TY - CONF AB - 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. AU - Althoff, Matthias AU - Bak, Stanley AU - Forets, Marcelo AU - Frehse, Goran AU - Kochdumper, Niklas AU - Ray, Rajarshi AU - Schilling, Christian AU - Schupp, Stefan ID - 8570 T2 - EPiC Series in Computing TI - ARCH-COMP19 Category Report: Continuous and hybrid systems with linear continuous dynamics VL - 61 ER - TY - JOUR AB - 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. AU - Bakail, May M AU - Rodriguez‐Marin, Silvia AU - Hegedüs, Zsófia AU - Perrin, Marie E. AU - Ochsenbein, Françoise AU - Wilson, Andrew J. ID - 9016 IS - 7 JF - ChemBioChem SN - 1439-4227 TI - Recognition of ASF1 by using hydrocarbon‐constrained peptides VL - 20 ER - TY - JOUR AB - 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. AU - Ramananarivo, Sophie AU - Ducrot, Etienne AU - Palacci, Jérémie A ID - 9060 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Activity-controlled annealing of colloidal monolayers VL - 10 ER - TY - JOUR AB - 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. AU - Kim, M. Yvonne AU - Ono, Akemi AU - Scholten, Stefan AU - Kinoshita, Tetsu AU - Zilberman, Daniel AU - Okamoto, Takashi AU - Fischer, Robert L. ID - 9460 IS - 19 JF - Proceedings of the National Academy of Sciences KW - Multidisciplinary SN - 0027-8424 TI - DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm VL - 116 ER - TY - JOUR AB - 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. AU - Cheng, Bingqing AU - Engel, Edgar A. AU - Behler, Jörg AU - Dellago, Christoph AU - Ceriotti, Michele ID - 9689 IS - 4 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Ab initio thermodynamics of liquid and solid water VL - 116 ER - TY - JOUR AB - 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. AU - Antoniou, Michael N. AU - Nicolas, Armel AU - Mesnage, Robin AU - Biserni, Martina AU - Rao, Francesco V. AU - Martin, Cristina Vazquez ID - 6819 JF - BMC Research Notes TI - Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells VL - 12 ER - TY - GEN AB - 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. AU - Antoniou, Michael N. AU - Nicolas, Armel AU - Mesnage, Robin AU - Biserni, Martina AU - Rao, Francesco V. AU - Martin, Cristina Vazquez ID - 9784 TI - MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells ER - TY - GEN AB - 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. AU - Polechova, Jitka ID - 9839 TI - Data from: Is the sky the limit? On the expansion threshold of a species' range ER - TY - JOUR AB - 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. AU - Guardia, Marcel AU - Kaloshin, Vadim AU - Zhang, Jianlu ID - 8418 IS - 2 JF - Archive for Rational Mechanics and Analysis KW - Mechanical Engineering KW - Mathematics (miscellaneous) KW - Analysis SN - 0003-9527 TI - Asymptotic density of collision orbits in the Restricted Circular Planar 3 Body Problem VL - 233 ER - TY - JOUR AB - 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. AU - Huang, Guan AU - Kaloshin, Vadim ID - 8416 IS - 2 JF - Moscow Mathematical Journal SN - 1609-4514 TI - On the finite dimensionality of integrable deformations of strictly convex integrable billiard tables VL - 19 ER - TY - JOUR AB - 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. AU - Chierchia, Luigi AU - Koudjinan, Edmond ID - 8693 JF - Regular and Chaotic Dynamics TI - V. I. Arnold’s “pointwise” KAM theorem VL - 24 ER - TY - JOUR AB - 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. AU - Bakail, May M AU - Gaubert, Albane AU - Andreani, Jessica AU - Moal, Gwenaëlle AU - Pinna, Guillaume AU - Boyarchuk, Ekaterina AU - Gaillard, Marie-Cécile AU - Courbeyrette, Regis AU - Mann, Carl AU - Thuret, Jean-Yves AU - Guichard, Bérengère AU - Murciano, Brice AU - Richet, Nicolas