TY - JOUR AB - We propose a new approach to probing ergodicity and its breakdown in one-dimensional quantum manybody systems based on their response to a local perturbation. We study the distribution of matrix elements of a local operator between the system's eigenstates, finding a qualitatively different behavior in the manybody localized (MBL) and ergodic phases. To characterize how strongly a local perturbation modifies the eigenstates, we introduce the parameter g(L) = (In (Vnm/δ)) which represents the disorder-averaged ratio of a typical matrix element of a local operator V to energy level spacing δ this parameter is reminiscent of the Thouless conductance in the single-particle localization. We show that the parameter g(L) decreases with system size L in the MBL phase and grows in the ergodic phase. We surmise that the delocalization transition occurs when g(L) is independent of system size, g(L)=gc ~ 1. We illustrate our approach by studying the many-body localization transition and resolving the many-body mobility edge in a disordered one-dimensional XXZ spin-1=2 chain using exact diagonalization and time-evolving block-decimation methods. Our criterion for the MBL transition gives insights into microscopic details of transition. Its direct physical consequences, in particular, logarithmically slow transport at the transition and extensive entanglement entropy of the eigenstates, are consistent with recent renormalization-group predictions. AU - Maksym Serbyn AU - Papić, Zlatko AU - Abanin, Dmitry A ID - 982 IS - 4 JF - Physical Review X TI - Criterion for many-body localization-delocalization phase transition VL - 5 ER - TY - JOUR AB - Quasiparticle excitations can compromise the performance of superconducting devices, causing high-frequency dissipation, decoherence in Josephson qubits, and braiding errors in proposed Majorana-based topological quantum computers. Quasiparticle dynamics have been studied in detail in metallic superconductors but remain relatively unexplored in semiconductor-superconductor structures, which are now being intensely pursued in the context of topological superconductivity. To this end, we use a system comprising a gate-confined semiconductor nanowire with an epitaxially grown superconductor layer, yielding an isolated, proximitized nanowire segment. We identify bound states in the semiconductor by means of bias spectroscopy, determine the characteristic temperatures and magnetic fields for quasiparticle excitations, and extract a parity lifetime (poisoning time) of the bound state in the semiconductor exceeding 10 ms. AU - Higginbotham, Andrew P AU - Albrecht, S M AU - Kiršanskas, Gediminas AU - Chang, W AU - Kuemmeth, Ferdinand AU - Krogstrup, Peter AU - Jespersen, Thomas AU - Nygård, Jesper AU - Flensberg, Karsten AU - Marcus, Charles ID - 99 IS - 12 JF - Nature Physics TI - Parity lifetime of bound states in a proximitized semiconductor nanowire VL - 11 ER - TY - JOUR AB - In this note, we consider the dynamics associated to a perturbation of an integrable Hamiltonian system in action-angle coordinates in any number of degrees of freedom and we prove the following result of ``micro-diffusion'': under generic assumptions on $ h$ and $ f$, there exists an orbit of the system for which the drift of its action variables is at least of order $ \sqrt {\varepsilon }$, after a time of order $ \sqrt {\varepsilon }^{-1}$. The assumptions, which are essentially minimal, are that there exists a resonant point for $ h$ and that the corresponding averaged perturbation is non-constant. The conclusions, although very weak when compared to usual instability phenomena, are also essentially optimal within this setting. AU - Bounemoura, Abed AU - Kaloshin, Vadim ID - 8495 IS - 4 JF - Proceedings of the American Mathematical Society SN - 0002-9939 TI - A note on micro-instability for Hamiltonian systems close to integrable VL - 144 ER - TY - JOUR AB - Proteases play important roles in many biologic processes and are key mediators of cancer, inflammation, and thrombosis. However, comprehensive and quantitative techniques to define the substrate specificity profile of proteases are lacking. The metalloprotease ADAMTS13 regulates blood coagulation by cleaving von Willebrand factor (VWF), reducing its procoagulant activity. A mutagenized substrate phage display library based on a 73-amino acid fragment of VWF was constructed, and the ADAMTS13-dependent change in library complexity was evaluated over reaction time points, using high-throughput sequencing. Reaction