@article{5678,
abstract = {The order-k Voronoi tessellation of a locally finite set đââđ decomposes âđ into convex domains whose points have the same k nearest neighbors in X. Assuming X is a stationary Poisson point process, we give explicit formulas for the expected number and total area of faces of a given dimension per unit volume of space. We also develop a relaxed version of discrete Morse theory and generalize by counting only faces, for which the k nearest points in X are within a given distance threshold.},
author = {Edelsbrunner, Herbert and Nikitenko, Anton},
issn = {14320444},
journal = {Discrete and Computational Geometry},
number = {4},
pages = {865â878},
publisher = {Springer},
title = {{PoissonâDelaunay Mosaics of Order k}},
doi = {10.1007/s00454-018-0049-2},
volume = {62},
year = {2019},
}
@article{5828,
abstract = {Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next.},
author = {Xu, Haibing and Baracskay, Peter and O'Neill, Joseph and Csicsvari, Jozsef L},
issn = {10974199},
journal = {Neuron},
number = {1},
pages = {119--132.e4},
publisher = {Elsevier},
title = {{Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze}},
doi = {10.1016/j.neuron.2018.11.015},
volume = {101},
year = {2019},
}
@article{5856,
abstract = {We give a bound on the ground-state energy of a system of N non-interacting fermions in a three-dimensional cubic box interacting with an impurity particle via point interactions. We show that the change in energy compared to the system in the absence of the impurity is bounded in terms of the gas density and the scattering length of the interaction, independently of N. Our bound holds as long as the ratio of the mass of the impurity to the one of the gas particles is larger than a critical value mâ ââ 0.36 , which is the same regime for which we recently showed stability of the system.},
author = {Moser, Thomas and Seiringer, Robert},
issn = {14240637},
journal = {Annales Henri Poincare},
number = {4},
pages = {1325â1365},
publisher = {Springer},
title = {{Energy contribution of a point-interacting impurity in a Fermi gas}},
doi = {10.1007/s00023-018-00757-0},
volume = {20},
year = {2019},
}
@article{6240,
abstract = {For a general class of large non-Hermitian random block matrices X we prove that there are no eigenvalues away from a deterministic set with very high probability. This set is obtained from the Dyson equation of the Hermitization of X as the self-consistent approximation of the pseudospectrum. We demonstrate that the analysis of the matrix Dyson equation from (Probab. Theory Related Fields (2018)) offers a unified treatment of many structured matrix ensembles.},
author = {Alt, Johannes and ErdĂ¶s, LĂĄszlĂł and KrĂŒger, Torben H and Nemish, Yuriy},
issn = {02460203},
journal = {Annales de l'institut Henri Poincare},
number = {2},
pages = {661--696},
publisher = {Institut Henri PoincarĂ©},
title = {{Location of the spectrum of Kronecker random matrices}},
doi = {10.1214/18-AIHP894},
volume = {55},
year = {2019},
}
@phdthesis{6957,
abstract = {In many shear flows like pipe flow, plane Couette flow, plane Poiseuille flow, etc. turbulence emerges subcritically. Here, when subjected to strong enough perturbations, the flow becomes turbulent in spite of the laminar base flow being linearly stable. The nature of this instability has puzzled the scientific community for decades. At onset, turbulence appears in localized patches and flows are spatio-temporally intermittent. In pipe flow the localized turbulent structures are referred to as puffs and in planar flows like plane Couette and channel flow, patches arise in the form of localized oblique bands. In this thesis, we study the onset of turbulence in channel flow in direct numerical simulations from a dynamical system theory perspective, as well as by performing experiments in a large aspect ratio channel.
