TY - JOUR AB - The rate of biological evolution depends on the fixation probability and on the fixation time of new mutants. Intensive research has focused on identifying population structures that augment the fixation probability of advantageous mutants. But these amplifiers of natural selection typically increase fixation time. Here we study population structures that achieve a tradeoff between fixation probability and time. First, we show that no amplifiers can have an asymptotically lower absorption time than the well-mixed population. Then we design population structures that substantially augment the fixation probability with just a minor increase in fixation time. Finally, we show that those structures enable higher effective rate of evolution than the well-mixed population provided that the rate of generating advantageous mutants is relatively low. Our work sheds light on how population structure affects the rate of evolution. Moreover, our structures could be useful for lab-based, medical, or industrial applications of evolutionary optimization. AU - Tkadlec, Josef AU - Pavlogiannis, Andreas AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 7210 JF - Communications Biology SN - 2399-3642 TI - Population structure determines the tradeoff between fixation probability and fixation time VL - 2 ER - TY - CONF AB - The verification of concurrent programs remains an open challenge, as thread interaction has to be accounted for, which leads to state-space explosion. Stateless model checking battles this problem by exploring traces rather than states of the program. As there are exponentially many traces, dynamic partial-order reduction (DPOR) techniques are used to partition the trace space into equivalence classes, and explore a few representatives from each class. The standard equivalence that underlies most DPOR techniques is the happens-before equivalence, however recent works have spawned a vivid interest towards coarser equivalences. The efficiency of such approaches is a product of two parameters: (i) the size of the partitioning induced by the equivalence, and (ii) the time spent by the exploration algorithm in each class of the partitioning. In this work, we present a new equivalence, called value-happens-before and show that it has two appealing features. First, value-happens-before is always at least as coarse as the happens-before equivalence, and can be even exponentially coarser. Second, the value-happens-before partitioning is efficiently explorable when the number of threads is bounded. We present an algorithm called value-centric DPOR (VCDPOR), which explores the underlying partitioning using polynomial time per class. Finally, we perform an experimental evaluation of VCDPOR on various benchmarks, and compare it against other state-of-the-art approaches. Our results show that value-happens-before typically induces a significant reduction in the size of the underlying partitioning, which leads to a considerable reduction in the running time for exploring the whole partitioning. AU - Chatterjee, Krishnendu AU - Pavlogiannis, Andreas AU - Toman, Viktor ID - 10190 KW - safety KW - risk KW - reliability and quality KW - software T2 - Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications TI - Value-centric dynamic partial order reduction VL - 3 ER - TY - CONF AB - Several classic problems in graph processing and computational geometry are solved via incremental algorithms, which split computation into a series of small tasks acting on shared state, which gets updated progressively. While the sequential variant of such algorithms usually specifies a fixed (but sometimes random) order in which the tasks should be performed, a standard approach to parallelizing such algorithms is to relax this constraint to allow for out-of-order parallel execution. This is the case for parallel implementations of Dijkstra's single-source shortest-paths (SSSP) algorithm, and for parallel Delaunay mesh triangulation. While many software frameworks parallelize incremental computation in this way, it is still not well understood whether this relaxed ordering approach can still provide any complexity guarantees. In this paper, we address this problem, and analyze the efficiency guarantees provided by a range of incremental algorithms when parallelized via relaxed schedulers. We show that, for algorithms such as Delaunay mesh triangulation and sorting by insertion, schedulers with a maximum relaxation factor of k in terms of the maximum priority inversion allowed will introduce a maximum amount of wasted work of O(łog n poly(k)), where n is the number of tasks to be executed. For SSSP, we show that the additional work is O(poly(k), dmax / wmin), where dmax is the maximum distance between two nodes, and wmin is the minimum such distance. In practical settings where n >> k, this suggests that the overheads of relaxation will be outweighed by the improved scalability of the relaxed scheduler. On the negative side, we provide lower bounds showing that certain algorithms will inherently incur a non-trivial amount of wasted work due to scheduler relaxation, even for relatively benign relaxed schedulers. AU - Alistarh, Dan-Adrian AU - Nadiradze, Giorgi AU - Koval, Nikita ID - 6673 SN - 9781450361842 T2 - 31st ACM Symposium on Parallelism in Algorithms and Architectures TI - Efficiency guarantees for parallel incremental algorithms under relaxed schedulers ER - TY - JOUR AB - Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation. AU - Erdem, Fatma Asli AU - Ilic, Marija AU - Koppensteiner, Peter AU - Gołacki, Jakub AU - Lubec, Gert AU - Freissmuth, Michael AU - Sandtner, Walter ID - 7398 IS - 8 JF - The Journal of General Physiology SN - 0022-1295 TI - A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2 VL - 151 ER - TY - JOUR AB - The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between “closed” and “open” conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs. AU - Letts, James A AU - Fiedorczuk, Karol AU - Degliesposti, Gianluca AU - Skehel, Mark AU - Sazanov, Leonid A ID - 7395 IS - 6 JF - Molecular Cell SN - 1097-2765 TI - Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk VL - 75 ER - TY - JOUR AB - Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena. AU - Dura-Bernal, Salvador AU - Suter, Benjamin AU - Gleeson, Padraig AU - Cantarelli, Matteo AU - Quintana, Adrian AU - Rodriguez, Facundo AU - Kedziora, David J AU - Chadderdon, George L AU - Kerr, Cliff C AU - Neymotin, Samuel A AU - McDougal, Robert A AU - Hines, Michael AU - Shepherd, Gordon MG AU - Lytton, William W ID - 7405 JF - eLife SN - 2050-084X TI - NetPyNE, a tool for data-driven multiscale modeling of brain circuits VL - 8 ER - TY - JOUR AB - Suppressed recombination allows divergence between homologous sex chromosomes and the functionality of their genes. Here, we reveal patterns of the earliest stages of sex-chromosome evolution in the diploid dioecious herb Mercurialis annua on the basis of cytological analysis, de novo genome assembly and annotation, genetic mapping, exome resequencing of natural populations, and transcriptome analysis. The genome assembly contained 34,105 expressed genes, of which 10,076 were assigned to linkage groups. Genetic mapping and exome resequencing of individuals across the species range both identified the largest linkage group, LG1, as the sex chromosome. Although the sex chromosomes of M. annua are karyotypically homomorphic, we estimate that about one-third of the Y chromosome, containing 568 transcripts and spanning 22.3 cM in the corresponding female map, has ceased recombining. Nevertheless, we found limited evidence for Y-chromosome degeneration in terms of gene loss and pseudogenization, and most X- and Y-linked genes appear to have diverged in the period subsequent to speciation between M. annua and its sister species M. huetii, which shares the same sex-determining region. Taken together, our results suggest that the M. annua Y chromosome has at least two evolutionary strata: a small old stratum shared with M. huetii, and a more recent larger stratum that is probably unique to M. annua and that stopped recombining ∼1 MYA. Patterns of gene expression within the nonrecombining region are consistent with the idea that sexually antagonistic selection may have played a role in favoring suppressed recombination. AU - Veltsos, Paris AU - Ridout, Kate E. AU - Toups, Melissa A AU - González-Martínez, Santiago C. AU - Muyle, Aline AU - Emery, Olivier AU - Rastas, Pasi AU - Hudzieczek, Vojtech AU - Hobza, Roman AU - Vyskot, Boris AU - Marais, Gabriel A. B. AU - Filatov, Dmitry A. AU - Pannell, John R. ID - 7400 IS - 3 JF - Genetics SN - 0016-6731 TI - Early sex-chromosome evolution in the diploid dioecious plant Mercurialis annua VL - 212 ER - TY - JOUR AB - The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation. AU - Stürner, Tomke AU - Tatarnikova, Anastasia AU - Müller, Jan AU - Schaffran, Barbara AU - Cuntz, Hermann AU - Zhang, Yun AU - Nemethova, Maria AU - Bogdan, Sven AU - Small, Vic AU - Tavosanis, Gaia ID - 7404 IS - 7 JF - Development SN - 0950-1991 TI - Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo VL - 146 ER - TY - CONF AB - Graph planning gives rise to fundamental algorithmic questions such as shortest path, traveling salesman problem, etc. A classical problem in discrete planning is to consider a weighted graph and construct a path that maximizes the sum of weights for a given time horizon T. However, in many scenarios, the time horizon is not fixed, but the stopping time is chosen according to some distribution such that the expected stopping time is T. If the stopping time distribution is not known, then to ensure robustness, the distribution is chosen by an adversary, to represent the worst-case scenario. A stationary plan for every vertex always chooses the same outgoing edge. For fixed horizon or fixed stopping-time distribution, stationary plans are not sufficient for optimality. Quite surprisingly we show that when an adversary chooses the stopping-time distribution with expected stopping time T, then stationary plans are sufficient. While computing optimal stationary plans for fixed horizon is NP-complete, we show that computing optimal stationary plans under adversarial stopping-time distribution can be achieved in polynomial time. Consequently, our polynomial-time algorithm for adversarial stopping time also computes an optimal plan among all possible plans. AU - Chatterjee, Krishnendu AU - Doyen, Laurent ID - 7402 SN - 9781728136080 T2 - 34th Annual ACM/IEEE Symposium on Logic in Computer Science TI - Graph planning with expected finite horizon ER - TY - JOUR AB - We prove that the observable telegraph signal accompanying the bistability in the photon-blockade-breakdown regime of the driven and lossy Jaynes–Cummings model is the finite-size precursor of what in the thermodynamic limit is a genuine first-order phase transition. We construct a finite-size scaling of the system parameters to a well-defined thermodynamic limit, in which the system remains the same microscopic system, but the telegraph signal becomes macroscopic both in its timescale and intensity. The existence of such a finite-size scaling completes and justifies the classification of the photon-blockade-breakdown effect as a first-order dissipative quantum phase transition. AU - Vukics, A. AU - Dombi, A. AU - Fink, Johannes M AU - Domokos, P. ID - 7451 JF - Quantum SN - 2521-327X TI - Finite-size scaling of the photon-blockade breakdown dissipative quantum phase transition VL - 3 ER - TY - CONF AB - We present a new proximal bundle method for Maximum-A-Posteriori (MAP) inference in structured energy minimization problems. The method optimizes a Lagrangean relaxation of the original energy minimization problem using a multi plane block-coordinate Frank-Wolfe