TY - CONF AB - We describe the design and implementation of P, a domain-specific language to write asynchronous event driven code. P allows the programmer to specify the system as a collection of interacting state machines, which communicate with each other using events. P unifies modeling and programming into one activity for the programmer. Not only can a P program be compiled into executable code, but it can also be tested using model checking techniques. P allows the programmer to specify the environment, used to "close" the system during testing, as nondeterministic ghost machines. Ghost machines are erased during compilation to executable code; a type system ensures that the erasure is semantics preserving. The P language is designed so that a P program can be checked for responsiveness-the ability to handle every event in a timely manner. By default, a machine needs to handle every event that arrives in every state. But handling every event in every state is impractical. The language provides a notion of deferred events where the programmer can annotate when she wants to delay processing an event. The default safety checker looks for presence of unhan-dled events. The language also provides default liveness checks that an event cannot be potentially deferred forever. P was used to implement and verify the core of the USB device driver stack that ships with Microsoft Windows 8. The resulting driver is more reliable and performs better than its prior incarnation (which did not use P); we have more confidence in the robustness of its design due to the language abstractions and verification provided by P. AU - Desai, Ankush AU - Gupta, Vivek AU - Jackson, Ethan AU - Qadeer, Shaz AU - Rajamani, Sriram AU - Zufferey, Damien ID - 2301 T2 - Proceedings of the 34th ACM SIGPLAN Conference on Programming Language Design and Implementation TI - P: Safe asynchronous event-driven programming ER - TY - JOUR AB - We consider Ising models in two and three dimensions with nearest neighbor ferromagnetic interactions and long-range, power law decaying, antiferromagnetic interactions. If the strength of the ferromagnetic coupling J is larger than a critical value Jc, then the ground state is homogeneous and ferromagnetic. As the critical value is approached from smaller values of J, it is believed that the ground state consists of a periodic array of stripes (d=2) or slabs (d=3), all of the same size and alternating magnetization. Here we prove rigorously that the ground state energy per site converges to that of the optimal periodic striped or slabbed state, in the limit that J tends to the ferromagnetic transition point. While this theorem does not prove rigorously that the ground state is precisely striped or slabbed, it does prove that in any suitably large box the ground state is striped or slabbed with high probability. AU - Giuliani, Alessandro AU - Lieb, Élliott AU - Seiringer, Robert ID - 2300 IS - 6 JF - Physical Review B TI - Realization of stripes and slabs in two and three dimensions VL - 88 ER - TY - JOUR AB - MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools. AU - Hippenmeyer, Simon ID - 2303 IS - 6 JF - Frontiers in Biology TI - Dissection of gene function at clonal level using mosaic analysis with double markers VL - 8 ER - TY - JOUR AB - This extended abstract is concerned with the irregularities of distribution of one-dimensional permuted van der Corput sequences that are generated from linear permutations. We show how to obtain upper bounds for the discrepancy and diaphony of these sequences, by relating them to Kronecker sequences and applying earlier results of Faure and Niederreiter. AU - Pausinger, Florian ID - 2304 JF - Electronic Notes in Discrete Mathematics TI - Van der Corput sequences and linear permutations VL - 43 ER - TY - CONF AB - We study the effects of random scatterers on the ground state of the one-dimensional Lieb-Liniger model of interacting bosons on the unit interval in the Gross-Pitaevskii regime. We prove that Bose Einstein condensation survives even a strong random potential with a high density of scatterers. The character of the wave function of the condensate, however, depends in an essential way on the interplay between randomness and the strength of the two-body interaction. For low density of scatterers or strong interactions the wave function extends over the whole interval. High density of scatterers and weak interaction, on the other hand, leads to localization of the wave function in a fragmented subset of the interval. AU - Seiringer, Robert AU - Yngvason, Jakob AU - Zagrebnov, Valentin ID - 2315 TI - Disordered Bose-Einstein condensates with