TY - JOUR
AB - Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung.
AU - Kainrath, Stephanie
AU - Stadler, Manuela
AU - Gschaider-Reichhart, Eva
AU - Distel, Martin
AU - Janovjak, Harald L
ID - 538
IS - 16
JF - Angewandte Chemie
TI - Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen
VL - 129
ER -
TY - JOUR
AB - RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.
AU - Khamina, Kseniya
AU - Lercher, Alexander
AU - Caldera, Michael
AU - Schliehe, Christopher
AU - Vilagos, Bojan
AU - Sahin, Mehmet
AU - Kosack, Lindsay
AU - Bhattacharya, Anannya
AU - Májek, Peter
AU - Stukalov, Alexey
AU - Sacco, Roberto
AU - James, Leo
AU - Pinschewer, Daniel
AU - Bennett, Keiryn
AU - Menche, Jörg
AU - Bergthaler, Andreas
ID - 540
IS - 12
JF - PLoS Pathogens
SN - 15537366
TI - Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein
VL - 13
ER -
TY - JOUR
AB - While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 541
IS - 12
JF - PLoS Genetics
SN - 15537390
TI - Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations
VL - 13
ER -
TY - CHAP
AB - Development of vascular tissue is a remarkable example of intercellular communication and coordinated development involving hormonal signaling and tissue polarity. Thus far, studies on vascular patterning and regeneration have been conducted mainly in trees—woody plants—with a well-developed layer of vascular cambium and secondary tissues. Trees are difficult to use as genetic models, i.e., due to long generation time, unstable environmental conditions, and lack of available mutants and transgenic lines. Therefore, the use of the main genetic model plant Arabidopsis thaliana (L.) Heynh., with a wealth of available marker and transgenic lines, provides a unique opportunity to address molecular mechanism of vascular tissue formation and regeneration. With specific treatments, the tiny weed Arabidopsis can serve as a model to understand the growth of mighty trees and interconnect a tree physiology with molecular genetics and cell biology of Arabidopsis.
AU - Mazur, Ewa
AU - Friml, Jirí
ED - Jurić, Snježana
ID - 545
T2 - Plant Engineering
TI - Vascular tissue development and regeneration in the model plant arabidopsis
ER -
TY - GEN
AB - In this report the implementation of the institutional data repository IST DataRep at IST Austria will be covered: Starting with the research phase when requirements for a repository were established, the procedure of choosing a repository-software and its customization based on the results of user-testings will be discussed. Followed by reflections on the marketing strategies in regard of impact, and at the end sharing some experiences of one year operating IST DataRep.
AU - Barbara Petritsch
ID - 5450
TI - Implementing the institutional data repository IST DataRep
ER -
TY - GEN
AB - A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graphwhere the edges are labeled with different types of opening and closing parentheses, and the reachabilityinformation is computed via paths whose parentheses are properly matched. We present new results for Dyckreachability problems with applications to alias analysis and data-dependence analysis. Our main contributions,that include improved upper bounds as well as lower bounds that establish optimality guarantees, are asfollows:First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph withnnodes andmedges, we present: (i) an algorithmwith worst-case running timeO(m+n·α(n)), whereα(n)is the inverse Ackermann function, improving thepreviously knownO(n2)time bound; (ii) a matching lower bound that shows that our algorithm is optimalwrt to worst-case complexity; and (iii) an optimal average-case upper bound ofO(m)time, improving thepreviously knownO(m·logn)bound.Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtainanalysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almostlinear time, after which the contribution of the library in the complexity of the client analysis is only linear,and only wrt the number of call sites.Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean MatrixMultiplication, which is a long-standing open problem. Thus we establish that the existing combinatorialalgorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the samehardness holds for graphs of constant treewidth.Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependenceanalysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform allexisting methods on the two problems, over real-world benchmarks.
AU - Chatterjee, Krishnendu
AU - Choudhary, Bhavya
AU - Pavlogiannis, Andreas
ID - 5455
SN - 2664-1690
TI - Optimal Dyck reachability for data-dependence and alias analysis
ER -
TY - GEN
AB - We present a new dynamic partial-order reduction method for stateless model checking of concurrent programs. A common approach for exploring program behaviors relies on enumerating the traces of the program, without storing the visited states (aka stateless exploration). As the number of distinct traces grows exponentially, dynamic partial-order reduction (DPOR) techniques have been successfully used to partition the space of traces into equivalence classes (Mazurkiewicz partitioning), with the goal of exploring only few representative traces from each class.
