TY - JOUR AB - We investigate the complexity of finding an embedded non-orientable surface of Euler genus g in a triangulated 3-manifold. This problem occurs both as a natural question in low-dimensional topology, and as a first non-trivial instance of embeddability of complexes into 3-manifolds. We prove that the problem is NP-hard, thus adding to the relatively few hardness results that are currently known in 3-manifold topology. In addition, we show that the problem lies in NP when the Euler genus g is odd, and we give an explicit algorithm in this case. AU - Burton, Benjamin AU - De Mesmay, Arnaud N AU - Wagner, Uli ID - 534 IS - 4 JF - Discrete & Computational Geometry SN - 01795376 TI - Finding non-orientable surfaces in 3-Manifolds VL - 58 ER - 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 - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem. AU - Chatterjee, Krishnendu AU - Křetínská, Zuzana AU - Kretinsky, Jan ID - 466 IS - 2 JF - Logical Methods in Computer Science SN - 18605974 TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes VL - 13 ER - TY - JOUR AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata or in any other known decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata, which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in runtime verification. We establish an almost-complete decidability picture for the basic decision problems about nested weighted automata and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan ID - 467 IS - 4 JF - ACM Transactions on Computational Logic (TOCL) SN - 15293785 TI - Nested weighted automata VL - 18 ER -