method that takes advantage of the specific structure of the Lagrangean decomposition. We show empirically that our method outperforms state-of-the-art Lagrangean decomposition based algorithms on some challenging Markov Random Field, multi-label discrete tomography and graph matching problems. AU - Swoboda, Paul AU - Kolmogorov, Vladimir ID - 7468 SN - 10636919 T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition TI - Map inference via block-coordinate Frank-Wolfe algorithm VL - 2019-June ER - TY - JOUR AU - Morandell, Jasmin AU - Nicolas, Armel AU - Schwarz, Lena A AU - Novarino, Gaia ID - 7415 IS - Supplement 6 JF - European Neuropsychopharmacology SN - 0924-977X TI - S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism VL - 29 ER - TY - JOUR AU - Knaus, Lisa AU - Tarlungeanu, Dora-Clara AU - Novarino, Gaia ID - 7414 IS - Supplement 6 JF - European Neuropsychopharmacology SN - 0924-977X TI - S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly VL - 29 ER - TY - JOUR AU - Benková, Eva AU - Dagdas, Yasin ID - 7394 IS - 12 JF - Current Opinion in Plant Biology SN - 1369-5266 TI - Editorial overview: Cell biology in the era of omics? VL - 52 ER - TY - CONF AB - Multi-exit architectures, in which a stack of processing layers is interleaved with early output layers, allow the processing of a test example to stop early and thus save computation time and/or energy. In this work, we propose a new training procedure for multi-exit architectures based on the principle of knowledge distillation. The method encourage searly exits to mimic later, more accurate exits, by matching their output probabilities. Experiments on CIFAR100 and ImageNet show that distillation-based training significantly improves the accuracy of early exits while maintaining state-of-the-art accuracy for late ones. The method is particularly beneficial when training data is limited and it allows a straightforward extension to semi-supervised learning,i.e. making use of unlabeled data at training time. Moreover, it takes only afew lines to implement and incurs almost no computational overhead at training time, and none at all at test time. AU - Bui Thi Mai, Phuong AU - Lampert, Christoph ID - 7479 SN - 15505499 T2 - IEEE International Conference on Computer Vision TI - Distillation-based training for multi-exit architectures VL - 2019-October ER - TY - CONF AB - We present a novel class of convolutional neural networks (CNNs) for set functions,i.e., data indexed with the powerset of a finite set. The convolutions are derivedas linear, shift-equivariant functions for various notions of shifts on set functions.The framework is fundamentally different from graph convolutions based on theLaplacian, as it provides not one but several basic shifts, one for each element inthe ground set. Prototypical experiments with several set function classificationtasks on synthetic datasets and on datasets derived from real-world hypergraphsdemonstrate the potential of our new powerset CNNs. AU - Wendler, Chris AU - Alistarh, Dan-Adrian AU - Püschel, Markus ID - 7542 SN - 1049-5258 TI - Powerset convolutional neural networks VL - 32 ER - TY - CHAP AB - Social insects (i.e., ants, termites and the social bees and wasps) protect their colonies from disease using a combination of individual immunity and collectively performed defenses, termed social immunity. The first line of social immune defense is sanitary care, which is performed by colony members to protect their pathogen-exposed nestmates from developing an infection. If sanitary care fails and an infection becomes established, a second line of social immune defense is deployed to stop disease transmission within the colony and to protect the valuable queens, which together with the males are the reproductive individuals of the colony. Insect colonies are separated into these reproductive individuals and the sterile worker force, forming a superorganismal reproductive unit reminiscent of the differentiated germline and soma in a multicellular organism. Ultimately, the social immune response preserves the germline of the superorganism insect colony and increases overall fitness of the colony in case of disease. AU - Cremer, Sylvia AU - Kutzer, Megan ED - Choe, Jae ID - 7513 SN - 9780128132517 T2 - Encyclopedia of Animal Behavior TI - Social immunity ER - TY - CONF AB - Bending-active structures are able to efficiently produce complex curved shapes starting from flat panels. The desired deformation of the panels derives from the proper selection of their elastic properties. Optimized panels, called FlexMaps, are designed such that, once they are bent and assembled, the resulting static equilibrium configuration matches a desired input 3D shape. The FlexMaps elastic properties are controlled by locally varying spiraling geometric mesostructures, which are optimized in size and shape to match the global curvature (i.e., bending requests) of the target shape. The design pipeline starts from a quad mesh representing the input 3D shape, which defines the edge size and the total amount of spirals: every quad will embed one spiral. Then, an optimization algorithm tunes the geometry of the spirals by using a simplified pre-computed rod model. This rod model is derived from a non-linear regression algorithm which approximates the non-linear behavior of solid FEM spiral models subject to hundreds of load combinations. This innovative pipeline has been applied to the project of a lightweight plywood pavilion named FlexMaps Pavilion, which is a single-layer piecewise twisted arc that fits a bounding box of 3.90x3.96x3.25 meters. AU - Laccone, Francesco AU - Malomo, Luigi AU - Perez Rodriguez, Jesus AU - Pietroni, Nico AU - Ponchio, Federico AU - Bickel, Bernd AU - Cignoni, Paolo ID - 9261 SN - 2518-6582 T2 - IASS Symposium 2019 - 60th Anniversary Symposium of the International Association for Shell and Spatial Structures; Structural Membranes 2019 - 9th International Conference on Textile Composites and Inflatable Structures, FORM and FORCE TI - FlexMaps Pavilion: A twisted arc made of mesostructured flat flexible panels ER - TY - CONF AB - We propose a new model for detecting visual relationships, such as "person riding motorcycle" or "bottle on table". This task is an important step towards comprehensive structured mage understanding, going beyond detecting individual objects. Our main novelty is a Box Attention mechanism that allows to model pairwise interactions between objects using standard object detection pipelines. The resulting model is conceptually clean, expressive and relies on well-justified training and prediction procedures. Moreover, unlike previously proposed approaches, our model does not introduce any additional complex components or hyperparameters on top of those already required by the underlying detection model. We conduct an experimental evaluation on two datasets, V-COCO and Open Images, demonstrating strong quantitative and qualitative results. AU - Kolesnikov, Alexander AU - Kuznetsova, Alina AU - Lampert, Christoph AU - Ferrari, Vittorio ID - 7640 SN - 9781728150239 T2 - Proceedings of the 2019 International Conference on Computer Vision Workshop TI - Detecting visual relationships using box attention ER - TY - CONF AB - Deep neural networks (DNNs) have become increasingly important due to their excellent empirical performance on a wide range of problems. However, regularization is generally achieved by indirect means, largely due to the complex set of functions defined by a network and the difficulty in measuring function complexity. There exists no method in the literature for additive regularization based on a norm of the function, as is classically considered in statistical learning theory. In this work, we study the tractability of function norms for deep neural networks with ReLU activations. We provide, to the best of our knowledge, the first proof in the literature of the NP-hardness of computing function norms of DNNs of 3 or more layers. We also highlight a fundamental difference between shallow and deep networks. In the light on these results, we propose a new regularization strategy based on approximate function norms, and show its efficiency on a segmentation task with a DNN. AU - Rannen-Triki, Amal AU - Berman, Maxim AU - Kolmogorov, Vladimir AU - Blaschko, Matthew B. ID - 7639 SN - 9781728150239 T2 - Proceedings of the 2019 International Conference on Computer Vision Workshop TI - Function norms for neural networks ER - TY - CHAP AB - We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it. AU - Barton, Nicholas H AU - Etheridge, Alison ED - Balding, David ED - Moltke, Ida ED - Marioni, John ID - 8281 SN - 9781119429142 T2 - Handbook of statistical genomics TI - Mathematical models in population genetics ER - TY - GEN AB - Denote by ∆N the N-dimensional simplex. A map f : ∆N → Rd is an almost r-embedding if fσ1∩. . .∩fσr = ∅ whenever σ1, . . . , σr are pairwise disjoint faces. A counterexample to the topological Tverberg conjecture asserts that if r is not a prime power and d ≥ 2r + 1, then there is an almost r-embedding ∆(d+1)(r−1) → Rd. This was improved by Blagojevi´c–Frick–Ziegler using a simple construction of higher-dimensional counterexamples by taking k-fold join power of lower-dimensional ones. We improve this further (for d large compared to r): If r is not a prime power and N := (d+ 1)r−r l d + 2 r + 1 m−2, then there is an almost r-embedding ∆N → Rd. For the r-fold van Kampen–Flores conjecture we also produce counterexamples which are stronger than previously known. Our proof is based on generalizations of the Mabillard–Wagner theorem on construction of almost r-embeddings from equivariant maps, and of the Ozaydin theorem on existence of equivariant maps. AU - Avvakumov, Sergey AU - Karasev, R. AU - Skopenkov, A. ID - 8184 T2 - arXiv TI - Stronger counterexamples to the topological Tverberg conjecture ER - TY - CONF AB - A proxy re-encryption (PRE) scheme is a public-key encryption scheme that allows the holder of a key pk to derive a re-encryption key for any other key 𝑝𝑘′. This re-encryption key lets anyone transform ciphertexts under pk into ciphertexts under 𝑝𝑘′ without having to know the underlying message, while transformations from 𝑝𝑘′ to pk should not be possible (unidirectional). Security is defined in a multi-user setting against an adversary that gets the users’ public keys and can ask for re-encryption keys and can corrupt users by requesting their secret keys. Any ciphertext that the adversary cannot trivially decrypt given the obtained secret and re-encryption keys should be secure. All existing security proofs for PRE only show selective security, where the adversary must first declare the users it wants to corrupt. This can be lifted to more meaningful adaptive security by guessing the set of corrupted users among the n users, which loses a factor exponential in Open image in new window , rendering the result meaningless already for moderate Open image in new window . Jafargholi et al. (CRYPTO’17) proposed a framework that in some cases allows to give adaptive security proofs for schemes which were previously only known to be selectively secure, while avoiding the exponential loss that results from guessing the adaptive choices made by an adversary. We apply their framework to PREs that satisfy some natural additional properties. Concretely, we give a more fine-grained reduction for several unidirectional PREs, proving adaptive security at a much smaller loss. The loss depends on the graph of users whose edges represent the re-encryption keys queried by the adversary. For trees and chains the loss is quasi-polynomial in the size and for general graphs it is exponential in their depth and indegree (instead of their size as for previous reductions). Fortunately, trees and low-depth graphs cover many, if