TY - JOUR AB - Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context. AU - Fiedorczuk, Karol AU - Sazanov, Leonid A ID - 152 IS - 10 JF - Trends in Cell Biology TI - Mammalian mitochondrial complex I structure and disease causing mutations VL - 28 ER - TY - CONF AB - A model of computation that is widely used in the formal analysis of reactive systems is symbolic algorithms. In this model the access to the input graph is restricted to consist of symbolic operations, which are expensive in comparison to the standard RAM operations. We give lower bounds on the number of symbolic operations for basic graph problems such as the computation of the strongly connected components and of the approximate diameter as well as for fundamental problems in model checking such as safety, liveness, and coliveness. Our lower bounds are linear in the number of vertices of the graph, even for constant-diameter graphs. For none of these problems lower bounds on the number of symbolic operations were known before. The lower bounds show an interesting separation of these problems from the reachability problem, which can be solved with O(D) symbolic operations, where D is the diameter of the graph. Additionally we present an approximation algorithm for the graph diameter which requires Õ(n/D) symbolic steps to achieve a (1 +ϵ)-approximation for any constant > 0. This compares to O(n/D) symbolic steps for the (naive) exact algorithm and O(D) symbolic steps for a 2-approximation. Finally we also give a refined analysis of the strongly connected components algorithms of [15], showing that it uses an optimal number of symbolic steps that is proportional to the sum of the diameters of the strongly connected components. AU - Chatterjee, Krishnendu AU - Dvorák, Wolfgang AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 310 TI - Lower bounds for symbolic computation on graphs: Strongly connected components, liveness, safety, and diameter ER - TY - JOUR AB - There has been significant interest recently in using complex quantum systems to create effective nonreciprocal dynamics. Proposals have been put forward for the realization of artificial magnetic fields for photons and phonons; experimental progress is fast making these proposals a reality. Much work has concentrated on the use of such systems for controlling the flow of signals, e.g., to create isolators or directional amplifiers for optical signals. In this Letter, we build on this work but move in a different direction. We develop the theory of and discuss a potential realization for the controllable flow of thermal noise in quantum systems. We demonstrate theoretically that the unidirectional flow of thermal noise is possible within quantum cascaded systems. Viewing an optomechanical platform as a cascaded system we show here that one can ultimately control the direction of the flow of thermal noise. By appropriately engineering the mechanical resonator, which acts as an artificial reservoir, the flow of thermal noise can be constrained to a desired direction, yielding a thermal rectifier. The proposed quantum thermal noise rectifier could potentially be used to develop devices such as a thermal modulator, a thermal router, and a thermal amplifier for nanoelectronic devices and superconducting circuits. AU - Barzanjeh, Shabir AU - Aquilina, Matteo AU - Xuereb, André ID - 436 IS - 6 JF - Physical Review Letters TI - Manipulating the flow of thermal noise in quantum devices VL - 120 ER - TY - JOUR AB - Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems; however, mechanisms causing spatial patterning often remain elusive. In recent years, spatio-temporal mathematical modelling has helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum-likelihood approach. We used this integrated modelling approach to study in vivo gradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parametrization and subsequent refinement of the model using additional mechanisms. Among other results, model-based hypothesis testing predicted lymphatic vessel-dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights. AU - Hross, Sabrina AU - Theis, Fabian J. AU - Sixt, Michael K AU - Hasenauer, Jan ID - 5858 IS - 149 JF - Journal of the Royal Society Interface SN - 17425689 TI - Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data VL - 15 ER - TY - JOUR AB - We report quantitative evidence of mixing-layer elastic instability in a viscoelastic fluid flow between two widely spaced obstacles hindering a channel flow at Re 1 and Wi 1. Two mixing layers with nonuniform shear velocity profiles are formed in the region between the obstacles. The mixing-layer instability arises in the vicinity of an inflection point on the shear velocity profile with a steep variation in the elastic stress. The instability results in an intermittent appearance of small vortices in the mixing layers and an amplification of spatiotemporal averaged vorticity in the elastic turbulence regime. The latter is characterized through scaling of friction factor with Wi and both pressure and velocity spectra. Furthermore, the observations reported provide improved understanding of the stability of the mixing layer in a viscoelastic fluid at large elasticity, i.e., Wi 1 and Re 1 and oppose the current view of suppression of vorticity solely by polymer additives. AU - Varshney, Atul AU - Steinberg, Victor ID - 16 IS - 10 JF - Physical Review Fluids TI - Mixing layer instability and vorticity amplification in a creeping viscoelastic flow VL - 3 ER - TY - JOUR AB - The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics. AU - Rybicki, Joel AU - Kisdi, Eva AU - Anttila, Jani ID - 43 IS - 42 JF - PNAS TI - Model of bacterial toxin-dependent