rate constants (kcat/KM) were calculated for nearly every possible single amino acid substitution within this fragment. This massively parallel enzyme kinetics analysis detailed the specificity of ADAMTS13 and demonstrated the critical importance of the P1-P1' substrate residues while defining exosite binding domains. These data provided empirical evidence for the propensity for epistasis within VWF and showed strong correlation to conservation across orthologs, highlighting evolutionary selective pressures for VWF. AU - Kretz, Colin A AU - Dai, Manhong AU - Soylemez, Onuralp AU - Yee, Andrew AU - Desch, Karl C AU - Siemieniak, David R AU - Tomberg, Kärt AU - Fyodor Kondrashov AU - Meng, Fan AU - Ginsburg, David B ID - 866 IS - 30 JF - PNAS TI - Massively parallel enzyme kinetics reveals the substrate recognition landscape of the metalloprotease ADAMTS13 VL - 112 ER - TY - JOUR AB - The factors that determine the tempo and mode of protein evolution continue to be a central question in molecular evolution. Traditionally, studies of protein evolution focused on the rates of amino acid substitutions. More recently, with the availability of sequence data and advanced experimental techniques, the focus of attention has shifted toward the study of evolutionary trajectories and the overall layout of protein fitness landscapes. In this review we describe the effect of epistasis on the topology of evolutionary pathways that are likely to be found in fitness landscapes and develop a simple theory to connect the number of maladapted genotypes to the topology of fitness landscapes with epistatic interactions. Finally, we review recent studies that have probed the extent of epistatic interactions and have begun to chart the fitness landscapes in protein sequence space. AU - Kondrashov, Dmitry A AU - Fyodor Kondrashov ID - 886 IS - 1 JF - Trends in Genetics TI - Topological features of rugged fitness landscapes in sequence space VL - 31 ER - TY - JOUR AB - MCM2 is a subunit of the replicative helicase machinery shown to interact with histones H3 and H4 during the replication process through its N-terminal domain. During replication, this interaction has been proposed to assist disassembly and assembly of nucleosomes on DNA. However, how this interaction participates in crosstalk with histone chaperones at the replication fork remains to be elucidated. Here, we solved the crystal structure of the ternary complex between the histone-binding domain of Mcm2 and the histones H3-H4 at 2.9 Å resolution. Histones H3 and H4 assemble as a tetramer in the crystal structure, but MCM2 interacts only with a single molecule of H3-H4. The latter interaction exploits binding surfaces that contact either DNA or H2B when H3-H4 dimers are incorporated in the nucleosome core particle. Upon binding of the ternary complex with the histone chaperone ASF1, the histone tetramer dissociates and both MCM2 and ASF1 interact simultaneously with the histones forming a 1:1:1:1 heteromeric complex. Thermodynamic analysis of the quaternary complex together with structural modeling support that ASF1 and MCM2 could form a chaperoning module for histones H3 and H4 protecting them from promiscuous interactions. This suggests an additional function for MCM2 outside its helicase function as a proper histone chaperone connected to the replication pathway. AU - Richet, Nicolas AU - Liu, Danni AU - Legrand, Pierre AU - Velours, Christophe AU - Corpet, Armelle AU - Gaubert, Albane AU - Bakail, May M AU - Moal-Raisin, Gwenaelle AU - Guerois, Raphael AU - Compper, Christel AU - Besle, Arthur AU - Guichard, Berengère AU - Almouzni, Genevieve AU - Ochsenbein, Françoise ID - 9017 IS - 3 JF - Nucleic Acids Research SN - 1362-4962 TI - Structural insight into how the human helicase subunit MCM2 may act as a histone chaperone together with ASF1 at the replication fork VL - 43 ER - TY - JOUR AB - This paper presents a numerical study of a Capillary Pumped Loop evaporator. A two-dimensional unsteady mathematical model of a flat evaporator is developed to simulate heat and mass transfer in unsaturated porous wick with phase change. The liquid-vapor phase change inside the porous wick is described by Langmuir's law. The governing equations are solved by the Finite Element Method. The results are presented then for a sintered nickel wick and methanol as a working fluid. The heat flux required to the transition from the all-liquid wick to the vapor-liquid wick is calculated. The dynamic and thermodynamic behavior of the working fluid