TY - JOUR
AB - High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Muellner, Markus
AU - Nowak, Matthias
AU - Nijman, Sebastian
AU - Grusch, Michael
AU - Janovjak, Harald L
ID - 1678
IS - 12
JF - Nature Chemical Biology
TI - Light-assisted small-molecule screening against protein kinases
VL - 11
ER -
TY - JOUR
AU - Lemoult, Grégoire M
AU - Maier, Philipp
AU - Hof, Björn
ID - 1679
IS - 9
JF - Physics of Fluids
TI - Taylor's Forest
VL - 27
ER -
TY - JOUR
AB - We consider the satisfiability problem for modal logic over first-order definable classes of frames.We confirm the conjecture from Hemaspaandra and Schnoor [2008] that modal logic is decidable over classes definable by universal Horn formulae. We provide a full classification of Horn formulae with respect to the complexity of the corresponding satisfiability problem. It turns out, that except for the trivial case of inconsistent formulae, local satisfiability is eitherNP-complete or PSPACE-complete, and global satisfiability is NP-complete, PSPACE-complete, or ExpTime-complete. We also show that the finite satisfiability problem for modal logic over Horn definable classes of frames is decidable. On the negative side, we show undecidability of two related problems. First, we exhibit a simple universal three-variable formula defining the class of frames over which modal logic is undecidable. Second, we consider the satisfiability problem of bimodal logic over Horn definable classes of frames, and also present a formula leading to undecidability.
AU - Michaliszyn, Jakub
AU - Otop, Jan
AU - Kieroňski, Emanuel
ID - 1680
IS - 1
JF - ACM Transactions on Computational Logic
TI - On the decidability of elementary modal logics
VL - 17
ER -
TY - JOUR
AB - In many social situations, individuals endeavor to find the single best possible partner, but are constrained to evaluate the candidates in sequence. Examples include the search for mates, economic partnerships, or any other long-term ties where the choice to interact involves two parties. Surprisingly, however, previous theoretical work on mutual choice problems focuses on finding equilibrium solutions, while ignoring the evolutionary dynamics of decisions. Empirically, this may be of high importance, as some equilibrium solutions can never be reached unless the population undergoes radical changes and a sufficient number of individuals change their decisions simultaneously. To address this question, we apply a mutual choice sequential search problem in an evolutionary game-theoretical model that allows one to find solutions that are favored by evolution. As an example, we study the influence of sequential search on the evolutionary dynamics of cooperation. For this, we focus on the classic snowdrift game and the prisoner’s dilemma game.
AU - Priklopil, Tadeas
AU - Chatterjee, Krishnendu
ID - 1681
IS - 4
JF - Games
TI - Evolution of decisions in population games with sequentially searching individuals
VL - 6
ER -
TY - JOUR
AB - We study the problem of robust satisfiability of systems of nonlinear equations, namely, whether for a given continuous function f:K→ ℝn on a finite simplicial complex K and α > 0, it holds that each function g: K → ℝn such that ||g - f || ∞ < α, has a root in K. Via a reduction to the extension problem of maps into a sphere, we particularly show that this problem is decidable in polynomial time for every fixed n, assuming dimK ≤ 2n - 3. This is a substantial extension of previous computational applications of topological degree and related concepts in numerical and interval analysis. Via a reverse reduction, we prove that the problem is undecidable when dim K > 2n - 2, where the threshold comes from the stable range in homotopy theory. For the lucidity of our exposition, we focus on the setting when f is simplexwise linear. Such functions can approximate general continuous functions, and thus we get approximation schemes and undecidability of the robust satisfiability in other possible settings.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1682
IS - 4
JF - Journal of the ACM
TI - Robust satisfiability of systems of equations
VL - 62
ER -
TY - JOUR
AB - The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.
AU - Letts, Jame A
AU - Sazanov, Leonid A
ID - 1683
IS - 8
JF - Current Opinion in Structural Biology
TI - Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions
VL - 33
ER -
TY - CONF
AB - Given a graph G cellularly embedded on a surface Σ of genus g, a cut graph is a subgraph of G such that cutting Σ along G yields a topological disk. We provide a fixed parameter tractable approximation scheme for the problem of computing the shortest cut graph, that is, for any ε > 0, we show how to compute a (1 + ε) approximation of the shortest cut graph in time f(ε, g)n3.
Our techniques first rely on the computation of a spanner for the problem using the technique of brick decompositions, to reduce the problem to the case of bounded tree-width. Then, to solve the bounded tree-width case, we introduce a variant of the surface-cut decomposition of Rué, Sau and Thilikos, which may be of independent interest.
AU - Cohen Addad, Vincent
AU - De Mesmay, Arnaud N
ID - 1685
TI - A fixed parameter tractable approximation scheme for the optimal cut graph of a surface
VL - 9294
ER -
TY - THES
AB - The human ability to recognize objects in complex scenes has driven research in the computer vision field over couple of decades. This thesis focuses on the object recognition task in images. That is, given the image, we want the computer system to be able to predict the class of the object that appears in the image. A recent succesful attempt to bridge semantic understanding of the image perceived by humans and by computers uses attribute-based models. Attributes are semantic properties of the objects shared across different categories, which humans and computers can decide on. To explore the attribute-based models we take a statistical machine learning approach, and address two key learning challenges in view of object recognition task: learning augmented attributes as mid-level discriminative feature representation, and learning with attributes as privileged information. Our main contributions are parametric and non-parametric models and algorithms to solve these frameworks. In the parametric approach, we explore an autoencoder model combined with the large margin nearest neighbor principle for mid-level feature learning, and linear support vector machines for learning with privileged information. In the non-parametric approach, we propose a supervised Indian Buffet Process for automatic augmentation of semantic attributes, and explore the Gaussian Processes classification framework for learning with privileged information. A thorough experimental analysis shows the effectiveness of the proposed models in both parametric and non-parametric views.
AU - Sharmanska, Viktoriia
ID - 1401
TI - Learning with attributes for object recognition: Parametric and non-parametrics views
ER -
TY - CONF
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 such sequences produced under a non-preemptive scheduler. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and rules for inserting synchronization. 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, and, since it does not require explicit specifications, is more practical than the conventional approach based on user-provided assertions.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1729
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 9207
ER -
TY - JOUR
AB - Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics.
AU - Tugrul, Murat
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 1666
IS - 11
JF - PLoS Genetics
TI - Dynamics of transcription factor binding site evolution
VL - 11
ER -