TY - JOUR AB - Molecular dynamics simulations of small Cu nanoparticles using three different interatomic potentials at rising temperature indicate that small nanoparticles can undergo solid-solid structural transitions through a direct geometrical conversion route. The direct geometrical conversion can happen for cuboctahedral nanoparticles, which turn into an icosahedra shape: one diagonal of the square faces contracts, and the faces are folded along the diagonal to give rise to two equilateral triangles. The transition is a kinetic process that cannot be fully explained through an energetic point of view. It has low activation energy and fast reaction time in the simulations. The transition mechanism is via the transmission of shear waves initiated from the particle surface and does not involve dislocation activity. AU - Cheng, Bingqing AU - Ngan, Alfonso H. W. ID - 9663 IS - 16 JF - The Journal of Chemical Physics SN - 0021-9606 TI - Thermally induced solid-solid structural transition of copper nanoparticles through direct geometrical conversion VL - 138 ER - TY - JOUR AB - In this work, we simulate the response of two Cu nanoparticles colliding at different approaching rates at room temperature by MD. For small nanospheres, the formation of single twins is favored at high approach rates, whereas larger nanospheres mainly deform by dislocation slip. For small nanocubes with large {100} flat surfaces, however, a dislocation-free direct geometrical conversion process that leads to five-fold twinning dominates except at highly retarded approaching rates. For larger nanocubes, single twin formation is the governing plasticity mechanism. The probability for plastic deformation by dislocation slip or twinning is attributed to the abundance of surface steps, which act as sites for dislocation nucleation. AU - Cheng, Bingqing AU - Ngan, Alfonso H.W. ID - 9682 JF - Materials Science and Engineering: A SN - 0921-5093 TI - Crystal plasticity of Cu nanocrystals during collision VL - 585 ER - TY - JOUR AB - Recently a new high-mobility Dirac material, trilayer graphene, was realized experimentally. The band structure of ABA-stacked trilayer graphene consists of a monolayer-like and a bilayer-like pair of bands. Here we study electronic properties of ABA-stacked trilayer graphene biased by a perpendicular electric field. We find that the combination of the bias and trigonal warping gives rise to a set of new Dirac points: In each valley, seven species of Dirac fermions with small masses of order of a few meV emerge. The positions and masses of the emergent Dirac fermions are tunable by bias, and one group of Dirac fermions becomes massless at a certain bias value. Therefore, in contrast to bilayer graphene, the conductivity at the neutrality point is expected to show nonmonotonic behavior, becoming of the order of a few e2/h when some Dirac masses vanish. Further, we analyze the evolution of the Landau level spectrum as a function of bias. The emergence of new Dirac points in the band structure translates into new threefold-degenerate groups of Landau levels. This leads to an anomalous quantum Hall effect, in which some quantum Hall steps have a height of 3e2/h. At an intermediate bias, the degeneracies of all Landau levels get lifted, and in this regime all quantum Hall plateaus are spaced by e2/h. Finally, we show that the pattern of Landau level crossings is very sensitive to certain band structure parameters, and can therefore provide a useful tool for determining their precise values. AU - Maksym Serbyn AU - Abanin, Dmitry A ID - 970 IS - 11 JF - Physical Review B - Condensed Matter and Materials Physics TI - New Dirac points and multiple Landau level crossings in biased trilayer graphene VL - 87 ER - TY - JOUR AB - We construct a complete set of local integrals of motion that characterize the many-body localized (MBL) phase. Our approach relies on the assumption that local perturbations act locally on the eigenstates in the MBL phase, which is supported by numerical simulations of the random-field XXZ spin chain. We describe the structure of the eigenstates in the MBL phase and discuss the implications of local conservation laws for its nonequilibrium quantum dynamics. We argue that the many-body localization can be used to protect coherence in the system by suppressing relaxation between eigenstates with different local integrals of motion. AU - Maksym Serbyn AU - Papić, Zlatko AU - Abanin, Dmitry A ID - 973 IS - 12 JF - Physical Review Letters TI - Local conservation laws and the structure of the many body localized states VL - 111 ER - TY - JOUR AB - We propose a possible realization of the overscreened Kondo impurity problem by a magnetic s=1/2 impurity embedded in a two-dimensional S=1 U(1) spin liquid with a Fermi surface. This problem contains an interesting interplay between non-Fermi-liquid behavior induced by a U(1) gauge field coupled to fermions and a non-Fermi-liquid fixed point in the overscreened Kondo problem. Using a large-N expansion together with an expansion in the dynamical exponent of the gauge field, we find that the coupling to the gauge field leads to weak but observable changes in the physical properties of the system at the overscreened Kondo fixed point. We discuss the extrapolation of this result to a physical case and argue that the realization of overscreened Kondo physics could lead to observations of effects due to gauge fields. AU - Serbyn, Maksym AU - Senthil, Todadri AU - Lee, Patrick ID - 974 IS - 2 JF - Physical Review B - Condensed Matter and Materials Physics TI - Overscreened Kondo fixed point in S=1 spin liquid VL - 88 ER - TY - JOUR AB - Background: The brood of ants and other social insects is highly susceptible to pathogens, particularly those that penetrate the soft larval and pupal cuticle. We here test whether the presence of a pupal cocoon, which occurs in some ant species but not in others, affects the sanitary brood care and fungal infection patterns after exposure to the entomopathogenic fungus Metarhizium brunneum. We use a) a comparative approach analysing four species with either naked or cocooned pupae and b) a within-species analysis of a single ant species, in which both pupal types co-exist in the same colony. Results: We found that the presence of a cocoon did not compromise fungal pathogen detection by the ants and that species with cocooned pupae increased brood grooming after pathogen exposure. All tested ant species further removed brood from their nests, which was predominantly expressed towards larvae and naked pupae treated with the live fungal pathogen. In contrast, cocooned pupae exposed to live fungus were not removed at higher rates