interaction ER - TY - CONF AB - In a recent paper [7] we give the first rigorous derivation of the celebrated Ginzburg-Landau (GL)theory, starting from the microscopic Bardeen- Cooper-Schrieffer (BCS)model. Here we present our results in the simplified case of a one-dimensional system of particles interacting via a δ-potential. AU - Frank, Rupert L AU - Hainzl, Christian AU - Robert Seiringer AU - Solovej, Jan P ID - 2319 TI - Derivation of Ginzburg-Landau theory for a one-dimensional system with contact interaction ER - TY - CONF AB - Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on identifying the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates. In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof. AU - Henzinger, Thomas A AU - Sezgin, Ali AU - Vafeiadis, Viktor ID - 2328 TI - Aspect-oriented linearizability proofs VL - 8052 ER - TY - JOUR AB - The Lieb-Thirring inequalities give a bound on the negative eigenvalues of a Schrödinger operator in terms of an Lp-norm of the potential. These are dual to bounds on the H1-norms of a system of orthonormal functions. Here we extend these bounds to analogous inequalities for perturbations of the Fermi sea of noninteracting particles (i.e., for perturbations of the continuous spectrum of the Laplacian by local potentials). AU - Frank, Rupert L AU - Lewin, Mathieu AU - Lieb, Élliott H AU - Robert Seiringer ID - 2404 IS - 3 JF - Duke Mathematical Journal TI - A positive density analogue of the Lieb-Thirring inequality VL - 162 ER - TY - JOUR AB - We study the effects of random scatterers on the ground state of the one-dimensional Lieb-Liniger model of interacting bosons on the unit interval. We prove that, in the Gross-Pitaevskii limit, Bose Einstein condensation takes place in the whole parameter range considered. The character of the wave function of the condensate, however, depends in an essential way on the interplay between randomness and the strength of the two-body interaction. For low density of scatterers or strong interactions the wave function extends over the whole interval. High density of scatterers and weak interaction, on the other hand, leads to localization of the wave function in a fragmented subset of the unit interval. AU - Robert Seiringer AU - Yngvason, Jakob AU - Zagrebnov, Valentin A ID - 2406 IS - 1 JF - European Physical Journal: Special Topics TI - Condensation of interacting bosons in a random potential VL - 217 ER - TY - JOUR AB - We consider the bipolaron in the Pekar-Tomasevich approximation and address the question whether the ground state is spherically symmetric or not. Numerical analysis has, so far, not completely settled the question. Our contribution is to prove rigorously that the ground state remains spherical for small values of the electron-electron Coulomb repulsion. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer ID - 2405 IS - 2 JF - Communications in Mathematical Physics TI - Symmetry of bipolaron bound states for small Coulomb repulsion VL - 319 ER - TY - JOUR AB - We investigate the low-energy excitation spectrum of a Bose gas confined in a trap, with weak long-range repulsive interactions. In particular, we prove that the spectrum can be described in terms of the eigenvalues of an effective one-particle operator, as predicted by the Bogoliubov approximation. AU - Grech, Philip AU - Robert Seiringer ID - 2408 IS - 2 JF - Communications in Mathematical Physics TI - The excitation spectrum for weakly interacting Bosons in a trap VL - 322 ER - TY - JOUR AB - Background: The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution.Methods We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration.Results Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set.Conclusions The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates. AU - Kupczok, Anne AU - Bollback, Jonathan P ID - 2412 IS - 1 JF - BMC Evolutionary Biology TI - Probabilistic models for CRISPR spacer content evolution VL - 13 ER - TY - CHAP AB - Progress in understanding the global brain dynamics has remained slow to date in large part because of the highly multiscale nature of brain activity. Indeed, normal brain dynamics is characterized by complex interactions between multiple levels: from the microscopic scale of single neurons to the mesoscopic level of local groups of neurons, and finally to the macroscopic level of the whole brain. Among the most difficult tasks are those of identifying which scales are significant for a given particular function and describing how the scales affect each other. It is important to realize that the scales of time and space are linked together, or even intertwined, and that causal inference