TY - GEN AB - Implementation of the inference method in Matlab, including three applications of the method: The first one for the model of ant motion, the second one for bacterial chemotaxis, and the third one for the motion of fish. AU - Bod’Ová, Katarína AU - Mitchell, Gabriel AU - Harpaz, Roy AU - Schneidman, Elad AU - Tkačik, Gašper ID - 9831 TI - Implementation of the inference method in Matlab ER - TY - CONF AB - We address the problem of analyzing the reachable set of a polynomial nonlinear continuous system by over-approximating the flowpipe of its dynamics. The common approach to tackle this problem is to perform a numerical integration over a given time horizon based on Taylor expansion and interval arithmetic. However, this method results to be very conservative when there is a large difference in speed between trajectories as time progresses. In this paper, we propose to use combinations of barrier functions, which we call piecewise barrier tube (PBT), to over-approximate flowpipe. The basic idea of PBT is that for each segment of a flowpipe, a coarse box which is big enough to contain the segment is constructed using sampled simulation and then in the box we compute by linear programming a set of barrier functions (called barrier tube or BT for short) which work together to form a tube surrounding the flowpipe. The benefit of using PBT is that (1) BT is independent of time and hence can avoid being stretched and deformed by time; and (2) a small number of BTs can form a tight over-approximation for the flowpipe, which means that the computation required to decide whether the BTs intersect the unsafe set can be reduced significantly. We implemented a prototype called PBTS in C++. Experiments on some benchmark systems show that our approach is effective. AU - Kong, Hui AU - Bartocci, Ezio AU - Henzinger, Thomas A ID - 142 TI - Reachable set over-approximation for nonlinear systems using piecewise barrier tubes VL - 10981 ER - TY - JOUR AB - We investigate the quantum interference induced shifts between energetically close states in highly charged ions, with the energy structure being observed by laser spectroscopy. In this work, we focus on hyperfine states of lithiumlike heavy-Z isotopes and quantify how much quantum interference changes the observed transition frequencies. The process of photon excitation and subsequent photon decay for the transition 2s→2p→2s is implemented with fully relativistic and full-multipole frameworks, which are relevant for such relativistic atomic systems. We consider the isotopes Pb79+207 and Bi80+209 due to experimental interest, as well as other examples of isotopes with lower Z, namely Pr56+141 and Ho64+165. We conclude that quantum interference can induce shifts up to 11% of the linewidth in the measurable resonances of the considered isotopes, if interference between resonances is neglected. The inclusion of relativity decreases the cross section by 35%, mainly due to the complete retardation form of the electric dipole multipole. However, the contribution of the next higher multipoles (e.g., magnetic quadrupole) to the cross section is negligible. This makes the contribution of relativity and higher-order multipoles to the quantum interference induced shifts a minor effect, even for heavy-Z elements. AU - Amaro, Pedro AU - Loureiro, Ulisses AU - Safari, Laleh AU - Fratini, Filippo AU - Indelicato, Paul AU - Stöhlker, Thomas AU - Santos, José ID - 427 IS - 2 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Quantum interference in laser spectroscopy of highly charged lithiumlike ions VL - 97 ER - TY - CONF AB - We present an efficient algorithm for a problem in the interface between clustering and graph embeddings. An embedding ' : G ! M of a graph G into a 2manifold 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 a common node or arc, due to data compression or low resolution. This raises the computational problem of deciding whether a given map ' : G ! M comes from an embedding. A map ' : G ! M is a weak embedding if it can be perturbed into an embedding ψ: G ! M with k' "k < " for every " > 0. A polynomial-time algorithm for recognizing weak embeddings was recently found by Fulek and Kyncl [14], which reduces to solving a system of linear equations over Z2. It runs in O(n2!) O(n4:75) time, where 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 than [14]: We perform a sequence of local operations that gradually "untangles" the image '(G) into an embedding (G), or reports that ' is not a weak embedding. It generalizes a recent technique developed for the case that G is a cycle and the embedding is a simple polygon [1], and 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 - 309 TI - Recognizing weak embeddings of graphs ER - TY - JOUR AB - We present an approach to interacting quantum many-body systems based on the notion of quantum groups, also known as q-deformed Lie algebras. In particular, we show that, if the symmetry of a free quantum particle corresponds to a Lie group G, in the presence of a many-body environment this particle can be described by a deformed group, Gq. Crucially, the single deformation parameter, q, contains all the information about the many-particle interactions in the system. We exemplify our approach by considering a quantum rotor interacting with a bath of bosons, and demonstrate that extracting the value of q from closed-form solutions in the perturbative regime allows one to predict the behavior of the system for arbitrary values of the impurity-bath coupling strength, in good agreement with nonperturbative calculations. Furthermore, the value of the deformation parameter allows one to predict at which coupling strengths rotor-bath interactions result in a formation of a stable quasiparticle. The approach based on quantum groups does not only allow for a drastic simplification of impurity problems, but also provides valuable insights into hidden symmetries of interacting many-particle systems. AU - Yakaboylu, Enderalp AU - Shkolnikov, Mikhail AU - Lemeshko, Mikhail ID - 5794 IS - 25 JF - Physical Review Letters SN - 00319007 TI - Quantum groups as hidden symmetries of quantum impurities VL - 121 ER - TY - JOUR AB - Using the geodesic distance on the n-dimensional sphere, we study the expected radius function of the Delaunay mosaic of a random set of points. Specifically, we consider the partition of the mosaic into intervals of the radius function and determine the expected number of intervals whose radii are less than or equal to a given threshold. We find that the expectations are essentially the same as for the Poisson–Delaunay mosaic in n-dimensional Euclidean space. Assuming the points are not contained in a hemisphere, the Delaunay mosaic is isomorphic to the boundary complex of the convex hull in Rn+1, so we also get the expected number of faces of a random inscribed polytope. As proved in Antonelli et al. [Adv. in Appl. Probab. 9–12 (1977–1980)], an orthant section of the n-sphere is isometric to the standard n-simplex equipped with the Fisher information metric. It follows that the latter space has similar stochastic properties as the n-dimensional Euclidean space. Our results are therefore relevant in information geometry and in population genetics. AU - Edelsbrunner, Herbert AU - Nikitenko, Anton ID - 87 IS - 5 JF - Annals of Applied Probability TI - Random inscribed polytopes have similar radius functions as Poisson-Delaunay mosaics VL - 28 ER - TY - JOUR AB - The phytohormone auxin is the information carrier in a plethora of developmental and physiological processes in plants(1). It has been firmly established that canonical, nuclear auxin signalling acts through regulation of gene transcription(2). Here, we combined microfluidics, live imaging, genetic engineering and computational modelling to reanalyse the classical case of root growth inhibition(3) by auxin. We show that Arabidopsis roots react to addition and removal of auxin by extremely rapid adaptation of growth rate. This process requires intracellular auxin perception but not transcriptional reprogramming. The formation of the canonical TIR1/AFB-Aux/IAA co-receptor complex is required for the growth regulation, hinting to a novel, non-transcriptional branch of this signalling pathway. Our results challenge the current understanding of root growth regulation by auxin and suggest another, presumably non-transcriptional, signalling output of the canonical auxin pathway. AU - Fendrych, Matyas AU - Akhmanova, Maria AU - Merrin, Jack AU - Glanc, Matous AU - Hagihara, Shinya AU - Takahashi, Koji AU - Uchida, Naoyuki AU - Torii, Keiko U AU - Friml, Jirí ID - 192 IS - 7 JF - Nature Plants TI - Rapid and reversible root growth inhibition by TIR1 auxin signalling VL - 4 ER - TY - JOUR AB - The intercellular transport of auxin is driven by PIN-formed (PIN) auxin efflux carriers. PINs are localized at the plasma membrane (PM) and on constitutively recycling endomembrane vesicles. Therefore, PINs can mediate auxin transport either by direct translocation across the PM or by pumping auxin into secretory vesicles (SVs), leading to its secretory release upon fusion with the PM. Which of these two mechanisms dominates is a matter of debate. Here, we addressed the issue with a mathematical modeling approach. We demonstrate that the efficiency of secretory transport depends on SV size, half-life of PINs on the PM, pH, exocytosis frequency and PIN density. 