pathogenesis explains infective dose VL - 115 ER - TY - JOUR AB - We propose a new method for fabricating digital objects through reusable silicone molds. Molds are generated by casting liquid silicone into custom 3D printed containers called metamolds. Metamolds automatically define the cuts that are needed to extract the cast object from the silicone mold. The shape of metamolds is designed through a novel segmentation technique, which takes into account both geometric and topological constraints involved in the process of mold casting. Our technique is simple, does not require changing the shape or topology of the input objects, and only requires off-the- shelf materials and technologies. We successfully tested our method on a set of challenging examples with complex shapes and rich geometric detail. © 2018 Association for Computing Machinery. AU - Alderighi, Thomas AU - Malomo, Luigi AU - Giorgi, Daniela AU - Pietroni, Nico AU - Bickel, Bernd AU - Cignoni, Paolo ID - 13 IS - 4 JF - ACM Trans. Graph. TI - Metamolds: Computational design of silicone molds VL - 37 ER - TY - JOUR AB - Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli. AU - Zhang, William AU - Herde, Michel AU - Mitchell, Joshua AU - Whitfield, Jason AU - Wulff, Andreas AU - Vongsouthi, Vanessa AU - Sanchez Romero, Inmaculada AU - Gulakova, Polina AU - Minge, Daniel AU - Breithausen, Björn AU - Schoch, Susanne AU - Janovjak, Harald L AU - Jackson, Colin AU - Henneberger, Christian ID - 137 IS - 9 JF - Nature Chemical Biology TI - Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS VL - 14 ER - TY - CHAP AB - Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters. AU - Renkawitz, Jörg AU - Reversat, Anne AU - Leithner, Alexander F AU - Merrin, Jack AU - Sixt, Michael K ID - 153 SN - 0091679X T2 - Methods in Cell Biology TI - Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments VL - 147 ER - TY - JOUR AB - During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and tissue dynamics. Mechanical forces play critical roles in AJs’ composition and dynamics. Recent findings highlight that beyond a well-established role in reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional remodeling and polarization, thereby regulating critical processes such as cell intercalation, division, and collective migration. Here, we provide an integrated view of mechanosensing mechanisms that regulate cell-cell contact composition, geometry, and integrity under tension and highlight pivotal roles for mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining tissue dynamics. AU - Nunes Pinheiro, Diana C AU - Bellaïche, Yohanns ID - 54 IS - 1 JF - Developmental Cell TI - Mechanical force-driven adherents junction remodeling and epithelial dynamics VL - 47 ER - TY - JOUR AB - Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo. AU - Frick, Corina AU - Dettinger, Philip AU - Renkawitz, Jörg AU - Jauch, Annaïse AU - Berger, Christoph AU - Recher, Mike AU - Schroeder, Timm AU - Mehling, Matthias ID - 276 IS - 6 JF - PLoS One TI - Nano-scale microfluidics to study 3D chemotaxis at the single cell level VL - 13 ER - TY - JOUR AB - Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors. AU - Ceinos, Rosa Maria AU - Frigato, Elena AU - Pagano, Cristina AU - Frohlich, Nadine AU - Negrini, Pietro AU - Cavallari, Nicola AU - Vallone, Daniela AU - Fuselli, Silvia AU - Bertolucci, Cristiano AU - Foulkes, Nicholas S ID - 283 IS - 1 JF - Scientific Reports TI - Mutations in blind cavefish target the light regulated circadian clock gene period 2 VL - 8 ER - TY - CONF AB - We solve the offline monitoring problem for timed propositional temporal logic (TPTL), interpreted over dense-time Boolean signals. The variant of TPTL we consider extends linear temporal logic (LTL) with clock variables and reset quantifiers, providing a mechanism to specify real-time constraints. We first describe a general monitoring algorithm based on an exhaustive computation of the set of satisfying clock assignments as a finite union of zones. We then propose a specialized monitoring algorithm for the one-variable case using a partition of the time domain based on the notion of region equivalence, whose complexity is linear in the length of the signal, thereby generalizing a known result regarding the monitoring of metric temporal logic (MTL). The region and zone representations of time constraints are known from timed automata verification and can also be used in the discrete-time case. Our prototype implementation appears to outperform previous discrete-time implementations of TPTL monitoring, AU - Elgyütt, Adrian AU - Ferrere, Thomas AU - Henzinger, Thomas A ID - 81 TI - Monitoring temporal logic with clock variables VL - 11022 ER - TY - JOUR AB - Consider a fully-connected synchronous distributed system consisting of n nodes, where up to f nodes may be faulty and every node starts in an arbitrary initial state. In the synchronous C-counting problem, all nodes need to eventually agree on a counter that is increased by one modulo C in each round for given C>1. In the self-stabilising firing squad problem, the task is to eventually guarantee that all non-faulty nodes have simultaneous responses to external inputs: if a subset of the correct nodes receive an external “go” signal as input, then all correct nodes should agree on a round (in the not-too-distant future) in which to jointly output a “fire” signal. Moreover, no node should generate a “fire” signal without some correct node having previously received a “go” signal as input. We present a framework reducing both tasks to binary consensus at very small cost. For example, we obtain a deterministic algorithm for self-stabilising Byzantine firing