in the capillary structure are discussed in this paper. AU - Boubaker, Riadh AU - Platel, Vincent AU - Bergès, Alexis AU - Bancelin, Mathieu AU - Hannezo, Edouard B ID - 924 JF - Applied Thermal Engineering TI - Dynamic model of heat and mass transfer in an unsaturated porous wick of capillary pumped loop VL - 76 ER - TY - JOUR AB - An essential question of morphogenesis is how patterns arise without preexisting positional information, as inspired by Turing. In the past few years, cytoskeletal flows in the cell cortex have been identified as a key mechanism of molecular patterning at the subcellular level. Theoretical and in vitro studies have suggested that biological polymers such as actomyosin gels have the property to self-organize, but the applicability of this concept in an in vivo setting remains unclear. Here, we report that the regular spacing pattern of supracellular actin rings in the Drosophila tracheal tubule is governed by a self-organizing principle. We propose a simple biophysical model where pattern formation arises from the interplay of myosin contractility and actin turnover. We validate the hypotheses of the model using photobleaching experiments and report that the formation of actin rings is contractility dependent. Moreover, genetic and pharmacological perturbations of the physical properties of the actomyosin gel modify the spacing of the pattern, as the model predicted. In addition, our model posited a role of cortical friction in stabilizing the spacing pattern of actin rings. Consistently, genetic depletion of apical extracellular matrix caused strikingly dynamic movements of actin rings, mirroring our model prediction of a transition from steady to chaotic actin patterns at low cortical friction. Our results therefore demonstrate quantitatively that a hydrodynamical instability of the actin cortex can trigger regular pattern formation and drive morphogenesis in an in vivo setting. AU - Hannezo, Edouard B AU - Dong, Bo AU - Recho, Pierre AU - Joanny, Jean AU - Hayashi, Shigeo ID - 929 IS - 28 JF - PNAS TI - Cortical instability drives periodic supracellular actin pattern formation in epithelial tubes VL - 112 ER - TY - JOUR AB - Although collective cell motion plays an important role, for example during wound healing, embryogenesis, or cancer progression, the fundamental rules governing this motion are still not well understood, in particular at high cell density. We study here the motion of human bronchial epithelial cells within a monolayer, over long times. We observe that, as the monolayer ages, the cells slow down monotonously, while the velocity correlation length first increases as the cells slow down but eventually decreases at the slowest motions. By comparing experiments, analytic model, and detailed particle-based simulations, we shed light on this biological amorphous solidification process, demonstrating that the observed dynamics can be explained as a consequence of the combined maturation and strengthening of cell-cell and cell-substrate adhesions. Surprisingly, the increase of cell surface density due to proliferation is only secondary in this process. This analysis is confirmed with two other cell types. The very general relations between the mean cell velocity and velocity correlation lengths, which apply for aggregates of self-propelled particles, as well as motile cells, can possibly be used to discriminate between various parameter changes in vivo, from noninvasive microscopy data. AU - García, Simón AU - Hannezo, Edouard B AU - Elgeti, Jens AU - Joanny, Jean AU - Silberzan, Pascal AU - Gov, Nir ID - 933 IS - 50 JF - PNAS TI - Physics of active jamming during collective cellular motion in a monolayer VL - 112 ER - TY - JOUR AB - Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and confirmed DNA and histone methylation as key regulators of plant imprinting. However, the biological roles of the vast majority of imprinted plant genes are unknown, and the evolutionary forces shaping plant imprinting remain rather opaque. Here, we review the mechanisms of plant genomic imprinting and discuss theories of imprinting evolution and biological significance in light of recent findings. AU - Rodrigues, Jessica A. AU - Zilberman, Daniel ID - 9532 IS - 24 JF - Genes and Development SN - 0890-9369 TI - Evolution and function of genomic imprinting in plants VL - 29 ER - TY - JOUR AB - The size dependence of the strength of nano- and micron-sized crystals is studied using a new simulation approach in which the dynamics of the density