@article{7055, abstract = {A recent class of topological nodal-line semimetals with the general formula MSiX (M = Zr, Hf and X = S, Se, Te) has attracted much experimental and theoretical interest due to their properties, particularly their large magnetoresistances and high carrier mobilities. The plateletlike nature of the MSiX crystals and their extremely low residual resistivities make measurements of the resistivity along the [001] direction extremely challenging. To accomplish such measurements, microstructures of single crystals were prepared using focused ion beam techniques. Microstructures prepared in this manner have very well-defined geometries and maintain their high crystal quality, verified by the observations of quantum oscillations. We present magnetoresistance and quantum oscillation data for currents applied along both [001] and [100] in ZrSiS and ZrSiSe, which are consistent with the nontrivial topology of the Dirac line-node, as determined by a measured π Berry phase. Surprisingly, we find that, despite the three dimensional nature of both the Fermi surfaces of ZrSiS and ZrSiSe, both the resistivity anisotropy under applied magnetic fields and the in-plane angular dependent magnetoresistance differ considerably between the two compounds. Finally, we discuss the role microstructuring can play in the study of these materials and our ability to make these microstructures free-standing.}, author = {Shirer, Kent R. and Modic, Kimberly A and Zimmerling, Tino and Bachmann, Maja D. and König, Markus and Moll, Philip J. W. and Schoop, Leslie and Mackenzie, Andrew P.}, issn = {2166-532X}, journal = {APL Materials}, number = {10}, publisher = {AIP}, title = {{Out-of-plane transport in ZrSiS and ZrSiSe microstructures}}, doi = {10.1063/1.5124568}, volume = {7}, year = {2019}, } @article{7057, abstract = {We present a high magnetic field study of NbP—a member of the monopnictide Weyl semimetal (WSM) family. While the monoarsenides (NbAs and TaAs) have topologically distinct left and right-handed Weyl fermi surfaces, NbP is argued to be “topologically trivial” due to the fact that all pairs of Weyl nodes are encompassed by a single Fermi surface. We use torque magnetometry to measure the magnetic response of NbP up to 60 tesla and uncover a Berry paramagnetic response, characteristic of the topological Weyl nodes, across the entire field range. At the quantum limit B* (≈32 T), τ/B experiences a change in slope when the chemical potential enters the last Landau level. Our calculations confirm that this magnetic response arises from band topology of the Weyl pocket, even though the Fermi surface encompasses both Weyl nodes at zero magnetic field. We also find that the magnetic field pulls the chemical potential to the chiral n = 0 Landau level in the quantum limit, providing a disorder-free way of accessing chiral Weyl fermions in systems that are “not quite” WSMs in zero magnetic field.}, author = {Modic, Kimberly A and Meng, Tobias and Ronning, Filip and Bauer, Eric D. and Moll, Philip J. W. and Ramshaw, B. J.}, issn = {2045-2322}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, title = {{Thermodynamic signatures of Weyl fermions in NbP}}, doi = {10.1038/s41598-018-38161-7}, volume = {9}, year = {2019}, } @article{7056, abstract = {In the Ca1−x La x FeAs2 (1 1 2) family of pnictide superconductors, we have investigated a highly overdoped composition (x  =  0.56), prepared by a high-pressure, high-temperature synthesis. Magnetic measurements show an antiferromagnetic transition at T N  =  120 K, well above the one at lower doping (0.15  <  x  <  0.27). Below the onset of long-range magnetic order at T N, the electrical resistivity is strongly reduced and is dominated by electron–electron interactions, as evident from its temperature dependence. The Seebeck coefficient shows a clear metallic behavior as in narrow band conductors. The temperature dependence of the Hall coefficient and the violation of Kohler's rule agree with the multiband character of the material. No superconductivity was observed down to 1.8 K. The success of the high-pressure synthesis encourages further investigations of the so far only partially explored phase diagram in this family of Iron-based high temperature superconductors. }, author = {Martino, Edoardo and Bachmann, Maja D and Rossi, Lidia and Modic, Kimberly A and Zivkovic, Ivica and Rønnow, Henrik M and Moll, Philip J W and Akrap, Ana and Forró, László and Katrych, Sergiy}, issn = {1361-648X}, journal = {Journal of Physics: Condensed Matter}, number = {48}, publisher = {IOP Publishing}, title = {{Persistent antiferromagnetic order in heavily overdoped Ca1−x La x FeAs2}}, doi = {10.1088/1361-648x/ab3b43}, volume = {31}, year = {2019}, } @article{7128, abstract = {Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a few microRNAs (miRNAs) that can induce cardiomyocyte proliferation and stimulate cardiac regeneration in mice. Here, we show that all of the most effective of these miRNAs activate nuclear localization of the master transcriptional cofactor Yes-associated protein (YAP) and induce expression of YAP-responsive genes. In particular, miR-199a-3p directly targets two mRNAs coding for proteins impinging on the Hippo pathway, the upstream YAP inhibitory kinase TAOK1, and the E3 ubiquitin ligase β-TrCP, which leads to YAP degradation. Several of the pro-proliferative miRNAs (including miR-199a-3p) also inhibit filamentous actin depolymerization by targeting Cofilin2, a process that by itself activates YAP nuclear translocation. Thus, activation of YAP and modulation of the actin cytoskeleton are major components of the pro-proliferative action of miR-199a-3p and other miRNAs that induce cardiomyocyte proliferation.}, author = {Torrini, Consuelo and Cubero, Ryan J and Dirkx, Ellen and Braga, Luca and Ali, Hashim and Prosdocimo, Giulia and Gutierrez, Maria Ines and Collesi, Chiara and Licastro, Danilo and Zentilin, Lorena and Mano, Miguel and Zacchigna, Serena and Vendruscolo, Michele and Marsili, Matteo and Samal, Areejit and Giacca, Mauro}, issn = {2211-1247}, journal = {Cell Reports}, keywords = {cardiomyocyte, cell cycle, Cofilin2, cytoskeleton, Hippo, microRNA, regeneration, YAP}, number = {9}, pages = {2759--2771.e5}, publisher = {Elsevier}, title = {{Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation}}, doi = {10.1016/j.celrep.2019.05.005}, volume = {27}, year = {2019}, } @article{7130, abstract = {We show that statistical criticality, i.e. the occurrence of power law frequency distributions, arises in samples that are maximally informative about the underlying generating process. In order to reach this conclusion, we first identify the frequency with which different outcomes occur in a sample, as the variable carrying useful information on the generative process. The entropy of the frequency, that we call relevance, provides an upper bound to the number of informative bits. This differs from the entropy of the data, that we take as a measure of resolution. Samples that maximise relevance at a given resolution—that we call maximally informative samples—exhibit statistical criticality. In particular, Zipf's law arises at the optimal trade-off between resolution (i.e. compression) and relevance. As a byproduct, we derive a bound of the maximal number of parameters that can be estimated from a dataset, in the absence of prior knowledge on the generative model. Furthermore, we relate criticality to the statistical properties of the representation of the data generating process. We show that, as a consequence of the concentration property of the asymptotic equipartition property, representations that are maximally informative about the data generating process are characterised by an exponential distribution of energy levels. This arises from a principle of minimal entropy, that is conjugate of the maximum entropy principle in statistical mechanics. This explains why statistical criticality requires no parameter fine tuning in maximally informative samples.}, author = {Cubero, Ryan J and Jo, Junghyo and Marsili, Matteo and Roudi, Yasser and Song, Juyong}, issn = {1742-5468}, journal = {Journal of Statistical Mechanics: Theory and Experiment}, keywords = {optimization under uncertainty, source coding, large deviation}, number = {6}, publisher = {IOP Publishing}, title = {{Statistical criticality arises in most informative representations}}, doi = {10.1088/1742-5468/ab16c8}, volume = {2019}, year = {2019}, } @article{7150, abstract = {In this work, we use algebraic methods for studying distance computation and subgraph detection tasks in the congested clique model. Specifically, we adapt parallel matrix multiplication implementations to the congested clique, obtaining an O(n1−2/ω) round matrix multiplication algorithm, where ω<2.3728639 is the exponent of matrix multiplication. In conjunction with known techniques from centralised algorithmics, this gives significant improvements over previous best upper bounds in the congested clique model. The highlight results include: 1. triangle and 4-cycle counting in O(n0.158) rounds, improving upon the O(n1/3) algorithm of Dolev et al. [DISC 2012], 2. a (1+o(1))-approximation of all-pairs shortest paths in O(n0.158) rounds, improving upon the O~(n1/2)-round (2+o(1))-approximation algorithm given by Nanongkai [STOC 2014], and 3. computing the girth in O(n0.158) rounds, which is the first non-trivial solution in this model. In addition, we present a novel constant-round combinatorial algorithm for detecting 4-cycles.