We introduce a new equivalence on traces under sequential consistency semantics, which we call the observation equivalence. Two traces are observationally equivalent if every read event observes the same write event in both traces. While the traditional Mazurkiewicz equivalence is control-centric, our new definition is data-centric. We show that our observation equivalence is coarser than the Mazurkiewicz equivalence, and in many cases even exponentially coarser. We devise a DPOR exploration of the trace space, called data-centric DPOR, based on the observation equivalence.
1. For acyclic architectures, our algorithm is guaranteed to explore exactly one representative trace from each observation class, while spending polynomial time per class. Hence, our algorithm is optimal wrt the observation equivalence, and in several cases explores exponentially fewer traces than any enumerative method based on the Mazurkiewicz equivalence.
2. For cyclic architectures, we consider an equivalence between traces which is finer than the observation equivalence; but coarser than the Mazurkiewicz equivalence, and in some cases is exponentially coarser. Our data-centric DPOR algorithm remains optimal under this trace equivalence.
Finally, we perform a basic experimental comparison between the existing Mazurkiewicz-based DPOR and our data-centric DPOR on a set of academic benchmarks. Our results show a significant reduction in both running time and the number of explored equivalence classes.
AU - Chalupa, Marek
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Sinha, Nishant
AU - Vaidya, Kapil
ID - 5456
SN - 2664-1690
TI - Data-centric dynamic partial order reduction
ER -
TY - JOUR
AB - In this work maximum entropy distributions in the space of steady states of metabolic networks are considered upon constraining the first and second moments of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux distributions, emerges upon considering control on the average growth (optimization) and its fluctuations (heterogeneity). This is applied to the carbon catabolic core of Escherichia coli where it quantifies the metabolic activity of slow growing phenotypes and it provides a quantitative map with metabolic fluxes, opening the possibility to detect coexistence from flux data. A preliminary analysis on data for E. coli cultures in standard conditions shows degeneracy for the inferred parameters that extend in the coexistence region.
AU - De Martino, Daniele
ID - 548
IS - 6
JF - Physical Review E
SN - 24700045
TI - Maximum entropy modeling of metabolic networks by constraining growth-rate moments predicts coexistence of phenotypes
VL - 96
ER -
TY - CONF
AB - Model checking is usually based on a comprehensive traversal of the state space. Causality-based model checking is a radically different approach that instead analyzes the cause-effect relationships in a program. We give an overview on a new class of model checking algorithms that capture the causal relationships in a special data structure called concurrent traces. Concurrent traces identify key events in an execution history and link them through their cause-effect relationships. The model checker builds a tableau of concurrent traces, where the case splits represent different causal explanations of a hypothetical error. Causality-based model checking has been implemented in the ARCTOR tool, and applied to previously intractable multi-threaded benchmarks.
AU - Finkbeiner, Bernd
AU - Kupriyanov, Andrey
ID - 549
SN - 20752180
T2 - Electronic Proceedings in Theoretical Computer Science
TI - Causality-based model checking
VL - 259
ER -
TY - JOUR
AB - For large random matrices X with independent, centered entries but not necessarily identical variances, the eigenvalue density of XX* is well-approximated by a deterministic measure on ℝ. We show that the density of this measure has only square and cubic-root singularities away from zero. We also extend the bulk local law in [5] to the vicinity of these singularities.