The aim of the experimental work is to determine the critical Reynolds number where turbulence first becomes sustained. Recently, the onset of turbulence has been described in analogy to absorbing state phase transition (i.e. directed percolation). In particular, it has been shown that the critical point can be estimated from the competition between spreading and decay processes. Here, by performing experiments, we identify the mechanisms underlying turbulence proliferation in channel flow and find the critical Reynolds number, above which turbulence becomes sustained. Above the critical point, the continuous growth at the tip of the stripes outweighs the stochastic shedding of turbulent patches at the tail and the stripes expand. For growing stripes, the probability to decay decreases while the probability of stripe splitting increases. Consequently, and unlike for the puffs in pipe flow, neither of these two processes is time-independent i.e. memoryless. Coupling between stripe expansion and creation of new stripes via splitting leads to a significantly lower critical point ($Re_c=670+/-10$) than most earlier studies suggest.
While the above approach sheds light on how turbulence first becomes sustained, it provides no insight into the origin of the stripes themselves. In the numerical part of the thesis we investigate how turbulent stripes form from invariant solutions of the Navier-Stokes equations. The origin of these turbulent stripes can be identified by applying concepts from the dynamical system theory. In doing so, we identify the exact coherent structures underlying stripes and their bifurcations and how they give rise to the turbulent attractor in phase space. We first report a family of localized nonlinear traveling wave solutions of the Navier-Stokes equations in channel flow. These solutions show structural similarities with turbulent stripes in experiments like obliqueness, quasi-streamwise streaks and vortices, etc. A parametric study of these traveling wave solution is performed, with parameters like Reynolds number, stripe tilt angle and domain size, including the stability of the solutions. These solutions emerge through saddle-node bifurcations and form a phase space skeleton for the turbulent stripes observed in the experiments. The lower branches of these TW solutions at different tilt angles undergo Hopf bifurcation and new solutions branches of relative periodic orbits emerge. These RPO solutions do not belong to the same family and therefore the routes to chaos for different angles are different.
In shear flows, turbulence at onset is transient in nature. Consequently,turbulence can not be tracked to lower Reynolds numbers, where the dynamics may simplify. Before this happens, turbulence becomes short-lived and laminarizes. In the last part of the thesis, we show that using numerical simulations we can continue turbulent stripes in channel flow past the 'relaminarization barrier' all the way to their origin. Here, turbulent stripe dynamics simplifies and the fluctuations are no longer stochastic and the stripe settles down to a relative periodic orbit. This relative periodic orbit originates from the aforementioned traveling wave solutions. Starting from the relative periodic orbit, a small increase in speed i.e. Reynolds number gives rise to chaos and the attractor dimension sharply increases in contrast to the classical transition scenario where the instabilities affect the flow globally and give rise to much more gradual route to turbulence.},
author = {Paranjape, Chaitanya S},
issn = {2663-337X},
keywords = {Instabilities, Turbulence, Nonlinear dynamics},
pages = {138},
publisher = {Institute of Science and Technology Austria},
title = {{Onset of turbulence in plane Poiseuille flow}},
doi = {10.15479/AT:ISTA:6957},
year = {2019},
}
@phdthesis{6071,
abstract = {Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. },
author = {Prizak, Roshan},
issn = {2663-337X},
pages = {189},
publisher = {Institute of Science and Technology Austria},
title = {{Coevolution of transcription factors and their binding sites in sequence space}},
doi = {10.15479/at:ista:th6071},
year = {2019},
}
@article{6182,
abstract = {We consider large random matrices with a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent away from the spectral edges, generalizing the recent result of Ajanki et al. [âStability of the matrix Dyson equation and random matrices with correlationsâ, Probab. Theory Related Fields 173(1â2) (2019), 293â373] to allow slow correlation decay and arbitrary expectation. The main novel tool is
a systematic diagrammatic control of a multivariate cumulant expansion.},
author = {ErdĂ¶s, LĂĄszlĂł and KrĂŒger, Torben H and SchrĂ¶der, Dominik J},
issn = {20505094},
journal = {Forum of Mathematics, Sigma},
publisher = {Cambridge University Press},
title = {{Random matrices with slow correlation decay}},
doi = {10.1017/fms.2019.2},
volume = {7},
year = {2019},
}
@article{6186,
abstract = {We prove that the local eigenvalue statistics of real symmetric Wigner-type
matrices near the cusp points of the eigenvalue density are universal. Together
with the companion paper [arXiv:1809.03971], which proves the same result for
the complex Hermitian symmetry class, this completes the last remaining case of
the Wigner-Dyson-Mehta universality conjecture after bulk and edge
universalities have been established in the last years. We extend the recent
Dyson Brownian motion analysis at the edge [arXiv:1712.03881] to the cusp
regime using the optimal local law from [arXiv:1809.03971] and the accurate
local shape analysis of the density from [arXiv:1506.05095, arXiv:1804.07752].