than cocooned pupae exposed to dead fungus or a sham control. Consistent with this, exposure to the live fungus caused high numbers of infections and fungal outgrowth in larvae and naked pupae, but not in cocooned pupae. Moreover, the ants consistently removed the brood prior to fungal outgrowth, ensuring a clean brood chamber. Conclusion: Our study suggests that the pupal cocoon has a protective effect against fungal infection, causing an adaptive change in sanitary behaviours by the ants. It further demonstrates that brood removal-originally described for honeybees as "hygienic behaviour"-is a widespread sanitary behaviour in ants, which likely has important implications on disease dynamics in social insect colonies. AU - Tragust, Simon AU - Ugelvig, Line V AU - Chapuisat, Michel AU - Heinze, Jürgen AU - Cremer, Sylvia ID - 2284 IS - 1 JF - BMC Evolutionary Biology TI - Pupal cocoons affect sanitary brood care and limit fungal infections in ant colonies VL - 13 ER - TY - JOUR AB - Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but they were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio-temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of pairwise correlations across stimuli where receptive field measurements were possible. AU - Simmons, Kristina AU - Prentice, Jason AU - Tkacik, Gasper AU - Homann, Jan AU - Yee, Heather AU - Palmer, Stephanie AU - Nelson, Philip AU - Balasubramanian, Vijay ID - 2277 IS - 12 JF - PLoS Computational Biology TI - Transformation of stimulus correlations by the retina VL - 9 ER - TY - GEN AB - Short-read sequencing technologies have in principle made it feasible to draw detailed inferences about the recent history of any organism. In practice, however, this remains challenging due to the difficulty of genome assembly in most organisms and the lack of statistical methods powerful enough to discriminate among recent, non-equilibrium histories. We address both the assembly and inference challenges. We develop a bioinformatic pipeline for generating outgroup-rooted alignments of orthologous sequence blocks from de novo low-coverage short-read data for a small number of genomes, and show how such sequence blocks can be used to fit explicit models of population divergence and admixture in a likelihood framework. To illustrate our approach, we reconstruct the Pleistocene history of an oak-feeding insect (the oak gallwasp Biorhiza pallida) which, in common with many other taxa, was restricted during Pleistocene ice ages to a longitudinal series of southern refugia spanning theWestern Palaearctic. Our analysis of sequence blocks sampled from a single genome from each of three major glacial refugia reveals support for an unexpected history dominated by recent admixture. Despite the fact that 80% of the genome is affected by admixture during the last glacial cycle, we are able to infer the deeper divergence history of these populations. These inferences are robust to variation in block length, mutation model, and the sampling location of individual genomes within refugia. This combination of de novo assembly and numerical likelihood calculation provides a powerful framework for estimating recent population history that can be applied to any organism without the need for prior genetic resources. AU - Hearn, Jack AU - Stone, Graham AU - Barton, Nicholas H AU - Lohse, Konrad AU - Bunnefeld, Lynsey ID - 9754 TI - Data from: Likelihood-based inference of population history from low coverage de novo genome assemblies ER - TY - JOUR AB - Motivated by a search for experimental probes to access the physics of fractionalized excitations called spinons in spin liquids, we study the interaction of spinons with lattice vibrations. We consider the case of algebraic spin liquid, when spinons have fermionic statistics and a Dirac-like dispersion. We establish the general procedure for deriving spinon-phonon interactions, which is based on symmetry considerations. The procedure is illustrated for four different algebraic spin liquids: π-flux and staggered-flux phases on a square lattice, π-flux phase on a kagome lattice, and zero-flux phase on a honeycomb lattice. Although the low-energy description is similar for all these phases, different underlying symmetry groups lead to a distinct form of spinon-phonon interaction Hamiltonian. The explicit form of the spinon-phonon interaction is used to estimate the attenuation of ultrasound in an algebraic spin liquid. The prospects of the sound attenuation as a probe of spinons are discussed. AU - Maksym Serbyn AU - Lee, Patrick ID - 976 IS - 17 JF - Physical Review B - Condensed Matter and Materials Physics TI - Spinon-phonon interaction in algebraic spin liquids VL - 87 ER - TY - JOUR AB - Central Asian water resources largely depend on melt water generated in the Pamir and Tien Shan mountain ranges. To estimate future water availability in this region, it is necessary to use climate projections to estimate the future glacier extent and volume. In this study, we evaluate the impact of uncertainty in climate change projections on the future glacier extent in the Amu and Syr Darya river basins. To this end we use the latest climate change projections generated for the upcoming IPCC report (CMIP5) and, for comparison, projections used in the fourth IPCC assessment (CMIP3). With these projections we force a regionalized glacier mass balance model, and estimate changes in the basins' glacier extent as a function of the glacier size distribution in the basins and projected temperature and precipitation. This glacier mass balance model is specifically developed for implementation in large scale hydrological models, where the spatial resolution does not allow for simulating individual glaciers and data scarcity is an issue. Although the CMIP5 ensemble results in greater regional warming than the CMIP3 ensemble and the range in projections for temperature as well as precipitation is wider for the CMIP5 than for the CMIP3, the spread in projections of future glacier extent in Central Asia is similar for both ensembles. This is because differences in temperature rise are small during periods of maximum melt (July–September) while differences in precipitation change are small during the period of maximum accumulation (October–February). However, the model uncertainty due to parameter uncertainty is high, and has roughly the same importance as uncertainty in the climate projections. Uncertainty about the size of the decline in glacier extent remains large, making estimates of future Central Asian glacier evolution and downstream water availability uncertain. AU - Lutz, A. F. AU - Immerzeel, W. W. AU - Gobiet, A. AU - Pellicciotti, Francesca AU - Bierkens, M. F. P. ID - 12638 IS - 9 JF - Hydrology and Earth System Sciences KW - General Earth and Planetary Sciences KW - General Engineering KW - General Environmental Science SN - 1607-7938 TI - Comparison of climate change signals in CMIP3 and CMIP5 multi-model ensembles and implications for Central Asian glaciers VL - 17 ER - TY - JOUR AB - In the headwater catchments of the main Asian rivers, glaciohydrological models are a useful tool to anticipate impacts of climatic changes. However, the reliability of their projections strongly depends on the quality and quantity of data that are available for parameter estimation, model calibration and validation, as well as on the accuracy of climate change projections. In this study the physically oriented, glaciohydrological model TOPKAPI-ETH is used to simulate future changes in snow, glacier, and runoff from the Hunza River Basin in northern Pakistan. Three key sources of model uncertainty in future runoff projections are compared: model parameters, climate projections, and natural climate variability. A novel approach, applicable also to ungauged catchments, is used to determine which model parameters and model components significantly affect the overall model uncertainty. We show that the model is capable of reproducing streamflow and glacier mass balances, but that all analyzed sources of uncertainty significantly affect the reliability of future projections, and that their effect is variable in time and in space. The effect of parametric uncertainty often exceeds the impact of climate uncertainty and natural climate variability, especially in heavily glacierized subcatchments. The results of the uncertainty analysis allow detailed recommendations on network design and the timing and location of field measurements, which could efficiently help to reduce model uncertainty in the future. AU - Ragettli, S. AU - Pellicciotti, Francesca AU - Bordoy, R. AU - Immerzeel, W. W. ID - 12639 IS - 9 JF - Water Resources Research KW - Water Science and Technology SN - 0043-1397 TI - Sources of uncertainty in modeling the glaciohydrological response of a Karakoram watershed to climate change VL - 49 ER - TY - JOUR AB - We use two hydrological models of varying complexity to study the Juncal River Basin in the Central Andes of Chile with the aim to understand the degree of conceptualization and the spatial structure that are needed to model present and future streamflows. We use a conceptual semi-distributed model based on elevation bands [Water Evaluation and Planning (WEAP)], frequently used for water management, and a physically oriented, fully distributed model [Topographic Kinematic Wave Approximation and Integration ETH Zurich (TOPKAPI-ETH)] developed for research purposes mainly. We evaluate the ability of the two models to reproduce the key hydrological processes in the basin with emphasis on snow accumulation and melt, streamflow and the relationships between internal processes. Both models are capable of reproducing observed runoff and the evolution of Moderate-resolution Imaging Spectroradiometer snow cover adequately. In spite of WEAP's simple and conceptual approach for modelling snowmelt and its lack of glacier representation and snow gravitational redistribution as well as a proper routing algorithm, this model can reproduce historical data with a similar goodness of fit as the more complex TOPKAPI-ETH. We show that the performance of both models can be improved by using measured precipitation gradients of higher temporal resolution. In contrast to the good performance of the conceptual model for the present climate, however, we demonstrate that the simplifications in WEAP lead to error compensation, which results in different predictions in simulated melt and runoff for a potentially warmer future climate. TOPKAPI-ETH, using a more physical representation of processes, depends less on calibration and thus is less subject to a compensation of errors through different model components. Our results show that data obtained locally in ad hoc short-term field campaigns are needed to complement data extrapolated from long-term records for simulating changes in the water cycle of high-elevation catchments but that these data can only be efficiently used by a model applying a spatially distributed physical representation of hydrological processes. AU - Ragettli, S. AU - Cortés, G. AU - McPhee, J. AU - Pellicciotti, Francesca ID - 12633 IS - 23 JF - Hydrological Processes KW - Water Science and Technology SN - 0885-6087 TI - An evaluation of approaches for modelling hydrological processes in high-elevation, glacierized Andean watersheds VL - 28 ER - TY - JOUR AB - Plants undergo alternation of generation in which reproductive cells develop in the plant body ("sporophytic generation") and then differentiate into a multicellular gamete-forming "gametophytic generation." Different populations of helper cells assist in this transgenerational journey, with somatic tissues supporting early development and single nurse cells supporting gametogenesis. New data reveal a two-way relationship between early reproductive cells and their helpers involving complex epigenetic and signaling networks determining cell number and fate. Later, the egg cell plays a central role in specifying accessory cells, whereas in both gametophytes, companion cells contribute non-cell-autonomously to the epigenetic landscape of the gamete genomes. AU - Feng, Xiaoqi AU - Zilberman, Daniel AU - Dickinson, Hugh ID - 9520 IS - 3 JF - Developmental Cell SN - 1534-5807 TI - A conversation across generations: Soma-germ cell crosstalk in plants VL - 24 ER - TY - JOUR AB - We report a method for preparing electrode–molecule–electrode junctions that incorporate nonsymmetrical azobenzene dithiols. Our approach is based on sequential deprotection of thiol moieties originally carrying two different protecting groups. The azobenzene derivatives retained their switching properties within monolayers and permitted the photocontrol of electrical conductance. AU - Ely, Tal AU - Das, Sanjib AU - Li, Wenjie AU - Kundu, Pintu AU - Tirosh, Einat AU - Cahen, David AU - Vilan, Ayelet AU - Klajn, Rafal ID - 13405 IS - 18 JF - Synlett KW - Organic Chemistry SN - 0936-5214 TI - Photocontrol of electrical conductance with a nonsymmetrical azobenzene dithiol VL - 24 ER - TY - JOUR AB - Dual-responsive nanoparticles are designed by functionalizing magnetic cores with light-responsive ligands. These materials respond to both light and magnetic fields and can be assembled into various higher-order structures, depending on the relative contributions of these two stimuli. AU - Das, Sanjib AU - Ranjan, Priyadarshi AU - Maiti, Pradipta Sankar AU - Singh, Gurvinder AU - Leitus, Gregory AU - Klajn, Rafal ID - 13406 IS - 3 JF - Advanced Materials KW - Mechanical Engineering KW - Mechanics of Materials KW - General Materials Science SN - 0935-9648 TI - Dual-responsive nanoparticles and their self-assembly VL - 25 ER - TY - JOUR AB - The scale invariance of natural images suggests an analogy to the statistical mechanics of physical systems at a critical point. Here we examine the distribution of pixels in small image patches and show how to construct the corresponding thermodynamics. We find evidence for criticality in a diverging specific heat, which corresponds to large fluctuations in how "surprising" we find individual images, and in the quantitative form of the entropy vs energy. We identify special image configurations as local energy minima and show that average patches within each basin are interpretable as lines and edges in all orientations. AU - Stephens, Greg AU - Mora, Thierry AU - Tkacik, Gasper AU - Bialek, William ID - 2914 IS - 1 JF - Physical Review Letters TI - Statistical thermodynamics of natural images VL - 110 ER - TY - CHAP AB - Leukocyte migration through the interstitial space is crucial for the maintenance of tolerance and immunity. The main cues for leukocyte trafficking are chemokines thought to directionally guide these cells towards their targets. However, model systems that facilitate quantification of chemokine-guided leukocyte migration in vivo are uncommon. Here we describe an ex vivo crawl-in assay using explanted mouse ears that allows the visualization of chemokine-dependent dendritic cell (DC) motility in the dermal interstitium in real time. We present methods for the preparation of mouse ear sheets and their use in multidimensional confocal imaging experiments to monitor and analyze the directional migration of fluorescently labelled DCs through the dermis and into afferent lymphatic vessels. The assay provides a more physiological approach to study leukocyte migration than in vitro three-dimensional (3D) or 2-dimensional (2D) migration assays such as collagen gels and transwell assays. AU - Weber, Michele AU - Sixt, Michael K ED - Cardona, Astrid ED - Ubogu, Eroboghene ID - 10900 SN - 1064-3745 T2 - Chemokines TI - Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations VL - 1013 ER - TY - CHAP AU - Dragoi, Cezara AU - Gupta, Ashutosh AU - Henzinger, Thomas A ID - 5747 SN - 0302-9743 T2 - Computer Aided Verification TI - Automatic Linearizability Proofs of Concurrent Objects with Cooperating Updates VL - 8044 ER - TY - CONF AB - We consider how to edit strings from a source language so that the edited strings belong to a target language, where the languages are given as deterministic finite automata. Non-streaming (or offline) transducers perform edits given the whole source string. We show that the class of deterministic one-pass transducers with registers along with increment and min operation suffices for computing optimal edit distance, whereas the same class of transducers without the min operation is not sufficient. Streaming (or online) transducers perform edits as the letters of the source string are received. We present a polynomial time algorithm for the partial-repair problem that given a bound α asks for the construction of a deterministic streaming transducer (if one exists) that ensures that the ‘maximum fraction’ η of the strings of the source language are edited, within cost α, to the target language. AU - Chatterjee, Krishnendu AU - Chaubal, Siddhesh AU - Rubin, Sasha ID - 10902 SN - 0302-9743 T2 - 7th International Conference on Language and Automata Theory and Applications TI - How to travel between languages VL - 7810 ER - TY - CONF AB - Taking images is an efficient way to collect data about the physical world. It can be done fast and in exquisite detail. By definition, image processing is the field that concerns itself with the computation aimed at harnessing the information contained in images [10]. This talk is concerned with topological information. Our main thesis is that persistent homology [5] is a useful method to quantify and summarize topological information, building a bridge that connects algebraic topology with applications. We provide supporting evidence for this thesis by touching upon four technical developments in the overlap between persistent homology and image processing. AU - Edelsbrunner, Herbert ID - 10897 SN - 0302-9743 T2 - Graph-Based Representations in Pattern Recognition TI - Persistent homology in image processing VL - 7877 ER - TY - THES AB - Motivated by the analysis of highly dynamic message-passing systems, i.e. unbounded thread creation, mobility, etc. we present a framework for the analysis of depth-bounded systems. Depth-bounded systems are one of the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. Even though they are infinite state systems depth-bounded systems are well-structured, thus can be analyzed algorithmically. We give an interpretation of depth-bounded systems as graph-rewriting systems. This gives more flexibility and ease of use to apply depth-bounded systems to other type of systems like shared memory concurrency. First, we develop an adequate domain of limits for depth-bounded systems, a prerequisite for the effective representation of downward-closed sets. Downward-closed sets are needed by forward saturation-based algorithms to represent potentially infinite sets of states. Then, we present an abstract interpretation framework to compute the covering set of well-structured transition systems. Because, in general, the covering set is not computable, our abstraction over-approximates the actual covering set. Our abstraction captures the essence of acceleration based-algorithms while giving up enough precision to ensure convergence. We have implemented the analysis in the PICASSO tool and show that it is accurate in practice. Finally, we build some further analyses like termination using the covering set as starting point. AU - Zufferey, Damien ID - 1405 SN - 2663-337X TI - Analysis of dynamic message passing programs ER - TY - CONF AB - Depth-Bounded Systems form an expressive class of well-structured transition systems. They can model a wide range of concurrent infinite-state systems including those with dynamic thread creation, dynamically changing communication topology, and complex shared heap structures. We present the first method to automatically prove fair termination of depth-bounded systems. Our method uses a numerical abstraction of the system, which we obtain by systematically augmenting an over-approximation of the system’s reachable states with a finite set of counters. This numerical