}, author = {Censor-Hillel, Keren and Kaski, Petteri and Korhonen, Janne and Lenzen, Christoph and Paz, Ami and Suomela, Jukka}, issn = {0178-2770}, journal = {Distributed Computing}, number = {6}, pages = {461--478}, publisher = {Springer Nature}, title = {{Algebraic methods in the congested clique}}, doi = {10.1007/s00446-016-0270-2}, volume = {32}, year = {2019}, } @article{7275, abstract = {Aprotic alkali metal–oxygen batteries require reversible formation of metal superoxide or peroxide on cycling. Severe parasitic reactions cause poor rechargeability, efficiency, and cycle life and have been shown to be caused by singlet oxygen (1O2) that forms at all stages of cycling. However, its formation mechanism remains unclear. We show that disproportionation of superoxide, the product or intermediate on discharge and charge, to peroxide and oxygen is responsible for 1O2 formation. While the overall reaction is driven by the stability of peroxide and thus favored by stronger Lewis acidic cations such as Li+, the 1O2 fraction is enhanced by weak Lewis acids such as organic cations. Concurrently, the metal peroxide yield drops with increasing 1O2. The results explain a major parasitic pathway during cell cycling and the growing severity in K–, Na–, and Li–O2 cells based on the growing propensity for disproportionation. High capacities and rates with peroxides are now realized to require solution processes, which form peroxide or release O2via disproportionation. The results therefore establish the central dilemma that disproportionation is required for high capacity but also responsible for irreversible reactions. Highly reversible cell operation requires hence finding reaction routes that avoid disproportionation.}, author = {Mourad, Eléonore and Petit, Yann K. and Spezia, Riccardo and Samojlov, Aleksej and Summa, Francesco F. and Prehal, Christian and Leypold, Christian and Mahne, Nika and Slugovc, Christian and Fontaine, Olivier and Brutti, Sergio and Freunberger, Stefan Alexander}, issn = {1754-5692}, journal = {Energy & Environmental Science}, number = {8}, pages = {2559--2568}, publisher = {RSC}, title = {{Singlet oxygen from cation driven superoxide disproportionation and consequences for aprotic metal–O2 batteries}}, doi = {10.1039/c9ee01453e}, volume = {12}, year = {2019}, } @article{7280, abstract = {Non-aqueous lithium-oxygen batteries cycle by forming lithium peroxide during discharge and oxidizing it during recharge. The significant problem of oxidizing the solid insulating lithium peroxide can greatly be facilitated by incorporating redox mediators that shuttle electron-holes between the porous substrate and lithium peroxide. Redox mediator stability is thus key for energy efficiency, reversibility, and cycle life. However, the gradual deactivation of redox mediators during repeated cycling has not conclusively been explained. Here, we show that organic redox mediators are predominantly decomposed by singlet oxygen that forms during cycling. Their reaction with superoxide, previously assumed to mainly trigger their degradation, peroxide, and dioxygen, is orders of magnitude slower in comparison. The reduced form of the mediator is markedly more reactive towards singlet oxygen than the oxidized form, from which we derive reaction mechanisms supported by density functional theory calculations. Redox mediators must thus be designed for stability against singlet oxygen.}, author = {Kwak, Won-Jin and Kim, Hun and Petit, Yann K. and Leypold, Christian and Nguyen, Trung Thien and Mahne, Nika and Redfern, Paul and Curtiss, Larry A. and Jung, Hun-Gi and Borisov, Sergey M. and Freunberger, Stefan Alexander and Sun, Yang-Kook}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Deactivation of redox mediators in lithium-oxygen batteries by singlet oxygen}}, doi = {10.1038/s41467-019-09399-0}, volume = {10}, year = {2019}, } @article{7276, abstract = {Singlet oxygen (1O2) causes a major fraction of the parasitic chemistry during the cycling of non‐aqueous alkali metal‐O2 batteries and also contributes to interfacial reactivity of transition‐metal oxide intercalation compounds. We introduce DABCOnium, the mono alkylated form of 1,4‐diazabicyclo[2.2.2]octane (DABCO), as an efficient 1O2 quencher with an unusually high oxidative stability of ca. 4.2 V vs. Li/Li+. Previous quenchers are strongly Lewis basic amines with too low oxidative stability. DABCOnium is an ionic liquid, non‐volatile, highly soluble in the electrolyte, stable against superoxide and peroxide, and compatible with lithium metal. The electrochemical stability covers the required range for metal–O2 batteries and greatly reduces 1O2 related parasitic chemistry as demonstrated for the Li–O2 cell.}, author = {Petit, Yann K. and Leypold, Christian and Mahne, Nika and Mourad, Eléonore and Schafzahl, Lukas and Slugovc, Christian and Borisov, Sergey M. and Freunberger, Stefan Alexander}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {20}, pages = {6535--6539}, publisher = {Wiley}, title = {{DABCOnium: An efficient and high-voltage stable singlet oxygen quencher for metal-O2 cells}}, doi = {10.1002/anie.201901869}, volume = {58}, year = {2019}, } @article{7281, abstract = {Li–O2 batteries are plagued by side reactions that cause poor rechargeability and efficiency. These reactions were recently revealed to be predominantly caused by singlet oxygen, which can be neutralized by chemical traps or physical quenchers. However, traps are irreversibly consumed and thus only active for a limited time, and so far identified quenchers lack oxidative stability to be suitable for typically required recharge potentials. Thus, reducing the charge potential within the stability limit of the quencher and/or finding more stable quenchers is required. Here, we show that dimethylphenazine as a redox mediator decreases the charge potential well within the stability limit of the quencher 1,4-diazabicyclo[2.2.2]octane. The quencher can thus mitigate the parasitic reactions without being oxidatively decomposed. At the same time the quencher protects the redox mediator from singlet oxygen attack. The mutual conservation of the redox mediator and the quencher is rational for stable and effective Li–O2 batteries.}, author = {Kwak, Won-Jin and Freunberger, Stefan Alexander and Kim, Hun and Park, Jiwon and Nguyen, Trung Thien and Jung, Hun-Gi and Byon, Hye Ryung and Sun, Yang-Kook}, issn = {2155-5435}, journal = {ACS Catalysis}, number = {11}, pages = {9914--9922}, publisher = {ACS}, title = {{Mutual conservation of redox mediator and singlet oxygen quencher in Lithium–Oxygen batteries}}, doi = {10.1021/acscatal.9b01337}, volume = {9}, year = {2019}, } @article{7282, abstract = {Interphases that form on the anode surface of lithium-ion batteries are critical for performance and lifetime, but are poorly understood. Now, a decade-old misconception regarding a main component of the interphase has been revealed, which could potentially lead to improved devices.}, author = {Freunberger, Stefan Alexander}, issn = {1755-4330}, journal = {Nature Chemistry}, number = {9}, pages = {761--763}, publisher = {Springer Nature}, title = {{Interphase identity crisis}}, doi = {10.1038/s41557-019-0311-0}, volume = {11}, year = {2019}, } @article{7283, abstract = {Potassium–air batteries, which suffer from oxygen cathode and potassium metal anode degradation, can be cycled thousands of times when an organic anode replaces the metal.}, author = {Petit, Yann K. and Freunberger, Stefan Alexander}, issn = {1476-1122}, journal = {Nature Materials}, number = {4}, pages = {301--302}, publisher = {Springer Nature}, title = {{Thousands of cycles}}, doi = {10.1038/s41563-019-0313-8}, volume = {18}, year = {2019}, } @article{7284, abstract = {In this issue of Joule, Dongmin Im and coworkers from Samsung in South Korea describe a prototype lithium-O2 battery that reaches ∼700 Wh kg–1 and ∼600 Wh L–1 on the cell level. They cut all components to the minimum to reach this value. Difficulties filling the pores with discharge product and inhomogeneous cell utilization turn out to limit the achievable energy. Their work underlines the importance of reporting performance with respect to full cell weight and volume.}, author = {Prehal, Christian and Freunberger, Stefan Alexander}, issn = {2542-4351}, journal = {Joule}, number = {2}, pages = {321--323}, publisher = {Elsevier}, title = {{Li-O2 cell-scale energy densities}}, doi = {10.1016/j.joule.2019.01.020}, volume = {3}, year = {2019}, } @unpublished{7358, abstract = {Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGFβ superfamily signaling pathways and increased expression of genes associated with naïve pluripotency. We further identify combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling.}, author = {Watanabe, Momoko and Haney, Jillian R. and Vishlaghi, Neda and Turcios, Felix and Buth, Jessie E. and Gu, Wen and Collier, Amanda J. and Miranda, Osvaldo and Chen, Di and Sabri, Shan and Clark, Amander T. and Plath, Kathrin and Christofk, Heather R. and Gandal, Michael J. and Novitch, Bennett G.}, booktitle = {bioRxiv}, pages = {75}, publisher = {Cold Spring Harbor Laboratory}, title = {{TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids}}, doi = {10.1101/2019.12.13.875773}, year = {2019}, } @inproceedings{7401, abstract = {The genus g(G) of a graph G is the minimum g such that G has an embedding on the orientable surface M_g of genus g. A drawing of a graph on a surface is independently even if every pair of nonadjacent edges in the drawing crosses an even number of times. The Z_2-genus of a graph G, denoted by g_0(G), is the minimum g such that G has an independently even drawing on M_g. By a result of Battle, Harary, Kodama and Youngs from 1962, the graph genus is additive over 2-connected blocks. In 2013, Schaefer and Stefankovic proved that the Z_2-genus of a graph is additive over 2-connected blocks as well, and asked whether this result can be extended to so-called 2-amalgamations, as an analogue of results by Decker, Glover, Huneke, and Stahl for the genus. We give the following partial answer. If G=G_1 cup G_2, G_1 and G_2 intersect in two vertices u and v, and G-u-v has k connected components (among which we count the edge uv if present), then |g_0(G)-(g_0(G_1)+g_0(G_2))|<=k+1. For complete bipartite graphs K_{m,n}, with n >= m >= 3, we prove that g_0(K_{m,n})/g(K_{m,n})=1-O(1/n). Similar results are proved also for the Euler Z_2-genus. We express the Z_2-genus of a graph using the minimum rank of partial symmetric matrices over Z_2; a problem that might be of independent interest. }, author = {Fulek, Radoslav and Kyncl, Jan}, booktitle = {35th International Symposium on Computational Geometry (SoCG 2019)}, isbn = {978-3-95977-104-7}, issn = {1868-8969}, location = {Portland, OR, United States}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Z_2-Genus of graphs and minimum rank of partial symmetric matrices}}, doi = {10.4230/LIPICS.SOCG.2019.39}, volume = {129}, year = {2019}, } @inbook{7453, abstract = {We illustrate the ingredients of the state-of-the-art of model-based approach for the formal design and verification of cyber-physical systems. To capture the interaction between a discrete controller and its continuously evolving environment, we use the formal models of timed and hybrid automata. We explain the steps of modeling and verification in the tools Uppaal and SpaceEx using a case study based on a dual-chamber implantable pacemaker monitoring a human heart. We show how to design a model as a composition of components, how to construct models at varying levels of detail, how to establish that one model is an abstraction of another, how to specify correctness requirements using temporal logic, and how to verify that a model satisfies a logical requirement.