We also present a PDE-based method to improve the estimate on eigenvalue
rigidity via the maximum principle of the heat flow related to the Dyson
Brownian motion.},
author = {Cipolloni, Giorgio and ErdĂ¶s, LĂĄszlĂł and KrĂŒger, Torben H and SchrĂ¶der, Dominik J},
issn = {2578-5885},
journal = {Pure and Applied Analysis },
number = {4},
pages = {615â707},
publisher = {MSP},
title = {{Cusp universality for random matrices, II: The real symmetric case}},
doi = {10.2140/paa.2019.1.615},
volume = {1},
year = {2019},
}
@article{6900,
abstract = {Across diverse biological systemsâranging from neural networks to intracellular signaling and genetic regulatory networksâthe information about changes in the environment is frequently encoded in the full temporal dynamics of the network nodes. A pressing data-analysis challenge has thus been to efficiently estimate the amount of information that these dynamics convey from experimental data. Here we develop and evaluate decoding-based estimation methods to lower bound the mutual information about a finite set of inputs, encoded in single-cell high-dimensional time series data. For biological reaction networks governed by the chemical Master equation, we derive model-based information approximations and analytical upper bounds, against which we benchmark our proposed model-free decoding estimators. In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based estimators robustly extract a large fraction of the available information from high-dimensional trajectories with a realistic number of data samples. We apply these estimators to previously published data on Erk and Ca2+ signaling in mammalian cells and to yeast stress-response, and find that substantial amount of information about environmental state can be encoded by non-trivial response statistics even in stationary signals. We argue that these single-cell, decoding-based information estimates, rather than the commonly-used tests for significant differences between selected population response statistics, provide a proper and unbiased measure for the performance of biological signaling networks.},
author = {Cepeda Humerez, Sarah A and Ruess, Jakob and TkaÄik, GaĆĄper},
issn = {15537358},
journal = {PLoS computational biology},
number = {9},
pages = {e1007290},
publisher = {Public Library of Science},
title = {{Estimating information in time-varying signals}},
doi = {10.1371/journal.pcbi.1007290},
volume = {15},
year = {2019},
}
@article{6377,
abstract = {Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.},
author = {Dejonghe, Wim and Sharma, Isha and Denoo, Bram and De Munck, Steven and Lu, Qing and Mishev, Kiril and Bulut, Haydar and Mylle, Evelien and De Rycke, Riet and Vasileva, Mina K and Savatin, Daniel V. and Nerinckx, Wim and Staes, An and Drozdzecki, Andrzej and Audenaert, Dominique and Yperman, Klaas and Madder, Annemieke and Friml, JiĆĂ and Van Damme, DaniĂ«l and Gevaert, Kris and Haucke, Volker and Savvides, Savvas N. and Winne, Johan and Russinova, Eugenia},
issn = {15524469},
journal = {Nature Chemical Biology},
number = {6},
pages = {641â649},
publisher = {Springer Nature},
title = {{Disruption of endocytosis through chemical inhibition of clathrin heavy chain function}},
doi = {10.1038/s41589-019-0262-1},
volume = {15},
year = {2019},
}
@phdthesis{7186,
abstract = {Tissue morphogenesis in developmental or physiological processes is regulated by molecular
and mechanical signals. While the molecular signaling cascades are increasingly well
described, the mechanical signals affecting tissue shape changes have only recently been
studied in greater detail. To gain more insight into the mechanochemical and biophysical
basis of an epithelial spreading process (epiboly) in early zebrafish development, we studied
cell-cell junction formation and actomyosin network dynamics at the boundary between
surface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,
the cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of
gastrulation. It has been previously shown that an actomyosin ring residing within the YSL
pulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby
dragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL
actomyosin ring to EVL cells; however, the nature and formation of the junctional structure
mediating this process has not been well described so far. Therefore, our main aim was to
determine the nature, dynamics and potential function of the EVL-YSL junction during this
epithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a
mechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process
of TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated
Zonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we
could demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk
cell, and ZO-1 undergoes a phase separation process that likely renders the protein
responsive to flows. These flows are directed towards the junction and mediate proper
tension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets
incorporated into the junctional pool mediated through its direct actin-binding domain.