abstraction can be analyzed with existing termination provers. What makes our approach unique is the way in which it exploits the well-structuredness of the analyzed system. We have implemented our work in a prototype tool and used it to automatically prove liveness properties of complex concurrent systems, including nonblocking algorithms such as Treiber’s stack and several distributed processes. Many of these examples are beyond the scope of termination analyses that are based on traditional counter abstractions. AU - Bansal, Kshitij AU - Koskinen, Eric AU - Wies, Thomas AU - Zufferey, Damien ED - Piterman, Nir ED - Smolka, Scott ID - 2847 TI - Structural Counter Abstraction VL - 7795 ER - TY - THES AB - Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading. AU - Campinho, Pedro ID - 1406 SN - 2663-337X TI - Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading ER - TY - JOUR AB - Cooperative behavior, where one individual incurs a cost to help another, is a wide spread phenomenon. Here we study direct reciprocity in the context of the alternating Prisoner's Dilemma. We consider all strategies that can be implemented by one and two-state automata. We calculate the payoff matrix of all pairwise encounters in the presence of noise. We explore deterministic selection dynamics with and without mutation. Using different error rates and payoff values, we observe convergence to a small number of distinct equilibria. Two of them are uncooperative strict Nash equilibria representing always-defect (ALLD) and Grim. The third equilibrium is mixed and represents a cooperative alliance of several strategies, dominated by a strategy which we call Forgiver. Forgiver cooperates whenever the opponent has cooperated; it defects once when the opponent has defected, but subsequently Forgiver attempts to re-establish cooperation even if the opponent has defected again. Forgiver is not an evolutionarily stable strategy, but the alliance, which it rules, is asymptotically stable. For a wide range of parameter values the most commonly observed outcome is convergence to the mixed equilibrium, dominated by Forgiver. Our results show that although forgiving might incur a short-term loss it can lead to a long-term gain. Forgiveness facilitates stable cooperation in the presence of exploitation and noise. AU - Zagorsky, Benjamin AU - Reiter, Johannes AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 2247 IS - 12 JF - PLoS One TI - Forgiver triumphs in alternating prisoner's dilemma VL - 8 ER - TY - JOUR AB - Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases. AU - Reiter, Johannes AU - Božić, Ivana AU - Allen, Benjamin AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 2858 IS - 1 JF - Evolutionary Applications TI - The effect of one additional driver mutation on tumor progression VL - 6 ER - TY - JOUR AB - In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. AU - Božić, Ivana AU - Reiter, Johannes AU - Allen, Benjamin AU - Antal, Tibor AU - Chatterjee, Krishnendu AU - Shah, Preya AU - Moon, Yo AU - Yaqubie, Amin AU - Kelly, Nicole AU - Le, Dung AU - Lipson, Evan AU - Chapman, Paul AU - Diaz, Luis AU - Vogelstein, Bert AU - Nowak, Martin ID - 2816 JF - eLife TI - Evolutionary dynamics of cancer in response to targeted combination therapy VL - 2 ER - TY - CONF AB - In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics. AU - Reiter, Johannes AU - Božić, Ivana AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 2000 T2 - Proceedings of 25th Int. Conf. on Computer Aided Verification TI - TTP: Tool for tumor progression VL - 8044 ER - TY - CONF AB - We develop program synthesis techniques that can help programmers fix concurrency-related bugs. We make two new contributions to synthesis for concurrency, the first improving the efficiency of the synthesized code, and the second improving the efficiency of the synthesis procedure itself. The first contribution is to have the synthesis procedure explore a variety of (sequential) semantics-preserving program transformations. Classically, only one such transformation has been considered, namely, the insertion of synchronization primitives (such as locks). Based on common manual bug-fixing techniques used by Linux device-driver developers, we explore additional, more efficient transformations, such as the reordering of independent instructions. The second contribution is to speed up the counterexample-guided removal of concurrency bugs within the synthesis procedure by considering partial-order traces (instead of linear traces) as counterexamples. A partial-order error trace represents a set of linear (interleaved) traces of a concurrent program all of which lead to the same error. By eliminating a partial-order error trace, we eliminate in a single iteration of the synthesis procedure all linearizations of the partial-order trace. We evaluated our techniques on several simplified examples of real concurrency bugs that occurred in Linux device drivers. AU - Cerny, Pavol AU - Henzinger, Thomas A AU - Radhakrishna, Arjun AU - Ryzhyk, Leonid AU - Tarrach, Thorsten ID - 2445 TI - Efficient synthesis for concurrency by semantics-preserving transformations VL - 8044 ER - TY - JOUR AB - To fight infectious diseases, host immune defenses are employed at multiple levels. Sanitary behavior, such as pathogen avoidance and removal, acts as a first line of defense to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care toward pathogen-exposed group members [2]. One of the most common behaviors is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores; it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behavior extends the current understanding of grooming and the establishment of social immunity in insect societies. AU - Tragust, Simon AU - Mitteregger, Barbara AU - Barone, Vanessa AU - Konrad, Matthias AU - Ugelvig, Line V AU - Cremer, Sylvia ID - 2926 IS - 1 JF - Current Biology TI - Ants disinfect fungus-exposed brood by oral uptake and spread of their poison VL - 23 ER - TY - CONF AB - We study the complexity of central controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize both the expected mean-payoff performance of the system and its stability. e argue that the basic theoretical notion of expressing the stability in terms of the variance of the mean-payoff (called global variance in our paper) is not always sufficient, since it ignores possible instabilities on respective runs. For this reason we propose alernative definitions of stability, which we call local and hybrid variance, and which express how rewards on each run deviate from the run's own mean-payoff and from the expected mean-payoff, respectively. We show that a strategy ensuring both