}, author = {Alur, Rajeev and Giacobbe, Mirco and Henzinger, Thomas A and Larsen, Kim G. and Mikučionis, Marius}, booktitle = {Computing and Software Science}, editor = {Steffen, Bernhard and Woeginger, Gerhard}, isbn = {9783319919072}, issn = {0302-9743}, pages = {452--477}, publisher = {Springer Nature}, title = {{Continuous-time models for system design and analysis}}, doi = {10.1007/978-3-319-91908-9_22}, volume = {10000}, year = {2019}, } @article{7476, abstract = {The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1,2. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.}, author = {Andersen, Marianne Stemann and Hannezo, Edouard B and Ulyanchenko, Svetlana and Estrach, Soline and Antoku, Yasuko and Pisano, Sabrina and Boonekamp, Kim E. and Sendrup, Sarah and Maimets, Martti and Pedersen, Marianne Terndrup and Johansen, Jens V. and Clement, Ditte L. and Feral, Chloe C. and Simons, Benjamin D. and Jensen, Kim B.}, issn = {1465-7392}, journal = {Nature Cell Biology}, number = {8}, pages = {924--932}, publisher = {Springer Nature}, title = {{Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states}}, doi = {10.1038/s41556-019-0362-x}, volume = {21}, year = {2019}, } @article{7550, abstract = {We consider an optimal control problem for an abstract nonlinear dissipative evolution equation. The differential constraint is penalized by augmenting the target functional by a nonnegative global-in-time functional which is null-minimized in the evolution equation is satisfied. Different variational settings are presented, leading to the convergence of the penalization method for gradient flows, noncyclic and semimonotone flows, doubly nonlinear evolutions, and GENERIC systems. }, author = {Portinale, Lorenzo and Stefanelli, Ulisse}, issn = {1343-4373}, journal = {Advances in Mathematical Sciences and Applications}, number = {2}, pages = {425--447}, publisher = {Gakko Tosho}, title = {{Penalization via global functionals of optimal-control problems for dissipative evolution}}, volume = {28}, year = {2019}, } @unpublished{7552, abstract = {There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests. }, author = {Bialek, William and Gregor, Thomas and Tkačik, Gašper}, booktitle = {arXiv:1912.08579}, pages = {5}, publisher = {ArXiv}, title = {{Action at a distance in transcriptional regulation}}, year = {2019}, } @inproceedings{7576, abstract = {We present the results of a friendly competition for formal verification of continuous and hybrid systems with nonlinear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In this year, 6 tools Ariadne, CORA, DynIbex, Flow*, Isabelle/HOL, and JuliaReach (in alphabetic order) participated. They are applied to solve reachability analysis problems on four benchmark problems, one of them with hybrid dynamics. We do not rank the tools based on the results, but show the current status and discover the potential advantages of different tools.}, author = {Immler, Fabian and Althoff, Matthias and Benet, Luis and Chapoutot, Alexandre and Chen, Xin and Forets, Marcelo and Geretti, Luca and Kochdumper, Niklas and Sanders, David P. and Schilling, Christian}, booktitle = {EPiC Series in Computing}, issn = {23987340}, location = {Montreal, Canada}, pages = {41--61}, publisher = {EasyChair Publications}, title = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with nonlinear dynamics}}, doi = {10.29007/m75b}, volume = {61}, year = {2019}, } @unpublished{7627, abstract = {Electrodepositing insulating and insoluble Li2O2 is the key process during discharge of aprotic Li-O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and solvated LiO2 governs whether Li2O2 grows as surface film, leading to low capacity even at low rates, or in solution, leading to particles and high capacities. Here we show that Li2O2 forms to the widest extent as particles via solution mediated LiO2 disproportionation. We describe a unified Li2O2 growth model that conclusively explains capacity limitations across the whole range of electrolytes. Deciding for particle morphology, achievable rate and capacities are species mobilities, electrode specific surface area (determining true areal rate) and the concentration distribution of associated LiO2 in solution. Provided that species mobilities and surface are high, high, capacities are possible even with low-donor-number electrolytes, previously considered prototypical for low capacity via surface growth. The tools for these insights are microscopy, hydrodynamic voltammetry, a numerical reaction model, and in situ small/wide angle X-ray scattering (SAXS/WAXS). Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative information from complex multi-phase systems. On a wider perspective, this SAXS method is a powerful in situ metrology with atomic to sub-micron resolution to study mechanisms in complex electrochemical systems and beyond. }, author = {Prehal, Christian and Samojlov, Aleksej and Nachtnebel, Manfred and Kriechbaum, Manfred and Amenitsch, Heinz and Freunberger, Stefan Alexander}, pages = {50}, publisher = {ChemRxiv}, title = {{A revised O2 reduction model in Li-O2 batteries as revealed by in situ small angle X-ray scattering}}, year = {2019}, } @article{7710, abstract = {The number of human genomes being genotyped or sequenced increases exponentially and efficient haplotype estimation methods able to handle this amount of data are now required. Here we present a method, SHAPEIT4, which substantially improves upon other methods to process large genotype and high coverage sequencing datasets. It notably exhibits sub-linear running times with sample size, provides highly accurate haplotypes and allows integrating external phasing information such as large reference panels of haplotypes, collections of pre-phased variants and long sequencing reads. We provide SHAPEIT4 in an open source format and demonstrate its performance in terms of accuracy and running times on two gold standard datasets: the UK Biobank data and the Genome In A Bottle.}, author = {Delaneau, Olivier and Zagury, Jean-François and Robinson, Matthew Richard and Marchini, Jonathan L. and Dermitzakis, Emmanouil T.}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Accurate, scalable and integrative haplotype estimation}}, doi = {10.1038/s41467-019-13225-y}, volume = {10}, year = {2019}, } @unpublished{7782, abstract = {As genome-wide association studies (GWAS) increased in size, numerous gene-environment interactions (GxE) have been discovered, many of which however explore only one environment at a time and may suffer from statistical artefacts leading to biased interaction estimates. Here we propose a maximum likelihood method to estimate the contribution of GxE to complex traits taking into account all interacting environmental variables at the same time, without the need to measure any. This is possible because GxE induces fluctuations in the conditional trait variance, the extent of which depends on the strength of GxE. The approach can be applied to continuous outcomes and for single SNPs or genetic risk scores (GRS). Extensive simulations demonstrated that our method yields unbiased interaction estimates and excellent confidence interval coverage. We also offer a strategy to distinguish specific GxE from general heteroscedasticity (scale effects). Applying our method to 32 complex traits in the UK Biobank reveals that for body mass index (BMI) the GRSxE explains an additional 1.9% variance on top of the 5.2% GRS contribution. However, this interaction is not specific to the GRS and holds for any variable similarly correlated with BMI. On the contrary, the GRSxE interaction effect for leg impedance Embedded Image is significantly (P < 10−56) larger than it would be expected for a similarly correlated variable Embedded Image. We showed that our method could robustly detect the global contribution of GxE to complex traits, which turned out to be substantial for certain obesity measures.}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, booktitle = {bioRxiv}, pages = {20}, publisher = {Cold Spring Harbor Laboratory}, title = {{Maximum likelihood method quantifies the overall contribution of gene-environment interaction to continuous traits: An application to complex traits in the UK Biobank}}, year = {2019}, } @article{8013, author = {Currin, Christopher B. and Khoza, Phumlani N. and Antrobus, Alexander D. and Latham, Peter E. and Vogels, Tim P and Raimondo, Joseph V.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Think: Theory for Africa}}, doi = {10.1371/journal.pcbi.1007049}, volume = {15}, year = {2019}, } @article{8014, abstract = {Working memory, the ability to keep recently accessed information available for immediate manipulation, has been proposed to rely on two mechanisms that appear difficult to reconcile: self-sustained neural firing, or the opposite—activity-silent synaptic traces. Here we review and contrast models of these two mechanisms, and then show that both phenomena can co-exist within a unified system in which neurons hold information in both activity and synapses. Rapid plasticity in flexibly-coding neurons allows features to be bound together into objects, with an important emergent property being the focus of attention. One memory item is held by persistent activity in an attended or “focused” state, and is thus remembered better than other items. Other, previously attended items can remain in memory but in the background, encoded in activity-silent synaptic traces. This dual functional architecture provides a unified common mechanism accounting for a diversity of perplexing attention and memory effects that have been hitherto difficult to explain in a single theoretical framework.