TY - JOUR
AB - The Ising model is one of the simplest and most famous models of interacting systems. It was originally proposed to model ferromagnetic interactions in statistical physics and is now widely used to model spatial processes in many areas such as ecology, sociology, and genetics, usually without testing its goodness-of-fit. Here, we propose an exact goodness-of-fit test for the finite-lattice Ising model. The theory of Markov bases has been developed in algebraic statistics for exact goodness-of-fit testing using a Monte Carlo approach. However, this beautiful theory has fallen short of its promise for applications, because finding a Markov basis is usually computationally intractable. We develop a Monte Carlo method for exact goodness-of-fit testing for the Ising model which avoids computing a Markov basis and also leads to a better connectivity of the Markov chain and hence to a faster convergence. We show how this method can be applied to analyze the spatial organization of receptors on the cell membrane.
AU - Martin Del Campo Sanchez, Abraham
AU - Cepeda Humerez, Sarah A
AU - Uhler, Caroline
ID - 2016
IS - 2
JF - Scandinavian Journal of Statistics
SN - 03036898
TI - Exact goodness-of-fit testing for the Ising model
VL - 44
ER -
TY - THES
AB - Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.
AU - Pleska, Maros
ID - 202
TI - Biology of restriction-modification systems at the single-cell and population level
ER -
TY - JOUR
AB - To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.
AU - Andergassen, Daniel
AU - Dotter, Christoph
AU - Wenzel, Dyniel
AU - Sigl, Verena
AU - Bammer, Philipp
AU - Muckenhuber, Markus
AU - Mayer, Daniela
AU - Kulinski, Tomasz
AU - Theussl, Hans
AU - Penninger, Josef
AU - Bock, Christoph
AU - Barlow, Denise
AU - Pauler, Florian
AU - Hudson, Quanah
ID - 713
JF - eLife
SN - 2050084X
TI - Mapping the mouse Allelome reveals tissue specific regulation of allelic expression
VL - 6
ER -
TY - JOUR
AB - Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.
AU - Brailoiu, Gabriela
AU - Deliu, Elena
AU - Barr, Jeffrey
AU - Console Bram, Linda
AU - Ciuciu, Alexandra
AU - Abood, Mary
AU - Unterwald, Ellen
AU - Brǎiloiu, Eugen
ID - 714
JF - Drug and Alcohol Dependence
SN - 03768716
TI - HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens
VL - 178
ER -
TY - JOUR
AB - D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome.
AU - Novarino, Gaia
ID - 715
IS - 405
JF - Science Translational Medicine
SN - 19466234
TI - More excitation for Rett syndrome
VL - 9
ER -
TY - JOUR
AB - Two-player games on graphs are central in many problems in formal verification and program analysis, such as synthesis and verification of open systems. In this work, we consider solving recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion.While pushdown games have been studied before with qualitative objectives-such as reachability and ?-regular objectives- in this work, we study for the first time such games with the most well-studied quantitative objective, the mean-payoff objective. In pushdown games, two types of strategies are relevant: (1) global strategies, which depend on the entire global history; and (2) modular strategies, which have only local memory and thus do not depend on the context of invocation but rather only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two-player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP-hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity by showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games and memoryless modular strategies are sufficient in two-player pushdown games. Finally, we also show that all the problems have the same complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 716
IS - 5
JF - Journal of the ACM
SN - 00045411
TI - The complexity of mean-payoff pushdown games
VL - 64
ER -
TY - DATA
AB - The de novo genome assemblies generated for this study, and the associated metadata.
AU - Fraisse, Christelle
ID - 7163
TI - Supplementary Files for "The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W"
ER -
TY - JOUR
AB - We consider finite-state and recursive game graphs with multidimensional mean-payoff objectives. In recursive games two types of strategies are relevant: global strategies and modular strategies. Our contributions are: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of weights are fixed; whereas for arbitrary dimensions the problem is coNP-complete. (2) We show that one-player recursive games with multidimensional mean-payoff objectives can be solved in polynomial time. Both above algorithms are based on hyperplane separation technique. (3) For recursive games we show that under modular strategies the multidimensional problem is undecidable. We show that if the number of modules, exits, and the maximal absolute value of the weights are fixed, then one-dimensional recursive mean-payoff games under modular strategies can be solved in polynomial time, whereas for unbounded number of exits or modules the problem is NP-hard.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 717
JF - Journal of Computer and System Sciences
TI - Hyperplane separation technique for multidimensional mean-payoff games
VL - 88
ER -
TY - JOUR
AB - Mapping every simplex in the Delaunay mosaic of a discrete point set to the radius of the smallest empty circumsphere gives a generalized discrete Morse function. Choosing the points from a Poisson point process in ℝ n , we study the expected number of simplices in the Delaunay mosaic as well as the expected number of critical simplices and nonsingular intervals in the corresponding generalized discrete gradient. Observing connections with other probabilistic models, we obtain precise expressions for the expected numbers in low dimensions. In particular, we obtain the expected numbers of simplices in the Poisson–Delaunay mosaic in dimensions n ≤ 4.
AU - Edelsbrunner, Herbert
AU - Nikitenko, Anton
AU - Reitzner, Matthias
ID - 718
IS - 3
JF - Advances in Applied Probability
SN - 00018678
TI - Expected sizes of poisson Delaunay mosaics and their discrete Morse functions
VL - 49
ER -
TY - JOUR
AB - The ubiquity of computation in modern machines and devices imposes a need to assert the correctness of their behavior. Especially in the case of safety-critical systems, their designers need to take measures that enforce their safe operation. Formal methods has emerged as a research field that addresses this challenge: by rigorously proving that all system executions adhere to their specifications, the correctness of an implementation under concern can be assured. To achieve this goal, a plethora of techniques are nowadays available, all of which are optimized for different system types and application domains.
AU - Chatterjee, Krishnendu
AU - Ehlers, Rüdiger
ID - 719
IS - 6
JF - Acta Informatica
SN - 00015903
TI - Special issue: Synthesis and SYNT 2014
VL - 54
ER -