AU - Poitou, Adeline AU - Frederic, Claire AU - Le Du, Marie-Hélène AU - Agez, Morgane AU - Roelants, Caroline AU - Gurard-Levin, Zachary A. AU - Almouzni, Geneviève AU - Cherradi, Nadia AU - Guerois, Raphael AU - Ochsenbein, Françoise ID - 9018 IS - 11 JF - Cell Chemical Biology KW - Clinical Biochemistry KW - Molecular Medicine KW - Biochemistry KW - Molecular Biology KW - Pharmacology KW - Drug Discovery SN - 2451-9456 TI - Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1 VL - 26 ER - TY - JOUR AB - 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. AU - Harris, Keith D. AU - Lloyd, James P. B. AU - Domb, Katherine AU - Zilberman, Daniel AU - Zemach, Assaf ID - 9530 JF - Epigenetics and Chromatin TI - DNA methylation is maintained with high fidelity in the honey bee germline and exhibits global non-functional fluctuations during somatic development VL - 12 ER - TY - JOUR AB - 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. AU - Kwan, Matthew Alan AU - Sudakov, Benny AU - Tran, Tuan ID - 9586 IS - 3 JF - Journal of the London Mathematical Society SN - 0024-6107 TI - Anticoncentration for subgraph statistics VL - 99 ER - TY - JOUR AB - 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. AU - Conlon, David AU - Fox, Jacob AU - Kwan, Matthew Alan AU - Sudakov, Benny ID - 9580 IS - 1 JF - Israel Journal of Mathematics SN - 0021-2172 TI - Hypergraph cuts above the average VL - 233 ER - TY - JOUR AB - 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. AU - Kwan, Matthew Alan AU - Sudakov, Benny ID - 9585 IS - 8 JF - Transactions of the American Mathematical Society SN - 0002-9947 TI - Proof of a conjecture on induced subgraphs of Ramsey graphs VL - 372 ER - TY - JOUR AB - 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. AU - Kapil, Venkat AU - Rossi, Mariana AU - Marsalek, Ondrej AU - Petraglia, Riccardo AU - Litman, Yair AU - Spura, Thomas AU - Cheng, Bingqing AU - Cuzzocrea, Alice AU - Meißner, Robert H. AU - Wilkins, David M. AU - Helfrecht, Benjamin A. AU - Juda, Przemysław AU - Bienvenue, Sébastien P. AU - Fang, Wei AU - Kessler, Jan AU - Poltavsky, Igor AU - Vandenbrande, Steven AU - Wieme, Jelle AU - Corminboeuf, Clemence AU - Kühne, Thomas D. AU - Manolopoulos, David E. AU - Markland, Thomas E. AU - Richardson, Jeremy O. AU - Tkatchenko, Alexandre AU - Tribello, Gareth A. AU - Van Speybroeck, Veronique AU - Ceriotti, Michele ID - 9677 JF - Computer Physics Communications SN - 0010-4655 TI - i-PI 2.0: A universal force engine for advanced molecular simulations VL - 236 ER - TY - JOUR AB - 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. AU - Giberti, F. AU - Cheng, Bingqing AU - Tribello, G. A. AU - Ceriotti, M. ID - 9680 IS - 1 JF - Journal of Chemical Theory and Computation SN - 1549-9618 TI - Iterative unbiasing of quasi-equilibrium sampling VL - 16 ER - TY - JOUR AB - 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. AU - Girona‐Mata, Marc AU - Miles, Evan S. AU - Ragettli, Silvan AU - Pellicciotti, Francesca ID - 12600 IS - 8 JF - Water Resources Research KW - Water Science and Technology SN - 0043-1397 TI - High‐resolution snowline delineation from Landsat imagery to infer snow cover controls in a Himalayan catchment VL - 55 ER - TY - JOUR AB - 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. AU - Wijngaard, René R. AU - Steiner, Jakob F. AU - Kraaijenbrink, Philip D. A. AU - Klug, Christoph AU - Adhikari, Surendra AU - Banerjee, Argha AU - Pellicciotti, Francesca AU - van Beek, Ludovicus P. H. AU - Bierkens, Marc F. P. AU - Lutz, Arthur F. AU - Immerzeel, Walter W. ID - 12602 JF - Frontiers in Earth Science SN - 2296-6463 TI - Modeling the response of the Langtang Glacier and the Hintereisferner to a changing climate since the Little Ice Age VL - 7 ER -