}, author = {Manohar, Sanjay G. and Zokaei, Nahid and Fallon, Sean J. and Vogels, Tim P and Husain, Masud}, issn = {0149-7634}, journal = {Neuroscience and Biobehavioral Reviews}, pages = {1--12}, publisher = {Elsevier }, title = {{Neural mechanisms of attending to items in working memory}}, doi = {10.1016/j.neubiorev.2019.03.017}, volume = {101}, year = {2019}, } @inproceedings{8175, abstract = {We study edge asymptotics of poissonized Plancherel-type measures on skew Young diagrams (integer partitions). These measures can be seen as generalizations of those studied by Baik--Deift--Johansson and Baik--Rains in resolving Ulam's problem on longest increasing subsequences of random permutations and the last passage percolation (corner growth) discrete versions thereof. Moreover they interpolate between said measures and the uniform measure on partitions. In the new KPZ-like 1/3 exponent edge scaling limit with logarithmic corrections, we find new probability distributions generalizing the classical Tracy--Widom GUE, GOE and GSE distributions from the theory of random matrices.}, author = {Betea, Dan and Bouttier, Jérémie and Nejjar, Peter and Vuletíc, Mirjana}, booktitle = {Proceedings on the 31st International Conference on Formal Power Series and Algebraic Combinatorics}, location = {Ljubljana, Slovenia}, publisher = {Formal Power Series and Algebraic Combinatorics}, title = {{New edge asymptotics of skew Young diagrams via free boundaries}}, year = {2019}, } @article{8228, abstract = {Background: Atopics have a lower risk for malignancies, and IgE targeted to tumors is superior to IgG in fighting cancer. Whether IgE-mediated innate or adaptive immune surveillance can confer protection against tumors remains unclear. Objective: We aimed to investigate the effects of active and passive immunotherapy to the tumor-associated antigen HER-2 in three murine models differing in Epsilon-B-cell-receptor expression affecting the levels of expressed IgE. Methods: We compared the levels of several serum specific anti-HER-2 antibodies (IgE, IgG1, IgG2a, IgG2b, IgA) and the survival rates in low-IgE ΔM1M2 mice lacking the transmembrane/cytoplasmic domain of Epsilon-B-cell-receptors expressing reduced IgE levels, high-IgE KN1 mice expressing chimeric Epsilon-Gamma1-B-cell receptors with 4-6-fold elevated serum IgE levels, and wild type (WT) BALB/c. Prior engrafting mice with D2F2/E2 mammary tumors overexpressing HER-2, mice were vaccinated with HER-2 or vehicle control PBS using the Th2-adjuvant Al(OH)3 (active immunotherapy), or treated with the murine anti-HER-2 IgG1 antibody 4D5 (passive immunotherapy). Results: Overall, among the three strains of mice, HER-2 vaccination induced significantly higher levels of HER-2 specific IgE and IgG1 in high-IgE KN1, while low-IgE ΔM1M2 mice had higher IgG2a levels. HER-2 vaccination and passive immunotherapy prolonged the survival in tumor-grafted WT and low-IgE ΔM1M2 strains compared with treatment controls; active vaccination provided the highest benefit. Notably, untreated high-IgE KN1 mice displayed the longest survival of all strains, which could not be further extended by active or passive immunotherapy. Conclusion: Active and passive immunotherapies prolong survival in wild type and low-IgE ΔM1M2 mice engrafted with mammary tumors. High-IgE KN1 mice have an innate survival benefit following tumor challenge.}, author = {Singer, Josef and Achatz-Straussberger, Gertrude and Bentley-Lukschal, Anna and Fazekas-Singer, Judit and Achatz, Gernot and Karagiannis, Sophia N. and Jensen-Jarolim, Erika}, issn = {1939-4551}, journal = {World Allergy Organization Journal}, number = {7}, publisher = {Elsevier}, title = {{AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice}}, doi = {10.1016/j.waojou.2019.100044}, volume = {12}, year = {2019}, } @article{8229, abstract = {Food proteins may get nitrated by various exogenous or endogenous mechanisms. As individuals might get recurrently exposed to nitrated proteins via daily diet, we aimed to investigate the effect of repeatedly ingested nitrated food proteins on the subsequent immune response in non-allergic and allergic mice using the milk allergen beta-lactoglobulin (BLG) as model food protein in a mouse model. Evaluating the presence of nitrated proteins in food, we could detect 3-nitrotyrosine (3-NT) in extracts of different foods and in stomach content extracts of non-allergic mice under physiological conditions. Chemically nitrated BLG (BLGn) exhibited enhanced susceptibility to degradation in simulated gastric fluid experiments compared to untreated BLG (BLGu). Gavage of BLGn to non-allergic animals increased interferon-γ and interleukin-10 release of stimulated spleen cells and led to the formation of BLG-specific serum IgA. Allergic mice receiving three oral gavages of BLGn had higher levels of mouse mast cell protease-1 (mMCP-1) compared to allergic mice receiving BLGu. Regardless of the preceding immune status, non-allergic or allergic, repeatedly ingested nitrated food proteins seem to considerably influence the subsequent immune response.}, author = {Ondracek, Anna S. and Heiden, Denise and Oostingh, Gertie J. and Fuerst, Elisabeth and Fazekas-Singer, Judit and Bergmayr, Cornelia and Rohrhofer, Johanna and Jensen-Jarolim, Erika and Duschl, Albert and Untersmayr, Eva}, issn = {2072-6643}, journal = {Nutrients}, number = {10}, publisher = {MDPI}, title = {{Immune effects of the nitrated food allergen beta-lactoglobulin in an experimental food allergy model}}, doi = {10.3390/nu11102463}, volume = {11}, year = {2019}, } @article{8227, author = {Ilieva, Kristina M. and Fazekas-Singer, Judit and Bax, Heather J. and Crescioli, Silvia and Montero‐Morales, Laura and Mele, Silvia and Sow, Heng Sheng and Stavraka, Chara and Josephs, Debra H. and Spicer, James F. and Steinkellner, Herta and Jensen‐Jarolim, Erika and Tutt, Andrew N. J. and Karagiannis, Sophia N.}, issn = {0105-4538}, journal = {Allergy}, number = {10}, pages = {1985--1989}, publisher = {Wiley}, title = {{AllergoOncology: Expression platform development and functional profiling of an anti‐HER2 IgE antibody}}, doi = {10.1111/all.13818}, volume = {74}, year = {2019}, } @article{8263, abstract = {Background: The genus Streptococcus comprises pathogens that strongly influence the health of humans and animals. Genome sequencing of multiple Streptococcus strains demonstrated high variability in gene content and order even in closely related strains of the same species and created a newly emerged object for genomic analysis, the pan-genome. Here we analysed the genome evolution of 25 strains of Streptococcus suis, 50 strains of Streptococcus pyogenes and 28 strains of Streptococcus pneumoniae. Results: Fractions of the pan-genome, unique, periphery, and universal genes differ in size, functional composition, the level of nucleotide substitutions, and predisposition to horizontal gene transfer and genomic rearrangements. The density of substitutions in intergenic regions appears to be correlated with selection acting on adjacent genes, implying that more conserved genes tend to have more conserved regulatory regions. The total pan-genome of the genus is open, but only due to strain-specific genes, whereas other pan-genome fractions reach saturation. We have identified the set of genes with phylogenies inconsistent with species and non-conserved location in the chromosome; these genes are rare in at least one species and have likely experienced recent horizontal transfer between species. The strain-specific fraction is enriched with mobile elements and hypothetical proteins, but also contains a number of candidate virulence-related genes, so it may have a strong impact on adaptability and pathogenicity. Mapping the rearrangements to the phylogenetic tree revealed large parallel inversions in all species. A parallel inversion of length 15 kB with breakpoints formed by genes encoding surface antigen proteins PhtD and PhtB in S. pneumoniae leads to replacement of gene fragments that likely indicates the action of an antigen variation mechanism. Conclusions: Members of genus Streptococcus have a highly dynamic, open pan-genome, that potentially confers them with the ability to adapt to changing environmental conditions, i.e. antibiotic resistance or transmission between different hosts. Hence, integrated analysis of all aspects of genome evolution is important for the identification of potential pathogens and design of drugs and vaccines.}, author = {Shelyakin, Pavel V. and Bochkareva, Olga and Karan, Anna A. and Gelfand, Mikhail S.}, issn = {1471-2148}, journal = {BMC Evolutionary Biology}, publisher = {Springer Nature}, title = {{Micro-evolution of three Streptococcus species: Selection, antigenic variation, and horizontal gene inflow}}, doi = {10.1186/s12862-019-1403-6}, volume = {19}, year = {2019}, } @unpublished{8304, abstract = {Enabling secure communication across distributed systems is usually studied under the assumption of trust between the different systems and an external adversary trying to compromise the messages. With the appearance of distributed ledgers or blockchains, numerous protocols have emerged, which attempt to achieve trustless communication between distrusting ledgers and participants. Cross-chain communication (CCC) thereby plays a fundamental role in cryptocurrency exchanges, sharding, bootstrapping of new and feature-extension of existing distributed ledgers. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence on their correctness and composability. We provide the first systematic exposition of protocols for CCC. First, we formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. We then develop a framework to evaluate existing and to design new cross-chain protocols. The framework is based on the use case, the trust model, and the security assumptions of interlinked blockchains. Finally, we identify security and privacy challenges faced by protocols in the cross-chain setting. This Systematization of Knowledge (SoK) offers a comprehensive guide for designing protocols bridging the numerous distributed ledgers available today. It aims to facilitate clearer communication between academia and industry in the field.}, author = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.}, booktitle = {Cryptology ePrint Archive}, title = {{SoK: Communication across distributed ledgers}}, year = {2019}, } @unpublished{8303, abstract = {ByzCoin, a promising alternative of Bitcoin, is a scalable consensus protocol used as a building block of many research and enterprise-level decentralized systems. In this paper, we show that ByzCoin is unsuitable for deployment in an anopen, adversarial network and instead introduceMOTOR. MOTORis designed as a secure, robust, and scalable consensus suitable for permissionless sharded blockchains. MOTORachieves these properties by making four key design choices: (a) it prioritizes robustness in adversarial environments while maintaining adequate scalability, (b) it employees provably correct cryptography that resists DoS attacks from individual nodes, (c) it deploys unpredictable rotating leaders to defend against mildly-adaptive adversaries and prevents censorship, and (d) it creates an incentive compatible reward mechanism. These choices are materialized as (a) a “rotating subleader” communication pattern that balances the scalability needs with the robustness requirements under failures, (b) deployment of provable secure BLS multi-signatures, (c) use of deterministic thresh-old signatures as a source of randomness and (d) careful design of the reward allocation mechanism. We have implemented MOTORand compare it withByzCoin. We show that MOTORcan scale similar to ByzCoin with an at most2xoverhead whereas it maintains good performance even under high-percentage of faults, unlike ByzCoin.}, author = {Kokoris Kogias, Eleftherios}, booktitle = {Cryptology ePrint Archive}, title = {{Robust and scalable consensus for sharded distributed ledgers}}, year = {2019}, } @phdthesis{8311, abstract = {One of the core promises of blockchain technology is that of enabling trustworthy data dissemination in a trustless environment. What current blockchain systems deliver, however, is slow dissemination of public data, rendering blockchain technology unusable in settings where latency, transaction capacity, or data confidentiality are important. In this thesis we focus on providing solutions on two of the most pressing problems blockchain technology currently faces: scalability and data confidentiality. To address the scalability issue, we present OMNILEDGER, a novel scale-out distributed ledger that preserves long-term security under permissionless operation. It ensures security and correctness by using a bias-resistant public-randomness protocol for choosing large, statistically representative shards that process transactions, and by introducing an efficient cross-shard commit protocol that atomically handles transactions affecting multiple shards. To enable secure sharing of confidential data we present CALYPSO, the first fully decentralized, auditable access-control framework for secure blockchain-based data sharing which builds upon two abstractions. First, on-chain secrets enable collective management of (verifiably shared) secrets under a Byzantine adversary where an access-control blockchain enforces user-specific access rules and a secret-management cothority administers encrypted data. Second, skipchain-based identity and access management enables efficient administration of dynamic, sovereign identities and access policies and, in particular, permits clients to maintain long-term relationships with respect to evolving user identities thanks to the trust-delegating forward links of skipchains. In order to build OMNILEDGER and CALYPSO, we first build a set of tools for efficient decentralization, which are presented in Part II of this dissertation. These tools can be used in decentralized and distributed systems to achieve (1) scalable consensus (BYZCOIN), (2) bias- resistant distributed randomness creations (RANDHOUND), and (3) relationship-keeping between independently updating communication endpoints (SKIPCHAINIAC). Although we use this tools in the scope off this thesis, they can be (and already have been) used in a far wider scope.}, author = {Kokoris Kogias, Eleftherios}, pages = {244}, publisher = {École Polytechnique Fédérale de Lausanne}, title = {{Secure, confidential blockchains providing high throughput and low latency}}, doi = {10.5075/epfl-thesis-7101}, year = {2019}, } @unpublished{8314, abstract = {Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called Wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee's approval for the last valid state. Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. Furthermore, we consider permissioned blockchains, where the additional property of auditability might be desired for regulatory purposes. We introduce Brick+, an off-chain construction that provides auditability on top of Brick without conflicting with its privacy guarantees. We formally define the properties our payment channel construction should fulfill, and prove that both Brick and Brick+ satisfy them. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.}, author = {Avarikioti, Georgia and Kokoris Kogias, Eleftherios and Wattenhofer, Roger and Zindros, Dionysis}, booktitle = {arXiv}, title = {{Brick: Asynchronous payment channels}}, year = {2019}, } @unpublished{8315, abstract = {Sharding distributed ledgers is the most promising on-chain solution for scaling blockchain technology. In this work, we define and analyze the properties a sharded distributed ledger should fulfill. More specifically, we show that a sharded blockchain cannot be scalable under a fully adaptive adversary, but it can scale up to $O(n/\log n)$ under an epoch-adaptive adversary. This is possible only if the distributed ledger creates succinct proofs of the valid state updates at the end of each epoch. Our model builds upon and extends the Bitcoin backbone protocol by defining consistency and scalability. Consistency encompasses the need for atomic execution of cross-shard transactions to preserve safety, whereas scalability encapsulates the speedup a sharded system can gain in comparison to a non-sharded system. In order to show the power of our framework, we analyze the most prominent sharded blockchains and either prove their correctness (OmniLedger, RapidChain) under our model or pinpoint where they fail to balance the consistency and scalability requirements (Elastico, Monoxide). }, author = {Avarikioti, Georgia and Kokoris Kogias, Eleftherios and Wattenhofer, Roger}, booktitle = {arXiv}, title = {{Divide and scale: Formalization of distributed ledger sharding protocols}}, year = {2019}, } @misc{8313, abstract = {The present invention concerns a computer-implemented method for secure data exchange between a sender (A) and a recipient (B), wherein the method is performed by the sender (A) and comprises encrypting data using a symmetric key k, creating a write transaction T W , wherein the write transaction T W comprises information usable to derive the symmetric key k and an access policy identifying the recipient (B) as being allowed to decrypt the encrypted data, providing the recipient (B) access to the encrypted data, and sending the write transaction T W to a first group of servers (AC) for being stored in a blockchain data structure maintained by the first group of servers (AC).}, author = {Ford, Bryan and Gasser, Linus and Kokoris Kogias, Eleftherios and Janovic, Philipp}, title = {{Methods and systems for secure data exchange}}, year = {2019}, } @article{8405, abstract = {Atomic-resolution structure determination is crucial for understanding protein function. Cryo-EM and NMR spectroscopy both provide structural information, but currently cryo-EM does not routinely give access to atomic-level structural data, and, generally, NMR structure determination is restricted to small (<30 kDa) proteins. We introduce an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enables structure determination of the 468 kDa large dodecameric aminopeptidase TET2 to a precision and accuracy below 1 Å by combining secondary-structure information obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large subunits, distance restraints from backbone amides and ILV methyl groups, and a 4.1 Å resolution EM map. The resulting structure exceeds current standards of NMR and EM structure determination in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution cryo-EM data are available.}, author = {Gauto, Diego F. and Estrozi, Leandro F. and Schwieters, Charles D. and Effantin, Gregory and Macek, Pavel and Sounier, Remy and Sivertsen, Astrid C. and Schmidt, Elena and Kerfah, Rime and Mas, Guillaume and Colletier, Jacques-Philippe and Güntert, Peter and Favier, Adrien and Schoehn, Guy and Schanda, Paul and Boisbouvier, Jerome}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex}}, doi = {10.1038/s41467-019-10490-9}, volume = {10}, year = {2019}, } @article{8406, abstract = {Coordinated conformational transitions in oligomeric enzymatic complexes modulate function in response to substrates and play a crucial role in enzyme inhibition and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which has emerged as a drug target against multiple pathogenic bacteria. Activation of different ClpPs by inhibitors has been independently reported from drug development efforts, but no rationale for inhibitor-induced activation has been hitherto proposed. Using an integrated approach that includes x-ray crystallography, solid- and solution-state nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP active-site serine, mimicking a peptide substrate, and induces a concerted allosteric activation of the complex. The bortezomib-activated conformation also exhibits a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric mechanism, where substrate binding to a single subunit locks ClpP into an active conformation optimized for chaperone association and protein processive degradation.