk of the spectrum for random Gram matrices XX∗, a generalization of sample covariance matrices, where X is a large matrix with independent, centered entries with arbitrary variances. The limiting eigenvalue density that generalizes the Marchenko-Pastur law is determined by solving a system of nonlinear equations. Our entrywise and averaged local laws are on the optimal scale with the optimal error bounds. They hold both in the square case (hard edge) and in the properly rectangular case (soft edge). In the latter case we also establish a macroscopic gap away from zero in the spectrum of XX∗.
AU - Alt, Johannes
AU - Erdös, László
AU - Krüger, Torben H
ID - 1010
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for random Gram matrices
VL - 22
ER -
TY - CONF
AB - Pushdown systems (PDSs) and recursive state machines (RSMs), which are linearly equivalent, are standard models for interprocedural analysis. Yet RSMs are more convenient as they (a) explicitly model function calls and returns, and (b) specify many natural parameters for algorithmic analysis, e.g., the number of entries and exits. We consider a general framework where RSM transitions are labeled from a semiring and path properties are algebraic with semiring operations, which can model, e.g., interprocedural reachability and dataflow analysis problems. Our main contributions are new algorithms for several fundamental problems. As compared to a direct translation of RSMs to PDSs and the best-known existing bounds of PDSs, our analysis algorithm improves the complexity for finite-height semirings (that subsumes reachability and standard dataflow properties). We further consider the problem of extracting distance values from the representation structures computed by our algorithm, and give efficient algorithms that distinguish the complexity of a one-time preprocessing from the complexity of each individual query. Another advantage of our algorithm is that our improvements carry over to the concurrent setting, where we improve the bestknown complexity for the context-bounded analysis of concurrent RSMs. Finally, we provide a prototype implementation that gives a significant speed-up on several benchmarks from the SLAM/SDV project.
AU - Chatterjee, Krishnendu
AU - Kragl, Bernhard
AU - Mishra, Samarth
AU - Pavlogiannis, Andreas
ED - Yang, Hongseok
ID - 1011
SN - 03029743
TI - Faster algorithms for weighted recursive state machines
VL - 10201
ER -
TY - JOUR
AB - From microwave ovens to satellite television to the GPS and data services on our mobile phones, microwave technology is everywhere today. But one technology that has so far failed to prove its worth in this wavelength regime is quantum communication that uses the states of single photons as information carriers. This is because single microwave photons, as opposed to classical microwave signals, are extremely vulnerable to noise from thermal excitations in the channels through which they travel. Two new independent studies, one by Ze-Liang Xiang at Technische Universität Wien (Vienna), Austria, and colleagues [1] and another by Benoît Vermersch at the University of Innsbruck, also in Austria, and colleagues [2] now describe a theoretical protocol for microwave quantum communication that is resilient to thermal and other types of noise. Their approach could become a powerful technique to establish fast links between superconducting data processors in a future all-microwave quantum network.
AU - Fink, Johannes M
ID - 1013
IS - 32
JF - Physics
TI - Viewpoint: Microwave quantum states beat the heat
VL - 10
ER -
TY - JOUR
AB - Vortices are commonly observed in the context of classical hydrodynamics: from whirlpools after stirring the coffee in a cup to a violent atmospheric phenomenon such as a tornado, all classical vortices are characterized by an arbitrary circulation value of the local velocity field. On the other hand the appearance of vortices with quantized circulation represents one of the fundamental signatures of macroscopic quantum phenomena. In two-dimensional superfluids quantized vortices play a key role in determining finite-temperature properties, as the superfluid phase and the normal state are separated by a vortex unbinding transition, the Berezinskii-Kosterlitz-Thouless transition. Very recent experiments with two-dimensional superfluid fermions motivate the present work: we present theoretical results based on the renormalization group showing that the universal jump of the superfluid density and the critical temperature crucially depend on the interaction strength, providing a strong benchmark for forthcoming investigations.
AU - Bighin, Giacomo
AU - Salasnich, Luca
ID - 1015
JF - Scientific Reports
SN - 20452322
TI - Vortices and antivortices in two-dimensional ultracold Fermi gases
VL - 7
ER -
TY - JOUR
AB - The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects.