When the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their
proper mechanosensitive responses resulting in slower tissue spreading. We could further
demonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin
ring formation. This suggests that a mechanochemical feedback loop is at work during
zebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin
contractility and flows positively influence ZO-1 junctional recruitment. Finally, such a
mesoscale polarization process mediated through the flow of phase-separated protein
clusters might have implications for other processes such as immunological synapse
formation, C. elegans zygote polarization and wound healing.},
author = {Schwayer, Cornelia},
issn = {2663-337X},
pages = {107},
publisher = {Institute of Science and Technology Austria},
title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}},
doi = {10.15479/AT:ISTA:7186},
year = {2019},
}
@phdthesis{6681,
abstract = {The first part of the thesis considers the computational aspects of the homotopy groups Ïd(X) of a topological space X. It is well known that there is no algorithm to decide whether the fundamental group Ï1(X) of a given finite simplicial complex X is trivial. On the other hand, there are several algorithms that, given a finite simplicial complex X that is simply connected (i.e., with Ï1(X) trivial), compute the higher homotopy group Ïd(X) for any given d â„ 2.
However, these algorithms come with a caveat: They compute the isomorphism type of Ïd(X), d â„ 2 as an abstract finitely generated abelian group given by generators and relations, but they work with very implicit representations of the elements of Ïd(X). We present an algorithm that, given a simply connected space X, computes Ïd(X) and represents its elements as simplicial maps from suitable triangulations of the d-sphere Sd to X. For fixed d, the algorithm runs in time exponential in size(X), the number of simplices of X. Moreover, we prove that this is optimal: For every fixed d â„ 2,
we construct a family of simply connected spaces X such that for any simplicial map representing a generator of Ïd(X), the size of the triangulation of S d on which the map is defined, is exponential in size(X).
In the second part of the thesis, we prove that the following question is algorithmically undecidable for d < â3(k+1)/2â, k â„ 5 and (k, d) Ìž= (5, 7), which covers essentially everything outside the meta-stable range: Given a finite simplicial complex K of dimension k, decide whether there exists a piecewise-linear (i.e., linear on an arbitrarily fine subdivision of K) embedding f : K âȘâ Rd of K into a d-dimensional Euclidean space.},
author = {Zhechev, Stephan Y},
issn = {2663-337X},
pages = {104},
publisher = {Institute of Science and Technology Austria},
title = {{Algorithmic aspects of homotopy theory and embeddability}},
doi = {10.15479/AT:ISTA:6681},
year = {2019},
}
@unpublished{8182,
abstract = {Suppose that $n\neq p^k$ and $n\neq 2p^k$ for all $k$ and all primes $p$. We prove that for any Hausdorff compactum $X$ with a free action of the symmetric group $\mathfrak S_n$ there exists an $\mathfrak S_n$-equivariant map $X \to
{\mathbb R}^n$ whose image avoids the diagonal $\{(x,x\dots,x)\in {\mathbb R}^n|x\in {\mathbb R}\}$.