is far more ambiguous between than within levels. We approach this problem from the perspective of our recent work on simultaneous recording from micro- and macroelectrodes in the human brain. We propose a physiological description of these multilevel interactions, based on phase–amplitude coupling of neuronal oscillations that operate at multiple frequencies and on different spatial scales. Specifically, the amplitude of the oscillations on a particular spatial scale is modulated by phasic variations in neuronal excitability induced by lower frequency oscillations that emerge on a larger spatial scale. Following this general principle, it is possible to scale up or scale down the multiscale brain dynamics. It is expected that large-scale network oscillations in the low-frequency range, mediating downward effects, may play an important role in attention and consciousness. AU - Valderrama, Mario AU - Botella Soler, Vicente AU - Le Van Quyen, Michel ED - Meyer, Misha ED - Pesenson, Z. ID - 2413 SN - 9783527411986 T2 - Multiscale Analysis and Nonlinear Dynamics: From Genes to the Brain TI - Neuronal oscillations scale up and scale down the brain dynamics ER - TY - JOUR AB - Here, we describe a novel virulent bacteriophage that infects Bacillus weihenstephanensis, isolated from soil in Austria. It is the first phage to be discovered that infects this species. Here, we present the complete genome sequence of this podovirus. AU - Fernandes Redondo, Rodrigo A AU - Kupczok, Anne AU - Stift, Gertraud AU - Bollback, Jonathan P ID - 2410 IS - 3 JF - Genome Announcements TI - Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis VL - 1 ER - TY - CONF AB - Separation logic (SL) has gained widespread popularity because of its ability to succinctly express complex invariants of a program’s heap configurations. Several specialized provers have been developed for decidable SL fragments. However, these provers cannot be easily extended or combined with solvers for other theories that are important in program verification, e.g., linear arithmetic. In this paper, we present a reduction of decidable SL fragments to a decidable first-order theory that fits well into the satisfiability modulo theories (SMT) framework. We show how to use this reduction to automate satisfiability, entailment, frame inference, and abduction problems for separation logic using SMT solvers. Our approach provides a simple method of integrating separation logic into existing verification tools that provide SMT backends, and an elegant way of combining SL fragments with other decidable first-order theories. We implemented this approach in a verification tool and applied it to heap-manipulating programs whose verification involves reasoning in theory combinations. AU - Piskac, Ruzica AU - Wies, Thomas AU - Zufferey, Damien ID - 2447 TI - Automating separation logic using SMT VL - 8044 ER - TY - JOUR AB - The mode of action of auxin is based on its non-uniform distribution within tissues and organs. Despite the wide use of several auxin analogues in research and agriculture, little is known about the specificity of different auxin-related transport and signalling processes towards these compounds. Using seedlings of Arabidopsis thaliana and suspension-cultured cells of Nicotiana tabacum (BY-2), the physiological activity of several auxin analogues was investigated, together with their capacity to induce auxin-dependent gene expression, to inhibit endocytosis and to be transported across the plasma membrane. This study shows that the specificity criteria for different auxin-related processes vary widely. Notably, the special behaviour of some synthetic auxin analogues suggests that they might be useful tools in investigations of the molecular mechanism of auxin action. Thus, due to their differential stimulatory effects on DR5 expression, indole-3-propionic (IPA) and 2,4,5-trichlorophenoxy acetic (2,4,5-T) acids can serve in studies of TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALLING F-BOX (TIR1/AFB)-mediated auxin signalling, and 5-fluoroindole-3-acetic acid (5-F-IAA) can help to discriminate between transcriptional and non-transcriptional pathways of auxin signalling. The results demonstrate that the major determinants for the auxin-like physiological potential of a particular compound are very complex and involve its chemical and metabolic stability, its ability to distribute in tissues in a polar manner and its activity towards auxin signalling machinery. AU - Simon, Sibu AU - Kubeš, Martin AU - Baster, Pawel AU - Robert, Stéphanie AU - Dobrev, Petre AU - Friml, Jirí AU - Petrášek, Jan AU - Zažímalová, Eva ID - 2443 IS - 4 JF - New