not most, interesting applications. Our results apply e.g. to the bilinear-map based PRE schemes by Ateniese et al. (NDSS’05 and CT-RSA’09), Gentry’s FHE-based scheme (STOC’09) and the LWE-based scheme by Chandran et al. (PKC’14). AU - Fuchsbauer, Georg AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z ID - 6430 SN - 03029743 TI - Adaptively secure proxy re-encryption VL - 11443 ER - TY - JOUR AB - Electron transport in two-dimensional conducting materials such as graphene, with dominant electron–electron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohm’s law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressure–speed relation is Stoke’s law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavity—analogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments. AU - Mayzel, Jonathan AU - Steinberg, Victor AU - Varshney, Atul ID - 6069 JF - Nature Communications SN - 2041-1723 TI - Stokes flow analogous to viscous electron current in graphene VL - 10 ER - TY - JOUR AB - Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity. AU - Varshney, Atul AU - Steinberg, Victor ID - 6014 JF - Nature Communications SN - 2041-1723 TI - Elastic alfven waves in elastic turbulence VL - 10 ER - TY - JOUR AB - Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis. AU - Amberg, Nicole AU - Sotiropoulou, Panagiota A. AU - Heller, Gerwin AU - Lichtenberger, Beate M. AU - Holcmann, Martin AU - Camurdanoglu, Bahar AU - Baykuscheva-Gentscheva, Temenuschka AU - Blanpain, Cedric AU - Sibilia, Maria ID - 6451 JF - iScience SN - 2589-0042 TI - EGFR controls hair shaft differentiation in a p53-independent manner VL - 15 ER - TY - JOUR AB - We study effects of a bounded and compactly supported perturbation on multidimensional continuum random Schrödinger operators in the region of complete localisation. Our main emphasis is on Anderson orthogonality for random Schrödinger operators. Among others, we prove that Anderson orthogonality does occur for Fermi energies in the region of complete localisation with a non-zero probability. This partially confirms recent non-rigorous findings [V. Khemani et al., Nature Phys. 11 (2015), 560–565]. The spectral shift function plays an important role in our analysis of Anderson orthogonality. We identify it with the index of the corresponding pair of spectral projections and explore the consequences thereof. All our results rely on the main technical estimate of this paper which guarantees separate exponential decay of the disorder-averaged Schatten p-norm of χa(f(H)−f(Hτ))χb in a and b. Here, Hτ is a perturbation of the random Schrödinger operator H, χa is the multiplication operator corresponding to the indicator function of a unit cube centred about a∈Rd, and f is in a suitable class of functions of bounded variation with distributional derivative supported in the region of complete localisation for H. AU - Dietlein, Adrian M AU - Gebert, Martin AU - Müller, Peter ID - 10879 IS - 3 JF - Journal of Spectral Theory KW - Random Schrödinger operators KW - spectral shift function KW - Anderson orthogonality SN - 1664-039X TI - Perturbations of continuum random Schrödinger operators with applications to Anderson orthogonality and the spectral shift function VL - 9 ER - TY - JOUR AB - Starting from a microscopic model for a system of neurons evolving in time which individually follow a stochastic integrate-and-fire type model, we study a mean-field limit of the system. Our model is described by a system of SDEs with discontinuous coefficients for the action potential of each neuron and takes into account the (random) spatial configuration of neurons allowing the interaction to depend on it. In the limit as the number of particles tends to infinity, we obtain a nonlinear Fokker-Planck type PDE in two variables, with derivatives only with respect to one variable and discontinuous coefficients. We also study strong well-posedness of the system of SDEs and prove the existence and uniqueness of a weak measure-valued solution to the PDE, obtained as the limit of the laws of the empirical measures for the system of particles. AU - Flandoli, Franco AU - Priola, Enrico AU - Zanco, Giovanni A ID - 10878 IS - 6 JF - Discrete and Continuous Dynamical Systems KW - Applied Mathematics KW - Discrete Mathematics and Combinatorics KW - Analysis SN - 1553-5231 TI - A mean-field model with discontinuous coefficients for neurons with spatial interaction VL - 39 ER - TY - CONF AB - This paper investigates the power of preprocessing in the CONGEST model. Schmid and Suomela (ACM HotSDN 2013) introduced the SUPPORTED CONGEST model to study the application of distributed algorithms in Software-Defined Networks (SDNs). In this paper, we show that a large class of lower bounds in the CONGEST model still hold in the SUPPORTED model, highlighting the robustness of these bounds. This also raises the question how much does preprocessing help in the CONGEST model. AU - Foerster, Klaus-Tycho AU - Korhonen, Janne AU - Rybicki, Joel AU - Schmid, Stefan ID - 6935 SN - 9781450362177 T2 - Proceedings of the 2019 ACM Symposium on Principles of Distributed Computing TI - Does preprocessing help under congestion? ER - TY - JOUR AB - Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche. AU - Nikolic, Nela ID - 138 IS - 1 JF - Current Genetics TI - Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system VL - 65 ER - TY - JOUR AB - We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function f∈Lp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for f∈L∞, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide. AU - Fischer, Julian L AU - Kneuss, Olivier ID - 151 IS - 1 JF - Journal of Differential Equations TI - Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity VL - 266 ER - TY - JOUR AB - The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved. AU - Amberg, Nicole AU - Laukoter, Susanne AU - Hippenmeyer, Simon ID - 27 IS - 1 JF - Journal of Neurochemistry TI - Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex VL - 149 ER - TY - JOUR AB - Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell–cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis. AU - Petridou, Nicoletta AU - Grigolon, Silvia AU - Salbreux, Guillaume AU - Hannezo, Edouard B AU - Heisenberg, Carl-Philipp J ID - 5789 JF - Nature Cell Biology SN - 14657392 TI - Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling VL - 21 ER - TY - JOUR AB - The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. AU - Lang, Moritz AU - Shkolnikov, Mikhail ID - 196 IS - 8 JF - Proceedings of the National Academy of Sciences TI - Harmonic dynamics of the Abelian sandpile VL - 116 ER - TY - JOUR AB - We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion. AU - Kavcic, Bor AU - Sakashita, A. AU - Noguchi, H. AU - Ziherl, P. ID - 5817 IS - 4 JF - Soft Matter SN - 1744-683X TI - Limiting shapes of confined lipid vesicles VL - 15 ER - TY - JOUR AB - We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset Y⊆X, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest. AU - Erbar, Matthias AU - Maas, Jan AU - Wirth, Melchior ID - 73 IS - 1 JF - Calculus of Variations and Partial Differential Equations SN - 09442669 TI - On the geometry of geodesics in discrete optimal transport VL - 58 ER - TY - JOUR AB - We present an efficient algorithm for a problem in the interface between clustering and graph embeddings. An embedding ϕ : G → M of a graph G into a 2-manifold M maps the vertices in V(G) to distinct points and the edges in E(G) to interior-disjoint Jordan arcs between the corresponding vertices. In applications in clustering, cartography, and visualization, nearby vertices and edges are often bundled to the same point or overlapping arcs due to data compression or low resolution. This raises the computational problem of deciding whether a given map ϕ : G → M comes from an embedding. A map ϕ : G → M is a weak embedding if it can be perturbed into an embedding ψ ϵ : G → M with ‖ ϕ − ψ ϵ ‖ < ϵ for every ϵ > 0, where ‖.‖ is the unform norm. A polynomial-time algorithm for recognizing weak embeddings has recently been found by Fulek and Kynčl. It reduces the problem to solving a system of linear equations over Z2. It runs in O(n2ω)≤ O(n4.75) time, where ω ∈ [2,2.373) is the matrix multiplication exponent and n is the number of vertices and edges of G. We improve the running time to O(n log n). Our algorithm is also conceptually simpler: We perform a sequence of local operations that gradually “untangles” the image ϕ(G) into an embedding ψ(G) or reports that ϕ is not a weak embedding. It combines local constraints on the orientation of subgraphs directly, thereby eliminating the need for solving large systems of linear equations. AU - Akitaya, Hugo AU - Fulek, Radoslav AU - Tóth, Csaba ID - 6982 IS - 4 JF - ACM Transactions on Algorithms TI - Recognizing weak embeddings of graphs VL - 15 ER - TY - THES AB - Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving. Nevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions. While, previously, directions were given by the user, we introduce (1) the first method for computing template directions from spurious counterexamples, so as to generalize and eliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid automata with (possibly non-linear) convex constraints on derivatives only, while for linear ODE requires further abstraction. Specifically, we introduce (2) the conic abstractions, which, partitioning the state space into appropriate (possibly non-uniform) cones, divide curvy trajectories into relatively straight sections, suitable for polyhedral abstractions. Finally, we introduce (3) space-time interpolation, which, combining interval arithmetic and template refinement, computes appropriate (possibly non-uniform) time partitioning and template directions along spurious trajectories, so as to eliminate them. We obtain sound and automatic methods for the reachability analysis over dense and unbounded time of convex hybrid automata and hybrid automata with linear ODE. We build prototype tools and compare—favorably—our methods against the respective state-of-the-art tools, on several benchmarks. AU - Giacobbe, Mirco ID - 6894 TI - Automatic time-unbounded reachability analysis of hybrid systems ER - TY - GEN AB - The spread of adaptive alleles is fundamental to evolution, and in theory, this process is well‐understood. However, only rarely can we follow this process—whether it originates from the spread of a new mutation, or by introgression from another population. In this issue of Molecular Ecology, Hanemaaijer et al. (2018) report on a 25‐year long study of the mosquitoes Anopheles gambiae (Figure 1) and Anopheles coluzzi in Mali, based on genotypes at 15 single‐nucleotide polymorphism (SNP). The species are usually reproductively isolated from each other, but in 2002 and 2006, bursts of hybridization were observed, when F1 hybrids became abundant. Alleles backcrossed from A. gambiae into A. coluzzi, but after the first event, these declined over the following years. In contrast, after 2006, an insecticide resistance allele that had established in A. gambiae spread into A. coluzzi, and rose to high frequency there, over 6 years (~75 generations). Whole genome sequences of 74 individuals showed that A. gambiae SNP from across the genome had become common in the A. coluzzi population, but that most of these were clustered in 34 genes around the resistance locus. A new set of SNP from 25 of these genes were assayed over time; over the 4 years since near‐fixation of the resistance allele; some remained common, whereas others declined. What do these patterns tell us about this introgression event? AU - Barton, Nicholas H ID - 9805 TI - Data from: The consequences of an introgression event ER - TY - JOUR AB - Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification. AU - Trébuchet, Guillaume AU - Cattenoz, Pierre B AU - Zsámboki, János AU - Mazaud, David AU - Siekhaus, Daria E AU - Fanto, Manolis AU - Giangrande, Angela ID - 8 IS - 2 JF - Journal of Neuroscience TI - The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate VL - 39 ER - TY - JOUR AB - In this paper, we introduce a quantum version of the wonderful compactification of a group as a certain noncommutative projective scheme. Our approach stems from the fact that the wonderful compactification encodes the asymptotics of matrix coefficients, and from its realization as a GIT quotient of the Vinberg semigroup. In order to define the wonderful compactification for a quantum group, we adopt a generalized formalism of Proj categories in the spirit of Artin and Zhang. Key to our construction is a quantum version of the Vinberg semigroup, which we define as a q-deformation of a certain Rees algebra, compatible with a standard Poisson structure. Furthermore, we discuss quantum analogues of the stratification of the wonderful compactification by orbits for a certain group action, and provide explicit computations in the case of SL2. AU - Ganev, Iordan V ID - 5 IS - 3 JF - Journal of the London Mathematical Society TI - The wonderful compactification for quantum groups VL - 99 ER - TY - THES AB - The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers. The first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone. The second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition. The third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24. In the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis. In the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results. In the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes. AU - Vasileva, Mina K ID - 7172 TI - Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana ER - TY - JOUR AB - Blebs are cellular protrusions observed in migrating cells and in cells undergoing spreading, cytokinesis, and apoptosis. Here we investigate the flow of cytoplasm during bleb formation and the concurrent changes in cell volume using zebrafish primordial germ cells (PGCs) as an in vivo model. We show that bleb inflation occurs concomitantly with cytoplasmic inflow into it and that during this process the total cell volume does not change. We thus show that bleb formation in primordial germ cells results primarily from redistribution of material within the cell rather than being driven by flow of water from an external source. AU - Goudarzi, Mohammad AU - Boquet-Pujadas, Aleix AU - Olivo-Marin, Jean Christophe AU - Raz, Erez ID - 6093 IS - 2 JF - PLOS ONE TI - Fluid dynamics during bleb formation in migrating cells in vivo VL - 14 ER - TY - THES AB - Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. The recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. Finally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. AU - Cepeda Humerez, Sarah A ID - 6473 KW - Information estimation KW - Time-series KW - data analysis SN - 2663-337X TI - Estimating information flow in single cells ER - TY - THES AB - Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. AU - Prizak, Roshan ID - 6071 SN - 2663-337X TI - Coevolution of transcription factors and their binding sites in sequence space ER - TY - JOUR AB - For an ordinary K3 surface over an algebraically closed field of positive characteristic we show that every automorphism lifts to characteristic zero. Moreover, we show that the Fourier-Mukai partners of an ordinary K3 surface are in one-to-one correspondence with the Fourier-Mukai partners of the geometric generic fiber of its canonical lift. We also prove that the explicit counting formula for Fourier-Mukai partners of the K3 surfaces with Picard rank two and with discriminant equal to minus of a prime number, in terms of the class number of the prime, holds over a field of positive characteristic as well. We show that the image of the derived autoequivalence group of a K3 surface of finite height in the group of isometries of its crystalline cohomology has index at least two. Moreover, we provide a conditional upper bound on the kernel of this natural cohomological descent map. Further, we give an extended remark in the appendix on the possibility of an F-crystal structure on the crystalline cohomology of a K3 surface over an algebraically closed field of positive characteristic and show that the naive F-crystal structure fails in being compatible with inner product. AU - Srivastava, Tanya K ID - 7436 JF - Documenta Mathematica SN - 1431-0635 TI - On derived equivalences of k3 surfaces in positive characteristic VL - 24 ER - TY - JOUR AB - We consider the totally asymmetric simple exclusion process (TASEP) with non-random initial condition having density ρ on ℤ− and λ on ℤ+, and a second class particle initially at the origin. For ρ<λ, there is a shock and the second class particle moves with speed 1−λ−ρ. For large time t, we show that the position of the second class particle fluctuates on a t1/3 scale and determine its limiting law. We also obtain the limiting distribution of the number of steps made by the second class particle until time t. AU - Ferrari, Patrick AU - Ghosal, Promit AU - Nejjar, Peter ID - 72 IS - 3 JF - Annales de l'institut Henri Poincare (B) Probability and Statistics SN - 0246-0203 TI - Limit law of a second class particle in TASEP with non-random initial condition VL - 55 ER - TY - JOUR AB - In this article a model is described how Open Access definitions can be formed on the basis of objective criteria. The common Open Access definitions such as "gold" and "green" are not exactly defined. This becomes a problem as soon as one begins to measure Open Access, for example if the development of the Open Access share should be monitored. This was discussed in the working group on Open Access Monitoring of the AT2OA project and the present model was developed, which is based on 5 critics with 4 characteristics: location, licence, version, embargo and conditions of the Open Access publication are taken into account. In the meantime, the model has also been tested in practice using R scripts, and the initial results are quite promising. AU - Danowski, Patrick ID - 6657 IS - 1 JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare TI - An Austrian proposal for the classification of Open Access Tuples (COAT) - distinguish different open access types beyond colors VL - 72 ER - TY - CONF AB - We demonstrate robust retention of valley coherence and its control via polariton pseudospin precession through the optical TE-TM splitting in bilayer WS2 microcavity exciton polaritons at room temperature. AU - Khatoniar, Mandeep AU - Yama, Nicholas AU - Ghazaryan, Areg AU - Guddala, Sriram AU - Ghaemi, Pouyan AU - Menon, Vinod ID - 6646 SN - 9781943580576 T2 - CLEO: Applications and Technology TI - Room temperature control of valley coherence in bilayer WS2 exciton polaritons ER - TY - CONF AB - We demonstrate electro-optic frequency comb generation using a doubly resonant system comprising a whispering gallery mode disk resonator made of lithium niobate mounted inside a three dimensional copper cavity. We observe 180 sidebands centred at 1550 nm. AU - Rueda Sanchez, Alfredo R AU - Sedlmeir, Florian AU - Leuchs, Gerd AU - Kumari, Madhuri AU - Schwefel, Harald G.L. ID - 7233 SN - 9781557528209 T2 - Nonlinear Optics, OSA Technical Digest TI - Resonant electro-optic frequency comb generation in lithium niobate disk resonator inside a microwave cavity ER - TY - JOUR AB - For a general class of large non-Hermitian random block matrices X we prove that there are no eigenvalues away from a deterministic set with very high probability. This set is obtained from the Dyson equation of the Hermitization of X as the self-consistent approximation of the pseudospectrum. We demonstrate that the analysis of the matrix Dyson equation from (Probab. Theory Related Fields (2018)) offers a unified treatment of many structured matrix ensembles. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H AU - Nemish, Yuriy ID - 6240 IS - 2 JF - Annales de l'institut Henri Poincare SN - 0246-0203 TI - Location of the spectrum of Kronecker random matrices VL - 55 ER - TY - JOUR AB - Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established. AU - Andergassen, Daniel AU - Muckenhuber, Markus AU - Bammer, Philipp C. AU - Kulinski, Tomasz M. AU - Theussl, Hans-Christian AU - Shimizu, Takahiko AU - Penninger, Josef M. AU - Pauler, Florian AU - Hudson, Quanah J. ID - 7399 IS - 7 JF - PLoS Genetics SN - 1553-7404 TI - The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes VL - 15 ER - TY - JOUR AB - Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics. AU - Wang, Jilin W. J. L. AU - Lombardi, Fabrizio AU - Zhang, Xiyun AU - Anaclet, Christelle AU - Ivanov, Plamen Ch. ID - 7103 IS - 11 JF - PLoS Computational Biology SN - 1553-7358 TI - Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture VL - 15 ER - TY - CONF AB - Knowledge distillation, i.e. one classifier being trained on the outputs of another classifier, is an empirically very successful technique for knowledge transfer between classifiers. It has even been observed that classifiers learn much faster and more reliably if trained with the outputs of another classifier as soft labels, instead of from ground truth data. So far, however, there is no satisfactory theoretical explanation of this phenomenon. In this work, we provide the first insights into the working mechanisms of distillation by studying the special case of linear and deep linear classifiers. Specifically, we prove a generalization bound that establishes fast convergence of the expected risk of a distillation-trained linear classifier. From the bound and its proof we extract three keyfactors that determine the success of distillation: data geometry – geometric properties of the datadistribution, in particular class separation, has an immediate influence on the convergence speed of the risk; optimization bias– gradient descentoptimization finds a very favorable minimum of the distillation objective; and strong monotonicity– the expected risk of the student classifier always decreases when the size of the training set grows. AU - Bui Thi Mai, Phuong AU - Lampert, Christoph ID - 6569 T2 - Proceedings of the 36th International Conference on Machine Learning TI - Towards understanding knowledge distillation VL - 97 ER - TY - CONF AB - Modern machine learning methods often require more data for training than a single expert can provide. Therefore, it has become a standard procedure to collect data from external sources, e.g. via crowdsourcing. Unfortunately, the quality of these sources is not always guaranteed. As additional complications, the data might be stored in a distributed way, or might even have to remain private. In this work, we address the question of how to learn robustly in such scenarios. Studying the problem through the lens of statistical learning theory, we derive a procedure that allows for learning from all available sources, yet automatically suppresses irrelevant or corrupted data. We show by extensive experiments that our method provides significant improvements over alternative approaches from robust statistics and distributed optimization. AU - Konstantinov, Nikola H AU - Lampert, Christoph ID - 6590 T2 - Proceedings of the 36th International Conference on Machine Learning TI - Robust learning from untrusted sources VL - 97 ER - TY - JOUR AB - Plasmodesmata (PD) are plant-specific membrane-lined channels that create cytoplasmic and membrane continuities between adjacent cells, thereby facilitating cell–cell communication and virus movement. Plant cells have evolved diverse mechanisms to regulate PD plasticity in response to numerous environmental stimuli. In particular, during defense against plant