squads with optimal resilience f<n/3, asymptotically optimal stabilisation and response time O(f), and message size O(log f). As our framework does not restrict the type of consensus routines used, we also obtain efficient randomised solutions. AU - Lenzen, Christoph AU - Rybicki, Joel ID - 76 JF - Distributed Computing TI - Near-optimal self-stabilising counting and firing squads ER - TY - JOUR AB - Inclusion–exclusion is an effective method for computing the volume of a union of measurable sets. We extend it to multiple coverings, proving short inclusion–exclusion formulas for the subset of Rn covered by at least k balls in a finite set. We implement two of the formulas in dimension n=3 and report on results obtained with our software. AU - Edelsbrunner, Herbert AU - Iglesias Ham, Mabel ID - 530 JF - Computational Geometry: Theory and Applications TI - Multiple covers with balls I: Inclusion–exclusion VL - 68 ER - TY - JOUR AB - Spontaneous emission spectra of two initially excited closely spaced identical atoms are very sensitive to the strength and the direction of the applied magnetic field. We consider the relevant schemes that ensure the determination of the mutual spatial orientation of the atoms and the distance between them by entirely optical means. A corresponding theoretical description is given accounting for the dipole-dipole interaction between the two atoms in the presence of a magnetic field and for polarizations of the quantum field interacting with magnetic sublevels of the two-atom system. AU - Redchenko, Elena AU - Makarov, Alexander AU - Yudson, Vladimir ID - 307 IS - 4 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Nanoscopy of pairs of atoms by fluorescence in a magnetic field VL - 97 ER - TY - JOUR AB - Background: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Results: Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes. Conclusions: In summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments. AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 279 JF - Genome Biology TI - Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome VL - 19 ER - TY - JOUR AB - Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to ~ 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional ~ 24–48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins. AU - Truckenbrodt, Sven M AU - Viplav, Abhiyan AU - Jähne, Sebsatian AU - Vogts, Angela AU - Denker, Annette AU - Wildhagen, Hanna AU - Fornasiero, Eugenio AU - Rizzoli, Silvio ID - 145 IS - 15 JF - The EMBO Journal SN - 0261-4189 TI - Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission VL - 37 ER - TY - JOUR AB - AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the ER-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were co-localized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+-leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes. AU - Fan, Ligang AU - Zhao, Lei AU - Hu, Wei AU - Li, Weina AU - Novák, Ondřej AU - Strnad, Miroslav AU - Simon, Sibu AU - Friml, Jirí AU - Shen, Jinbo AU - Jiang, Liwen AU - Qiu, Quan ID - 462 JF - Plant, Cell and Environment TI - NHX antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development VL - 41 ER - TY - JOUR AB - This study treats with the influence of a symmetry-breaking transversal magnetic field on the nonlinear dynamics of ferrofluidic Taylor-Couette flow – flow confined between two concentric independently rotating cylinders. We detected alternating ‘flip’ solutions which are flow states featuring typical characteristics of slow-fast-dynamics in dynamical systems. The flip corresponds to a temporal change in the axial wavenumber and we find them to appear either as pure 2-fold axisymmetric (due to the symmetry-breaking nature of the applied transversal magnetic field) or involving non-axisymmetric, helical modes in its interim solution. The latter ones show features of typical ribbon solutions. In any case the flip solutions have a preferential first axial wavenumber which corresponds to the more stable state (slow dynamics) and second axial wavenumber, corresponding to the short appearing more unstable state (fast dynamics). However, in both cases the flip time grows exponential with increasing the magnetic field strength before the flip solutions, living on 2-tori invariant manifolds, cease to exist, with lifetime going to infinity. Further we show that ferrofluidic flow turbulence differ from the classical, ordinary (usually at high Reynolds number) turbulence. The applied magnetic field hinders the free motion of ferrofluid partials and therefore smoothen typical turbulent quantities and features so that speaking of mildly chaotic dynamics seems to be a more appropriate expression for the observed motion. AU - Altmeyer, Sebastian ID - 519 JF - Journal of Magnetism and Magnetic Materials TI - Non-linear dynamics and alternating ‘flip’ solutions in ferrofluidic Taylor-Couette flow VL - 452 ER - TY - CONF AB - We study the almost-sure termination problem for probabilistic programs. First, we show that supermartingales with lower bounds on conditional absolute difference provide a sound approach for the almost-sure termination problem. Moreover, using this approach we can obtain explicit optimal bounds on tail probabilities of non-termination within a given number of steps. Second, we present a new approach based on Central Limit Theorem for the almost-sure termination problem, and show that this approach can establish almost-sure termination of programs which none of the existing approaches can handle. Finally, we discuss algorithmic approaches for the two above methods that lead to automated analysis techniques for almost-sure termination of probabilistic programs. AU - Huang, Mingzhang AU - Fu, Hongfei AU - Chatterjee, Krishnendu ED - Ryu, Sukyoung ID - 5679 SN - 03029743 TI - New approaches for almost-sure termination of probabilistic programs VL - 11275 ER - TY - JOUR AB - The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies. AU - Sacco, Roberto AU - Cacci, Emanuele AU - Novarino, Gaia ID - 546 IS - 2 JF - Current Opinion in Neurobiology TI - Neural stem cells in neuropsychiatric disorders VL - 48 ER - TY - GEN AB - This document contains the full list of genes with their respective significance and dN/dS values. (TXT 4499Â kb) AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 9812 TI - Additional file 2: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome ER - TY - GEN AB - This document contains additional supporting evidence presented as supplemental tables. (XLSX 50Â kb) AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 9811 TI - Additional file 1: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome ER - TY - JOUR AB - Background: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level. Results: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses. Conclusions: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function. AU - Higareda Almaraz, Juan AU - Karbiener, Michael AU - Giroud, Maude AU - Pauler, Florian AU - Gerhalter, Teresa AU - Herzig, Stephan AU - Scheideler, Marcel ID - 20 IS - 1 JF - BMC Genomics SN - 1471-2164 TI - Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes VL - 19 ER - TY - JOUR AB - We introduce the notion of “non-malleable codes” which relaxes the notion of error correction and error detection. Informally, a code is non-malleable if the message contained in a modified codeword is either the original message, or a completely unrelated value. In contrast to error correction and error detection, non-malleability can be achieved for very rich classes of modifications. We construct an efficient code that is non-malleable with respect to modifications that affect each bit of the codeword arbitrarily (i.e., leave it untouched, flip it, or set it to either 0 or 1), but independently of the value of the other bits of the codeword. Using the probabilistic method, we also show a very strong and general statement: there exists a non-malleable code for every “small enough” family F of functions via which codewords can be modified. Although this probabilistic method argument does not directly yield efficient constructions, it gives us efficient non-malleable codes in the random-oracle model for very general classes of tampering functions—e.g., functions where every bit in the tampered codeword can depend arbitrarily on any 99% of the bits in the original codeword. As an application of non-malleable codes, we show that they provide an elegant algorithmic solution to the task of protecting functionalities implemented in hardware (e.g., signature cards) against “tampering attacks.” In such attacks, the secret state of a physical system is tampered, in the hopes that future interaction with the modified system will reveal some secret information. This problem was previously studied in the work of Gennaro et al. in 2004 under the name “algorithmic tamper proof security” (ATP). We show that non-malleable codes can be used to achieve important improvements over the prior work. In particular, we show that any functionality can be made secure against a large class of tampering attacks, simply by encoding the secret state with a non-malleable code while it is stored in memory. AU - Dziembowski, Stefan AU - Pietrzak, Krzysztof Z AU - Wichs, Daniel ID - 107 IS - 4 JF - Journal of the ACM TI - Non-malleable codes VL - 65 ER - TY - JOUR AB - In epithelial tissues, cells tightly connect to each other through cell–cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge. AU - Carvalho, Lara AU - Patricio, Pedro AU - Ponte, Susana AU - Heisenberg, Carl-Philipp J AU - Almeida, Luis AU - Nunes, André S. AU - Araújo, Nuno A.M. AU - Jacinto, Antonio ID - 5676 IS - 12 JF - Journal of Cell Biology SN - 00219525 TI - Occluding junctions as novel regulators of tissue mechanics during wound repair VL - 217 ER - TY - CONF AB - Clustering is a cornerstone of unsupervised learning which can be thought as disentangling multiple generative mechanisms underlying the data. In this paper we introduce an algorithmic framework to train mixtures of implicit generative models which we particularize for variational autoencoders. Relying on an additional set of discriminators, we propose a competitive procedure in which the models only need to approximate the portion of the data distribution from which they can produce realistic samples. As a byproduct, each model is simpler to train, and a clustering interpretation arises naturally from the partitioning of the training points among the models. We empirically show that our approach splits the training distribution in a reasonable way and increases the quality of the generated samples. AU - Locatello, Francesco AU - Vincent, Damien AU - Tolstikhin, Ilya AU - Ratsch, Gunnar AU - Gelly, Sylvain AU - Scholkopf, Bernhard ID - 14224 T2 - 6th International Conference on Learning Representations TI - Clustering meets implicit generative models ER - TY - GEN AB - Table S1. Genes with highest betweenness. Table S2. Local and Master regulators up-regulated. Table S3. Local and Master regulators down-regulated (XLSX 23 kb). AU - Higareda Almaraz, Juan AU - Karbiener, Michael AU - Giroud, Maude AU - Pauler, Florian AU - Gerhalter, Teresa AU - Herzig, Stephan AU - Scheideler, Marcel ID - 9807 TI - Additional file 1: Of Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes ER - TY - GEN AB - Table S4. Counts per Gene per Million Reads