3D structured illumination microscopy (SIM) was used to determine PIN density on the PM. Combining this data with published values of the other parameters, we show that the transport activity of PINs in SVs would have to be at least 1000× greater than on the PM in order to produce a comparable macroscopic auxin transport. If both transport mechanisms operated simultaneously and PINs were equally active on SVs and PM, the contribution of secretion to the total auxin flux would be negligible. In conclusion, while secretory vesicle-mediated transport of auxin is an intriguing and theoretically possible model, it is unlikely to be a major mechanism of auxin transport inplanta. AU - Hille, Sander AU - Akhmanova, Maria AU - Glanc, Matous AU - Johnson, Alexander J AU - Friml, Jirí ID - 14 IS - 11 JF - International Journal of Molecular Sciences TI - Relative contribution of PIN-containing secretory vesicles and plasma membrane PINs to the directed auxin transport: Theoretical estimation VL - 19 ER - TY - JOUR AB - We study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression and selection on fine-scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation. AU - Sachdeva, Himani AU - Barton, Nicholas H ID - 39 IS - 4 JF - Genetics SN - 00166731 TI - Replicability of introgression under linked, polygenic selection VL - 210 ER - TY - JOUR AB - We analyze the theoretical derivation of the beyond-mean-field equation of state for two-dimensional gas of dilute, ultracold alkali-metal atoms in the Bardeen–Cooper–Schrieffer (BCS) to Bose–Einstein condensate (BEC) crossover. We show that at zero temperature our theory — considering Gaussian fluctuations on top of the mean-field equation of state — is in very good agreement with experimental data. Subsequently, we investigate the superfluid density at finite temperature and its renormalization due to the proliferation of vortex–antivortex pairs. By doing so, we determine the Berezinskii–Kosterlitz–Thouless (BKT) critical temperature — at which the renormalized superfluid density jumps to zero — as a function of the inter-atomic potential strength. We find that the Nelson–Kosterlitz criterion overestimates the BKT temperature with respect to the renormalization group equations, this effect being particularly relevant in the intermediate regime of the crossover. AU - Bighin, Giacomo AU - Salasnich, Luca ID - 420 IS - 17 JF - International Journal of Modern Physics B TI - Renormalization of the superfluid density in the two-dimensional BCS-BEC crossover VL - 32 ER - TY - JOUR AB - Genomes of closely-related species or populations often display localized regions of enhanced relative sequence divergence, termed genomic islands. It has been proposed that these islands arise through selective sweeps and/or barriers to gene flow. Here, we genetically dissect a genomic island that controls flower color pattern differences between two subspecies of Antirrhinum majus, A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a natural hybrid zone. We show that selective sweeps likely raised relative divergence at two tightly-linked MYB-like transcription factors, leading to distinct flower patterns in the two subspecies. The two patterns provide alternate floral guides and create a strong barrier to gene flow where populations come into contact. This barrier affects the selected flower color genes and tightlylinked loci, but does not extend outside of this domain, allowing gene flow to lower relative divergence for the rest of the chromosome. Thus, both selective sweeps and barriers to gene flow play a role in shaping genomic islands: sweeps cause elevation in relative divergence, while heterogeneous gene flow flattens the surrounding "sea," making the island of divergence stand out. By showing how selective sweeps establish alternative adaptive phenotypes that lead to barriers to gene flow, our study sheds light on possible mechanisms leading to reproductive isolation and speciation. AU - Tavares, Hugo AU - Whitley, Annabel AU - Field, David AU - Bradley, Desmond AU - Couchman, Matthew AU - Copsey, Lucy AU - Elleouet, Joane AU - Burrus, Monique AU - Andalo, Christophe AU - Li, Miaomiao AU - Li, Qun AU - Xue, Yongbiao AU - Rebocho, Alexandra B AU - Barton, Nicholas H AU - Coen, Enrico ID - 38 IS - 43 JF - PNAS SN - 00278424 TI - Selection and gene flow shape genomic islands that control floral guides VL - 115 ER - TY - CONF AB - There is currently significant interest in operating devices in the quantum regime, where their behaviour cannot be explained through classical mechanics. Quantum states, including entangled states, are fragile and easily disturbed by excessive thermal noise. Here we address the question of whether it is possible to create non-reciprocal devices that encourage the flow of thermal noise towards or away from a particular quantum device in a network. Our work makes use of the cascaded systems formalism to answer this question in the affirmative, showing how a three-port device can be used as an effective thermal transistor, and illustrates how this formalism maps onto an experimentally-realisable optomechanical system. Our results pave the way to more resilient quantum devices and to the use of thermal noise as a resource. AU - Xuereb, André AU - Aquilina, Matteo AU - Barzanjeh, Shabir ED - Andrews, D L ED - Ostendorf, A ED - Bain, A J ED - Nunzi, J M ID - 155 TI - Routing thermal noise through quantum networks VL - 10672 ER - TY - JOUR AB - Cuprate superconductors have long been thought of as having strong electronic correlations but negligible spin-orbit coupling. Using spin- and angle-resolved photoemission spectroscopy, we discovered that one of the most studied cuprate superconductors, Bi2212, has a nontrivial spin texture with a spin-momentum locking that circles the Brillouin zone center and a spin-layer locking that allows states of opposite spin to be localized in different parts of the unit cell. Our findings pose challenges for the vast majority of models of cuprates, such as the Hubbard model and its variants, where spin-orbit interaction has been mostly neglected, and open the intriguing question of how the high-temperature superconducting state emerges in the presence of this nontrivial spin texture. AU - Gotlieb, Kenneth AU - Lin, Chiu-Yun AU - Serbyn, Maksym AU - Zhang, Wentao AU - Smallwood, Christopher L. AU - Jozwiak, Christopher AU - Eisaki, Hiroshi AU - Hussain, Zahid AU - Vishwanath, Ashvin AU - Lanzara, Alessandra ID - 5767 IS - 6420 JF - Science SN - 0036-8075 TI - Revealing hidden spin-momentum locking in a high-temperature cuprate superconductor VL - 362 ER - TY - JOUR AB - In this paper, we present a formal model-driven design approach to establish a safety-assured implementation of multifunction vehicle bus controller (MVBC), which controls the data transmission among the devices of the vehicle. First, the generic models and safety requirements described in International Electrotechnical Commission Standard 61375 are formalized as time automata and timed computation tree logic formulas, respectively. With model checking tool Uppaal, we verify whether or not the constructed timed automata satisfy the formulas and several logic inconsistencies in the original standard are detected and corrected. Then, we apply the code generation tool Times to generate C code from the verified model, which is later synthesized into a real MVBC chip, with some handwriting glue code. Furthermore, the runtime verification tool RMOR is applied on the integrated code, to verify some safety requirements that cannot be formalized on the timed automata. For evaluation, we compare the proposed approach with existing MVBC design methods, such as