}, author = {Felix, Jan and Weinhäupl, Katharina and Chipot, Christophe and Dehez, François and Hessel, Audrey and Gauto, Diego F. and Morlot, Cecile and Abian, Olga and Gutsche, Irina and Velazquez-Campoy, Adrian and Schanda, Paul and Fraga, Hugo}, issn = {2375-2548}, journal = {Science Advances}, number = {9}, publisher = {American Association for the Advancement of Science}, title = {{Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors}}, doi = {10.1126/sciadv.aaw3818}, volume = {5}, year = {2019}, } @article{8415, abstract = {We consider billiards obtained by removing three strictly convex obstacles satisfying the non-eclipse condition on the plane. The restriction of the dynamics to the set of non-escaping orbits is conjugated to a subshift on three symbols that provides a natural labeling of all periodic orbits. We study the following inverse problem: does the Marked Length Spectrum (i.e., the set of lengths of periodic orbits together with their labeling), determine the geometry of the billiard table? We show that from the Marked Length Spectrum it is possible to recover the curvature at periodic points of period two, as well as the Lyapunov exponent of each periodic orbit.}, author = {Bálint, Péter and De Simoi, Jacopo and Kaloshin, Vadim and Leguil, Martin}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {1531--1575}, publisher = {Springer Nature}, title = {{Marked length spectrum, homoclinic orbits and the geometry of open dispersing billiards}}, doi = {10.1007/s00220-019-03448-x}, volume = {374}, year = {2019}, } @article{8410, author = {Schanda, Paul and Chekmenev, Eduard Y.}, issn = {1439-4235}, journal = {ChemPhysChem}, number = {2}, pages = {177--177}, publisher = {Wiley}, title = {{NMR for Biological Systems}}, doi = {10.1002/cphc.201801100}, volume = {20}, year = {2019}, } @inproceedings{8570, abstract = {This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with linear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In its third edition, seven tools have been applied to solve six different benchmark problems in the category for linear continuous dynamics (in alphabetical order): CORA, CORA/SX, HyDRA, Hylaa, JuliaReach, SpaceEx, and XSpeed. This report is a snapshot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results provide one of the most complete assessments of tools for the safety verification of continuous and hybrid systems with linear continuous dynamics up to this date.}, author = {Althoff, Matthias and Bak, Stanley and Forets, Marcelo and Frehse, Goran and Kochdumper, Niklas and Ray, Rajarshi and Schilling, Christian and Schupp, Stefan}, booktitle = {EPiC Series in Computing}, issn = {23987340}, location = {Montreal, Canada}, pages = {14--40}, publisher = {EasyChair}, title = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with linear continuous dynamics}}, doi = {10.29007/bj1w}, volume = {61}, year = {2019}, } @article{9016, abstract = {Inhibiting the histone H3–ASF1 (anti‐silencing function 1) protein–protein interaction (PPI) represents a potential approach for treating numerous cancers. As an α‐helix‐mediated PPI, constraining the key histone H3 helix (residues 118–135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3118–135 peptides bearing pentenylglycine residues at the i and i+4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that the potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy–entropy compensation occurs.}, author = {Bakail, May M and Rodriguez‐Marin, Silvia and Hegedüs, Zsófia and Perrin, Marie E. and Ochsenbein, Françoise and Wilson, Andrew J.}, issn = {1439-4227}, journal = {ChemBioChem}, number = {7}, pages = {891--895}, publisher = {Wiley}, title = {{Recognition of ASF1 by using hydrocarbon‐constrained peptides}}, doi = {10.1002/cbic.201800633}, volume = {20}, year = {2019}, } @article{9060, abstract = {Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.}, author = {Ramananarivo, Sophie and Ducrot, Etienne and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Activity-controlled annealing of colloidal monolayers}}, doi = {10.1038/s41467-019-11362-y}, volume = {10}, year = {2019}, } @article{9460, abstract = {Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In Arabidopsis, active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown. One candidate is the rice REPRESSOR OF SILENCING 1a (ROS1a) gene, which is related to DME and is essential for rice seed viability and pollen function. Here, we report genome-wide analyses of DNA methylation in wild-type and ros1a mutant sperm and vegetative cells. We find that the rice vegetative cell genome is locally hypomethylated compared with sperm by a process that requires ROS1a activity. We show that many ROS1a target sequences in the vegetative cell are hypomethylated in the rice central cell, suggesting that ROS1a also demethylates the central cell genome. Similar to Arabidopsis, we show that sperm non-CG methylation is indirectly promoted by DNA demethylation in the vegetative cell. These results reveal that DNA glycosylase-mediated DNA demethylation processes are conserved in Arabidopsis and rice, plant species that diverged 150 million years ago. Finally, although global non-CG methylation levels of sperm and egg differ, the maternal and paternal embryo genomes show similar non-CG methylation levels, suggesting that rice gamete genomes undergo dynamic DNA methylation reprogramming after cell fusion.}, author = {Kim, M. Yvonne and Ono, Akemi and Scholten, Stefan and Kinoshita, Tetsu and Zilberman, Daniel and Okamoto, Takashi and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {19}, pages = {9652--9657}, publisher = {National Academy of Sciences}, title = {{DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm}}, doi = {10.1073/pnas.1821435116}, volume = {116}, year = {2019}, } @article{9689, abstract = {A central goal of computational physics and chemistry is to predict material properties by using first-principles methods based on the fundamental laws of quantum mechanics. However, the high computational costs of these methods typically prevent rigorous predictions of macroscopic quantities at finite temperatures, such as heat capacity, density, and chemical potential. Here, we enable such predictions by marrying advanced free-energy methods with data-driven machine-learning interatomic potentials. We show that, for the ubiquitous and technologically essential system of water, a first-principles thermodynamic description not only leads to excellent agreement with experiments, but also reveals the crucial role of nuclear quantum fluctuations in modulating the thermodynamic stabilities of different phases of water.}, author = {Cheng, Bingqing and Engel, Edgar A. and Behler, Jörg and Dellago, Christoph and Ceriotti, Michele}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {4}, pages = {1110--1115}, publisher = {National Academy of Sciences}, title = {{Ab initio thermodynamics of liquid and solid water}}, doi = {10.1073/pnas.1815117116}, volume = {116}, year = {2019}, } @article{6819, abstract = {Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, issn = {1756-0500}, journal = {BMC Research Notes}, publisher = {BioMed Central}, title = {{Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.1186/s13104-019-4534-3}, volume = {12}, year = {2019}, } @misc{9784, abstract = {Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1 of seeding flasks and following 6-days of continuous culture. Note: no differences in cell numbers were observed between negative control and glyphosate treated cultures.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, publisher = {Springer Nature}, title = {{MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.6084/m9.figshare.9411761.v1}, year = {2019}, } @misc{9839, abstract = {More than 100 years after Grigg’s influential analysis of species’ borders, the causes of limits to species’ ranges still represent a puzzle that has never been understood with clarity. The topic has become especially important recently as many scientists have become interested in the potential for species’ ranges to shift in response to climate change—and yet nearly all of those studies fail to recognise or incorporate evolutionary genetics in a way that relates to theoretical developments. I show that range margins can be understood based on just two measurable parameters: (i) the fitness cost of dispersal—a measure of environmental heterogeneity—and (ii) the strength of genetic drift, which reduces genetic diversity. Together, these two parameters define an ‘expansion threshold’: adaptation fails when genetic drift reduces genetic diversity below that required for adaptation to a heterogeneous environment. When the key parameters drop below this expansion threshold locally, a sharp range margin forms. When they drop below this threshold throughout the species’ range, adaptation collapses everywhere, resulting in either extinction or formation of a fragmented metapopulation. Because the effects of dispersal differ fundamentally with dimension, the second parameter—the strength of genetic drift—is qualitatively different compared to a linear habitat. In two-dimensional habitats, genetic drift becomes effectively independent of selection. It decreases with ‘neighbourhood size’—the number of individuals accessible by dispersal within one generation. Moreover, in contrast to earlier predictions, which neglected evolution of genetic variance and/or stochasticity in two dimensions, dispersal into small marginal populations aids adaptation. This is because the reduction of both genetic and demographic stochasticity has a stronger effect than the cost of dispersal through increased maladaptation. The expansion threshold thus provides a novel, theoretically justified, and testable prediction for formation of the range margin and collapse of the species’ range.