Mapped. (XLSX 2751 kb). AU - Higareda Almaraz, Juan AU - Karbiener, Michael AU - Giroud, Maude AU - Pauler, Florian AU - Gerhalter, Teresa AU - Herzig, Stephan AU - Scheideler, Marcel ID - 9808 TI - Additional file 3: Of Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes ER - TY - CONF AB - We show attacks on five data-independent memory-hard functions (iMHF) that were submitted to the password hashing competition (PHC). Informally, an MHF is a function which cannot be evaluated on dedicated hardware, like ASICs, at significantly lower hardware and/or energy cost than evaluating a single instance on a standard single-core architecture. Data-independent means the memory access pattern of the function is independent of the input; this makes iMHFs harder to construct than data-dependent ones, but the latter can be attacked by various side-channel attacks. Following [Alwen-Blocki'16], we capture the evaluation of an iMHF as a directed acyclic graph (DAG). The cumulative parallel pebbling complexity of this DAG is a measure for the hardware cost of evaluating the iMHF on an ASIC. Ideally, one would like the complexity of a DAG underlying an iMHF to be as close to quadratic in the number of nodes of the graph as possible. Instead, we show that (the DAGs underlying) the following iMHFs are far from this bound: Rig.v2, TwoCats and Gambit each having an exponent no more than 1.75. Moreover, we show that the complexity of the iMHF modes of the PHC finalists Pomelo and Lyra2 have exponents at most 1.83 and 1.67 respectively. To show this we investigate a combinatorial property of each underlying DAG (called its depth-robustness. By establishing upper bounds on this property we are then able to apply the general technique of [Alwen-Block'16] for analyzing the hardware costs of an iMHF. AU - Alwen, Joel F AU - Gazi, Peter AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Osang, Georg F AU - Pietrzak, Krzysztof Z AU - Reyzin, Lenoid AU - Rolinek, Michal AU - Rybar, Michal ID - 193 T2 - Proceedings of the 2018 on Asia Conference on Computer and Communication Security TI - On the memory hardness of data independent password hashing functions ER - TY - CONF AB - We introduce a formal quantitative notion of “bit security” for a general type of cryptographic games (capturing both decision and search problems), aimed at capturing the intuition that a cryptographic primitive with k-bit security is as hard to break as an ideal cryptographic function requiring a brute force attack on a k-bit key space. Our new definition matches the notion of bit security commonly used by cryptographers and cryptanalysts when studying search (e.g., key recovery) problems, where the use of the traditional definition is well established. However, it produces a quantitatively different metric in the case of decision (indistinguishability) problems, where the use of (a straightforward generalization of) the traditional definition is more problematic and leads to a number of paradoxical situations or mismatches between theoretical/provable security and practical/common sense intuition. Key to our new definition is to consider adversaries that may explicitly declare failure of the attack. We support and justify the new definition by proving a number of technical results, including tight reductions between several standard cryptographic problems, a new hybrid theorem that preserves bit security, and an application to the security analysis of indistinguishability primitives making use of (approximate) floating point numbers. This is the first result showing that (standard precision) 53-bit floating point numbers can be used to achieve 100-bit security in the context of cryptographic primitives with general indistinguishability-based security definitions. Previous results of this type applied only to search problems, or special types of decision problems. AU - Micciancio, Daniele AU - Walter, Michael ID - 300 TI - On the bit security of cryptographic primitives VL - 10820 ER - TY - JOUR AB - Motivated by biological questions, we study configurations of equal spheres that neither pack nor cover. Placing their centers on a lattice, we define the soft density of the configuration by penalizing multiple overlaps. Considering the 1-parameter family of diagonally distorted 3-dimensional integer lattices, we show that the soft density is maximized at the FCC lattice. AU - Edelsbrunner, Herbert AU - Iglesias Ham, Mabel ID - 312 IS - 1 JF - SIAM J Discrete Math SN - 08954801 TI - On the optimality of the FCC lattice for soft sphere packing VL - 32 ER - TY - JOUR AB - We give a simple proof of T. Stehling's result [4], whereby in any normal tiling of the plane with convex polygons with number of sides not less than six, all tiles except a finite number are hexagons. AU - Akopyan, Arseniy ID - 409 IS - 4 JF - Comptes Rendus Mathematique SN - 1631073X TI - On the number of non-hexagons in a planar tiling VL - 356 ER - TY - JOUR AB - Reciprocity is a major factor in human social life and accounts for a large part of cooperation in our communities. Direct reciprocity arises when repeated interactions occur between the same individuals. The framework of iterated games formalizes this phenomenon. Despite being introduced more than five decades ago, the concept keeps offering beautiful surprises. Recent theoretical research driven by new mathematical tools has proposed a remarkable dichotomy among the crucial strategies: successful individuals either act as partners or as rivals. Rivals strive for unilateral advantages by applying selfish or extortionate strategies. Partners aim to share the payoff for mutual cooperation, but are ready to fight back when being exploited. Which of