the expected mean-payoff and the variance below given bounds requires randomization and memory, under all the above semantics of variance. We then look at the problem of determining whether there is a such a strategy. For the global variance, we show that the problem is in PSPACE, and that the answer can be approximated in pseudo-polynomial time. For the hybrid variance, the analogous decision problem is in NP, and a polynomial-time approximating algorithm also exists. For local variance, we show that the decision problem is in NP. Since the overall performance can be traded for stability (and vice versa), we also present algorithms for approximating the associated Pareto curve in all the three cases. Finally, we study a special case of the decision problems, where we require a given expected mean-payoff together with zero variance. Here we show that the problems can be all solved in polynomial time. AU - Brázdil, Tomáš AU - Chatterjee, Krishnendu AU - Forejt, Vojtěch AU - Kučera, Antonín ID - 2305 T2 - 28th Annual ACM/IEEE Symposium TI - Trading performance for stability in Markov decision processes ER - TY - CONF AB - In this paper, we introduce the powerful framework of graph games for the analysis of real-time scheduling with firm deadlines. We introduce a novel instance of a partial-observation game that is suitable for this purpose, and prove decidability of all the involved decision problems. We derive a graph game that allows the automated computation of the competitive ratio (along with an optimal witness algorithm for the competitive ratio) and establish an NP-completeness proof for the graph game problem. For a given on-line algorithm, we present polynomial time solution for computing (i) the worst-case utility; (ii) the worst-case utility ratio w.r.t. a clairvoyant off-line algorithm; and (iii) the competitive ratio. A major strength of the proposed approach lies in its flexibility w.r.t. incorporating additional constraints on the adversary and/or the algorithm, including limited maximum or average load, finiteness of periods of overload, etc., which are easily added by means of additional instances of standard objective functions for graph games. AU - Chatterjee, Krishnendu AU - Kößler, Alexander AU - Schmid, Ulrich ID - 2820 SN - 978-1-4503-1567-8 T2 - Proceedings of the 16th International conference on Hybrid systems: Computation and control TI - Automated analysis of real-time scheduling using graph games ER - TY - CONF AB - We consider Conditional Random Fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) x1...xn is the sum of terms over intervals [i,j] where each term is non-zero only if the substring xi...xj equals a prespecified pattern α. Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively O(nL), O(nLℓmax) and O(nLmin{|D|,log(ℓmax+1)}) where L is the combined length of input patterns, ℓmax is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of (Ye et al., 2009) whose complexities are respectively O(nL|D|), O(n|Γ|L2ℓ2max) and O(nL|D|), where |Γ| is the number of input patterns. In addition, we give an efficient algorithm for sampling. Finally, we consider the case of non-positive weights. (Komodakis & Paragios, 2009) gave an O(nL) algorithm for computing the MAP. We present a modification that has the same worst-case complexity but can beat it in the best case. AU - Takhanov, Rustem AU - Kolmogorov, Vladimir ID - 2272 IS - 3 T2 - ICML'13 Proceedings of the 30th International Conference on International TI - Inference algorithms for pattern-based CRFs on sequence data VL - 28 ER - TY - JOUR AB - Cell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN2 carrier in epidermal root tip cells under conditions normally triggering PIN2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots. AU - Remy, Estelle AU - Baster, Pawel AU - Friml, Jirí AU - Duque, Paula ID - 2448 IS - 10 JF - Plant Signaling & Behavior TI - ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs in Arabidopsis root tip VL - 8 ER - TY - JOUR AB - High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation. AU - Refardt, Dominik AU - Bergmiller, Tobias AU - Kümmerli, Rolf ID - 2853 IS - 1759 JF - Proceedings of the Royal Society of London Series B Biological Sciences TI - Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection VL - 280 ER - TY - GEN AB - High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared to its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation. AU - Refardt, Dominik AU - Bergmiller, Tobias AU - Kümmerli, Rolf ID - 9751 TI - Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection ER - TY - JOUR AB - Neural circuit assembly requires selection of specific cell fates, axonal trajectories, and synaptic targets. By analyzing the function of a secreted semaphorin, Sema-2b, in Drosophila olfactory receptor neuron (ORN) development, we identified multiple molecular and cellular mechanisms that link these events. Notch signaling limits Sema-2b expression to ventromedial ORN classes, within which Sema-2b cell-autonomously sensitizes ORN axons to external semaphorins. Central-brain-derived Sema-2a and Sema-2b attract Sema-2b-expressing axons to the ventromedial trajectory. In addition, Sema-2b/PlexB-mediated axon-axon interactions consolidate this trajectory choice and promote ventromedial axon-bundle formation. Selecting the correct developmental trajectory is ultimately essential for proper target choice. These findings demonstrate that Sema-2b couples ORN axon guidance to postsynaptic target neuron dendrite patterning well before the final target selection phase, and exemplify how a single guidance molecule can drive consecutive stages of neural circuit assembly with the help of sophisticated spatial and temporal regulation. AU - Joo, William J. AU - Sweeney, Lora Beatrice Jaeger AU - Liang, Liang AU - Luo, Liqun ID - 7785 IS - 4 JF - Neuron SN - 0896-6273 TI - Linking cell fate, trajectory choice, and target selection: Genetic analysis of sema-2b in olfactory axon targeting VL - 78 ER - TY - GEN AB - Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto'92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system. In this work, we put forward an alternative concept for PoWs -- so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model, using graphs with high "pebbling complexity" and Merkle hash-trees. AU - Dziembowski, Stefan AU - Faust, Sebastian AU - Kolmogorov, Vladimir AU - Pietrzak, Krzysztof Z ID - 2274 TI - Proofs of Space ER - TY - JOUR AB - Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP to evaluate a library of nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide range of biological pathways. We developed informatics techniques for