Previously, the special cases of this statement for certain $X$ were usually proved using the equivartiant obstruction theory. Such calculations are difficult and may become infeasible past the first (primary) obstruction. We
take a different approach which allows us to prove the vanishing of all obstructions simultaneously. The essential step in the proof is classifying the possible degrees of $\mathfrak S_n$-equivariant maps from the boundary
$\partial\Delta^{n-1}$ of $(n-1)$-simplex to itself. Existence of equivariant maps between spaces is important for many questions arising from discrete mathematics and geometry, such as Kneser's conjecture, the Square Peg conjecture, the Splitting Necklace problem, and the Topological Tverberg conjecture, etc. We demonstrate the utility of our result applying it to one such question, a specific instance of envy-free division problem.},
author = {Avvakumov, Sergey and Kudrya, Sergey},
booktitle = {arXiv},
publisher = {arXiv},
title = {{Vanishing of all equivariant obstructions and the mapping degree}},
year = {2019},
}
@unpublished{8185,
abstract = {In this paper we study envy-free division problems. The classical approach to some of such problems, used by David Gale, reduces to considering continuous maps of a simplex to itself and finding sufficient conditions when this map hits the center of the simplex. The mere continuity is not sufficient for such a conclusion, the usual assumption (for example, in the Knaster--Kuratowski--Mazurkiewicz and the Gale theorem) is a certain boundary condition.
We follow Erel Segal-Halevi, Fr\'ed\'eric Meunier, and Shira Zerbib, and replace the boundary condition by another assumption, which has the economic meaning of possibility for a player to prefer an empty part in the segment
partition problem. We solve the problem positively when $n$, the number of players that divide the segment, is a prime power, and we provide counterexamples for every $n$ which is not a prime power. We also provide counterexamples relevant to a wider class of fair or envy-free partition problems when $n$ is odd and not a prime power.},
author = {Avvakumov, Sergey and Karasev, Roman},
booktitle = {arXiv},
title = {{Envy-free division using mapping degree}},
doi = {10.48550/arXiv.1907.11183},
year = {2019},
}
@unpublished{7524,
abstract = {We prove a lower bound for the free energy (per unit volume) of the two-dimensional Bose gas in the thermodynamic limit. We show that the free energy at density $\rho$ and inverse temperature $\beta$ differs from the one of the non-interacting system by the correction term $4 \pi \rho^2 |\ln a^2 \rho|^{-1} (2 - [1 - \beta_{\mathrm{c}}/\beta]_+^2)$. Here $a$ is the scattering length of the interaction potential, $[\cdot]_+ = \max\{ 0, \cdot \}$ and $\beta_{\mathrm{c}}$ is the inverse Berezinskii--Kosterlitz--Thouless critical temperature for superfluidity. The result is valid in the dilute limit
$a^2\rho \ll 1$ and if $\beta \rho \gtrsim 1$.},
author = {Deuchert, Andreas and Mayer, Simon and Seiringer, Robert},
booktitle = {arXiv:1910.03372},
pages = {61},
publisher = {ArXiv},
title = {{The free energy of the two-dimensional dilute Bose gas. I. Lower bound}},
year = {2019},
}
@article{6608,
abstract = {We use the canonical bases produced by the tri-partition algorithm in (Edelsbrunner and ĂlsbĂ¶ck, 2018) to open and close holes in a polyhedral complex, K. In a concrete application, we consider the Delaunay mosaic of a finite set, we let K be an Alpha complex, and we use the persistence diagram of the distance function to guide the hole opening and closing operations. The dependences between the holes define a partial order on the cells in K that characterizes what can and what cannot be constructed using the operations. The relations in this partial order reveal structural information about the underlying filtration of complexes beyond what is expressed by the persistence diagram.},
author = {Edelsbrunner, Herbert and ĂlsbĂ¶ck, Katharina},
journal = {Computer Aided Geometric Design},
pages = {1--15},
publisher = {Elsevier},
title = {{Holes and dependences in an ordered complex}},
doi = {10.1016/j.cagd.2019.06.003},
volume = {73},
year = {2019},
}
@inproceedings{6677,
abstract = {The Fiat-Shamir heuristic transforms a public-coin interactive proof into a non-interactive argument, by replacing the verifier with a cryptographic hash function that is applied to the protocolâs transcript. Constructing hash functions for which this transformation is sound is a central and long-standing open question in cryptography.