BeagleBone, Galsblock, and Simulink. Experiments show that more ambiguousness or bugs in the standard are detected during Uppaal verification, and the generated code of Times outperforms the C code generated by others in terms of the synthesized binary code size. The errors in the standard have been confirmed and the resulting MVBC has been deployed in the real train communication network. AU - Jiang, Yu AU - Liu, Han AU - Song, Huobing AU - Kong, Hui AU - Wang, Rui AU - Guan, Yong AU - Sha, Lui ID - 434 IS - 10 JF - IEEE Transactions on Intelligent Transportation Systems TI - Safety-assured model-driven design of the multifunction vehicle bus controller VL - 19 ER - TY - JOUR AB - Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts. AU - Kaucka, Marketa AU - Petersen, Julian AU - Tesarova, Marketa AU - Szarowska, Bara AU - Kastriti, Maria AU - Xie, Meng AU - Kicheva, Anna AU - Annusver, Karl AU - Kasper, Maria AU - Symmons, Orsolya AU - Pan, Leslie AU - Spitz, Francois AU - Kaiser, Jozef AU - Hovorakova, Maria AU - Zikmund, Tomas AU - Sunadome, Kazunori AU - Matise, Michael P AU - Wang, Hui AU - Marklund, Ulrika AU - Abdo, Hind AU - Ernfors, Patrik AU - Maire, Pascal AU - Wurmser, Maud AU - Chagin, Andrei S AU - Fried, Kaj AU - Adameyko, Igor ID - 162 JF - eLife TI - Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage VL - 7 ER - TY - CONF AB - At ITCS 2013, Mahmoody, Moran and Vadhan [MMV13] introduce and construct publicly verifiable proofs of sequential work, which is a protocol for proving that one spent sequential computational work related to some statement. The original motivation for such proofs included non-interactive time-stamping and universally verifiable CPU benchmarks. A more recent application, and our main motivation, are blockchain designs, where proofs of sequential work can be used – in combination with proofs of space – as a more ecological and economical substitute for proofs of work which are currently used to secure Bitcoin and other cryptocurrencies. The construction proposed by [MMV13] is based on a hash function and can be proven secure in the random oracle model, or assuming inherently sequential hash-functions, which is a new standard model assumption introduced in their work. In a proof of sequential work, a prover gets a “statement” χ, a time parameter N and access to a hash-function H, which for the security proof is modelled as a random oracle. Correctness requires that an honest prover can make a verifier accept making only N queries to H, while soundness requires that any prover who makes the verifier accept must have made (almost) N sequential queries to H. Thus a solution constitutes a proof that N time passed since χ was received. Solutions must be publicly verifiable in time at most polylogarithmic in N. The construction of [MMV13] is based on “depth-robust” graphs, and as a consequence has rather poor concrete parameters. But the major drawback is that the prover needs not just N time, but also N space to compute a proof. In this work we propose a proof of sequential work which is much simpler, more efficient and achieves much better concrete bounds. Most importantly, the space required can be as small as log (N) (but we get better soundness using slightly more memory than that). An open problem stated by [MMV13] that our construction does not solve either is achieving a “unique” proof, where even a cheating prover can only generate a single accepting proof. This property would be extremely useful for applications to blockchains. AU - Cohen, Bram AU - Pietrzak, Krzysztof Z ID - 302 TI - Simple proofs of sequential work VL - 10821 ER - TY - JOUR AB - Correlations in sensory neural networks have both extrinsic and intrinsic origins. Extrinsic or stimulus correlations arise from shared inputs to the network and, thus, depend strongly on the stimulus ensemble. Intrinsic or noise correlations reflect biophysical mechanisms of interactions between neurons, which are expected to be robust to changes in the stimulus ensemble. Despite the importance of this distinction for understanding how sensory networks encode information collectively, no method exists to reliably separate intrinsic interactions from extrinsic correlations in neural activity data, limiting our ability to build predictive models of the network response. In this paper we introduce a general strategy to infer population models of interacting neurons that collectively encode stimulus information. The key to disentangling intrinsic from extrinsic correlations is to infer the couplings between neurons separately from the encoding model and to combine the two using corrections calculated in a mean-field approximation. We demonstrate the effectiveness of this approach in retinal recordings. The same coupling network is inferred from responses to radically different stimulus ensembles, showing that these couplings indeed reflect stimulus-independent interactions between neurons. The inferred model predicts accurately the collective response of retinal ganglion cell populations as a function of the stimulus. AU - Ferrari, Ulisse AU - Deny, Stephane AU - Chalk, Matthew J AU - Tkacik, Gasper AU - Marre, Olivier AU - Mora, Thierry ID - 31 IS - 4 JF - Physical Review E SN - 24700045 TI - Separating intrinsic interactions from extrinsic correlations in a network of sensory neurons VL - 98 ER - TY - JOUR AB - Tropical geometry, an established field in pure mathematics, is a place where string theory, mirror symmetry, computational algebra, auction theory, and so forth meet and influence one another. In this paper, we report on our discovery of a tropical model with self-organized criticality (SOC) behavior. Our model is continuous, in contrast to all known models of SOC, and is a certain scaling limit of the sandpile model, the first and archetypical model of SOC. We describe how our model is related to pattern formation and proportional growth phenomena and discuss the dichotomy between continuous and discrete models in several contexts. Our aim in this context is to present an idealized tropical toy model (cf. Turing reaction-diffusion model), requiring further investigation. AU - Kalinin, Nikita AU - Guzmán Sáenz, Aldo AU - Prieto, Y AU - Shkolnikov, Mikhail AU - Kalinina, V AU - Lupercio, Ernesto ID - 64 IS - 35 JF - PNAS: Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Self-organized criticality and pattern emergence through the lens of tropical geometry VL - 115 ER - TY - GEN AB - Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts. AU - Kaucka, Marketa AU - Petersen, Julian AU - Tesarova, Marketa AU - Szarowska, Bara AU - Kastriti, Maria Eleni AU - Xie, Meng AU - Kicheva, Anna AU - Annusver, Karl AU - Kasper, Maria AU - Symmons, Orsolya AU - Pan, Leslie AU - Spitz, Francois AU - Kaiser, Jozef AU - Hovorakova, Maria AU - Zikmund, Tomas AU - Sunadome, Kazunori AU - Matise, Michael P AU - Wang, Hui AU - Marklund, Ulrika AU - Abdo, Hind AU - Ernfors, Patrik AU - Maire, Pascal AU - Wurmser, Maud AU - Chagin, Andrei S AU - Fried, Kaj AU - Adameyko, Igor ID - 9838 TI - Data from: Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage ER - TY - JOUR AB - The small-conductance, Ca2+-activated K+ (SK) channel subtype SK2 regulates the spike rate and firing frequency, as well as Ca2+ transients in Purkinje cells (PCs). To understand the molecular basis by which SK2 channels mediate these functions, we analyzed the exact location and densities of SK2 channels along the neuronal surface of the mouse cerebellar PCs using SDS-digested freeze-fracture replica labeling (SDS-FRL) of high sensitivity combined with quantitative analyses. Immunogold particles for SK2 were observed on post- and pre-synaptic compartments showing both scattered and clustered distribution patterns. We found an axo-somato-dendritic gradient of the SK2 particle density increasing 12-fold from soma to dendritic spines. Using two different immunogold approaches, we also found that SK2 immunoparticles were frequently adjacent to, but never overlap with, the postsynaptic density of excitatory synapses in PC spines. Co-immunoprecipitation analysis demonstrated that SK2 channels form macromolecular complexes with two types of proteins that mobilize Ca2+: CaV2.1 channels and mGlu1α receptors in the cerebellum. Freeze-fracture replica double-labeling showed significant co-clustering of particles for SK2 with those for CaV2.1 channels and mGlu1α receptors. SK2 channels were also detected at presynaptic sites, mostly at the presynaptic active zone (AZ), where they are close to CaV2.1 channels, though