Phytologist TI - Defining the selectivity of processes along the auxin response chain: A study using auxin analogues VL - 200 ER - TY - CONF AB - The model-checking problem for probabilistic systems crucially relies on the translation of LTL to deterministic Rabin automata (DRW). Our recent Safraless translation [KE12, GKE12] for the LTL(F,G) fragment produces smaller automata as compared to the traditional approach. In this work, instead of DRW we consider deterministic automata with acceptance condition given as disjunction of generalized Rabin pairs (DGRW). The Safraless translation of LTL(F,G) formulas to DGRW results in smaller automata as compared to DRW. We present algorithms for probabilistic model-checking as well as game solving for DGRW conditions. Our new algorithms lead to improvement both in terms of theoretical bounds as well as practical evaluation. We compare PRISM with and without our new translation, and show that the new translation leads to significant improvements. AU - Chatterjee, Krishnendu AU - Gaiser, Andreas AU - Kretinsky, Jan ID - 2446 TI - Automata with generalized Rabin pairs for probabilistic model checking and LTL synthesis VL - 8044 ER - TY - CONF AB - We consider two core algorithmic problems for probabilistic verification: the maximal end-component decomposition and the almost-sure reachability set computation for Markov decision processes (MDPs). For MDPs with treewidth k, we present two improved static algorithms for both the problems that run in time O(n·k 2.38·2k ) and O(m·logn· k), respectively, where n is the number of states and m is the number of edges, significantly improving the previous known O(n·k·√n· k) bound for low treewidth. We also present decremental algorithms for both problems for MDPs with constant treewidth that run in amortized logarithmic time, which is a huge improvement over the previously known algorithms that require amortized linear time. AU - Chatterjee, Krishnendu AU - Ła̧Cki, Jakub ID - 2444 TI - Faster algorithms for Markov decision processes with low treewidth VL - 8044 ER - TY - JOUR AB - Intracellular protein routing is mediated by vesicular transport which is tightly regulated in eukaryotes. The protein and lipid homeostasis depends on coordinated delivery of de novo synthesized or recycled cargoes to the plasma membrane by exocytosis and their subsequent removal by rerouting them for recycling or degradation. Here, we report the characterization of protein affected trafficking 3 (pat3) mutant that we identified by an epifluorescence-based forward genetic screen for mutants defective in subcellular distribution of Arabidopsis auxin transporter PIN1–GFP. While pat3 displays largely normal plant morphology and development in nutrient-rich conditions, it shows strong ectopic intracellular accumulations of different plasma membrane cargoes in structures that resemble prevacuolar compartments (PVC) with an aberrant morphology. Genetic mapping revealed that pat3 is defective in vacuolar protein sorting 35A (VPS35A), a putative subunit of the retromer complex that mediates retrograde trafficking between the PVC and trans-Golgi network. Similarly, a mutant defective in another retromer subunit, vps29, shows comparable subcellular defects in PVC morphology and protein accumulation. Thus, our data provide evidence that the retromer components VPS35A and VPS29 are essential for normal PVC morphology and normal trafficking of plasma membrane proteins in plants. In addition, we show that, out of the three VPS35 retromer subunits present in Arabidopsis thaliana genome, the VPS35 homolog A plays a prevailing role in trafficking to the lytic vacuole, presenting another level of complexity in the retromer-dependent vacuolar sorting. AU - Nodzyński, Tomasz AU - Feraru, Murguel AU - Hirsch, Sibylle AU - De Rycke, Riet AU - Nicuales, Claudiu AU - Van Leene, Jelle AU - De Jaeger, Geert AU - Vanneste, Steffen AU - Friml, Jirí ID - 2449 IS - 6 JF - Molecular Plant TI - Retromer subunits VPS35A and VPS29 mediate prevacuolar compartment (PVC) function in Arabidopsis VL - 6 ER - TY - JOUR AB - Background: Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures.Results: We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN)2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport.Conclusions: This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin. AU - Barbez, Elke AU - Laňková, Martina AU - Pařezová, Markéta AU - Maizel, Alexis AU - Zažímalová, Eva AU - Petrášek, Jan AU - Jirí Friml AU - Kleine-Vehn, Jürgen ID - 2452 IS - 1 JF - BMC Plant Biology TI - Single-cell-based system to monitor carrier driven cellular auxin homeostasis VL - 13 ER -