these behaviours evolves depends on the environment. Whereas small population sizes and a limited number of rounds favour rivalry, partner strategies are selected when populations are large and relationships stable. Only partners allow for evolution of cooperation, while the rivals’ attempt to put themselves first leads to defection. Hilbe et al. synthesize recent theoretical work on zero-determinant and ‘rival’ versus ‘partner’ strategies in social dilemmas. They describe the environments under which these contrasting selfish or cooperative strategies emerge in evolution. AU - Hilbe, Christian AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 419 JF - Nature Human Behaviour TI - Partners and rivals in direct reciprocity VL - 2 ER - TY - CONF AB - We provide a procedure for detecting the sub-segments of an incrementally observed Boolean signal ω that match a given temporal pattern ϕ. As a pattern specification language, we use timed regular expressions, a formalism well-suited for expressing properties of concurrent asynchronous behaviors embedded in metric time. We construct a timed automaton accepting the timed language denoted by ϕ and modify it slightly for the purpose of matching. We then apply zone-based reachability computation to this automaton while it reads ω, and retrieve all the matching segments from the results. Since the procedure is automaton based, it can be applied to patterns specified by other formalisms such as timed temporal logics reducible to timed automata or directly encoded as timed automata. The procedure has been implemented and its performance on synthetic examples is demonstrated. AU - Bakhirkin, Alexey AU - Ferrere, Thomas AU - Nickovic, Dejan AU - Maler, Oded AU - Asarin, Eugene ID - 78 SN - 978-3-030-00150-6 TI - Online timed pattern matching using automata VL - 11022 ER - TY - JOUR AB - We replace the established aluminium gates for the formation of quantum dots in silicon with gates made from palladium. We study the morphology of both aluminium and palladium gates with transmission electron microscopy. The native aluminium oxide is found to be formed all around the aluminium gates, which could lead to the formation of unintentional dots. Therefore, we report on a novel fabrication route that replaces aluminium and its native oxide by palladium with atomic-layer-deposition-grown aluminium oxide. Using this approach, we show the formation of low-disorder gate-defined quantum dots, which are reproducibly fabricated. Furthermore, palladium enables us to further shrink the gate design, allowing us to perform electron transport measurements in the few-electron regime in devices comprising only two gate layers, a major technological advancement. It remains to be seen, whether the introduction of palladium gates can improve the excellent results on electron and nuclear spin qubits defined with an aluminium gate stack. AU - Brauns, Matthias AU - Amitonov, Sergey AU - Spruijtenburg, Paul AU - Zwanenburg, Floris ID - 317 IS - 1 JF - Scientific Reports TI - Palladium gates for reproducible quantum dots in silicon VL - 8 ER - TY - JOUR AB - Ants are emerging model systems to study cellular signaling because distinct castes possess different physiologic phenotypes within the same colony. Here we studied the functionality of inotocin signaling, an insect ortholog of mammalian oxytocin (OT), which was recently discovered in ants. In Lasius ants, we determined that specialization within the colony, seasonal factors, and physiologic conditions down-regulated the expression of the OT-like signaling system. Given this natural variation, we interrogated its function using RNAi knockdowns. Next-generation RNA sequencing of OT-like precursor knock-down ants highlighted its role in the regulation of genes involved in metabolism. Knock-down ants exhibited higher walking activity and increased self-grooming in the brood chamber. We propose that OT-like signaling in ants is important for regulating metabolic processes and locomotion. AU - Liutkeviciute, Zita AU - Gil Mansilla, Esther AU - Eder, Thomas AU - Casillas Perez, Barbara E AU - Giulia Di Giglio, Maria AU - Muratspahić, Edin AU - Grebien, Florian AU - Rattei, Thomas AU - Muttenthaler, Markus AU - Cremer, Sylvia AU - Gruber, Christian ID - 194 IS - 12 JF - The FASEB Journal SN - 08926638 TI - Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity VL - 32 ER - TY - JOUR AB - L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control. AU - Fehrentz, Timm AU - Huber, Florian AU - Hartrampf, Nina AU - Bruegmann, Tobias AU - Frank, James AU - Fine, Nicholas AU - Malan, Daniela AU - Danzl, Johann G AU - Tikhonov, Denis AU - Sumser, Maritn AU - Sasse, Philipp AU - Hodson, David AU - Zhorov, Boris AU - Klocker, Nikolaj AU - Trauner, Dirk ID - 159 IS - 8 JF - Nature Chemical Biology TI - Optical control of L-type Ca2+ channels using a diltiazem photoswitch VL - 14 ER - TY - CONF AB - Markov Decision Processes (MDPs) are a popular class of models suitable for solving control decision problems in probabilistic reactive systems. We consider parametric MDPs (pMDPs) that include parameters in some of the transition probabilities to account for stochastic uncertainties of the environment such as noise or input disturbances. We study pMDPs with reachability objectives where the parameter values are unknown and impossible to measure directly during execution, but there is a probability distribution known over the parameter values. We study for the first time computing parameter-independent strategies that are expectation optimal, i.e., optimize the expected reachability probability under the probability distribution over the parameters. We present an encoding of our