they are not significantly co-clustered. These data demonstrate that SK2 channels located in different neuronal compartments can associate with distinct proteins mobilizing Ca2+, and suggest that the ultrastructural association of SK2 with CaV2.1 and mGlu1α provides the mechanism that ensures voltage (excitability) regulation by distinct intracellular Ca2+ transients in PCs. AU - Luján, Rafæl AU - Aguado, Carolina AU - Ciruela, Francisco AU - Arus, Xavier AU - Martín Belmonte, Alejandro AU - Alfaro Ruiz, Rocío AU - Martinez Gomez, Jesus AU - De La Ossa, Luis AU - Watanabe, Masahiko AU - Adelman, John AU - Shigemoto, Ryuichi AU - Fukazawa, Yugo ID - 41 JF - Frontiers in Cellular Neuroscience SN - 16625102 TI - Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells VL - 12 ER - TY - JOUR AB - The strong atomistic spin–orbit coupling of holes makes single-shot spin readout measurements difficult because it reduces the spin lifetimes. By integrating the charge sensor into a high bandwidth radio frequency reflectometry setup, we were able to demonstrate single-shot readout of a germanium quantum dot hole spin and measure the spin lifetime. Hole spin relaxation times of about 90 μs at 500 mT are reported, with a total readout visibility of about 70%. By analyzing separately the spin-to-charge conversion and charge readout fidelities, we have obtained insight into the processes limiting the visibilities of hole spins. The analyses suggest that high hole visibilities are feasible at realistic experimental conditions, underlying the potential of hole spins for the realization of viable qubit devices. AU - Vukušić, Lada AU - Kukucka, Josip AU - Watzinger, Hannes AU - Milem, Joshua M AU - Schäffler, Friedrich AU - Katsaros, Georgios ID - 23 IS - 11 JF - Nano Letters SN - 15306984 TI - Single-shot readout of hole spins in Ge VL - 18 ER - TY - CONF AB - Concurrent accesses to shared data structures must be synchronized to avoid data races. Coarse-grained synchronization, which locks the entire data structure, is easy to implement but does not scale. Fine-grained synchronization can scale well, but can be hard to reason about. Hand-over-hand locking, in which operations are pipelined as they traverse the data structure, combines fine-grained synchronization with ease of use. However, the traditional implementation suffers from inherent overheads. This paper introduces snapshot-based synchronization (SBS), a novel hand-over-hand locking mechanism. SBS decouples the synchronization state from the data, significantly improving cache utilization. Further, it relies on guarantees provided by pipelining to minimize synchronization that requires cross-thread communication. Snapshot-based synchronization thus scales much better than traditional hand-over-hand locking, while maintaining the same ease of use. AU - Gilad, Eran AU - Brown, Trevor A AU - Oskin, Mark AU - Etsion, Yoav ID - 85 SN - 03029743 TI - Snapshot based synchronization: A fast replacement for Hand-over-Hand locking VL - 11014 ER - TY - JOUR AB - Many-body quantum systems typically display fast dynamics and ballistic spreading of information. Here we address the open problem of how slow the dynamics can be after a generic breaking of integrability by local interactions. We develop a method based on degenerate perturbation theory that reveals slow dynamical regimes and delocalization processes in general translation invariant models, along with accurate estimates of their delocalization time scales. Our results shed light on the fundamental questions of the robustness of quantum integrable systems and the possibility of many-body localization without disorder. As an example, we construct a large class of one-dimensional lattice models where, despite the absence of asymptotic localization, the transient dynamics is exceptionally slow, i.e., the dynamics is indistinguishable from that of many-body localized systems for the system sizes and time scales accessible in experiments and numerical simulations. AU - Michailidis, Alexios AU - Žnidarič, Marko AU - Medvedyeva, Mariya AU - Abanin, Dmitry AU - Prosen, Tomaž AU - Papić, Zlatko ID - 327 IS - 10 JF - Physical Review B TI - Slow dynamics in translation-invariant quantum lattice models VL - 97 ER - TY - JOUR AB - Social insects have evolved enormous capacities to collectively build nests and defend their colonies against both predators and pathogens. The latter is achieved by a combination of individual immune responses and sophisticated collective behavioral and organizational disease defenses, that is, social immunity. We investigated how the presence or absence of these social defense lines affects individual-level immunity in ant queens after bacterial infection. To this end, we injected queens of the ant Linepithema humile with a mix of gram+ and gram− bacteria or a control solution, reared them either with workers or alone and analyzed their gene expression patterns at 2, 4, 8, and 12 hr post-injection, using RNA-seq. This allowed us to test for the effect of bacterial infection, social context, as well as the interaction between the two over the course of infection and raising of an immune response. We found that social isolation per se affected queen gene expression for metabolism genes, but not for immune genes. When infected, queens reared with and without workers up-regulated similar numbers of innate immune genes revealing activation of Toll and Imd signaling pathways and melanization. Interestingly, however, they mostly regulated different genes along the pathways and showed a different pattern of overall gene up-regulation or down-regulation. Hence, we can conclude that the absence of workers does not compromise the onset of an individual immune response by the queens, but that the social environment impacts the route of the individual innate immune responses. AU - Viljakainen, Lumi AU - Jurvansuu, Jaana AU - Holmberg, Ida AU - Pamminger, Tobias AU - Erler, Silvio AU - Cremer, Sylvia ID - 29 IS - 22 JF - Ecology and Evolution SN - 20457758 TI - Social environment affects the transcriptomic response to bacteria in ant queens VL - 8 ER - TY - JOUR AB - Social insect colonies have evolved many collectively performed adaptations that reduce the impact of infectious disease and that are expected to maximize their fitness. This colony-level protection is termed social immunity, and it enhances the health and survival of the colony. In this review, we address how social immunity emerges from its mechanistic components to produce colony-level disease avoidance, resistance, and tolerance. To understand the evolutionary causes and consequences of social immunity, we highlight the need for studies that evaluate the effects of social immunity on colony fitness. We discuss the role that host life history and ecology have on predicted eco-evolutionary dynamics, which differ among the social insect lineages. Throughout the review, we highlight current gaps in our knowledge and promising avenues for future research, which we hope will bring us closer to an integrated understanding of socio-eco-evo-immunology. AU - Cremer, Sylvia AU - Pull, Christopher AU - Fürst, Matthias ID - 806 JF - Annual Review of Entomology SN - 1545-4487 TI - Social immunity: Emergence and evolution of colony-level disease protection VL - 63 ER - TY - CONF AB - Reachability analysis is difficult for hybrid automata with affine differential equations, because the reach set needs to be approximated. Promising abstraction techniques usually employ interval methods or template polyhedra. Interval methods account for dense time and guarantee soundness, and there are interval-based tools that overapproximate affine flowpipes. But interval methods impose bounded and rigid shapes, which make refinement expensive and fixpoint detection difficult. Template polyhedra, on the other hand, can be adapted flexibly and can be unbounded, but sound template refinement for unbounded reachability analysis has been implemented only for systems with piecewise constant dynamics. We capitalize on the advantages of both techniques, combining interval arithmetic and template polyhedra, using the former to abstract time and the latter to abstract space. During a CEGAR loop, whenever a spurious error trajectory is found, we compute additional space constraints and split time intervals, and use these space-time interpolants to eliminate the counterexample. Space-time interpolation offers a lazy, flexible framework for increasing precision while guaranteeing soundness, both for error avoidance and fixpoint