}, author = {Polechova, Jitka}, publisher = {Dryad}, title = {{Data from: Is the sky the limit? On the expansion threshold of a species' range}}, doi = {10.5061/dryad.5vv37}, year = {2019}, } @article{8418, abstract = {For the Restricted Circular Planar 3 Body Problem, we show that there exists an open set U in phase space of fixed measure, where the set of initial points which lead to collision is O(μ120) dense as μ→0.}, author = {Guardia, Marcel and Kaloshin, Vadim and Zhang, Jianlu}, issn = {0003-9527}, journal = {Archive for Rational Mechanics and Analysis}, keywords = {Mechanical Engineering, Mathematics (miscellaneous), Analysis}, number = {2}, pages = {799--836}, publisher = {Springer Nature}, title = {{Asymptotic density of collision orbits in the Restricted Circular Planar 3 Body Problem}}, doi = {10.1007/s00205-019-01368-7}, volume = {233}, year = {2019}, } @article{8416, abstract = {In this paper, we show that any smooth one-parameter deformations of a strictly convex integrable billiard table Ω0 preserving the integrability near the boundary have to be tangent to a finite dimensional space passing through Ω0.}, author = {Huang, Guan and Kaloshin, Vadim}, issn = {1609-4514}, journal = {Moscow Mathematical Journal}, number = {2}, pages = {307--327}, publisher = {American Mathematical Society}, title = {{On the finite dimensionality of integrable deformations of strictly convex integrable billiard tables}}, doi = {10.17323/1609-4514-2019-19-2-307-327}, volume = {19}, year = {2019}, } @article{8693, abstract = {We review V. I. Arnold’s 1963 celebrated paper [1] Proof of A. N. Kolmogorov’s Theorem on the Conservation of Conditionally Periodic Motions with a Small Variation in the Hamiltonian, and prove that, optimising Arnold’s scheme, one can get “sharp” asymptotic quantitative conditions (as ε → 0, ε being the strength of the perturbation). All constants involved are explicitly computed.}, author = {Chierchia, Luigi and Koudjinan, Edmond}, journal = {Regular and Chaotic Dynamics}, pages = {583–606}, publisher = {Springer}, title = {{V. I. Arnold’s “pointwise” KAM theorem}}, doi = {10.1134/S1560354719060017}, volume = {24}, year = {2019}, } @article{9018, abstract = {Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.}, author = {Bakail, May M and Gaubert, Albane and Andreani, Jessica and Moal, Gwenaëlle and Pinna, Guillaume and Boyarchuk, Ekaterina and Gaillard, Marie-Cécile and Courbeyrette, Regis and Mann, Carl and Thuret, Jean-Yves and Guichard, Bérengère and Murciano, Brice and Richet, Nicolas and Poitou, Adeline and Frederic, Claire and Le Du, Marie-Hélène and Agez, Morgane and Roelants, Caroline and Gurard-Levin, Zachary A. and Almouzni, Geneviève and Cherradi, Nadia and Guerois, Raphael and Ochsenbein, Françoise}, issn = {2451-9456}, journal = {Cell Chemical Biology}, keywords = {Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery}, number = {11}, pages = {1573--1585.e10}, publisher = {Elsevier}, title = {{Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1}}, doi = {10.1016/j.chembiol.2019.09.002}, volume = {26}, year = {2019}, } @article{9530, abstract = {Background DNA methylation of active genes, also known as gene body methylation, is found in many animal and plant genomes. Despite this, the transcriptional and developmental role of such methylation remains poorly understood. Here, we explore the dynamic range of DNA methylation in honey bee, a model organism for gene body methylation. Results Our data show that CG methylation in gene bodies globally fluctuates during honey bee development. However, these changes cause no gene expression alterations. Intriguingly, despite the global alterations, tissue-specific CG methylation patterns of complete genes or exons are rare, implying robust maintenance of genic methylation during development. Additionally, we show that CG methylation maintenance fluctuates in somatic cells, while reaching maximum fidelity in sperm cells. Finally, unlike universally present CG methylation, we discovered non-CG methylation specifically in bee heads that resembles such methylation in mammalian brain tissue. Conclusions Based on these results, we propose that gene body CG methylation can oscillate during development if it is kept to a level adequate to preserve function. Additionally, our data suggest that heightened non-CG methylation is a conserved regulator of animal nervous systems.}, author = {Harris, Keith D. and Lloyd, James P. B. and Domb, Katherine and Zilberman, Daniel and Zemach, Assaf}, issn = {1756-8935}, journal = {Epigenetics and Chromatin}, publisher = {Springer Nature}, title = {{DNA methylation is maintained with high fidelity in the honey bee germline and exhibits global non-functional fluctuations during somatic development}}, doi = {10.1186/s13072-019-0307-4}, volume = {12}, year = {2019}, } @article{9586, abstract = {Consider integers 𝑘,ℓ such that 0⩽ℓ⩽(𝑘2) . Given a large graph 𝐺 , what is the fraction of 𝑘 -vertex subsets of 𝐺 which span exactly ℓ edges? When 𝐺 is empty or complete, and ℓ is zero or (𝑘2) , this fraction can be exactly 1. On the other hand, if ℓ is far from these extreme values, one might expect that this fraction is substantially smaller than 1. This was recently proved by Alon, Hefetz, Krivelevich, and Tyomkyn who initiated the systematic study of this question and proposed several natural conjectures. Let ℓ∗=min{ℓ,(𝑘2)−ℓ} . Our main result is that for any 𝑘 and ℓ , the fraction of 𝑘 -vertex subsets that span ℓ edges is at most log𝑂(1)(ℓ∗/𝑘)√ 𝑘/ℓ∗, which is best-possible up to the logarithmic factor. This improves on multiple results of Alon, Hefetz, Krivelevich, and Tyomkyn, and resolves one of their conjectures. In addition, we also make some first steps towards some analogous questions for hypergraphs. Our proofs involve some Ramsey-type arguments, and a number of different probabilistic tools, such as polynomial anticoncentration inequalities, hypercontractivity, and a coupling trick for random variables defined on a ‘slice’ of the Boolean hypercube.}, author = {Kwan, Matthew Alan and Sudakov, Benny and Tran, Tuan}, issn = {1469-7750}, journal = {Journal of the London Mathematical Society}, number = {3}, pages = {757--777}, publisher = {Wiley}, title = {{Anticoncentration for subgraph statistics}}, doi = {10.1112/jlms.12192}, volume = {99}, year = {2019}, } @article{9580, abstract = {An r-cut of a k-uniform hypergraph H is a partition of the vertex set of H into r parts and the size of the cut is the number of edges which have a vertex in each part. A classical result of Edwards says that every m-edge graph has a 2-cut of size m/2+Ω)(m−−√) and this is best possible. That is, there exist cuts which exceed the expected size of a random cut by some multiple of the standard deviation. We study analogues of this and related results in hypergraphs. First, we observe that similarly to graphs, every m-edge k-uniform hypergraph has an r-cut whose size is Ω(m−−√) larger than the expected size of a random r-cut. Moreover, in the case where k = 3 and r = 2 this bound is best possible and is attained by Steiner triple systems. Surprisingly, for all other cases (that is, if k ≥ 4 or r ≥ 3), we show that every m-edge k-uniform hypergraph has an r-cut whose size is Ω(m5/9) larger than the expected size of a random r-cut. This is a significant difference in behaviour, since the amount by which the size of the largest cut exceeds the expected size of a random cut is now considerably larger than the standard deviation.}, author = {Conlon, David and Fox, Jacob and Kwan, Matthew Alan and Sudakov, Benny}, issn = {1565-8511}, journal = {Israel Journal of Mathematics}, number = {1}, pages = {67--111}, publisher = {Springer}, title = {{Hypergraph cuts above the average}}, doi = {10.1007/s11856-019-1897-z}, volume = {233}, year = {2019}, } @article{9585, abstract = {An n-vertex graph is called C-Ramsey if it has no clique or independent set of size C log n. All known constructions of Ramsey graphs involve randomness in an essential way, and there is an ongoing line of research towards showing that in fact all Ramsey graphs must obey certain “richness” properties characteristic of random graphs. More than 25 years ago, Erdős, Faudree and Sós conjectured that in any C-Ramsey graph there are Ω(n^5/2) induced subgraphs, no pair of which have the same numbers of vertices and edges. Improving on earlier results of Alon, Balogh, Kostochka and Samotij, in this paper we prove this conjecture.}, author = {Kwan, Matthew Alan and Sudakov, Benny}, issn = {1088-6850}, journal = {Transactions of the American Mathematical Society}, number = {8}, pages = {5571--5594}, publisher = {American Mathematical Society}, title = {{Proof of a conjecture on induced subgraphs of Ramsey graphs}}, doi = {10.1090/tran/7729}, volume = {372}, year = {2019}, } @article{9677, abstract = {Progress in the atomic-scale modeling of matter over the past decade has been tremendous. This progress has been brought about by improvements in methods for evaluating interatomic forces that work by either solving the electronic structure problem explicitly, or by computing accurate approximations of the solution and by the development of techniques that use the Born–Oppenheimer (BO) forces to move the atoms on the BO potential energy surface. As a consequence of these developments it is now possible to identify stable or metastable states, to sample configurations consistent with the appropriate thermodynamic ensemble, and to estimate the kinetics of reactions and phase transitions. All too often, however, progress is slowed down by the bottleneck associated with implementing new optimization algorithms and/or sampling techniques into the many existing electronic-structure and empirical-potential codes. To address this problem, we are thus releasing a new version of the i-PI software. This piece of software is an easily extensible framework for implementing advanced atomistic simulation techniques using interatomic potentials and forces calculated by an external driver code. While the original version of the code (Ceriotti et al., 2014) was developed with a focus on path integral molecular dynamics techniques, this second release of i-PI not only includes several new advanced path integral methods, but also offers other classes of algorithms. In other words, i-PI is moving towards becoming a universal force engine that is both modular and tightly coupled to the driver codes that evaluate the potential energy surface and its derivatives.