We show that solving the ENDâOFâMETEREDâLINE problem is no easier than breaking the soundness of the Fiat-Shamir transformation when applied to the sumcheck protocol. In particular, if the transformed protocol is sound, then any hard problem in #P gives rise to a hard distribution in the class CLS, which is contained in PPAD. Our result opens up the possibility of sampling moderately-sized games for which it is hard to find a Nash equilibrium, by reducing the inversion of appropriately chosen one-way functions to #SAT.
Our main technical contribution is a stateful incrementally verifiable procedure that, given a SAT instance over n variables, counts the number of satisfying assignments. This is accomplished via an exponential sequence of small steps, each computable in time poly(n). Incremental verifiability means that each intermediate state includes a sumcheck-based proof of its correctness, and the proof can be updated and verified in time poly(n).},
author = {Choudhuri, Arka Rai and HubĂĄÄek, Pavel and Kamath Hosdurg, Chethan and Pietrzak, Krzysztof Z and Rosen, Alon and Rothblum, Guy N.},
booktitle = {Proceedings of the 51st Annual ACM SIGACT Symposium on Theory of Computing - STOC 2019},
isbn = {9781450367059},
location = {Phoenix, AZ, United States},
pages = {1103--1114},
publisher = {ACM Press},
title = {{Finding a Nash equilibrium is no easier than breaking Fiat-Shamir}},
doi = {10.1145/3313276.3316400},
year = {2019},
}
@article{5986,
abstract = {Given a triangulation of a point set in the plane, a flip deletes an edge e whose removal leaves a convex quadrilateral, and replaces e by the opposite diagonal of the quadrilateral. It is well known that any triangulation of a point set can be reconfigured to any other triangulation by some sequence of flips. We explore this question in the setting where each edge of a triangulation has a label, and a flip transfers the label of the removed edge to the new edge. It is not true that every labelled triangulation of a point set can be reconfigured to every other labelled triangulation via a sequence of flips, but we characterize when this is possible. There is an obvious necessary condition: for each label l, if edge e has label l in the first triangulation and edge f has label l in the second triangulation, then there must be some sequence of flips that moves label l from e to f, ignoring all other labels. Bose, Lubiw, Pathak and Verdonschot formulated the Orbit Conjecture, which states that this necessary condition is also sufficient, i.e. that all labels can be simultaneously mapped to their destination if and only if each label individually can be mapped to its destination. We prove this conjecture. Furthermore, we give a polynomial-time algorithm (with đ(đ8) being a crude bound on the run-time) to find a sequence of flips to reconfigure one labelled triangulation to another, if such a sequence exists, and we prove an upper bound of đ(đ7) on the length of the flip sequence. Our proof uses the topological result that the sets of pairwise non-crossing edges on a planar point set form a simplicial complex that is homeomorphic to a high-dimensional ball (this follows from a result of Orden and Santos; we give a different proof based on a shelling argument). The dual cell complex of this simplicial ball, called the flip complex, has the usual flip graph as its 1-skeleton. We use properties of the 2-skeleton of the flip complex to prove the Orbit Conjecture.},
author = {Lubiw, Anna and MasĂĄrovĂĄ, Zuzana and Wagner, Uli},
issn = {1432-0444},
journal = {Discrete & Computational Geometry},
number = {4},
pages = {880--898},
publisher = {Springer Nature},
title = {{A proof of the orbit conjecture for flipping edge-labelled triangulations}},
doi = {10.1007/s00454-018-0035-8},
volume = {61},
year = {2019},
}
@article{5886,
abstract = {Problems involving quantum impurities, in which one or a few particles are interacting with a macroscopic environment, represent a pervasive paradigm, spanning across atomic, molecular, and condensed-matter physics. In this paper we introduce new variational approaches to quantum impurities and apply them to the FrĂ¶hlich polaronâa quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulonâa quasiparticle formed out of a rotating molecule in a bosonic bath. We benchmark these approaches against established theories, evaluating their accuracy as a function of the impurity-bath coupling.},