detection. To the best of out knowledge, this is the first abstraction refinement scheme for the reachability analysis over unbounded and dense time of affine hybrid systems, which is both sound and automatic. We demonstrate the effectiveness of our algorithm with several benchmark examples, which cannot be handled by other tools. AU - Frehse, Goran AU - Giacobbe, Mirco AU - Henzinger, Thomas A ID - 140 SN - 03029743 TI - Space-time interpolants VL - 10981 ER - TY - JOUR AB - We give a lower bound on the ground state energy of a system of two fermions of one species interacting with two fermions of another species via point interactions. We show that there is a critical mass ratio m2 ≈ 0.58 such that the system is stable, i.e., the energy is bounded from below, for m∈[m2,m2−1]. So far it was not known whether this 2 + 2 system exhibits a stable region at all or whether the formation of four-body bound states causes an unbounded spectrum for all mass ratios, similar to the Thomas effect. Our result gives further evidence for the stability of the more general N + M system. AU - Moser, Thomas AU - Seiringer, Robert ID - 154 IS - 3 JF - Mathematical Physics Analysis and Geometry SN - 13850172 TI - Stability of the 2+2 fermionic system with point interactions VL - 21 ER - TY - JOUR AB - Branching morphogenesis remains a subject of abiding interest. Although much is known about the gene regulatory programs and signaling pathways that operate at the cellular scale, it has remained unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Lately, it has been proposed that, these features can be explained quantitatively in several organs within a single unifying framework. Based on large- scale organ recon - structions and cell lineage tracing, it has been argued that morphogenesis follows from the collective dynamics of sublineage- restricted self- renewing progenitor cells, localized at ductal tips, that act cooperatively to drive a serial process of ductal elon - gation and stochastic tip bifurcation. By correlating differentiation or cell cycle exit with proximity to maturing ducts, this dynamic results in the specification of a com- plex network of defined density and statistical organization. These results suggest that, for several mammalian tissues, branched epithelial structures develop as a self- organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events. Here, we review the basis of these findings and discuss their implications. AU - Hannezo, Edouard B AU - Simons, Benjamin D. ID - 5787 IS - 9 JF - Development Growth and Differentiation SN - 00121592 TI - Statistical theory of branching morphogenesis VL - 60 ER - TY - CONF AB - Graph games played by two players over finite-state graphs are central in many problems in computer science. In particular, graph games with ω -regular winning conditions, specified as parity objectives, which can express properties such as safety, liveness, fairness, are the basic framework for verification and synthesis of reactive systems. The decisions for a player at various states of the graph game are represented as strategies. While the algorithmic problem for solving graph games with parity objectives has been widely studied, the most prominent data-structure for strategy representation in graph games has been binary decision diagrams (BDDs). However, due to the bit-level representation, BDDs do not retain the inherent flavor of the decisions of strategies, and are notoriously hard to minimize to obtain succinct representation. In this work we propose decision trees for strategy representation in graph games. Decision trees retain the flavor of decisions of strategies and allow entropy-based minimization to obtain succinct trees. However, decision trees work in settings (e.g., probabilistic models) where errors are allowed, and overfitting of data is typically avoided. In contrast, for strategies in graph games no error is allowed, and the decision tree must represent the entire strategy. We develop new techniques to extend decision trees to overcome the above obstacles, while retaining the entropy-based techniques to obtain succinct trees. We have implemented our techniques to extend the existing decision tree solvers. We present experimental results for problems in reactive synthesis to show that decision trees provide a much more efficient data-structure for strategy representation as compared to BDDs. AU - Brázdil, Tomáš AU - Chatterjee, Krishnendu AU - Kretinsky, Jan AU - Toman, Viktor ID - 297 TI - Strategy representation by decision trees in reactive synthesis VL - 10805 ER - TY - CONF AB - Given a model and a specification, the fundamental model-checking problem asks for algorithmic verification of whether the model satisfies the specification. We consider graphs and Markov decision processes (MDPs), which are fundamental models for reactive systems. One of the very basic specifications that arise in verification of reactive systems is the strong fairness (aka Streett) objective. Given different types of requests and corresponding grants, the objective requires that for each type, if the request event happens infinitely often, then the corresponding grant event must also happen infinitely often. All ω -regular objectives can be expressed as Streett objectives and hence they are canonical in verification. To handle the state-space explosion, symbolic algorithms are required that operate on a succinct implicit representation of the system rather than explicitly accessing the system. While explicit algorithms for graphs and MDPs with Streett objectives have been widely studied, there has been no improvement of the basic symbolic algorithms. The worst-case numbers of symbolic steps required for the basic symbolic algorithms are as follows: quadratic for graphs and cubic for MDPs. In this work we present the first sub-quadratic symbolic algorithm for graphs with Streett objectives, and our algorithm is sub-quadratic even for MDPs. Based on our algorithmic insights we present an implementation of the new symbolic approach and show that it improves the existing approach on several academic benchmark examples. AU - Chatterjee, Krishnendu AU - Henzinger, Monika H AU - Loitzenbauer, Veronika AU - Oraee, Simin AU - Toman, Viktor ID - 141 TI - Symbolic algorithms for graphs and Markov decision processes with fairness objectives VL - 10982 ER - TY - CONF AB - Memory-hard functions (MHF) are functions whose evaluation cost is dominated by memory cost. MHFs are egalitarian, in the sense that evaluating them on dedicated hardware (like FPGAs or ASICs) is not much cheaper than on off-the-shelf hardware (like x86 CPUs). MHFs have interesting cryptographic applications, most notably to password hashing and securing blockchains. Alwen and Serbinenko [STOC’15] define the cumulative memory complexity (cmc) of a function as the sum (over all time-steps) of the amount of memory required to compute the function. They advocate that a good MHF must have high cmc. Unlike previous notions, cmc takes into account that dedicated hardware might exploit amortization and parallelism. Still, cmc has been critizised as insufficient, as it fails to capture possible time-memory trade-offs; as memory cost doesn’t scale linearly, functions with the same cmc could still have very different actual hardware cost. In this work we address this problem, and introduce the notion of sustained-memory complexity, which requires that any algorithm evaluating the function must use a large amount of memory for many steps. We construct functions (in the parallel random oracle model) whose sustained-memory complexity is almost optimal: our function can be evaluated using n steps and O(n/log(n)) memory, in each step making one query to the (fixed-input length) random oracle, while any algorithm that can make arbitrary many parallel queries to the random oracle, still needs Ω(n/log(n)) memory for Ω(n) steps. As has been done for various notions (including cmc) before, we reduce the task of constructing an MHFs with high sustained-memory complexity to proving pebbling lower bounds on DAGs. Our main technical contribution is the construction is a family of DAGs on n nodes with constant indegree with high “sustained-space complexity”, meaning that any parallel black-pebbling strategy requires Ω(n/log(n)) pebbles for at least Ω(n) steps. Along the way we construct a family of maximally “depth-robust” DAGs with maximum indegree O(logn) , improving upon the construction of Mahmoody et al. [ITCS’13] which had maximum indegree O(log2n⋅ AU - Alwen, Joel F AU - Blocki, Jeremiah