AU - Breuss, Martin
AU - Nguyen, Thai
AU - Srivatsan, Anjana
AU - Leca, Ines
AU - Tian, Guoling
AU - Fritz, Tanja
AU - Hansen, Andi H
AU - Musaev, Damir
AU - Mcevoy Venneri, Jennifer
AU - Kiely, James
AU - Rosti, Rasim
AU - Scott, Eric
AU - Tan, Uner
AU - Kolodner, Richard
AU - Cowan, Nicholas
AU - Keays, David
AU - Gleeson, Joseph
ID - 1016
IS - 2
JF - Human Molecular Genetics
SN - 09646906
TI - Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability
VL - 26
ER -
TY - JOUR
AB - The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot.
AU - Breuss, Martin
AU - Leca, Ines
AU - Gstrein, Thomas
AU - Hansen, Andi H
AU - Keays, David
ID - 1017
JF - Molecular and Cellular Neuroscience
SN - 10447431
TI - Tubulins and brain development: The origins of functional specification
VL - 84
ER -
TY - JOUR
AB - In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The crosstalk between cytokinin response and light is known for a long time. However, the molecular mechanism underlying the interactionbetween light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL (LPH) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT-1 (CKI1), encoding the constitutively active sensor histidine kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE 1 (HY1) which encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertiblephytochromes. Our analysis confirmed the light-dependent regulation oftheCKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors PHYTOCHROME INTERACTING FACTOR 3 (PIF3) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Changes in CKI1 expression observed in lph/hy1-7 and phy mutants correlatewithmisregulation of MSP signaling, changedcytokinin sensitivity and developmental aberrations,previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development.
AU - Dobisova, Tereza
AU - Hrdinova, Vendula
AU - Cuesta, Candela
AU - Michlickova, Sarka
AU - Urbankova, Ivana
AU - Hejatkova, Romana
AU - Zadnikova, Petra
AU - Pernisová, Markéta
AU - Benková, Eva
AU - Hejátko, Jan
ID - 1018
IS - 1
JF - Plant Physiology
TI - Light regulated expression of sensor histidine kinase CKI1 controls cytokinin related development
VL - 174
ER -
TY - JOUR
AB - As a consequence of its difference in copy number between males and females, the X chromosome is subject to unique evolutionary forces and gene regulatory mechanisms. Previous studies of Drosophila melanogaster have shown that the expression of X-linked, testis-specific reporter genes is suppressed in the male germline. However, it is not known whether this phenomenon is restricted to testis-expressed genes or if it is a more general property of genes with tissue-specific expression, which are also underrepresented on the X chromosome. To test this, we compared the expression of three tissue-specific reporter genes (ovary, accessory gland and Malpighian tubule) inserted at various autosomal and X-chromosomal locations. In contrast to testis-specific reporter genes, we found no reduction of X-linked expression in any of the other tissues. In accessory gland and Malpighian tubule, we detected higher expression of the X-linked reporter genes, which suggests that they are at least partially dosage compensated. We found no difference in the tissue-specificity of X-linked and autosomal reporter genes. These findings indicate that, in general, the X chromosome is not a detrimental environment for tissue-specific gene expression and that the suppression of X-linked expression is limited to the male germline.
AU - Argyridou, Eliza
AU - Huylmans, Ann K
AU - Königer, Annabella
AU - Parsch, John
ID - 1019
IS - 1
JF - Heredity
SN - 0018067X
TI - X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster
VL - 119
ER -
TY - JOUR
AB - Cellulose is the most abundant biopolymer on Earth. Cellulose fibers, such as the one extracted form cotton or woodpulp, have been used by humankind for hundreds of years to make textiles and paper. Here we show how, by engineering light-matter interaction, we can optimize light scattering using exclusively cellulose nanocrystals. The produced material is sustainable, biocompatible, and when compared to ordinary microfiber-based paper, it shows enhanced scattering strength (×4), yielding a transport mean free path as low as 3.5 μm in the visible light range. The experimental results are in a good agreement with the theoretical predictions obtained with a diffusive model for light propagation.
AU - Caixeiro, Soraya
AU - Peruzzo, Matilda
AU - Onelli, Olimpia
AU - Vignolini, Silvia
AU - Sapienza, Riccardo
ID - 1020
IS - 9
JF - ACS Applied Materials and Interfaces
SN - 19448244
TI - Disordered cellulose based nanostructures for enhanced light scattering
VL - 9
ER -
TY - JOUR
AB - Most flows in nature and engineering are turbulent because of their large velocities and spatial scales. Laboratory experiments on rotating quasi-Keplerian flows, for which the angular velocity decreases radially but the angular momentum increases, are however laminar at Reynolds numbers exceeding one million. This is in apparent contradiction to direct numerical simulations showing that in these experiments turbulence transition is triggered by the axial boundaries. We here show numerically that as the Reynolds number increases, turbulence becomes progressively confined to the boundary layers and the flow in the bulk fully relaminarizes. Our findings support that turbulence is unlikely to occur in isothermal constant-density quasi-Keplerian flows.