generating dosage-independent phenotypic “fingerprints” for each compound, and for quantifying the likelihood that a compound's CP fingerprint corresponds to its annotated MOA. We identified groups of features that distinguish classes with closely related phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis vs. proteasome inhibitors. We tested several cases in which cytological profiles indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma ligand that acts as a proteasome inhibitor, using independent biochemical assays to confirm the MOAs predicted by the CP signatures. We also applied maximal-information statistics to identify correlations between cytological features and kinase inhibitory activities by combining the CP fingerprints of 24 kinase inhibitors with published data on their specificities against a diverse panel of kinases. The resulting analysis suggests a strategy for probing the biological functions of specific kinases by compiling cytological data from inhibitors of varying specificities. AU - Woehrmann, Marcos H. AU - Bray, Walter M. AU - Durbin, James K. AU - Nisam, Sean C. AU - Michael, Alicia Kathleen AU - Glassey, Emerson AU - Stuart, Joshua M. AU - Lokey, R. Scott ID - 15162 IS - 11 JF - Molecular BioSystems KW - Molecular Biology KW - Biotechnology SN - 1742-206X TI - Large-scale cytological profiling for functional analysis of bioactive compounds VL - 9 ER - TY - JOUR AB - We report numerical simulations of membrane tubulation driven by large colloidal particles. Using Monte Carlo simulations we study how the process depends on particle size and binding strength, and present accurate free energy calculations to sort out how tube formation compares with the competing budding process. We find that tube formation is a result of the collective behavior of the particles adhering on the surface, and it occurs for binding strengths that are smaller than those required for budding. We also find that long linear aggregates of particles forming on the membrane surface act as nucleation seeds for tubulation by lowering the free energy barrier associated to the process. AU - Šarić, Anđela AU - Cacciuto, Angelo ID - 10387 IS - 18 JF - Physical Review Letters KW - general physics and astronomy SN - 0031-9007 TI - Mechanism of membrane tube formation induced by adhesive nanocomponents VL - 109 ER - TY - JOUR AB - Using computer simulations, we show that lipid membranes can mediate linear aggregation of spherical nanoparticles binding to it for a wide range of biologically relevant bending rigidities. This result is in net contrast with the isotropic aggregation of nanoparticles on fluid interfaces or the expected clustering of isotropic insertions in biological membranes. We present a phase diagram indicating where linear aggregation is expected and compute explicitly the free-energy barriers associated with linear and isotropic aggregation. Finally, we provide simple scaling arguments to explain this phenomenology. AU - Šarić, Anđela AU - Cacciuto, Angelo ID - 10388 IS - 11 JF - Physical Review Letters KW - general physics and astronomy SN - 0031-9007 TI - Fluid membranes can drive linear aggregation of adsorbed spherical nanoparticles VL - 108 ER - TY - JOUR AB - In July, 2011, a 32-year-old man presented with thoracic pain radiating to the left arm and upper dorsum, shortness of breath, and palpitations. He had had upper back tension for 6 months. Medical history was unremarkable apart from moderate nicotine use (two pack-years). Echocardiography, electrocardiography, and laboratory tests were unremarkable, excluding a cardiac event. CT of the chest after chest radiography showed a large bulla of 16 cm diameter in the right hemithorax (figure A). We did not detect radiological evidence of underlying pulmonary disease. The bulla wall was unremarkable and no structures were seen within the bulla. AU - Erne, Barbara AU - Graff, Mareike AU - Klemm, Wolfram AU - Danzl, Johann G AU - Leschber, Gunda ID - 1055 IS - 9849 JF - The Lancet TI - Bulla in the lung VL - 380 ER - TY - JOUR AB - We prepare and study a metastable attractive Mott-insulator state formed with bosonic atoms in a three-dimensional optical lattice. Starting from a Mott insulator with Cs atoms at weak repulsive interactions, we use a magnetic Feshbach resonance to tune the interactions to large attractive values and produce a metastable state pinned by attractive interactions with a lifetime on the order of 10 s. We probe the (de)excitation spectrum via lattice modulation spectroscopy, measuring the interaction dependence of two- and three-body bound-state energies. As a result of increased on-site three-body loss we observe resonance broadening and suppression of tunneling processes that produce three-body occupation. AU - Mark, Manfred AU - Haller, Elmar AU - Lauber, Katharina AU - Danzl, Johann G AU - Janisch, Alexander AU - Büchler, Hans AU - Daley, Andrew AU - Nägerl, Hanns ID - 1056 IS - 21 JF - Physical Review Letters TI - Preparation and spectroscopy of a metastable mott-insulator state with attractive interactions VL - 108 ER - TY - CONF AB - The goal of this work is to study the superconducting coherence length in the fluctuation regime in cuprate superconductors. In this work we present cantilever torque magnetometry measurements of micron-size BSCCO flakes patterned with arrays of nanometer scale rings or holes. Using ultrasensitive dynamic torque magnetometry, oscillations in magnetization are observed near Tc as a function of the applied magnetic flux threading the array. Special effort was made to detect the oscillations in magnetization at temperatures above Tc, where the Nernst effect and magnetization measurements suggest the possibility of pairing. To constrain the magnitude of the coherence length in the fluctuation regime, we will present the dependence of the amplitude of the h/2e period oscillations as a function of temperature and hole size. AU - Polshyn, Hryhoriy AU - Budakian, Raffi ID - 10750 IS - 1 SN - 0003-0503 T2 - APS March Meeting 2012 TI - Cantilever torque magnetometry study of multiply connected BSCCO arrays near Tc VL - 57 ER - TY - CHAP AB - Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals D-ribose and adenine, and the functional, and potential therapeutic, implications of doing so. AU - zur Nedden, Stephanie AU - Doney, Alexander S. AU - Frenguelli, Bruno G. ED - Masino, Susan ED - Boison, Detlev ID - 10896 SN - 9781461439028 T2 - Adenosine TI - The double-edged sword: Gaining Adenosine at the expense of ATP. How to balance the books ER - TY - JOUR AB - The Nuclear Envelope (NE) contains over 100 different proteins that associate with nuclear components such as chromatin, the