AU - Pietrzak, Krzysztof Z ID - 298 TI - Sustained space complexity VL - 10821 ER - TY - JOUR AB - Wheat (Triticum ssp.) is one of the most important human food sources. However, this crop is very sensitive to temperature changes. Specifically, processes during wheat leaf, flower, and seed development and photosynthesis, which all contribute to the yield of this crop, are affected by high temperature. While this has to some extent been investigated on physiological, developmental, and molecular levels, very little is known about early signalling events associated with an increase in temperature. Phosphorylation-mediated signalling mechanisms, which are quick and dynamic, are associated with plant growth and development, also under abiotic stress conditions. Therefore, we probed the impact of a short-term and mild increase in temperature on the wheat leaf and spikelet phosphoproteome. In total, 3822 (containing 5178 phosphosites) and 5581 phosphopeptides (containing 7023 phosphosites) were identified in leaf and spikelet samples, respectively. Following statistical analysis, the resulting data set provides the scientific community with a first large-scale plant phosphoproteome under the control of higher ambient temperature. This community resource on the high temperature-mediated wheat phosphoproteome will be valuable for future studies. Our analyses also revealed a core set of common proteins between leaf and spikelet, suggesting some level of conserved regulatory mechanisms. Furthermore, we observed temperature-regulated interconversion of phosphoforms, which probably impacts protein activity. AU - Vu, Lam AU - Zhu, Tingting AU - Verstraeten, Inge AU - Van De Cotte, Brigitte AU - Gevaert, Kris AU - De Smet, Ive ID - 36 IS - 19 JF - Journal of Experimental Botany TI - Temperature-induced changes in the wheat phosphoproteome reveal temperature-regulated interconversion of phosphoforms VL - 69 ER - TY - JOUR AB - Three-dimensional (3D) super-resolution microscopy technique structured illumination microscopy (SIM) imaging of dendritic spines along the dendrite has not been previously performed in fixed tissues, mainly due to deterioration of the stripe pattern of the excitation laser induced by light scattering and optical aberrations. To address this issue and solve these optical problems, we applied a novel clearing reagent, LUCID, to fixed brains. In SIM imaging, the penetration depth and the spatial resolution were improved in LUCID-treated slices, and 160-nm spatial resolution was obtained in a large portion of the imaging volume on a single apical dendrite. Furthermore, in a morphological analysis of spine heads of layer V pyramidal neurons (L5PNs) in the medial prefrontal cortex (mPFC) of chronic dexamethasone (Dex)-treated mice, SIM imaging revealed an altered distribution of spine forms that could not be detected by high-NA confocal imaging. Thus, super-resolution SIM imaging represents a promising high-throughput method for revealing spine morphologies in single dendrites. AU - Sawada, Kazuaki AU - Kawakami, Ryosuke AU - Shigemoto, Ryuichi AU - Nemoto, Tomomi ID - 326 IS - 9 JF - European Journal of Neuroscience TI - Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices VL - 47 ER - TY - JOUR AB - Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical γ-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine the structures of immature and mature MLV CA layers within authentic viral particles. This reveals the structural changes associated with maturation, and, by comparison with HIV-1, uncovers conserved and variable features. In contrast to HIV-1, most MLV CA is used for assembly of the mature core, which adopts variable, multilayered morphologies and does not form a closed structure. Unlike in HIV-1, there is similarity between protein–protein interfaces in the immature MLV CA layer and those in the mature CA layer, and structural maturation of MLV could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, the dramatic architectural change on maturation indicates that extensive disassembly and reassembly are required for mature core growth. The core morphology suggests that wrapping of the genome in CA sheets may be sufficient to protect the MLV ribonucleoprotein during cell entry. AU - Qu, Kun AU - Glass, Bärbel AU - Doležal, Michal AU - Schur, Florian AU - Murciano, Brice AU - Rein, Alan AU - Rumlová, Michaela AU - Ruml, Tomáš AU - Kräusslich, Hans-Georg AU - Briggs, John A. G. ID - 5770 IS - 50 JF - Proceedings of the National Academy of Sciences SN - 00278424 TI - Structure and architecture of immature and mature murine leukemia virus capsids VL - 115 ER - TY - JOUR AB - Synthesis is the automated construction of a system from its specification. In real life, hardware and software systems are rarely constructed from scratch. Rather, a system is typically constructed from a library of components. Lustig and Vardi formalized this intuition and studied LTL synthesis from component libraries. In real life, designers seek optimal systems. In this paper we add optimality considerations to the setting. We distinguish between quality considerations (for example, size - the smaller a system is, the better it is), and pricing (for example, the payment to the company who manufactured the component). We study the problem of designing systems with minimal quality-cost and price. A key point is that while the quality cost is individual - the choices of a designer are independent of choices made by other designers that use the same library, pricing gives rise to a resource-allocation game - designers that use the same component share its price, with the share being proportional to the number of uses (a component can be used several times in a design). We study both closed and open settings, and in both we solve the problem of finding an optimal design. In a setting with multiple designers, we also study the game-theoretic problems of the induced resource-allocation game. AU - Avni, Guy AU - Kupferman, Orna ID - 608 JF - Theoretical Computer Science TI - Synthesis from component libraries with costs VL - 712 ER - TY - JOUR AB - Although dopamine receptors D1 and D2 play key roles in hippocampal function, their synaptic localization within the hippocampus has not been fully elucidated. In order to understand precise functions of pre- or postsynaptic dopamine receptors (DRs), the development of protocols to differentiate pre- and postsynaptic DRs is essential. So far, most studies on determination and quantification of DRs did not discriminate between subsynaptic localization. Therefore, the aim of the study was to generate a robust workflow for the localization of DRs. This work provides the basis for future work on hippocampal DRs, in light that DRs may have different functions at pre- or postsynaptic sites. Synaptosomes from rat hippocampi isolated by a sucrose gradient protocol were prepared for super-resolution direct stochastic optical reconstruction microscopy (dSTORM) using Bassoon as a presynaptic zone and Homer1 as postsynaptic density marker. Direct labeling of primary validated antibodies against dopamine receptors D1 (D1R) and D2 (D2R) with Alexa Fluor 594 enabled unequivocal assignment of D1R and D2R to both, pre- and postsynaptic sites. D1R immunoreactivity clusters were observed within the presynaptic active zone as well as at perisynaptic sites at the edge of the presynaptic active zone. The results may be useful for the interpretation of previous studies and the design of future work on DRs in the hippocampus. Moreover, the reduction of the complexity of brain tissue by the use of synaptosomal preparations and dSTORM technology may represent a useful tool for synaptic localization of brain proteins. AU - Miklosi, Andras AU - Del Favero, Giorgia AU - Bulat, Tanja AU - Höger, Harald AU - Shigemoto, Ryuichi AU - Marko, Doris AU - Lubec, Gert ID - 705 IS - 6 JF - Molecular Neurobiology TI - Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes VL - 55 ER - TY - JOUR AB - Land plants evolved from charophytic algae, among which Charophyceae possess the most complex body plans. We present the genome of Chara braunii; comparison of the genome to those of land plants identified evolutionary novelties for plant terrestrialization and land plant heritage genes. C. braunii employs unique xylan synthases for cell wall biosynthesis, a phragmoplast (cell separation) mechanism similar to that of land plants, and many phytohormones. C. braunii plastids are controlled via land-plant-like retrograde signaling, and transcriptional regulation