pathogens, the defense hormone, salicylic acid (SA), plays a crucial role in the regulation of PD permeability in a callose-dependent manner. Here, we uncover a mechanism by which plants restrict the spreading of virus and PD cargoes using SA signaling by increasing lipid order and closure of PD. We showed that exogenous SA application triggered the compartmentalization of lipid raft nanodomains through a modulation of the lipid raft-regulatory protein, Remorin (REM). Genetic studies, superresolution imaging, and transmission electron microscopy observation together demonstrated that Arabidopsis REM1.2 and REM1.3 are crucial for plasma membrane nanodomain assembly to control PD aperture and functionality. In addition, we also found that a 14-3-3 epsilon protein modulates REM clustering and membrane nanodomain compartmentalization through its direct interaction with REM proteins. This study unveils a molecular mechanism by which the key plant defense hormone, SA, triggers membrane lipid nanodomain reorganization, thereby regulating PD closure to impede virus spreading. AU - Huang, D AU - Sun, Y AU - Ma, Z AU - Ke, M AU - Cui, Y AU - Chen, Z AU - Chen, C AU - Ji, C AU - Tran, TM AU - Yang, L AU - Lam, SM AU - Han, Y AU - Shu, G AU - Friml, Jiří AU - Miao, Y AU - Jiang, L AU - Chen, X ID - 6999 IS - 42 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 TI - Salicylic acid-mediated plasmodesmal closure via Remorin-dependent lipid organization VL - 116 ER - TY - JOUR AB - We read with great interest the recent work in PNAS by Bergero et al. (1) describing differences in male and female recombination patterns on the guppy (Poecilia reticulata) sex chromosome. We fully agree that recombination in males is largely confined to the ends of the sex chromosome. Bergero et al. interpret these results to suggest that our previous findings of population-level variation in the degree of sex chromosome differentiation in this species (2) are incorrect. However, we suggest that their results are entirely consistent with our previous report, and that their interpretation presents a false controversy. AU - Wright, Alison E. AU - Darolti, Iulia AU - Bloch, Natasha I. AU - Oostra, Vicencio AU - Sandkam, Benjamin A. AU - Buechel, Séverine D. AU - Kolm, Niclas AU - Breden, Felix AU - Vicoso, Beatriz AU - Mank, Judith E. ID - 6621 IS - 26 JF - Proceedings of the National Academy of Sciences of the United States of America TI - On the power to detect rare recombination events VL - 116 ER - TY - JOUR AB - Plant mating systems play a key role in structuring genetic variation both within and between species. In hybrid zones, the outcomes and dynamics of hybridization are usually interpreted as the balance between gene flow and selection against hybrids. Yet, mating systems can introduce selective forces that alter these expectations; with diverse outcomes for the level and direction of gene flow depending on variation in outcrossing and whether the mating systems of the species pair are the same or divergent. We present a survey of hybridization in 133 species pairs from 41 plant families and examine how patterns of hybridization vary with mating system. We examine if hybrid zone mode, level of gene flow, asymmetries in gene flow and the frequency of reproductive isolating barriers vary in relation to mating system/s of the species pair. We combine these results with a simulation model and examples from the literature to address two general themes: (i) the two‐way interaction between introgression and the evolution of reproductive systems, and (ii) how mating system can facilitate or restrict interspecific gene flow. We conclude that examining mating system with hybridization provides unique opportunities to understand divergence and the processes underlying reproductive isolation. AU - Pickup, Melinda AU - Barton, Nicholas H AU - Brandvain, Yaniv AU - Fraisse, Christelle AU - Yakimowski, Sarah AU - Dixit, Tanmay AU - Lexer, Christian AU - Cereghetti, Eva AU - Field, David ID - 6856 IS - 3 JF - New Phytologist SN - 0028-646X TI - Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow VL - 224 ER - TY - CONF AB - The Tverberg theorem is one of the cornerstones of discrete geometry. It states that, given a set X of at least (d+1)(r-1)+1 points in R^d, one can find a partition X=X_1 cup ... cup X_r of X, such that the convex hulls of the X_i, i=1,...,r, all share a common point. In this paper, we prove a strengthening of this theorem that guarantees a partition which, in addition to the above, has the property that the boundaries of full-dimensional convex hulls have pairwise nonempty intersections. Possible generalizations and algorithmic aspects are also discussed. As a concrete application, we show that any n points in the plane in general position span floor[n/3] vertex-disjoint triangles that are pairwise crossing, meaning that their boundaries have pairwise nonempty intersections; this number is clearly best possible. A previous result of Alvarez-Rebollar et al. guarantees floor[n/6] pairwise crossing triangles. Our result generalizes to a result about simplices in R^d,d >=2. AU - Fulek, Radoslav AU - Gärtner, Bernd AU - Kupavskii, Andrey AU - Valtr, Pavel AU - Wagner, Uli ID - 6647 SN - 1868-8969 T2 - 35th International Symposium on Computational Geometry TI - The crossing Tverberg theorem VL - 129 ER - TY - CONF AB - It is impossible to deterministically solve wait-free consensus in an asynchronous system. The classic proof uses a valency argument, which constructs an infinite execution by repeatedly extending a finite execution. We introduce extension-based proofs, a class of impossibility proofs that are modelled as an interaction between a prover and a protocol and that include valency arguments. Using proofs based on combinatorial topology, it has been shown that it is impossible to deterministically solve k-set agreement among n > k ≥ 2 processes in a wait-free manner. However, it was unknown whether proofs based on simpler techniques were possible. We show that this impossibility result cannot be obtained by an extension-based proof and, hence, extension-based proofs are limited in power. AU - Alistarh, Dan-Adrian AU - Aspnes, James AU - Ellen, Faith AU - Gelashvili, Rati AU - Zhu, Leqi ID - 6676 SN - 9781450367059 T2 - Proceedings of the 51st Annual ACM SIGACT Symposium on Theory of Computing TI - Why extension-based proofs fail ER - TY - GEN AB - The input to the token swapping problem is a graph with vertices v1, v2, . . . , vn, and n tokens with labels 1,2, . . . , n, one on each vertex. The goal is to get token i to vertex vi for all i= 1, . . . , n using a minimum number of swaps, where a swap exchanges the tokens on the endpoints of an edge.Token swapping on a tree, also known as “sorting with a transposition tree,” is not known to be in P nor NP-complete. We present some partial results: 1. An optimum swap sequence may need to perform a swap on a leaf vertex that has the correct token (a “happy leaf”), disproving a conjecture of Vaughan. 2. Any algorithm that fixes happy leaves—as all known approximation algorithms for the problem do—has approximation factor at least 4/3. Furthermore, the two best-known 2-approximation algorithms have approximation factor exactly 2. 3. A generalized problem—weighted coloured token swapping—is NP-complete on trees, but solvable in polynomial time on paths and stars. In this version, tokens and vertices have colours, and colours have weights. The goal is to get every token to a vertex of the same colour, and the cost of a swap is the sum of the weights of the two tokens involved. AU - Biniaz, Ahmad AU - Jain, Kshitij AU - Lubiw, Anna AU - Masárová, Zuzana AU - Miltzow, Tillmann AU - Mondal, Debajyoti AU - Naredla, Anurag Murty AU - Tkadlec, Josef AU - Turcotte, Alexi ID - 7950 T2 - arXiv TI - Token swapping on trees ER - TY - JOUR AB - Males and females of Artemia franciscana, a crustacean commonly used in the aquarium trade, are highly dimorphic. Sex is determined by a pair of ZW chromosomes, but the nature and extent of differentiation of these chromosomes is unknown. Here, we characterize the Z chromosome by detecting genomic regions that show lower genomic coverage in female than in male samples, and regions that harbor an excess of female-specific SNPs. We detect many Z-specific genes, which no longer have homologs on the W, but also Z-linked genes that appear to have diverged very recently from their existing W-linked homolog. We assess patterns of male and female expression in two tissues with extensive morphological dimorphism, gonads, and heads. In agreement with their morphology, sex-biased expression is common in both tissues. Interestingly, the Z chromosome is not enriched for sex-biased genes, and seems to in fact have a mechanism of dosage compensation that leads to equal expression in males and in females. Both of these patterns are contrary to most ZW systems studied so far, making A. franciscana an excellent model for investigating the interplay between the evolution of sexual dimorphism and dosage compensation, as well as Z chromosome evolution in general. AU - Huylmans, Ann K AU - Toups, Melissa A AU - Macon, Ariana AU - Gammerdinger, William J AU - Vicoso, Beatriz ID - 6418 IS - 4 JF - Genome biology and evolution TI - Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome VL - 11 ER - TY - DATA AB - Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature. AU - Tomanek, Isabella ID - 7016 KW - Escherichia coli KW - gene amplification KW - galactose KW - DOG KW - experimental evolution KW - Illumina sequence data KW - FACS data KW - microfluidics data TI - Data for the paper "Gene amplification as a form of population-level gene expression regulation" ER - TY - DATA AU - Guseinov, Ruslan ID - 7154 TI - Supplementary data for "Programming temporal morphing of self-actuated shells" ER - TY - DATA AU - Vicoso, Beatriz ID - 6060 TI - Supplementary data for "Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome" (Huylman, Toups et al., 2019). ER - TY - DATA AB - This dataset contains the supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition". The contained files have the following content: 'Supplementary Figures.pdf' Additional figures (as referenced in the paper). 'Supplementary Table 1. Statistics.xlsx' Details on statistical tests performed in the paper. 'Supplementary Table 2. Differentially expressed gene analysis.xlsx' Results for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples. 'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx' Results for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down). 'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx' Results for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant. 'Supplementary Table 5. Cluster identification.xlsx' Results for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories). 'Supplementary Table 6. GO term cluster analysis.xlsx' Results for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1). 'Supplementary Table 7. Setd5 mass spectrometry results.xlsx' Results showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma. 