AU - Alt, Johannes
ID - 550
JF - Electronic Communications in Probability
SN - 1083589X
TI - Singularities of the density of states of random Gram matrices
VL - 22
ER -
TY - CONF
AB - Evolutionary graph theory studies the evolutionary dynamics in a population structure given as a connected graph. Each node of the graph represents an individual of the population, and edges determine how offspring are placed. We consider the classical birth-death Moran process where there are two types of individuals, namely, the residents with fitness 1 and mutants with fitness r. The fitness indicates the reproductive strength. The evolutionary dynamics happens as follows: in the initial step, in a population of all resident individuals a mutant is introduced, and then at each step, an individual is chosen proportional to the fitness of its type to reproduce, and the offspring replaces a neighbor uniformly at random. The process stops when all individuals are either residents or mutants. The probability that all individuals in the end are mutants is called the fixation probability, which is a key factor in the rate of evolution. We consider the problem of approximating the fixation probability. The class of algorithms that is extremely relevant for approximation of the fixation probabilities is the Monte-Carlo simulation of the process. Previous results present a polynomial-time Monte-Carlo algorithm for undirected graphs when r is given in unary. First, we present a simple modification: instead of simulating each step, we discard ineffective steps, where no node changes type (i.e., either residents replace residents, or mutants replace mutants). Using the above simple modification and our result that the number of effective steps is concentrated around the expected number of effective steps, we present faster polynomial-time Monte-Carlo algorithms for undirected graphs. Our algorithms are always at least a factor O(n2/ log n) faster as compared to the previous algorithms, where n is the number of nodes, and is polynomial even if r is given in binary. We also present lower bounds showing that the upper bound on the expected number of effective steps we present is asymptotically tight for undirected graphs.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 551
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster Monte Carlo algorithms for fixation probability of the Moran process on undirected graphs
VL - 83
ER -
TY - CONF
AB - Graph games provide the foundation for modeling and synthesis of reactive processes. Such games are played over graphs where the vertices are controlled by two adversarial players. We consider graph games where the objective of the first player is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a meanpayoff condition). There are two variants of the problem, namely, the threshold problem where the quantitative goal is to ensure that the mean-payoff value is above a threshold, and the value problem where the quantitative goal is to ensure the optimal mean-payoff value; in both cases ensuring the qualitative parity objective. The previous best-known algorithms for game graphs with n vertices, m edges, parity objectives with d priorities, and maximal absolute reward value W for mean-payoff objectives, are as follows: O(nd+1 . m . w) for the threshold problem, and O(nd+2 · m · W) for the value problem. Our main contributions are faster algorithms, and the running times of our algorithms are as follows: O(nd-1 · m ·W) for the threshold problem, and O(nd · m · W · log(n · W)) for the value problem. For mean-payoff parity objectives with two priorities, our algorithms match the best-known bounds of the algorithms for mean-payoff games (without conjunction with parity objectives). Our results are relevant in synthesis of reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Svozil, Alexander
ID - 552
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster algorithms for mean payoff parity games
VL - 83
ER -
TY - CONF
AB - We consider two player, zero-sum, finite-state concurrent reachability games, played for an infinite number of rounds, where in every round, each player simultaneously and independently of the other players chooses an action, whereafter the successor state is determined by a probability distribution given by the current state and the chosen actions. Player 1 wins iff a designated goal state is eventually visited. We are interested in the complexity of stationary strategies measured by their patience, which is defined as the inverse of the smallest non-zero probability employed. Our main results are as follows: We show that: (i) the optimal bound on the patience of optimal and -optimal strategies, for both players is doubly exponential; and (ii) even in games with a single non-absorbing state exponential (in the number of actions) patience is necessary.
AU - Chatterjee, Krishnendu
AU - Hansen, Kristofer
AU - Ibsen-Jensen, Rasmus
ID - 553
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Strategy complexity of concurrent safety games
VL - 83
ER -
TY - DATA
AB - Strong amplifiers of natural selection
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak , Martin
ID - 5559
KW - natural selection
TI - Strong amplifiers of natural selection
ER -
TY - DATA
AB - This repository contains the data collected for the manuscript "Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity".
The data is compressed into a single archive. Within the archive, different folders correspond to figures of the main text and the SI of the related publication.
Data is saved as plain text, with each folder containing a separate readme file describing the format. Typically, the data is from fluorescence microscopy measurements of single cells growing in a microfluidic "mother machine" device, and consists of relevant values (primarily arbitrary unit or normalized fluorescence measurements, and division times / growth rates) after raw microscopy images have been processed, segmented, and their features extracted, as described in the methods section of the related publication.
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 - 5560
KW - single cell microscopy
KW - mother machine microfluidic device
KW - AcrAB-TolC pump
KW - multi-drug efflux
KW - Escherichia coli
TI - Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity
ER -
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 -