problem to partially observable MDPs (POMDPs), i.e., a reduction of our problem to computing optimal strategies in POMDPs. We evaluate our method experimentally on several benchmarks: a motivating (repeated) learner model; a series of benchmarks of varying configurations of a robot moving on a grid; and a consensus protocol. AU - Arming, Sebastian AU - Bartocci, Ezio AU - Chatterjee, Krishnendu AU - Katoen, Joost P AU - Sokolova, Ana ID - 79 TI - Parameter-independent strategies for pMDPs via POMDPs VL - 11024 ER - TY - GEN AB - A common assumption in causal modeling posits that the data is generated by a set of independent mechanisms, and algorithms should aim to recover this structure. Standard unsupervised learning, however, is often concerned with training a single model to capture the overall distribution or aspects thereof. Inspired by clustering approaches, we consider mixtures of implicit generative models that ``disentangle'' the independent generative mechanisms underlying the data. Relying on an additional set of discriminators, we propose a competitive training procedure in which the models only need to capture the portion of the data distribution from which they can produce realistic samples. As a by-product, each model is simpler and faster to train. We empirically show that our approach splits the training distribution in a sensible way and increases the quality of the generated samples. AU - Locatello, Francesco AU - Vincent, Damien AU - Tolstikhin, Ilya AU - Rätsch, Gunnar AU - Gelly, Sylvain AU - Schölkopf, Bernhard ID - 14327 T2 - arXiv TI - Competitive training of mixtures of independent deep generative models ER - TY - JOUR AB - We consider the two-dimensional BCS functional with a radial pair interaction. We show that the translational symmetry is not broken in a certain temperature interval below the critical temperature. In the case of vanishing angular momentum, our results carry over to the three-dimensional case. AU - Deuchert, Andreas AU - Geisinge, Alissa AU - Hainzl, Christian AU - Loss, Michael ID - 400 IS - 5 JF - Annales Henri Poincare TI - Persistence of translational symmetry in the BCS model with radial pair interaction VL - 19 ER - TY - JOUR AB - Recent developments in automated tracking allow uninterrupted, high-resolution recording of animal trajectories, sometimes coupled with the identification of stereotyped changes of body pose or other behaviors of interest. Analysis and interpretation of such data represents a challenge: the timing of animal behaviors may be stochastic and modulated by kinematic variables, by the interaction with the environment or with the conspecifics within the animal group, and dependent on internal cognitive or behavioral state of the individual. Existing models for collective motion typically fail to incorporate the discrete, stochastic, and internal-state-dependent aspects of behavior, while models focusing on individual animal behavior typically ignore the spatial aspects of the problem. Here we propose a probabilistic modeling framework to address this gap. Each animal can switch stochastically between different behavioral states, with each state resulting in a possibly different law of motion through space. Switching rates for behavioral transitions can depend in a very general way, which we seek to identify from data, on the effects of the environment as well as the interaction between the animals. We represent the switching dynamics as a Generalized Linear Model and show that: (i) forward simulation of multiple interacting animals is possible using a variant of the Gillespie’s Stochastic Simulation Algorithm; (ii) formulated properly, the maximum likelihood inference of switching rate functions is tractably solvable by gradient descent; (iii) model selection can be used to identify factors that modulate behavioral state switching and to appropriately adjust model complexity to data. To illustrate our framework, we apply it to two synthetic models of animal motion and to real zebrafish tracking data. AU - Bod’Ová, Katarína AU - Mitchell, Gabriel AU - Harpaz, Roy AU - Schneidman, Elad AU - Tkacik, Gasper ID - 406 IS - 3 JF - PLoS One TI - Probabilistic models of individual and collective animal behavior VL - 13 ER - TY - JOUR AB - Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages AU - Pleska, Maros AU - Lang, Moritz AU - Refardt, Dominik AU - Levin, Bruce AU - Guet, Calin C ID - 457 IS - 2 JF - Nature Ecology and Evolution TI - Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity VL - 2 ER - TY - JOUR AB - Many animals use antimicrobials to prevent or cure disease [1,2]. For example, some animals will ingest plants with medicinal properties, both prophylactically to prevent infection and therapeutically to self-medicate when sick. Antimicrobial substances are also used as topical disinfectants, to prevent infection, protect offspring and to sanitise their surroundings [1,2]. Social insects (ants, bees, wasps and termites) build nests in environments with a high abundance and diversity of pathogenic microorganisms — such as soil and rotting wood — and colonies are often densely crowded, creating conditions that favour disease outbreaks. Consequently, social insects have evolved collective disease defences to protect their colonies from epidemics. These traits can be seen as functionally analogous to the immune system of individual organisms [3,4]. This ‘social immunity’ utilises antimicrobials to prevent and eradicate infections, and to keep the brood and nest clean. However, these antimicrobial compounds can be harmful to the insects themselves, and it is unknown how colonies prevent collateral damage when using them. Here, we demonstrate