functions of dislocations are modeled. Since any quantity of dislocations can be represented by a density, this approach can handle large systems containing large quantities of dislocations, which may handicap discrete dislocation dynamics schemes due to the excessive computation time involved. For this reason, pillar sizes spanning a large range, from the sub-micron to micron regimes, can be simulated. The simulation results reveal the power-law relationship between strength and specimen size up to a certain size, beyond which the strength varies much more slowly with size. For specimens smaller than ~4000b, their strength is found to be controlled by the dislocation depletion condition, in which the total dislocation density remains almost constant throughout the loading process. In specimens larger than ~4000b, the initial dislocation distribution is of critical importance since the presence of dislocation entanglements is found to obstruct deformation in the neighboring regions within a distance of ~2000b. This length scale suggests that the effects of dense dislocation clusters are greater in intermediate-sized specimens (e.g. 4000b and 8000b) than in larger specimens (e.g. 16 000b), according to the weakest-link concept. AU - Leung, P S S AU - Leung, H S AU - Cheng, Bingqing AU - Ngan, A H W ID - 9684 IS - 3 JF - Modelling and Simulation in Materials Science and Engineering SN - 0965-0393 TI - Size dependence of yield strength simulated by a dislocation-density function dynamics approach VL - 23 ER - TY - JOUR AB - Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease. AU - Gómez Sicilia, Àngel AU - Sikora, Mateusz K AU - Cieplak, Marek AU - Carrión Vázquez, Mariano ID - 1566 IS - 10 JF - PLoS Computational Biology TI - An exploration of the universe of polyglutamine structures VL - 11 ER - TY - GEN AU - Tugrul, Murat AU - Paixao, Tiago AU - Barton, Nicholas H AU - Tkačik, Gašper ID - 9712 TI - Other fitness models for comparison & for interacting TFBSs ER - TY - GEN AU - Gómez Sicilia, Àngel AU - Sikora, Mateusz K AU - Cieplak, Marek AU - Carrión Vázquez, Mariano ID - 9714 TI - An exploration of the universe of polyglutamine structures - submission to PLOS journals ER - TY - GEN AU - Trubenova, Barbora AU - Novak, Sebastian AU - Hager, Reinmar ID - 9715 TI - Mathematical inference of the results ER - TY - JOUR AB - The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens. AU - Konrad, Matthias AU - Grasse, Anna V AU - Tragust, Simon AU - Cremer, Sylvia ID - 1993 IS - 1799 JF - Proceedings of the Royal Society of London Series B Biological Sciences SN - 0962-8452 TI - Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host VL - 282 ER - TY - GEN AB - Repeated pathogen exposure is a common threat in colonies of social insects, posing selection pressures on colony members to respond with improved disease-defense performance. We here tested whether experience gained by repeated tending of low-level fungus-exposed (Metarhizium robertsii) larvae may alter the performance of sanitary brood care in the clonal ant, Platythyrea punctata. We trained ants individually over nine consecutive trials to either sham-treated or fungus-exposed larvae. We then compared the larval grooming behavior of naive and trained ants and measured how effectively they removed infectious fungal conidiospores from the fungus-exposed larvae. We found that the ants changed the duration of larval grooming in response to both, larval treatment and their level of experience: (1) sham-treated larvae received longer grooming than the fungus-exposed larvae and (2) trained ants performed less self-grooming but longer larval grooming than naive ants, which was true for both, ants trained to fungus-exposed and also to sham-treated larvae. Ants that groomed the fungus-exposed larvae for longer periods removed a higher number of fungal conidiospores from the surface of the fungus-exposed larvae. As experienced ants performed longer larval grooming, they were more effective in fungal removal, thus making them better caretakers under pathogen attack of the colony. By studying this clonal ant, we can thus conclude that even in the absence of genetic variation between colony members, differences in experience levels of brood care may affect performance of sanitary brood care in social insects. AU - Westhus, Claudia AU - Ugelvig, Line V AU - Tourdot, Edouard AU - Heinze, Jürgen AU - Doums, Claudie AU - Cremer, Sylvia ID - 9742 TI - Data from: Increased grooming after repeated brood care provides sanitary