}, author = {Kapil, Venkat and Rossi, Mariana and Marsalek, Ondrej and Petraglia, Riccardo and Litman, Yair and Spura, Thomas and Cheng, Bingqing and Cuzzocrea, Alice and Meißner, Robert H. and Wilkins, David M. and Helfrecht, Benjamin A. and Juda, Przemysław and Bienvenue, Sébastien P. and Fang, Wei and Kessler, Jan and Poltavsky, Igor and Vandenbrande, Steven and Wieme, Jelle and Corminboeuf, Clemence and Kühne, Thomas D. and Manolopoulos, David E. and Markland, Thomas E. and Richardson, Jeremy O. and Tkatchenko, Alexandre and Tribello, Gareth A. and Van Speybroeck, Veronique and Ceriotti, Michele}, issn = {0010-4655}, journal = {Computer Physics Communications}, pages = {214--223}, publisher = {Elsevier}, title = {{i-PI 2.0: A universal force engine for advanced molecular simulations}}, doi = {10.1016/j.cpc.2018.09.020}, volume = {236}, year = {2019}, } @article{9680, abstract = {Atomistic modeling of phase transitions, chemical reactions, or other rare events that involve overcoming high free energy barriers usually entails prohibitively long simulation times. Introducing a bias potential as a function of an appropriately chosen set of collective variables can significantly accelerate the exploration of phase space, albeit at the price of distorting the distribution of microstates. Efficient reweighting to recover the unbiased distribution can be nontrivial when employing adaptive sampling techniques such as metadynamics, variationally enhanced sampling, or parallel bias metadynamics, in which the system evolves in a quasi-equilibrium manner under a time-dependent bias. We introduce an iterative unbiasing scheme that makes efficient use of all the trajectory data and that does not require the distribution to be evaluated on a grid. The method can thus be used even when the bias has a high dimensionality. We benchmark this approach against some of the existing schemes on model systems with different complexity and dimensionality.}, author = {Giberti, F. and Cheng, Bingqing and Tribello, G. A. and Ceriotti, M.}, issn = {1549-9626}, journal = {Journal of Chemical Theory and Computation}, number = {1}, pages = {100--107}, publisher = {American Chemical Society}, title = {{Iterative unbiasing of quasi-equilibrium sampling}}, doi = {10.1021/acs.jctc.9b00907}, volume = {16}, year = {2019}, } @article{12600, abstract = {The snow cover dynamics of High Mountain Asia are usually assessed at spatial resolutions of 250 m or greater, but this scale is too coarse to clearly represent the rugged topography common to the region. Higher-resolution measurement of snow-covered area often results in biased sampling due to cloud cover and deep shadows. We therefore develop a Normalized Difference Snow Index-based workflow to delineate snow lines from Landsat Thematic Mapper/Enhanced Thematic Mapper+ imagery and apply it to the upper Langtang Valley in Nepal, processing 194 scenes spanning 1999 to 2013. For each scene, we determine the spatial distribution of snow line altitudes (SLAs) with respect to aspect and across six subcatchments. Our results show that the mean SLA exhibits distinct seasonal behavior based on aspect and subcatchment position. We find that SLA dynamics respond to spatial and seasonal trade-offs in precipitation, temperature, and solar radiation, which act as primary controls. We identify two SLA spatial gradients, which we attribute to the effect of spatially variable precipitation. Our results also reveal that aspect-related SLA differences vary seasonally and are influenced by solar radiation. In terms of seasonal dominant controls, we demonstrate that the snow line is controlled by snow precipitation in winter, melt in premonsoon, a combination of both in postmonsoon, and temperature in monsoon, explaining to a large extent the spatial and seasonal variability of the SLA in the upper Langtang Valley. We conclude that while SLA and snow-covered area are complementary metrics, the SLA has a strong potential for understanding local-scale snow cover dynamics and their controlling mechanisms.}, author = {Girona‐Mata, Marc and Miles, Evan S. and Ragettli, Silvan and Pellicciotti, Francesca}, issn = {1944-7973}, journal = {Water Resources Research}, keywords = {Water Science and Technology}, number = {8}, pages = {6754--6772}, publisher = {American Geophysical Union}, title = {{High‐resolution snowline delineation from Landsat imagery to infer snow cover controls in a Himalayan catchment}}, doi = {10.1029/2019wr024935}, volume = {55}, year = {2019}, } @article{12602, abstract = {This study aims at developing and applying a spatially-distributed coupled glacier mass balance and ice-flow model to attribute the response of glaciers to natural and anthropogenic climate change. We focus on two glaciers with contrasting surface characteristics: a debris-covered glacier (Langtang Glacier in Nepal) and a clean-ice glacier (Hintereisferner in Austria). The model is applied from the end of the Little Ice Age (1850) to the present-day (2016) and is forced with four bias-corrected General Circulation Models (GCMs) from the historical experiment of the CMIP5 archive. The selected GCMs represent region-specific warm-dry, warm-wet, cold-dry, and cold-wet climate conditions. To isolate the effects of anthropogenic climate change on glacier mass balance and flow runs from these GCMs with and without further anthropogenic forcing after 1970 until 2016 are selected. The outcomes indicate that both glaciers experience the largest reduction in area and volume under warm climate conditions, whereas area and volume reductions are smaller under cold climate conditions. Simultaneously with changes in glacier area and volume, surface velocities generally decrease over time. Without further anthropogenic forcing the results reveal a 3% (9%) smaller decline in glacier area (volume) for the debris-covered glacier and a 18% (39%) smaller decline in glacier area (volume) for the clean-ice glacier. The difference in the magnitude between the two glaciers can mainly be attributed to differences in the response time of the glaciers, where the clean-ice glacier shows a much faster response to climate change. We conclude that the response of the two glaciers can mainly be attributed to anthropogenic climate change and that the impact is larger on the clean-ice glacier. The outcomes show that the model performs well under different climate conditions and that the developed approach can be used for regional-scale glacio-hydrological modeling.}, author = {Wijngaard, René R. and Steiner, Jakob F. and Kraaijenbrink, Philip D. A. and Klug, Christoph and Adhikari, Surendra and Banerjee, Argha and Pellicciotti, Francesca and van Beek, Ludovicus P. H. and Bierkens, Marc F. P. and Lutz, Arthur F. and Immerzeel, Walter W.}, issn = {2296-6463}, journal = {Frontiers in Earth Science}, publisher = {Frontiers Media}, title = {{Modeling the response of the Langtang Glacier and the Hintereisferner to a changing climate since the Little Ice Age}}, doi = {10.3389/feart.2019.00143}, volume = {7}, year = {2019}, } @article{12601, abstract = {Ice cliffs and ponds on debris-covered glaciers have received increased attention due to their role in amplifying local melt. However, very few studies have looked at these features on the catchment scale to determine their patterns and changes in space and time. We have compiled a detailed inventory of cliffs and ponds in the Langtang catchment, central Himalaya, from six high-resolution satellite orthoimages and DEMs between 2006 and 2015, and a historic orthophoto from 1974. Cliffs cover between 1.4% (± 0.4%) in the dry and 3.4% (± 0.9%) in the wet seasons and ponds between 0.6% (± 0.1%) and 1.6% (± 0.3%) of the total debris-covered tongues. We find large variations between seasons, as cliffs and ponds tend to grow in the wetter monsoon period, but there is no obvious trend in total area over the study period. The inventory further shows that cliffs are predominately north-facing irrespective of the glacier flow direction. Both cliffs and ponds appear in higher densities several hundred metres from the terminus in areas where tributaries reach the main glacier tongue. On the largest glacier in the catchment ~10% of all cliffs and ponds persisted over nearly a decade.}, author = {STEINER, JAKOB F. and BURI, PASCAL and MILES, EVAN S. and RAGETTLI, SILVAN and Pellicciotti, Francesca}, issn = {1727-5652}, journal = {Journal of Glaciology}, number = {252}, pages = {617--632}, publisher = {Cambridge University Press}, title = {{Supraglacial ice cliffs and ponds on debris-covered glaciers: Spatio-temporal distribution and characteristics}}, doi = {10.1017/jog.2019.40}, volume = {65}, year = {2019}, } @article{12192, abstract = {Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.}, author = {He, Shengbo and Vickers, Martin and Zhang, Jingyi and Feng, Xiaoqi}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications, Ltd}, title = {{Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation}}, doi = {10.7554/elife.42530}, volume = {8}, year = {2019}, } @unpublished{8305, abstract = {In this paper, we present the first fully asynchronous distributed key generation (ADKG) algorithm as well as the first distributed key generation algorithm that can create keys with a dual (f,2f+1)−threshold that are necessary for scalable consensus (which so far needs a trusted dealer assumption). In order to create a DKG with a dual (f,2f+1)− threshold we first answer in the affirmative the open question posed by Cachin et al. how to create an AVSS protocol with recovery thresholds f+1