lamina and the transcription machinery. Mutations in genes encoding NE proteins have been shown to result in tissue-specific defects and disease, suggesting cell-type specific differences in NE composition and function. Consistent with these observations, recent studies have revealed unexpected functions for numerous NE associated proteins during cell differentiation and development. Here we review the latest insights into the roles played by the NE in cell differentiation, development, disease and aging, focusing primarily on inner nuclear membrane (INM) proteins and nuclear pore components. AU - Gomez-Cavazos, J Sebastian AU - HETZER, Martin W ID - 11089 IS - 6 JF - Current Opinion in Cell Biology KW - Cell Biology SN - 0955-0674 TI - Outfits for different occasions: tissue-specific roles of Nuclear Envelope proteins VL - 24 ER - TY - JOUR AB - Neoplastic cells are often characterized by specific morphological abnormalities of the nuclear envelope (NE), which have been used for cancer diagnosis for more than a century. The NE is a double phospholipid bilayer that encapsulates the nuclear genome, regulates all nuclear trafficking of RNAs and proteins and prevents the passive diffusion of macromolecules between the nucleoplasm and the cytoplasm. Whether there is a consequence to the proper functioning of the cell and loss of structural integrity of the nucleus remains unclear. Using live cell imaging, we characterize a phenomenon wherein nuclei of several proliferating human cancer cell lines become temporarily ruptured during interphase. Strikingly, NE rupturing was associated with the mislocalization of nucleoplasmic and cytoplasmic proteins and, in the most extreme cases, the entrapment of cytoplasmic organelles in the nuclear interior. In addition, we observed the formation of micronuclei-like structures during interphase and the movement of chromatin out of the nuclear space. The frequency of these NE rupturing events was higher in cells in which the nuclear lamina, a network of intermediate filaments providing mechanical support to the NE, was not properly formed. Our data uncover the existence of a NE instability that has the potential to change the genomic landscape of cancer cells. AU - Vargas, Jesse D. AU - Hatch, Emily M. AU - Anderson, Daniel J. AU - HETZER, Martin W ID - 11091 IS - 1 JF - Nucleus KW - Cell Biology SN - 1949-1034 TI - Transient nuclear envelope rupturing during interphase in human cancer cells VL - 3 ER - TY - JOUR AB - Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem cells (ESCs) but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ESCs into neuroprogenitors. We found that the addition of Nup210 to NPCs does not affect nuclear transport but is required for the induction of genes that are essential for cell differentiation. Our results identify a single change in NPC composition as an essential step in cell differentiation and establish a role for Nup210 in gene expression regulation and cell fate determination. AU - D'Angelo, Maximiliano A. AU - Gomez-Cavazos, J. Sebastian AU - Mei, Arianna AU - Lackner, Daniel H. AU - HETZER, Martin W ID - 11093 IS - 2 JF - Developmental Cell KW - Developmental Biology KW - Cell Biology KW - General Biochemistry KW - Genetics and Molecular Biology KW - Molecular Biology SN - 1534-5807 TI - A change in nuclear pore complex composition regulates cell differentiation VL - 22 ER - TY - JOUR AB - To combat the functional decline of the proteome, cells use the process of protein turnover to replace potentially impaired polypeptides with new functional copies. We found that extremely long-lived proteins (ELLPs) did not turn over in postmitotic cells of the rat central nervous system. These ELLPs were associated with chromatin and the nuclear pore complex, the central transport channels that mediate all molecular trafficking in and out of the nucleus. The longevity of these proteins would be expected to expose them to potentially harmful metabolites, putting them at risk of accumulating damage over extended periods of time. Thus, it is possible that failure to maintain proper levels and functional integrity of ELLPs in nonproliferative cells might contribute to age-related deterioration in cell and tissue function. AU - Savas, Jeffrey N. AU - Toyama, Brandon H. AU - Xu, Tao AU - Yates, John R. AU - HETZER, Martin W ID - 11092 IS - 6071 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - Extremely long-lived nuclear pore proteins in the rat brain VL - 335 ER - TY - JOUR AB - Nuclear export of mRNAs is thought to occur exclusively through nuclear pore complexes. In this issue of Cell, Speese et al. identify an alternate pathway for mRNA export in muscle cells where ribonucleoprotein complexes involved in forming neuromuscular junctions transit the nuclear envelope by fusing with and budding through the nuclear membrane. AU - Hatch, Emily M. AU - HETZER, Martin W ID - 11090 IS - 4 JF - Cell KW - General Biochemistry KW - Genetics and Molecular Biology SN - 0092-8674 TI - RNP export by nuclear envelope budding VL - 149 ER - TY - JOUR AB - Although liquids typically flow around intruding objects, a counterintuitive phenomenon occurs in dense suspensions of micrometre-sized particles: they become liquid-like when perturbed lightly, but harden when driven strongly. Rheological experiments have investigated how such thickening arises under shear, and linked it to hydrodynamic interactions or granular dilation. However, neither of these mechanisms alone can explain the ability of suspensions to generate very large, positive normal stresses under impact. To illustrate the phenomenon, such stresses can be large enough to allow a person to run across a suspension without sinking, and far exceed the upper limit observed under shear or extension. Here we show that these stresses originate from an impact-generated solidification front that transforms an initially compressible particle matrix into a rapidly growing jammed region, ultimately leading to extraordinary amounts of momentum absorption. Using high-speed videography, embedded force sensing and X-ray imaging, we capture the detailed dynamics of this process as it decelerates a metal rod hitting a suspension of cornflour (cornstarch) in water. We develop a model for the dynamic solidification and its effect on the surrounding suspension that reproduces the observed behaviour quantitatively. Our findings suggest that prior interpretations of the impact resistance as dominated by shear thickening need to be revisited. AU - Waitukaitis, Scott R AU - Jaeger, Heinrich ID - 113 IS - 7406 JF - Nature TI - Impact-activated solidification of dense suspensions via dynamic jamming fronts VL - 487 ER -