benefits in a clonal ant ER - TY - GEN AU - Chevereau, Guillaume AU - Lukacisinova, Marta AU - Batur, Tugce AU - Guvenek, Aysegul AU - Ayhan, Dilay Hazal AU - Toprak, Erdal AU - Bollenbach, Mark Tobias ID - 9765 TI - Gene ontology enrichment analysis for the most sensitive gene deletion strains for all drugs ER - TY - JOUR AB - The hydrology of high-elevation watersheds of the Hindu Kush-Himalaya region (HKH) is poorly known. The correct representation of internal states and process dynamics in glacio-hydrological models can often not be verified due to missing in situ measurements. We use a new set of detailed ground data from the upper Langtang valley in Nepal to systematically guide a state-of-the art glacio-hydrological model through a parameter assigning process with the aim to understand the hydrology of the catchment and contribution of snow and ice processes to runoff. 14 parameters are directly calculated on the basis of local data, and 13 parameters are calibrated against 5 different datasets of in situ or remote sensing data. Spatial fields of debris thickness are reconstructed through a novel approach that employs data from an Unmanned Aerial Vehicle (UAV), energy balance modeling and statistical techniques. The model is validated against measured catchment runoff (Nash–Sutcliffe efficiency 0.87) and modeled snow cover is compared to Landsat snow cover. The advanced representation of processes allowed assessing the role played by avalanching for runoff for the first time for a Himalayan catchment (5% of annual water inputs to the hydrological system are due to snow redistribution) and to quantify the hydrological significance of sub-debris ice melt (9% of annual water inputs). Snowmelt is the most important contributor to total runoff during the hydrological year 2012/2013 (representing 40% of all sources), followed by rainfall (34%) and ice melt (26%). A sensitivity analysis is used to assess the efficiency of the monitoring network and identify the timing and location of field measurements that constrain model uncertainty. The methodology to set up a glacio-hydrological model in high-elevation regions presented in this study can be regarded as a benchmark for modelers in the HKH seeking to evaluate their calibration approach, their experimental setup and thus to reduce the predictive model uncertainty. AU - Ragettli, S. AU - Pellicciotti, Francesca AU - Immerzeel, W.W. AU - Miles, E.S. AU - Petersen, L. AU - Heynen, M. AU - Shea, J.M. AU - Stumm, D. AU - Joshi, S. AU - Shrestha, A. ID - 12630 IS - 4 JF - Advances in Water Resources KW - Water Science and Technology SN - 0309-1708 TI - Unraveling the hydrology of a Himalayan catchment through integration of high resolution in situ data and remote sensing with an advanced simulation model VL - 78 ER - TY - JOUR AB - Thick debris cover on glaciers can significantly reduce ice melt. However, several studies have suggested that debris-covered glaciers in the Himalaya might have lost mass at a rate similar to debris-free glaciers. We reconstruct elevation and mass changes for the debris-covered glaciers of the upper Langtang valley, Nepalese Himalaya, using a digital elevation model (DEM) from 1974 stereo Hexagon satellite data and the 2000 SRTM (Shuttle Radar Topography Mission) DEM. Uncertainties are high in the accumulation areas, due to data gaps in the SRTM and difficulties with delineation of the glacier borders. Even with these uncertainties, we obtain thinning rates comparable to those of several other studies in the Himalaya. In particular, we obtain a total mass balance for the investigated debris-covered glaciers of the basin of –0.32 ± 0.18 m w.e. a−1. However, there are major spatial differences both between glaciers and within any single glacier, exhibiting a very distinct nonlinear mass-balance profile with elevation. Through analysis of surface velocities derived from Landsat ETM+ imagery, we show that thinning occurs in areas of low velocity and low slope. These areas are prone to a general, dynamic decay of surface features and to the development of supraglacial lakes and ice cliffs, which may be responsible for a considerable increase in overall glacier ablation. AU - Pellicciotti, Francesca AU - Stephan, Christa AU - Miles, Evan AU - Herreid, Sam AU - Immerzeel, Walter W. AU - Bolch, Tobias ID - 12628 IS - 226 JF - Journal of Glaciology KW - Earth-Surface Processes SN - 0022-1430 TI - Mass-balance changes of the debris-covered glaciers in the Langtang Himal, Nepal, from 1974 to 1999 VL - 61 ER -