'Supplementary Table 8. PolII ChIP-seq analysis.xlsx' Results for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS. AU - Dotter, Christoph AU - Novarino, Gaia ID - 6074 TI - Supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition" ER - TY - DATA AB - Open the files in Jupyter Notebook (reccomended https://www.anaconda.com/distribution/#download-section with Python 3.7). AU - Nardin, Michele ID - 6062 TI - Supplementary Code and Data for the paper "The Entorhinal Cognitive Map is Attracted to Goals" ER - TY - JOUR AB - Pleiotropy is the well-established idea that a single mutation affects multiple phenotypes. If a mutation has opposite effects on fitness when expressed in different contexts, then genetic conflict arises. Pleiotropic conflict is expected to reduce the efficacy of selection by limiting the fixation of beneficial mutations through adaptation, and the removal of deleterious mutations through purifying selection. Although this has been widely discussed, in particular in the context of a putative “gender load,” it has yet to be systematically quantified. In this work, we empirically estimate to which extent different pleiotropic regimes impede the efficacy of selection in Drosophila melanogaster. We use whole-genome polymorphism data from a single African population and divergence data from D. simulans to estimate the fraction of adaptive fixations (α), the rate of adaptation (ωA), and the direction of selection (DoS). After controlling for confounding covariates, we find that the different pleiotropic regimes have a relatively small, but significant, effect on selection efficacy. Specifically, our results suggest that pleiotropic sexual antagonism may restrict the efficacy of selection, but that this conflict can be resolved by limiting the expression of genes to the sex where they are beneficial. Intermediate levels of pleiotropy across tissues and life stages can also lead to maladaptation in D. melanogaster, due to inefficient purifying selection combined with low frequency of mutations that confer a selective advantage. Thus, our study highlights the need to consider the efficacy of selection in the context of antagonistic pleiotropy, and of genetic conflict in general. AU - Fraisse, Christelle AU - Puixeu Sala, Gemma AU - Vicoso, Beatriz ID - 6089 IS - 3 JF - Molecular biology and evolution SN - 0737-4038 TI - Pleiotropy modulates the efficacy of selection in drosophila melanogaster VL - 36 ER - TY - THES AB - In the first part of this thesis we consider large random matrices with arbitrary expectation and a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent in the bulk and edge regime. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion. In the second part we consider Wigner-type matrices and show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are uni- versal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner- Dyson-Mehta universality conjecture for the last remaining universality type. Our analysis holds not only for exact cusps, but approximate cusps as well, where an ex- tended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp, and extend the fast relaxation to equilibrium of the Dyson Brow- nian motion to the cusp regime. In the third and final part we explore the entrywise linear statistics of Wigner ma- trices and identify the fluctuations for a large class of test functions with little regularity. This enables us to study the rectangular Young diagram obtained from the interlacing eigenvalues of the random matrix and its minor, and we find that, despite having the same limit, the fluctuations differ from those of the algebraic Young tableaux equipped with the Plancharel measure. AU - Schröder, Dominik J ID - 6179 SN - 2663-337X TI - From Dyson to Pearcey: Universal statistics in random matrix theory ER - TY - CONF AB - Computer vision systems for automatic image categorization have become accurate and reliable enough that they can run continuously for days or even years as components of real-world commercial applications. A major open problem in this context, however, is quality control. Good classification performance can only be expected if systems run under the specific conditions, in particular data distributions, that they were trained for. Surprisingly, none of the currently used deep network architectures have a built-in functionality that could detect if a network operates on data from a distribution it was not trained for, such that potentially a warning to the human users could be triggered. In this work, we describe KS(conf), a procedure for detecting such outside of specifications (out-of-specs) operation, based on statistical testing of the network outputs. We show by extensive experiments using the ImageNet, AwA2 and DAVIS datasets on a variety of ConvNets architectures that KS(conf) reliably detects out-of-specs situations. It furthermore has a number of properties that make it a promising candidate for practical deployment: it is easy to implement, adds almost no overhead to the system, works with all networks, including pretrained ones, and requires no a priori knowledge of how the data distribution could change. AU - Sun, Rémy AU - Lampert, Christoph ID - 6482 SN - 0302-9743 TI - KS(conf): A light-weight test if a ConvNet operates outside of Its specifications VL - 11269 ER - TY - CONF AB - We present a thermodynamically based approach to the design of models for viscoelastic fluids with stress diffusion effect. In particular, we show how to add a stress diffusion term to some standard viscoelastic rate-type models (Giesekus, FENE-P, Johnson–Segalman, Phan-Thien–Tanner and Bautista–Manero–Puig) so that the resulting models with the added stress diffusion term are thermodynamically consistent in the sense that they obey the first and the second law of thermodynamics. We point out the potential applications of the provided thermodynamical background in the study of flows of fluids described by the proposed models. AU - Dostalík, Mark AU - Pruša, Vít AU - Skrivan, Tomas ID - 6642 T2 - AIP Conference Proceedings TI - On diffusive variants of some classical viscoelastic rate-type models VL - 2107 ER - TY - JOUR AU - Jaksic, Vojkan AU - Seiringer, Robert ID - 7226 IS - 12 JF - Journal of Mathematical Physics SN - 00222488 TI - Introduction to the Special Collection: International Congress on Mathematical Physics (ICMP) 2018 VL - 60 ER - TY - JOUR AB - We investigate the ground-state energy of a one-dimensional Fermi gas with two bosonic impurities. We consider spinless fermions with no fermion-fermion interactions. The fermion-impurity and impurity-impurity interactions are modeled with Dirac delta functions. First, we study the case where impurity and fermion have equal masses, and the impurity-impurity two-body interaction is identical to the fermion-impurity interaction, such that the system is solvable with the Bethe ansatz. For attractive interactions, we find that the energy of the impurity-impurity subsystem is below the energy of the bound state that exists without the Fermi gas. We interpret this as a manifestation of attractive boson-boson interactions induced by the fermionic medium, and refer to the impurity-impurity subsystem as an in-medium bound state. For repulsive interactions, we find no in-medium bound states. Second, we construct an effective model to describe these interactions, and compare its predictions to the exact solution. We use this effective model to study nonintegrable systems with unequal masses and/or potentials. We discuss parameter regimes for which impurity-impurity attraction induced by the Fermi gas can lead to the formation of in-medium bound states made of bosons that repel each other in the absence of the Fermi gas. AU - Huber, D. AU - Hammer, H.-W. AU - Volosniev, Artem ID - 7190 IS - 3 JF - Physical Review Research SN - 2643-1564 TI - In-medium bound states of two bosonic impurities in a one-dimensional Fermi gas VL - 1 ER - TY - JOUR AB - Motivated by recent experimental observations of coherent many-body revivals in a constrained Rydbergatom chain, we construct a weak quasilocal deformation of the Rydberg-blockaded Hamiltonian, whichmakes the revivals virtually perfect. Our analysis suggests the existence of an underlying nonintegrableHamiltonian which supports an emergent SU(2)-spin dynamics within a small subspace of the many-bodyHilbert space. We show that such perfect dynamics necessitates the existence of atypical, nonergodicenergy eigenstates—quantum many-body scars. Furthermore, using these insights, we construct a toymodel that hosts exact quantum many-body scars, providing an intuitive explanation of their origin. Ourresults offer specific routes to enhancing coherent many-body revivals and provide a step towardestablishing the stability of quantum many-body scars in the thermodynamic limit. AU - Choi, Soonwon AU - Turner, Christopher J. AU - Pichler, Hannes AU - Ho, Wen Wei AU - Michailidis, Alexios AU - Papić, Zlatko AU - Serbyn, Maksym AU - Lukin, Mikhail D. AU - Abanin, Dmitry A. ID - 6575 IS - 22 JF - Physical Review Letters SN - 00319007 TI - Emergent SU(2) dynamics and perfect quantum many-body scars VL - 122 ER - TY - JOUR AB - In 1915, Einstein and de Haas and Barnett demonstrated that changing the magnetization of a magnetic material results in mechanical rotation and vice versa. At the microscopic level, this effect governs the transfer between electron spin and orbital angular momentum, and lattice degrees of freedom, understanding which is key for molecular magnets, nano-magneto-mechanics, spintronics, and ultrafast magnetism. Until now, the timescales of electron-to-lattice angular momentum transfer remain unclear, since modeling this process on a microscopic level requires the addition of an infinite amount of quantum angular momenta. We show that this problem can be solved by reformulating it in terms of the recently discovered angulon quasiparticles, which results in a rotationally invariant quantum many-body theory. In particular, we demonstrate that nonperturbative effects take place even if the electron-phonon coupling is weak and give rise to angular momentum transfer on femtosecond timescales. AU - Mentink, Johann H AU - Katsnelson, Mikhail AU - Lemeshko, Mikhail ID - 6092 IS - 6 JF - Physical Review B TI - Quantum many-body dynamics of the Einstein-de Haas effect VL - 99 ER - TY - JOUR AB - Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems, leading to crosstalk between ligand-receptor pairs. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of noncognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the noncognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing. AU - Carballo-Pacheco, Martín AU - Desponds, Jonathan AU - Gavrilchenko, Tatyana AU - Mayer, Andreas AU - Prizak, Roshan AU - Reddy, Gautam AU - Nemenman, Ilya AU - Mora, Thierry ID - 6090 IS - 2 JF - Physical Review E TI - Receptor crosstalk improves concentration sensing of multiple ligands VL - 99 ER - TY - JOUR AB - Dipolar coupling plays a fundamental role in the interaction between electrically or magnetically polarized species such as magnetic atoms and dipolar molecules in a gas or dipolar excitons in the solid state. Unlike Coulomb or contactlike interactions found in many atomic, molecular, and condensed-matter systems, this interaction is long-ranged and highly anisotropic, as it changes from repulsive to attractive depending on the relative positions and orientation of the dipoles. Because of this unique property, many exotic, symmetry-breaking collective states have been recently predicted for cold dipolar gases, but only a few have been experimentally detected and only in dilute atomic dipolar Bose-Einstein condensates. Here, we report on the first observation of attractive dipolar coupling between excitonic dipoles using a new design of stacked semiconductor bilayers. We show that the presence of a dipolar exciton fluid in one bilayer modifies the spatial distribution and increases the binding energy of excitonic dipoles in a vertically remote layer. The binding energy changes are explained using a many-body polaron model describing the deformation of the exciton cloud due to its interaction with a remote dipolar exciton. The surprising nonmonotonic dependence on the cloud density indicates the important role of dipolar correlations, which is unique to dense, strongly interacting dipolar solid-state systems. Our concept provides a route for the realization of dipolar lattices with strong anisotropic interactions in semiconductor systems, which open