AU - Lopez Alonso, Jose M
AU - Avila, Marc
ID - 1021
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Boundary layer turbulence in experiments on quasi Keplerian flows
VL - 817
ER -
TY - JOUR
AB - We introduce a multiscale topological description of the Megaparsec web-like cosmic matter distribution. Betti numbers and topological persistence offer a powerful means of describing the rich connectivity structure of the cosmic web and of its multiscale arrangement of matter and galaxies. Emanating from algebraic topology and Morse theory, Betti numbers and persistence diagrams represent an extension and deepening of the cosmologically familiar topological genus measure and the related geometric Minkowski functionals. In addition to a description of the mathematical background, this study presents the computational procedure for computing Betti numbers and persistence diagrams for density field filtrations. The field may be computed starting from a discrete spatial distribution of galaxies or simulation particles. The main emphasis of this study concerns an extensive and systematic exploration of the imprint of different web-like morphologies and different levels of multiscale clustering in the corresponding computed Betti numbers and persistence diagrams. To this end, we use Voronoi clustering models as templates for a rich variety of web-like configurations and the fractal-like Soneira-Peebles models exemplify a range of multiscale configurations. We have identified the clear imprint of cluster nodes, filaments, walls, and voids in persistence diagrams, along with that of the nested hierarchy of structures in multiscale point distributions. We conclude by outlining the potential of persistent topology for understanding the connectivity structure of the cosmic web, in large simulations of cosmic structure formation and in the challenging context of the observed galaxy distribution in large galaxy surveys.
AU - Pranav, Pratyush
AU - Edelsbrunner, Herbert
AU - Van De Weygaert, Rien
AU - Vegter, Gert
AU - Kerber, Michael
AU - Jones, Bernard
AU - Wintraecken, Mathijs
ID - 1022
IS - 4
JF - Monthly Notices of the Royal Astronomical Society
SN - 00358711
TI - The topology of the cosmic web in terms of persistent Betti numbers
VL - 465
ER -
TY - JOUR
AB - We consider products of independent square non-Hermitian random matrices. More precisely, let X1,…, Xn be independent N × N random matrices with independent entries (real or complex with independent real and imaginary parts) with zero mean and variance 1/N. Soshnikov-O’Rourke [19] and Götze-Tikhomirov [15] showed that the empirical spectral distribution of the product of n random matrices with iid entries converges to (equation found). We prove that if the entries of the matrices X1,…, Xn are independent (but not necessarily identically distributed) and satisfy uniform subexponential decay condition, then in the bulk the convergence of the ESD of X1,…, Xn to (0.1) holds up to the scale N–1/2+ε.
AU - Nemish, Yuriy
ID - 1023
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for the product of independent non-Hermitian random matrices with independent entries
VL - 22
ER -
TY - JOUR
AB - Many organ surfaces are covered by a protective epithelial-cell layer. It emerges that such layers are maintained by cell stretching that triggers cell division mediated by the force-sensitive ion-channel protein Piezo1. See Letter p.118
AU - Heisenberg, Carl-Philipp J
ID - 1025
IS - 7643
JF - Nature
SN - 00280836
TI - Cell biology: Stretched divisions
VL - 543
ER -
TY - JOUR
AB - The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.
AU - Agus, Viviana
AU - Janovjak, Harald L
ID - 1026
JF - Current Opinion in Biotechnology
SN - 09581669
TI - Optogenetic methods in drug screening: Technologies and applications
VL - 48
ER -
TY - JOUR
AB - Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.