author = {Li, Xiang and Bighin, Giacomo and Yakaboylu, Enderalp and Lemeshko, Mikhail},
issn = {00268976},
journal = {Molecular Physics},
publisher = {Taylor and Francis},
title = {{Variational approaches to quantum impurities: from the FrĂ¶hlich polaron to the angulon}},
doi = {10.1080/00268976.2019.1567852},
year = {2019},
}
@unpublished{7950,
abstract = {The input to the token swapping problem is a graph with vertices v1, v2, . . . , vn, and n tokens with labels 1,2, . . . , n, one on each vertex. The goal is to get token i to vertex vi for all i= 1, . . . , n using a minimum number of swaps, where a swap exchanges the tokens on the endpoints of an edge.Token swapping on a tree, also known as âsorting with a transposition tree,â is not known to be in P nor NP-complete. We present some partial results:
1. An optimum swap sequence may need to perform a swap on a leaf vertex that has the correct token (a âhappy leafâ), disproving a conjecture of Vaughan.
2. Any algorithm that fixes happy leavesâas all known approximation algorithms for the problem doâhas approximation factor at least 4/3. Furthermore, the two best-known 2-approximation algorithms have approximation factor exactly 2.
3. A generalized problemâweighted coloured token swappingâis NP-complete on trees, but solvable in polynomial time on paths and stars. In this version, tokens and vertices have colours, and colours have weights. The goal is to get every token to a vertex of the same colour, and the cost of a swap is the sum of the weights of the two tokens involved.},
author = {Biniaz, Ahmad and Jain, Kshitij and Lubiw, Anna and MasĂĄrovĂĄ, Zuzana and Miltzow, Tillmann and Mondal, Debajyoti and Naredla, Anurag Murty and Tkadlec, Josef and Turcotte, Alexi},
booktitle = {arXiv},
title = {{Token swapping on trees}},
year = {2019},
}
@inproceedings{6556,
abstract = {Motivated by fixed-parameter tractable (FPT) problems in computational topology, we consider the treewidth tw(M) of a compact, connected 3-manifold M, defined to be the minimum treewidth of the face pairing graph of any triangulation T of M. In this setting the relationship between the topology of a 3-manifold and its treewidth is of particular interest. First, as a corollary of work of Jaco and Rubinstein, we prove that for any closed, orientable 3-manifold M the treewidth tw(M) is at most 4g(M)-2, where g(M) denotes Heegaard genus of M. In combination with our earlier work with Wagner, this yields that for non-Haken manifolds the Heegaard genus and the treewidth are within a constant factor. Second, we characterize all 3-manifolds of treewidth one: These are precisely the lens spaces and a single other Seifert fibered space. Furthermore, we show that all remaining orientable Seifert fibered spaces over the 2-sphere or a non-orientable surface have treewidth two. In particular, for every spherical 3-manifold we exhibit a triangulation of treewidth at most two. Our results further validate the parameter of treewidth (and other related parameters such as cutwidth or congestion) to be useful for topological computing, and also shed more light on the scope of existing FPT-algorithms in the field.},
author = {HuszĂĄr, KristĂłf and Spreer, Jonathan},
booktitle = {35th International Symposium on Computational Geometry},
isbn = {978-3-95977-104-7},
issn = {1868-8969},
keywords = {computational 3-manifold topology, fixed-parameter tractability, layered triangulations, structural graph theory, treewidth, cutwidth, Heegaard genus},
location = {Portland, Oregon, United States},
pages = {44:1--44:20},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum fĂŒr Informatik},
title = {{3-manifold triangulations with small treewidth}},
doi = {10.4230/LIPIcs.SoCG.2019.44},
volume = {129},
year = {2019},
}
@article{7093,
abstract = {In graph theory, as well as in 3-manifold topology, there exist several width-type parameters to describe how "simple" or "thin" a given graph or 3-manifold is. These parameters, such as pathwidth or treewidth for graphs, or the concept of thin position for 3-manifolds, play an important role when studying algorithmic problems; in particular, there is a variety of problems in computational 3-manifold topology - some of them known to be computationally hard in general - that become solvable in polynomial time as soon as the dual graph of the input triangulation has bounded treewidth.