that antimicrobial acids, produced by workers to disinfect the colony, are harmful to the delicate pupal brood stage, but that the pupae are protected from the acids by the presence of a silk cocoon. Garden ants spray their nests with an antimicrobial poison to sanitize contaminated nestmates and brood. Here, Pull et al show that they also prophylactically sanitise their colonies, and that the silk cocoon serves as a barrier to protect developing pupae, thus preventing collateral damage during nest sanitation. AU - Pull, Christopher AU - Metzler, Sina AU - Naderlinger, Elisabeth AU - Cremer, Sylvia ID - 55 IS - 19 JF - Current Biology TI - Protection against the lethal side effects of social immunity in ants VL - 28 ER - TY - JOUR AB - We consider large random matrices X with centered, independent entries but possibly di erent variances. We compute the normalized trace of f(X)g(X∗) for f, g functions analytic on the spectrum of X. We use these results to compute the long time asymptotics for systems of coupled di erential equations with random coe cients. We show that when the coupling is critical, the norm squared of the solution decays like t−1/2. AU - Erdös, László AU - Krüger, Torben H AU - Renfrew, David T ID - 181 IS - 3 JF - SIAM Journal on Mathematical Analysis TI - Power law decay for systems of randomly coupled differential equations VL - 50 ER - TY - JOUR AB - We construct quantizations of multiplicative hypertoric varieties using an algebra of q-difference operators on affine space, where q is a root of unity in C. The quantization defines a matrix bundle (i.e. Azumaya algebra) over the multiplicative hypertoric variety and admits an explicit finite étale splitting. The global sections of this Azumaya algebra is a hypertoric quantum group, and we prove a localization theorem. We introduce a general framework of Frobenius quantum moment maps and their Hamiltonian reductions; our results shed light on an instance of this framework. AU - Ganev, Iordan V ID - 322 JF - Journal of Algebra TI - Quantizations of multiplicative hypertoric varieties at a root of unity VL - 506 ER - TY - GEN AB - Implementation of the inference method in Matlab, including three applications of the method: The first one for the model of ant motion, the second one for bacterial chemotaxis, and the third one for the motion of fish. AU - Bod’Ová, Katarína AU - Mitchell, Gabriel AU - Harpaz, Roy AU - Schneidman, Elad AU - Tkačik, Gašper ID - 9831 TI - Implementation of the inference method in Matlab ER - TY - CONF AB - We address the problem of analyzing the reachable set of a polynomial nonlinear continuous system by over-approximating the flowpipe of its dynamics. The common approach to tackle this problem is to perform a numerical integration over a given time horizon based on Taylor expansion and interval arithmetic. However, this method results to be very conservative when there is a large difference in speed between trajectories as time progresses. In this paper, we propose to use combinations of barrier functions, which we call piecewise barrier tube (PBT), to over-approximate flowpipe. The basic idea of PBT is that for each segment of a flowpipe, a coarse box which is big enough to contain the segment is constructed using sampled simulation and then in the box we compute by linear programming a set of barrier functions (called barrier tube or BT for short) which work together to form a tube surrounding the flowpipe. The benefit of using PBT is that (1) BT is independent of time and hence can avoid being stretched and deformed by time; and (2) a small number of BTs can form a tight over-approximation for the flowpipe, which means that the computation required to decide whether the BTs intersect the unsafe set can be reduced significantly. We implemented a prototype called PBTS in C++. Experiments on some benchmark systems show that our approach is effective. AU - Kong, Hui AU - Bartocci, Ezio AU - Henzinger, Thomas A ID - 142 TI - Reachable set over-approximation for nonlinear systems using piecewise barrier tubes VL - 10981 ER - TY - JOUR AB - We investigate the quantum interference induced shifts between energetically close states in highly charged ions, with the energy structure being observed by laser spectroscopy. In this work, we focus on hyperfine states of lithiumlike heavy-Z isotopes and quantify how much quantum interference changes the observed transition frequencies. The process of photon excitation and subsequent photon decay for the transition 2s→2p→2s is implemented with fully relativistic and full-multipole frameworks, which are relevant for such relativistic atomic systems. We consider the isotopes Pb79+207 and Bi80+209 due to experimental interest, as well as other examples of isotopes with lower Z, namely Pr56+141 and Ho64+165. We conclude that quantum interference can induce shifts up to 11% of the linewidth in the measurable resonances of the considered isotopes, if interference between resonances is neglected. The inclusion of relativity decreases the cross section by 35%, mainly due to the complete retardation form of the electric dipole multipole. However, the contribution of the next higher multipoles (e.g., magnetic quadrupole) to the cross section is negligible. This makes the contribution of relativity and higher-order multipoles to the quantum interference induced shifts a minor effect, even for heavy-Z elements. AU - Amaro, Pedro AU - Loureiro, Ulisses AU - Safari, Laleh AU - Fratini, Filippo AU - Indelicato, Paul AU - Stöhlker, Thomas AU - Santos, José ID - 427 IS - 2 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Quantum interference in laser spectroscopy of highly charged lithiumlike ions VL - 97 ER -