is more elaborate than in other algae. The morphological complexity of this organism may result from expanded gene families, with three cases of particular note: genes effecting tolerance to reactive oxygen species (ROS), LysM receptor-like kinases, and transcription factors (TFs). Transcriptomic analysis of sexual reproductive structures reveals intricate control by TFs, activity of the ROS gene network, and the ancestral use of plant-like storage and stress protection proteins in the zygote. AU - Nishiyama, Tomoaki AU - Sakayama, Hidetoshi AU - De Vries, Jan AU - Buschmann, Henrik AU - Saint Marcoux, Denis AU - Ullrich, Kristian AU - Haas, Fabian AU - Vanderstraeten, Lisa AU - Becker, Dirk AU - Lang, Daniel AU - Vosolsobě, Stanislav AU - Rombauts, Stephane AU - Wilhelmsson, Per AU - Janitza, Philipp AU - Kern, Ramona AU - Heyl, Alexander AU - Rümpler, Florian AU - Calderón Villalobos, Luz AU - Clay, John AU - Skokan, Roman AU - Toyoda, Atsushi AU - Suzuki, Yutaka AU - Kagoshima, Hiroshi AU - Schijlen, Elio AU - Tajeshwar, Navindra AU - Catarino, Bruno AU - Hetherington, Alexander AU - Saltykova, Assia AU - Bonnot, Clemence AU - Breuninger, Holger AU - Symeonidi, Aikaterini AU - Radhakrishnan, Guru AU - Van Nieuwerburgh, Filip AU - Deforce, Dieter AU - Chang, Caren AU - Karol, Kenneth AU - Hedrich, Rainer AU - Ulvskov, Peter AU - Glöckner, Gernot AU - Delwiche, Charles AU - Petrášek, Jan AU - Van De Peer, Yves AU - Friml, Jirí AU - Beilby, Mary AU - Dolan, Liam AU - Kohara, Yuji AU - Sugano, Sumio AU - Fujiyama, Asao AU - Delaux, Pierre Marc AU - Quint, Marcel AU - Theissen, Gunter AU - Hagemann, Martin AU - Harholt, Jesper AU - Dunand, Christophe AU - Zachgo, Sabine AU - Langdale, Jane AU - Maumus, Florian AU - Van Der Straeten, Dominique AU - Gould, Sven B AU - Rensing, Stefan ID - 148 IS - 2 JF - Cell TI - The Chara genome: Secondary complexity and implications for plant terrestrialization VL - 174 ER - TY - JOUR AB - The ability to adapt growth and development to temperature variations is crucial to generate plant varieties resilient to predicted temperature changes. However, the mechanisms underlying plant response to progressive increases in temperature have just started to be elucidated. Here, we report that the Cyclin-dependent Kinase G1 (CDKG1) is a central element in a thermo-sensitive mRNA splicing cascade that transduces changes in ambient temperature into differential expression of the fundamental spliceosome component, ATU2AF65A. CDKG1 is alternatively spliced in a temperature-dependent manner. We found that this process is partly dependent on both the Cyclin-dependent Kinase G2 (CDKG2) and the interacting co-factor CYCLIN L1 resulting in two distinct messenger RNAs. Relative abundance of both CDKG1 transcripts correlates with ambient temperature and possibly with different expression levels of the associated protein isoforms. Both CDKG1 alternative transcripts are necessary to fully complement the expression of ATU2AF65A across the temperature range. Our data support a previously unidentified temperature-dependent mechanism based on the alternative splicing of CDKG1 and regulated by CDKG2 and CYCLIN L1. We propose that changes in ambient temperature affect the relative abundance of CDKG1 transcripts and this in turn translates into differential CDKG1 protein expression coordinating the alternative splicing of ATU2AF65A. This article is protected by copyright. All rights reserved. AU - Cavallari, Nicola AU - Nibau, Candida AU - Fuchs, Armin AU - Dadarou, Despoina AU - Barta, Andrea AU - Doonan, John ID - 403 IS - 6 JF - The Plant Journal TI - The cyclin‐dependent kinase G group defines a thermo‐sensitive alternative splicing circuit modulating the expression of Arabidopsis ATU 2AF 65A VL - 94 ER - TY - CONF AB - Imprecision in timing can sometimes be beneficial: Metric interval temporal logic (MITL), disabling the expression of punctuality constraints, was shown to translate to timed automata, yielding an elementary decision procedure. We show how this principle extends to other forms of dense-time specification using regular expressions. By providing a clean, automaton-based formal framework for non-punctual languages, we are able to recover and extend several results in timed systems. Metric interval regular expressions (MIRE) are introduced, providing regular expressions with non-singular duration constraints. We obtain that MIRE are expressively complete relative to a class of one-clock timed automata, which can be determinized using additional clocks. Metric interval dynamic logic (MIDL) is then defined using MIRE as temporal modalities. We show that MIDL generalizes known extensions of MITL, while translating to timed automata at comparable cost. AU - Ferrere, Thomas ID - 156 TI - The compound interest in relaxing punctuality VL - 10951 ER - TY - JOUR AB - The biotrophic pathogen Ustilago maydis, the causative agent of corn smut disease, infects one of the most important crops worldwide – Zea mays. To successfully colonize its host, U. maydis secretes proteins, known as effectors, that suppress plant defense responses and facilitate the establishment of biotrophy. In this work, we describe the U. maydis effector protein Cce1. Cce1 is essential for virulence and is upregulated during infection. Through microscopic analysis and in vitro assays, we show that Cce1 is secreted from hyphae during filamentous growth of the fungus. Strikingly, Δcce1 mutants are blocked at early stages of infection and induce callose deposition as a plant defense response. Cce1 is highly conserved among smut fungi and the Ustilago bromivora ortholog complemented the virulence defect of the SG200Δcce1 deletion strain. These data indicate that Cce1 is a core effector with apoplastic localization that is essential for U. maydis to infect its host. AU - Seitner, Denise AU - Uhse, Simon AU - Gallei, Michelle C AU - Djamei, Armin ID - 104 IS - 10 JF - Molecular Plant Pathology TI - The core effector Cce1 is required for early infection of maize by Ustilago maydis VL - 19 ER - TY - JOUR AB - Hanemaaijer et al. (Molecular Ecology, 27, 2018) describe the genetic consequences of the introgression of an insecticide resistance allele into a mosquito population. Linked alleles initially increased, but many of these later declined. It is hard to determine whether this decline was due to counter‐selection, rather than simply to chance. AU - Barton, Nicholas H ID - 40 IS - 24 JF - Molecular Ecology SN - 1365294X TI - The consequences of an introgression event VL - 27 ER - TY - JOUR AB - In zebrafish larvae, it is the cell type that determines how the cell responds to a chemokine signal. AU - Alanko, Jonna H AU - Sixt, Michael K ID - 5861 JF - eLife SN - 2050084X TI - The cell sets the tone VL - 7 ER - TY - JOUR AB - The trafficking of subcellular cargos in eukaryotic cells crucially depends on vesicle budding, a process mediated by ARF-GEFs (ADP-ribosylation factor guanine nucleotide exchange factors). In plants, ARF-GEFs play essential roles in endocytosis, vacuolar trafficking, recycling, secretion, and polar trafficking. Moreover, they are important for plant development, mainly through controlling the polar subcellular localization of PIN-FORMED (PIN) transporters of the plant hormone auxin. Here, using a chemical genetics screen in Arabidopsis thaliana, we identified Endosidin 4 (ES4), an inhibitor of eukaryotic ARF-GEFs. ES4 acts similarly to and synergistically with the established ARF-GEF inhibitor Brefeldin A and has broad effects on intracellular trafficking, including endocytosis, exocytosis, and vacuolar targeting. Additionally, Arabidopsis and yeast (Sacharomyces cerevisiae) mutants defective in ARF-GEF show altered sensitivity to ES4. ES4 interferes with the activation-based membrane association of the ARF1 GTPases, but not of their mutant variants that are activated independently of ARF-GEF activity. Biochemical approaches and docking simulations confirmed that ES4 specifically targets the SEC7 domain-containing ARF-GEFs. These observations collectively identify ES4 as a chemical tool enabling the study of ARF-GEF-mediated processes, including ARF-GEF-mediated plant development. AU - Kania, Urszula AU - Nodzyński, Tomasz AU - Lu, Qing AU - Hicks, Glenn R AU - Nerinckx, Wim AU - Mishev, Kiril AU - Peurois, Francois AU - Cherfils, Jacqueline AU - De, Rycke Riet Maria AU - Grones, Peter AU - Robert, Stéphanie AU - Russinova, Eugenia AU - Friml, Jirí ID - 147 IS - 10 JF - The Plant Cell SN - 1040-4651 TI - The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes VL - 30 ER - TY - JOUR AB - The root cap protects the stem cell niche of angiosperm roots from damage. In Arabidopsis, lateral root cap (LRC) cells covering the meristematic zone are regularly lost through programmed cell death, while the outermost layer of the root cap covering the tip is repeatedly sloughed. Efficient coordination with stem cells producing new layers is needed to maintain a constant size of the cap. We present a signalling pair, the peptide IDA-LIKE1 (IDL1) and its receptor HAESA-LIKE2 (HSL2), mediating such communication. Live imaging over several days characterized this process from initial fractures in LRC cell files to full separation of a layer. Enhanced expression of IDL1 in the separating root cap layers resulted in increased frequency of sloughing, balanced with generation of new layers in a HSL2-dependent manner. Transcriptome analyses linked IDL1-HSL2 signalling to the transcription factors BEARSKIN1/2 and genes associated with programmed cell death. Mutations in either IDL1 or HSL2 slowed down cell division, maturation and separation. Thus, IDL1-HSL2 signalling potentiates dynamic regulation of the homeostatic balance between stem cell division and sloughing activity. AU - Shi, Chun Lin AU - Von Wangenheim, Daniel AU - Herrmann, Ullrich AU - Wildhagen, Mari AU - Kulik, Ivan AU - Kopf, Andreas AU - Ishida, Takashi AU - Olsson, Vilde AU - Anker, Mari Kristine AU - Albert, Markus AU - Butenko, Melinka A AU - Felix, Georg AU - Sawa, Shinichiro AU - Claassen, Manfred AU - Friml, Jirí AU - Aalen, Reidunn B ID - 146 IS - 8 JF - Nature Plants TI - The dynamics of root cap sloughing in Arabidopsis is regulated by peptide signalling VL - 4 ER - TY - JOUR AB - People sometimes make their admirable deeds and accomplishments hard to spot, such as by giving anonymously or avoiding bragging. Such ‘buried’ signals are hard to reconcile with standard models of signalling or indirect reciprocity, which motivate costly pro-social behaviour by reputational gains. To explain these phenomena, we design a simple game theory model, which we call the signal-burying game. This game has the feature that senders can bury their signal by deliberately reducing the probability of the signal being observed. If the signal is observed, however, it is identified as having been buried. We show under which conditions buried signals can be maintained, using static equilibrium concepts and calculations of the evolutionary dynamics. We apply our analysis to shed light on a number of otherwise puzzling social phenomena, including modesty, anonymous donations, subtlety in art and fashion, and overeagerness. AU - Hoffman, Moshe AU - Hilbe, Christian AU - Nowak, Martin ID - 293 JF - Nature Human Behaviour TI - The signal-burying game can explain why we obscure positive traits and good deeds VL - 2 ER - TY - JOUR AB - The derivation of effective evolution equations is central to the study of non-stationary quantum many-body systems, and widely used in contexts such as superconductivity, nuclear physics, Bose–Einstein condensation and quantum chemistry. We reformulate the Dirac–Frenkel approximation principle in terms of reduced density matrices and apply it to fermionic and bosonic many-body systems. We obtain the Bogoliubov–de Gennes and Hartree–Fock–Bogoliubov equations, respectively. While we do not prove quantitative error estimates, our formulation does show that the approximation is optimal within the class of quasifree states. Furthermore, we prove well-posedness of the Bogoliubov–de Gennes equations in energy space and discuss conserved quantities AU - Benedikter, Niels P AU - Sok, Jérémy AU - Solovej, Jan ID - 455 IS - 4 JF - Annales Henri Poincare TI - The Dirac–Frenkel principle for reduced density matrices and the Bogoliubov–de Gennes equations VL - 19 ER - TY - JOUR AB - The interface of physics and biology pro-vides a fruitful environment for generatingnew concepts and exciting ways forwardto understanding living matter. Examplesof successful studies include the estab-lishment and readout of morphogen gra-dients during development, signal pro-cessing in protein and genetic networks,the role of fluctuations in determining thefates of cells and tissues, and collectiveeffects in proteins and in tissues. It is nothard to envision that significant further ad-vances will translate to societal benefitsby initiating the development of new de-vices and strategies for curing disease.However, research at the interface posesvarious challenges, in particular for youngscientists, and current institutions arerarely designed to facilitate such scientificprograms. In this Letter, we propose aninternational initiative that addressesthese challenges through the establish-ment of a worldwide network of platformsfor cross-disciplinary training and incuba-tors for starting new collaborations. AU - Bauer, Guntram AU - Fakhri, Nikta AU - Kicheva, Anna AU - Kondev, Jané AU - Kruse, Karsten AU - Noji, Hiroyuki AU - Riveline, Daniel AU - Saunders, Timothy AU - Thatta, Mukund AU - Wieschaus, Eric ID - 314 IS - 4 JF - Cell Systems TI - The science of living matter for tomorrow VL - 6 ER - TY - JOUR AB - We re-examine the model of Kirkpatrick and Barton for the spread of an inversion into a local population. This model assumes that local selection maintains alleles at two or more loci, despite immigration of alternative alleles at these loci from another population. We show that an inversion is favored because it prevents the breakdown of linkage disequilibrium generated by migration; the selective advantage of an inversion is proportional to the amount of recombination between the loci involved, as in other cases where inversions are selected for. We derive expressions for the rate of spread of an inversion; when the loci covered by the inversion are tightly linked, these conditions deviate substantially from those proposed previously, and imply that an inversion can then have only a small advantage. AU - Charlesworth, Brian AU - Barton, Nicholas H ID - 565 IS - 1 JF - Genetics TI - The spread of an inversion with migration and selection VL - 208 ER - TY - JOUR AB - We prove that in Thomas–Fermi–Dirac–von Weizsäcker theory, a nucleus of charge Z > 0 can bind at most Z + C electrons, where C is a universal constant. This result is obtained through a comparison with Thomas-Fermi theory which, as a by-product, gives bounds on the screened nuclear potential and the radius of the minimizer. A key ingredient of the proof is a novel technique to control the particles in the exterior region, which also applies to the liquid drop model with a nuclear background potential. AU - Frank, Rupert AU - Phan Thanh, Nam AU - Van Den Bosch, Hanne ID - 446 IS - 3 JF - Communications on Pure and Applied Mathematics TI - The ionization conjecture in Thomas–Fermi–Dirac–von Weizsäcker theory VL - 71 ER - TY - JOUR AB - In this issue of GENETICS, a new method for detecting natural selection on polygenic traits is developed and applied to sev- eral human examples ( Racimo et al. 2018 ). By de fi nition, many loci contribute to variation in polygenic traits, and a challenge for evolutionary ge neticists has been that these traits can evolve by small, nearly undetectable shifts in allele frequencies across each of many, typically unknown, loci. Recently, a helpful remedy has arisen. Genome-wide associ- ation studies (GWAS) have been illuminating sets of loci that can be interrogated jointly for c hanges in allele frequencies. By aggregating small signal s of change across many such loci, directional natural selection is now in principle detect- able using genetic data, even for highly polygenic traits. This is an exciting arena of progress – with these methods, tests can be made for selection associated with traits, and we can now study selection in what may be its most prevalent mode. The continuing fast pace of GWAS publications suggest there will be many more polygenic tests of selection in the near future, as every new GWAS is an opportunity for an accom- panying test of polygenic selection. However, it is important to be aware of complications th at arise in interpretation, especially given that these studies may easily be misinter- preted both in and outside the evolutionary genetics commu- nity. Here, we provide context for understanding polygenic tests and urge caution regarding how these results are inter- preted and reported upon more broadly. AU - Novembre, John AU - Barton, Nicholas H ID - 430 IS - 4 JF - Genetics TI - Tread lightly interpreting polygenic tests of selection VL - 208 ER -