AU - Kainrath, Stephanie
AU - Stadler, Manuela
AU - Gschaider-Reichhart, Eva
AU - Distel, Martin
AU - Janovjak, Harald L
ID - 1028
IS - 16
JF - Angewandte Chemie - International Edition
SN - 14337851
TI - Green-light-induced inactivation of receptor signaling using cobalamin-binding domains
VL - 56
ER -
TY - JOUR
AB - Auf der Suche nach einem Bibliothekssystem entschied sich die Forschungseinrichtung IST Austria im Jahr 2014 für das Open-Source-Produkt Koha. In einem ersten Schritt wurden zunächst Grundfunktionen aktiviert um im Anschluss diverse zusätzliche Tools zum Einsatz zu bringen. Die große Flexibilität des Systems erlaubt maßgeschneiderte Lösungen für unterschiedlichste Institutionen. Trotz Herausforderungen kann die Bibliothek auf eine erfolgreiche Implementierung zurückblicken.
AU - Villányi, Márton
ID - 1030
IS - 1
JF - Informationspraxis
SN - 2297-3249
TI - Ein freies Bibliothekssystem für wissenschaftliche Bibliotheken – Werkstattbericht der IST Austria Library
VL - 3
ER -
TY - JOUR
AB - Severe environmental change can drive a population extinct unless the population adapts in time to the new conditions (“evolutionary rescue”). How does biparental sexual reproduction influence the chances of population persistence compared to clonal reproduction or selfing? In this article, we set up a one‐locus two‐allele model for adaptation in diploid species, where rescue is contingent on the establishment of the mutant homozygote. Reproduction can occur by random mating, selfing, or clonally. Random mating generates and destroys the rescue mutant; selfing is efficient at generating it but at the same time depletes the heterozygote, which can lead to a low mutant frequency in the standing genetic variation. Due to these (and other) antagonistic effects, we find a nontrivial dependence of population survival on the rate of sex/selfing, which is strongly influenced by the dominance coefficient of the mutation before and after the environmental change. Importantly, since mating with the wild‐type breaks the mutant homozygote up, a slow decay of the wild‐type population size can impede rescue in randomly mating populations.
AU - Uecker, Hildegard
ID - 1063
IS - 4
JF - Evolution
SN - 00143820
TI - Evolutionary rescue in randomly mating, selfing, and clonal populations
VL - 71
ER -
TY - JOUR
AB - We consider the problem of reachability in pushdown graphs. We study the problem for pushdown graphs with constant treewidth. Even for pushdown graphs with treewidth 1, for the reachability problem we establish the following: (i) the problem is PTIME-complete, and (ii) any subcubic algorithm for the problem would contradict the k-clique conjecture and imply faster combinatorial algorithms for cliques in graphs.
AU - Chatterjee, Krishnendu
AU - Osang, Georg F
ID - 1065
JF - Information Processing Letters
SN - 00200190
TI - Pushdown reachability with constant treewidth
VL - 122
ER -
TY - JOUR
AB - Simulation is an attractive alternative to language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. While fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable in general, whereas the (quantitative) simulation reduces to quantitative games, which admit pseudo-polynomial time algorithms.
In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games, yet they still admit pseudo-polynomial time algorithms.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Velner, Yaron
ID - 1066
IS - 2
JF - Information and Computation
TI - Quantitative fair simulation games
VL - 254
ER -
TY - JOUR
AB - Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during “doming,” when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.
AU - Morita, Hitoshi
AU - Grigolon, Silvia
AU - Bock, Martin
AU - Krens, Gabriel
AU - Salbreux, Guillaume
AU - Heisenberg, Carl-Philipp J
ID - 1067
IS - 4
JF - Developmental Cell
SN - 15345807
TI - The physical basis of coordinated tissue spreading in zebrafish gastrulation
VL - 40
ER -
TY - JOUR
AB - Given a finite set of points in Rn and a radius parameter, we study the Čech, Delaunay–Čech, Delaunay (or alpha), and Wrap complexes in the light of generalized discrete Morse theory. Establishing the Čech and Delaunay complexes as sublevel sets of generalized discrete Morse functions, we prove that the four complexes are simple-homotopy equivalent by a sequence of simplicial collapses, which are explicitly described by a single discrete gradient field.