the way for the observation of theoretically predicted new and exotic collective phases, as well as for engineering and sensing their collective excitations. AU - Hubert, Colin AU - Baruchi, Yifat AU - Mazuz-Harpaz, Yotam AU - Cohen, Kobi AU - Biermann, Klaus AU - Lemeshko, Mikhail AU - West, Ken AU - Pfeiffer, Loren AU - Rapaport, Ronen AU - Santos, Paulo ID - 6786 IS - 2 JF - Physical Review X TI - Attractive dipolar coupling between stacked exciton fluids VL - 9 ER - TY - JOUR AB - Chains of superconducting circuit devices provide a natural platform for studies of synthetic bosonic quantum matter. Motivated by the recent experimental progress in realizing disordered and interacting chains of superconducting transmon devices, we study the bosonic many-body localization phase transition using the methods of exact diagonalization as well as matrix product state dynamics. We estimate the location of transition separating the ergodic and the many-body localized phases as a function of the disorder strength and the many-body on-site interaction strength. The main difference between the bosonic model realized by superconducting circuits and similar fermionic model is that the effect of the on-site interaction is stronger due to the possibility of multiple excitations occupying the same site. The phase transition is found to be robust upon including longer-range hopping and interaction terms present in the experiments. Furthermore, we calculate experimentally relevant local observables and show that their temporal fluctuations can be used to distinguish between the dynamics of Anderson insulator, many-body localization, and delocalized phases. While we consider unitary dynamics, neglecting the effects of dissipation, decoherence, and measurement back action, the timescales on which the dynamics is unitary are sufficient for observation of characteristic dynamics in the many-body localized phase. Moreover, the experimentally available disorder strength and interactions allow for tuning the many-body localization phase transition, thus making the arrays of superconducting circuit devices a promising platform for exploring localization physics and phase transition. AU - Orell, Tuure AU - Michailidis, Alexios AU - Serbyn, Maksym AU - Silveri, Matti ID - 7013 IS - 13 JF - Physical Review B SN - 2469-9950 TI - Probing the many-body localization phase transition with superconducting circuits VL - 100 ER - TY - JOUR AB - Recent scanning tunneling microscopy experiments in NbN thin disordered superconducting films found an emergent inhomogeneity at the scale of tens of nanometers. This inhomogeneity is mirrored by an apparent dimensional crossover in the paraconductivity measured in transport above the superconducting critical temperature Tc. This behavior was interpreted in terms of an anomalous diffusion of fluctuating Cooper pairs that display a quasiconfinement (i.e., a slowing down of their diffusive dynamics) on length scales shorter than the inhomogeneity identified by tunneling experiments. Here, we assume this anomalous diffusive behavior of fluctuating Cooper pairs and calculate the effect of these fluctuations on the electron density of states above Tc. We find that the density of states is substantially suppressed up to temperatures well above Tc. This behavior, which is closely reminiscent of a pseudogap, only arises from the anomalous diffusion of fluctuating Cooper pairs in the absence of stable preformed pairs, setting the stage for an intermediate behavior between the two common paradigms in the superconducting-insulator transition, namely, the localization of Cooper pairs (the so-called bosonic scenario) and the breaking of Cooper pairs into unpaired electrons due to strong disorder (the so-called fermionic scenario). AU - Brighi, Pietro AU - Grilli, Marco AU - Leridon, Brigitte AU - Caprara, Sergio ID - 7200 IS - 17 JF - Physical Review B SN - 2469-9950 TI - Effect of anomalous diffusion of fluctuating Cooper pairs on the density of states of superconducting NbN thin films VL - 100 ER - TY - JOUR AB - Recent studies suggest that unstable recurrent solutions of the Navier-Stokes equation provide new insights into dynamics of turbulent flows. In this study, we compute an extensive network of dynamical connections between such solutions in a weakly turbulent quasi-two-dimensional Kolmogorov flow that lies in the inversion symmetric subspace. In particular, we find numerous isolated heteroclinic connections between different types of solutions—equilibria, periodic, and quasiperiodic orbits—as well as continua of connections forming higher-dimensional connecting manifolds. We also compute a homoclinic connection of a periodic orbit and provide strong evidence that the associated homoclinic tangle forms the chaotic repeller that underpins transient turbulence in the symmetric subspace. AU - Suri, Balachandra AU - Pallantla, Ravi Kumar AU - Schatz, Michael F. AU - Grigoriev, Roman O. ID - 6779 IS - 1 JF - Physical Review E SN - 2470-0045 TI - Heteroclinic and homoclinic connections in a Kolmogorov-like flow VL - 100 ER - TY - JOUR AB - We modify the "floating crystal" trial state for the classical homogeneous electron gas (also known as jellium), in order to suppress the boundary charge fluctuations that are known to lead to a macroscopic increase of the energy. The argument is to melt a thin layer of the crystal close to the boundary and consequently replace it by an incompressible fluid. With the aid of this trial state we show that three different definitions of the ground-state energy of jellium coincide. In the first point of view the electrons are placed in a neutralizing uniform background. In the second definition there is no background but the electrons are submitted to the constraint that their density is constant, as is appropriate in density functional theory. Finally, in the third system each electron interacts with a periodic image of itself; that is, periodic boundary conditions are imposed on the interaction potential. AU - Lewin, Mathieu AU - Lieb, Elliott H. AU - Seiringer, Robert ID - 7015 IS - 3 JF - Physical Review B SN - 2469-9950 TI - Floating Wigner crystal with no boundary charge fluctuations VL - 100 ER - TY - JOUR AB - End-to-end correlated bound states are investigated in superconductor-semiconductor hybrid nanowires at zero magnetic field. Peaks in subgap conductance are independently identified from each wire end, and a cross-correlation function is computed that counts end-to-end coincidences, averaging over thousands of subgap features. Strong correlations in a short, 300-nm device are reduced by a factor of 4 in a long, 900-nm device. In addition, subgap conductance distributions are investigated, and correlations between the left and right distributions are identified based on their mutual information. AU - Anselmetti, G. L. R. AU - Martinez, E. A. AU - Ménard, G. C. AU - Puglia, D. AU - Malinowski, F. K. AU - Lee, J. S. AU - Choi, S. AU - Pendharkar, M. AU - Palmstrøm, C. J. AU - Marcus, C. M. AU - Casparis, L. AU - Higginbotham, Andrew P ID - 7145 IS - 20 JF - Physical Review B SN - 2469-9950 TI - End-to-end correlated subgap states in hybrid nanowires VL - 100 ER - TY - JOUR AB - We introduce a simple, exactly solvable strong-randomness renormalization group (RG) model for the many-body localization (MBL) transition in one dimension. Our approach relies on a family of RG flows parametrized by the asymmetry between thermal and localized phases. We identify the physical MBL transition in the limit of maximal asymmetry, reflecting the instability of MBL against rare thermal inclusions. We find a critical point that is localized with power-law distributed thermal inclusions. The typical size of critical inclusions remains finite at the transition, while the average size is logarithmically diverging. We propose a two-parameter scaling theory for the many-body localization transition that falls into the Kosterlitz-Thouless universality class, with the MBL phase corresponding to a stable line of fixed points with multifractal behavior. AU - Goremykina, Anna AU - Vasseur, Romain AU - Serbyn, Maksym ID - 5906 IS - 4 JF - Physical Review Letters SN - 0031-9007 TI - Analytically solvable renormalization group for the many-body localization transition VL - 122 ER - TY - JOUR AB - We consider a two-component Bose gas in two dimensions at a low temperature with short-range repulsive interaction. In the coexistence phase where both components are superfluid, interspecies interactions induce a nondissipative drag between the two superfluid flows (Andreev-Bashkin effect). We show that this behavior leads to a modification of the usual Berezinskii-Kosterlitz-Thouless (BKT) transition in two dimensions. We extend the renormalization of the superfluid densities at finite temperature using the renormalization-group approach and find that the vortices of one component have a large influence on the superfluid properties of the other, mediated by the nondissipative drag. The extended BKT flow equations indicate that the occurrence of the vortex unbinding transition in one of the components can induce the breakdown of superfluidity also in the other, leading to a locking phenomenon for the critical temperatures of the two gases. AU - Karle, Volker AU - Defenu, Nicolò AU - Enss, Tilman ID - 6632 IS - 6 JF - Physical Review A SN - 24699926 TI - Coupled superfluidity of binary Bose mixtures in two dimensions VL - 99 ER - TY - JOUR AB - The angular momentum of molecules, or, equivalently, their rotation in three-dimensional space, is ideally suited for quantum control. Molecular angular momentum is naturally quantized, time evolution is governed by a well-known Hamiltonian with only a few accurately known parameters, and transitions between rotational levels can be driven by external fields from various parts of the electromagnetic spectrum. Control over the rotational motion can be exerted in one-, two-, and many-body scenarios, thereby allowing one to probe Anderson localization, target stereoselectivity of bimolecular reactions, or encode quantum information to name just a few examples. The corresponding approaches to quantum control are pursued within separate, and typically disjoint, subfields of physics, including ultrafast science, cold collisions, ultracold gases, quantum information science, and condensed-matter physics. It is the purpose of this review to present the various control phenomena, which all rely on the same underlying physics, within a unified framework. To this end, recall the Hamiltonian for free rotations, assuming the rigid rotor approximation to be valid, and summarize the different ways for a rotor to interact with external electromagnetic fields. These interactions can be exploited for control—from achieving alignment, orientation, or laser cooling in a one-body framework, steering bimolecular collisions, or realizing a quantum computer or quantum simulator in the many-body setting. AU - Koch, Christiane P. AU - Lemeshko, Mikhail AU - Sugny, Dominique ID - 7396 IS - 3 JF - Reviews of Modern Physics SN - 0034-6861 TI - Quantum control of molecular rotation VL - 91 ER - TY - CONF AB - We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound. AU - Hledik, Michal AU - Sokolowski, Thomas R AU - Tkačik, Gašper ID - 7606 SN - 9781538669006 T2 - IEEE Information Theory Workshop, ITW 2019 TI - A tight upper bound on mutual information ER - TY - CONF AB - We design fast deterministic algorithms for distance computation in the CONGESTED CLIQUE model. Our key contributions include: - A (2+ε)-approximation for all-pairs shortest paths problem in O(log²n / ε) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model. - A (1+ε)-approximation for multi-source shortest paths problem from O(√n) sources in O(log² n / ε) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size. Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in Õ(n^{1/6}) rounds. AU - Censor-Hillel, Keren AU - Dory, Michal AU - Korhonen, Janne AU - Leitersdorf, Dean ID - 6933 SN - 9781450362177 T2 - Proceedings of the 2019 ACM Symposium on Principles of Distributed Computin TI - Fast approximate shortest paths in the congested clique ER - TY - THES AB - Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ cells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are in charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units (i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''. Social immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social immunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop the collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of social immune responses have been dissected, but many more questions remain open. I present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals carrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate. The second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive and challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation. In addition to the two experimental chapters, this thesis includes a co-authored published review on organisational immunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built, identify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in two collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant behaviour. AU - Casillas Perez, Barbara E ID - 6435 KW - Social Immunity KW - Sanitary care KW - Social Insects KW - Organisational Immunity KW - Colony development KW - Multi-target tracking SN - 2663-337X TI - Collective defenses of garden ants against a fungal pathogen ER - TY - THES AB - Clathrin-Mediated Endocytosis (CME) is an aspect of cellular trafficking that is constantly regulated for mediating developmental and physiological responses. The main aim of my thesis is to decipher the basic mechanisms of CME and post-endocytic trafficking in the whole multicellular organ systems of Arabidopsis. The first chapter of my thesis describes the search for new components involved in CME. Tandem affinity purification was conducted using CLC and its interacting partners were identified. Amongst the identified proteins were the Auxilin-likes1 and 2 (Axl1/2), putative uncoating factors, for which we made a full functional analysis. Over-expression of Axl1/2 causes extreme modifications in the dynamics of the machinery proteins and inhibition of endocytosis altogether. However the loss of function of the axl1/2 did not present any cellular or physiological phenotype, meaning Auxilin-likes do not form the major uncoating machinery. The second chapter of my thesis describes the establishment/utilisation of techniques to capture the dynamicity and the complexity of CME and post-endocytic trafficking. We have studied the development of endocytic pits at the PM – specifically, the mode of membrane remodeling during pit development and the role of actin in it, given plant cells possess high turgor pressure. Utilizing the improved z-resolution of TIRF and VAEM techniques, we captured the time-lapse of the endocytic events at the plasma membrane; and using particle detection software, we quantitatively analysed all the endocytic trajectories in an unbiased way to obtain the endocytic rate of the system. This together with the direct analysis of cargo internalisation from the PM provided an estimate on the endocytic potential of the cell. We also developed a methodology for ultrastructural analysis of different populations of Clathrin-Coated Structures (CCSs) in both PM and endomembranes in unroofed protoplasts. Structural analysis, together with the intensity profile of CCSs at the PM show that the mode of CCP development at the PM follows ‘Constant curvature model’; meaning that clathrin polymerisation energy is a major contributing factor of membrane remodeling. In addition, other analyses clearly show that actin is not required for membrane remodeling during invagination or any other step of CCP development, despite the prevalent high turgor pressure. However, actin is essential in orchestrating the post-endocytic trafficking of CCVs facilitating the EE formation. We also observed that the uncoating process post-endocytosis is not immediate; an alternative mechanism of uncoating – Sequential multi-step process – functions in the cell. Finally we also looked at one of the important physiological stimuli modulating the process – hormone, auxin. auxin has been known to influence CME before. We have made a detailed study on the concentration-time based effect of auxin on the machinery proteins, CCP development, and the specificity of cargoes endocytosed. To this end, we saw no general effect of auxin on CME at earlier time points. However, very low concentration of IAA, such as 50nM, accelerates endocytosis of specifically PIN2 through CME. Such a tight regulatory control with high specificity to PIN2 could be essential in modulating its polarity. AU - Narasimhan, Madhumitha ID - 6269 SN - 2663-337X TI - Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants ER - TY - GEN AU - Kim, Olena AU - Borges Merjane, Carolina AU - Jonas, Peter M ID - 11222 IS - Suppl. 1 KW - hippocampus KW - mossy fibers KW - readily releasable pool KW - electron microscopy SN - 2309-8503 T2 - Intrinsic Activity TI - Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy VL - 7 ER - TY - THES AB - Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues. AU - Assen, Frank P ID - 6947 SN - 2663-337X TI - Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking ER - TY - THES AB - Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. AU - Rangel Guerrero, Dámaris K ID - 6849 SN - 2663-337X TI - The role of CCK-interneurons in regulating hippocampal network dynamics ER - TY - JOUR AB - A process of restorative patterning in plant roots correctly replaces eliminated cells to heal local injuries despite the absence of cell migration, which underpins wound healing in animals. Patterning in plants relies on oriented cell divisions and acquisition of specific cell identities. Plants regularly endure wounds caused by abiotic or biotic environmental stimuli and have developed extraordinary abilities to restore their tissues after injuries. Here, we provide insight into a mechanism of restorative patterning that repairs tissues after wounding. Laser-assisted elimination of different cells in Arabidopsis root combined with live-imaging tracking during vertical growth allowed analysis of the regeneration processes in vivo. Specifically, the cells adjacent to the inner side of the injury re-activated their stem cell transcriptional programs. They accelerated their progression through cell cycle, coordinately changed the cell division orientation, and ultimately acquired de novo the correct cell fates to replace missing cells. These observations highlight existence of unknown intercellular positional signaling and demonstrate the capability of specified cells to re-acquire stem cell programs as a crucial part of the plant-specific mechanism of wound healing. AU - Marhavá, Petra AU - Hörmayer, Lukas AU - Yoshida, Saiko AU - Marhavy, Peter AU - Benková, Eva AU - Friml, Jiří ID - 6351 IS - 4 JF - Cell SN - 00928674 TI - Re-activation of stem cell pathways for pattern restoration in plant wound healing VL - 177 ER - TY - JOUR AB - Plants as sessile organisms are constantly under attack by herbivores, rough environmental situations, or mechanical pressure. These challenges often lead to the induction of wounds or destruction of already specified and developed tissues. Additionally, wounding makes plants vulnerable to invasion by pathogens, which is why wound signalling often triggers specific defence responses. To stay competitive or, eventually, survive under these circumstances, plants need to regenerate efficiently, which in rigid, tissue migration-incompatible plant tissues requires post-embryonic patterning and organogenesis. Now, several studies used laser-assisted single cell ablation in the Arabidopsis root tip as a minimal wounding proxy. Here, we discuss their findings and put them into context of a broader spectrum of wound signalling, pathogen responses and tissue as well as organ regeneration. AU - Hörmayer, Lukas AU - Friml, Jiří ID - 6943 JF - Current Opinion in Plant Biology SN - 1369-5266 TI - Targeted cell ablation-based insights into wound healing and restorative patterning VL - 52 ER - TY - JOUR AB - Electron microscopy (EM) is a technology that enables visualization of single proteins at a nanometer resolution. However, current protein analysis by EM mainly relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised by large size of antibody, precluding precise detection of protein location in biological samples. Here, we develop a specific chemical labeling method for EM detection of proteins at single-molecular level. Rational design of α-helical peptide tag and probe structure provided a complementary reaction pair that enabled specific cysteine conjugation of the tag. The developed chemical labeling with gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency and detectability of high-density clusters of tag-fused G protein-coupled receptors in freeze-fracture replicas compared with immunogold labeling. Furthermore, in ultrathin sections, the spatial resolution of the chemical labeling was significantly higher than that of antibody-mediated labeling. These results demonstrate substantial advantages of the chemical labeling approach for single protein visualization by EM. AU - Tabata, Shigekazu AU - Jevtic, Marijo AU - Kurashige, Nobutaka AU - Fuchida, Hirokazu AU - Kido, Munetsugu AU - Tani, Kazushi AU - Zenmyo, Naoki AU - Uchinomiya, Shohei AU - Harada, Harumi AU - Itakura, Makoto AU - Hamachi, Itaru AU - Shigemoto, Ryuichi AU - Ojida, Akio ID - 7391 IS - 12 JF - iScience SN - 2589-0042 TI - Electron microscopic detection of single membrane proteins by a specific chemical labeling VL - 22 ER - TY - JOUR AB - Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9. AU - Kampjut, Domen AU - Sazanov, Leonid A ID - 6848 IS - 7773 JF - Nature SN - 0028-0836 TI - Structure and mechanism of mitochondrial proton-translocating transhydrogenase VL - 573 ER - TY - JOUR AB - Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space. AU - Boccara, Charlotte N. AU - Nardin, Michele AU - Stella, Federico AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 6194 IS - 6434 JF - Science SN - 0036-8075 TI - The entorhinal cognitive map is attracted to goals VL - 363 ER - TY - THES AB - A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta. Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing. AU - Mckenzie, Catherine ID - 7132 SN - 2663-337X TI - Design and characterization of methods and biological components to realize synthetic neurotransmission ER - TY - JOUR AB - Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms. AU - Käfer, Karola AU - Malagon-Vina, Hugo AU - Dickerson, Desiree AU - O'Neill, Joseph AU - Trossbach, Svenja V. AU - Korth, Carsten AU - Csicsvari, Jozsef L ID - 5949 IS - 9 JF - Hippocampus TI - Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization VL - 29 ER - TY - THES AB - The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions. With tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay. We found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by maze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between cell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC trajectory-replay at the goal positively correlated with rule-switching performance. Finally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. AU - Käfer, Karola ID - 6825 SN - 2663-337X TI - The hippocampus and medial prefrontal cortex during flexible behavior ER -