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 1072
IS - 5
JF - Transactions of the American Mathematical Society
TI - The Morse theory of Čech and delaunay complexes
VL - 369
ER -
TY - JOUR
AB - Let X and Y be finite simplicial sets (e.g. finite simplicial complexes), both equipped with a free simplicial action of a finite group G. Assuming that Y is d-connected and dimX≤2d, for some d≥1, we provide an algorithm that computes the set of all equivariant homotopy classes of equivariant continuous maps |X|→|Y|; the existence of such a map can be decided even for dimX≤2d+1. This yields the first algorithm for deciding topological embeddability of a k-dimensional finite simplicial complex into Rn under the condition k≤23n−1. More generally, we present an algorithm that, given a lifting-extension problem satisfying an appropriate stability assumption, computes the set of all homotopy classes of solutions. This result is new even in the non-equivariant situation.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Vokřínek, Lukáš
ID - 1073
IS - 4
JF - Discrete & Computational Geometry
SN - 01795376
TI - Algorithmic solvability of the lifting extension problem
VL - 54
ER -
TY - JOUR
AB - Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.
AU - Ringbauer, Harald
AU - Coop, Graham
AU - Barton, Nicholas H
ID - 1074
IS - 3
JF - Genetics
SN - 00166731
TI - Inferring recent demography from isolation by distance of long shared sequence blocks
VL - 205
ER -
TY - JOUR
AB - Signatures of the Coulomb corrections in the photoelectron momentum distribution during laser-induced ionization of atoms or ions in tunneling and multiphoton regimes are investigated analytically in the case of a one-dimensional problem. A high-order Coulomb-corrected strong-field approximation is applied, where the exact continuum state in the S matrix is approximated by the eikonal Coulomb-Volkov state including the second-order corrections to the eikonal. Although without high-order corrections our theory coincides with the known analytical R-matrix (ARM) theory, we propose a simplified procedure for the matrix element derivation. Rather than matching the eikonal Coulomb-Volkov wave function with the bound state as in the ARM theory to remove the Coulomb singularity, we calculate the matrix element via the saddle-point integration method by time as well as by coordinate, and in this way avoiding the Coulomb singularity. The momentum shift in the photoelectron momentum distribution with respect to the ARM theory due to high-order corrections is analyzed for tunneling and multiphoton regimes. The relation of the quantum corrections to the tunneling delay time is discussed.
AU - Klaiber, Michael
AU - Daněk, Jiří
AU - Yakaboylu, Enderalp
AU - Hatsagortsyan, Karen
AU - Keitel, Christoph
ID - 1076
IS - 2
JF - Physical Review A - Atomic, Molecular, and Optical Physics
SN - 24699926
TI - Strong-field ionization via a high-order Coulomb-corrected strong-field approximation
VL - 95
ER -
TY - JOUR
AB - Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.
AU - Fernandes Redondo, Rodrigo A
AU - Vladar, Harold
AU - Włodarski, Tomasz
AU - Bollback, Jonathan P
ID - 1077
IS - 126
JF - Journal of the Royal Society Interface
SN - 17425689
TI - Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family
VL - 14
ER -
TY - JOUR
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.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Friml, Jirí
ID - 1078
IS - 119
JF - Journal of visualized experiments JoVE
TI - Light sheet fluorescence microscopy of plant roots growing on the surface of a gel
VL - 2017
ER -
TY - JOUR
AB - We study the ionization problem in the Thomas-Fermi-Dirac-von Weizsäcker theory for atoms and molecules. We prove the nonexistence of minimizers for the energy functional when the number of electrons is large and the total nuclear charge is small. This nonexistence result also applies to external potentials decaying faster than the Coulomb potential. In the case of arbitrary nuclear charges, we obtain the nonexistence of stable minimizers and radial minimizers.
AU - Nam, Phan
AU - Van Den Bosch, Hanne
ID - 1079
IS - 2
JF - Mathematical Physics, Analysis and Geometry
SN - 13850172
TI - Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges
VL - 20
ER -
TY - JOUR
AB - Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods.
AU - Reiter, Johannes
AU - Makohon Moore, Alvin
AU - Gerold, Jeffrey
AU - Božić, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 1080
JF - Nature Communications
SN - 20411723
TI - Reconstructing metastatic seeding patterns of human cancers
VL - 8
ER -
TY - JOUR
AB - BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.
AU - Fang, Chong
AU - Nagy-Staron, Anna A
AU - Grafe, Martin
AU - Heermann, Ralf
AU - Jung, Kirsten
AU - Gebhard, Susanne
AU - Mascher, Thorsten
ID - 1084
IS - 1
JF - Molecular Microbiology
SN - 0950382X
TI - Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis
VL - 104
ER -
TY - JOUR
AB - Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution.
AU - Wright, Alison
AU - Darolti, Iulia
AU - Bloch, Natasha
AU - Oostra, Vicencio
AU - Sandkam, Benjamin
AU - Buechel, Séverine
AU - Kolm, Niclas
AU - Breden, Felix
AU - Vicoso, Beatriz
AU - Mank, Judith
ID - 1085
JF - Nature Communications
SN - 20411723
TI - Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation
VL - 8
ER -
TY - JOUR
AB - Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.
AU - Di Giglio, Maria
AU - Muttenthaler, Markus
AU - Harpsøe, Kasper
AU - Liutkeviciute, Zita
AU - Keov, Peter
AU - Eder, Thomas
AU - Rattei, Thomas
AU - Arrowsmith, Sarah
AU - Wray, Susan
AU - Marek, Ales
AU - Elbert, Tomas
AU - Alewood, Paul
AU - Gloriam, David
AU - Gruber, Christian
ID - 1086
JF - Scientific Reports
TI - Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide
VL - 7
ER -
TY - JOUR
AB - Using extensive direct numerical simulations, the dynamics of laminar-turbulent fronts in pipe flow is investigated for Reynolds numbers between and 5500. We here investigate the physical distinction between the fronts of weak and strong slugs both by analysing the turbulent kinetic energy budget and by comparing the downstream front motion to the advection speed of bulk turbulent structures. Our study shows that weak downstream fronts travel slower than turbulent structures in the bulk and correspond to decaying turbulence at the front. At the downstream front speed becomes faster than the advection speed, marking the onset of strong fronts. In contrast to weak fronts, turbulent eddies are generated at strong fronts by feeding on the downstream laminar flow. Our study also suggests that temporal fluctuations of production and dissipation at the downstream laminar-turbulent front drive the dynamical switches between the two types of front observed up to.
AU - Song, Baofang
AU - Barkley, Dwight
AU - Hof, Björn
AU - Avila, Marc
ID - 1087
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Speed and structure of turbulent fronts in pipe flow
VL - 813
ER -
TY - JOUR
AB - We discuss properties of distributions that are multivariate totally positive of order two (MTP2) related to conditional independence. In particular, we show that any independence model generated by an MTP2 distribution is a compositional semigraphoid which is upward-stable and singleton-transitive. In addition, we prove that any MTP2 distribution satisfying an appropriate support condition is faithful to its concentration graph. Finally, we analyze factorization properties of MTP2 distributions and discuss ways of constructing MTP2 distributions; in particular we give conditions on the log-linear parameters of a discrete distribution which ensure MTP2 and characterize conditional Gaussian distributions which satisfy MTP2.
AU - Fallat, Shaun
AU - Lauritzen, Steffen
AU - Sadeghi, Kayvan
AU - Uhler, Caroline
AU - Wermuth, Nanny
AU - Zwiernik, Piotr
ID - 1089
IS - 3
JF - Annals of Statistics
SN - 00905364
TI - Total positivity in Markov structures
VL - 45
ER -
TY - JOUR
AB - In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems.
AU - Deny, Stephane
AU - Ferrari, Ulisse
AU - Mace, Emilie
AU - Yger, Pierre
AU - Caplette, Romain
AU - Picaud, Serge
AU - Tkacik, Gasper
AU - Marre, Olivier
ID - 1104
IS - 1
JF - Nature Communications
SN - 20411723
TI - Multiplexed computations in retinal ganglion cells of a single type
VL - 8
ER -
TY - CONF
AB - In this work we study the learnability of stochastic processes with respect to the conditional risk, i.e. the existence of a learning algorithm that improves its next-step performance with the amount of observed data. We introduce a notion of pairwise discrepancy between conditional distributions at different times steps and show how certain properties of these discrepancies can be used to construct a successful learning algorithm. Our main results are two theorems that establish criteria for learnability for many classes of stochastic processes, including all special cases studied previously in the literature.
AU - Zimin, Alexander
AU - Lampert, Christoph
ID - 1108
TI - Learning theory for conditional risk minimization
VL - 54
ER -
TY - JOUR
AB - Rotation of molecules embedded in He nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear -- instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its He shell. Our results open novel opportunities for studying non-equilibrium solute-solvent dynamics and quantum thermalization.
AU - Shepperson, Benjamin
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Kaczmarczyk, Jan
AU - Zillich, Robert
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 1109
IS - 20
JF - Physical Review Letters
TI - Laser-induced rotation of iodine molecules in helium nanodroplets: Revivals and breaking-free
VL - 118
ER -