In view of these algorithmic results, it is natural to ask whether every 3-manifold admits a triangulation of bounded treewidth. We show that this is not the case, i.e., that there exists an infinite family of closed 3-manifolds not admitting triangulations of bounded pathwidth or treewidth (the latter implies the former, but we present two separate proofs).
We derive these results from work of Agol, of Scharlemann and Thompson, and of Scharlemann, Schultens and Saito by exhibiting explicit connections between the topology of a 3-manifold M on the one hand and width-type parameters of the dual graphs of triangulations of M on the other hand, answering a question that had been raised repeatedly by researchers in computational 3-manifold topology. In particular, we show that if a closed, orientable, irreducible, non-Haken 3-manifold M has a triangulation of treewidth (resp. pathwidth) k then the Heegaard genus of M is at most 18(k+1) (resp. 4(3k+1)).},
author = {HuszĂĄr, KristĂłf and Spreer, Jonathan and Wagner, Uli},
issn = {1920-180X},
journal = {Journal of Computational Geometry},
number = {2},
pages = {70â98},
publisher = {Computational Geometry Laborartoy},
title = {{On the treewidth of triangulated 3-manifolds}},
doi = {10.20382/JOGC.V10I2A5},
volume = {10},
year = {2019},
}
@article{7197,
abstract = {During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.},
author = {Dos Santos Caldas, Paulo R and Lopez Pelegrin, Maria D and Pearce, Daniel J. G. and Budanur, Nazmi B and BruguĂ©s, Jan and Loose, Martin},
issn = {2041-1723},
journal = {Nature Communications},
publisher = {Springer Nature},
title = {{Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA}},
doi = {10.1038/s41467-019-13702-4},
volume = {10},
year = {2019},
}
@article{7210,
abstract = {The rate of biological evolution depends on the fixation probability and on the fixation time of new mutants. Intensive research has focused on identifying population structures that augment the fixation probability of advantageous mutants. But these amplifiers of natural selection typically increase fixation time. Here we study population structures that achieve a tradeoff between fixation probability and time. First, we show that no amplifiers can have an asymptotically lower absorption time than the well-mixed population. Then we design population structures that substantially augment the fixation probability with just a minor increase in fixation time. Finally, we show that those structures enable higher effective rate of evolution than the well-mixed population provided that the rate of generating advantageous mutants is relatively low. Our work sheds light on how population structure affects the rate of evolution. Moreover, our structures could be useful for lab-based, medical, or industrial applications of evolutionary optimization.},
author = {Tkadlec, Josef and Pavlogiannis, Andreas and Chatterjee, Krishnendu and Nowak, Martin A.},
issn = {2399-3642},
journal = {Communications Biology},
publisher = {Springer Nature},
title = {{Population structure determines the tradeoff between fixation probability and fixation time}},
doi = {10.1038/s42003-019-0373-y},
volume = {2},
year = {2019},
}
@inproceedings{10190,
abstract = {The verification of concurrent programs remains an open challenge, as thread interaction has to be accounted for, which leads to state-space explosion. Stateless model checking battles this problem by exploring traces rather than states of the program. As there are exponentially many traces, dynamic partial-order reduction (DPOR) techniques are used to partition the trace space into equivalence classes, and explore a few representatives from each class. The standard equivalence that underlies most DPOR techniques is the happens-before equivalence, however recent works have spawned a vivid interest towards coarser equivalences. The efficiency of such approaches is a product of two parameters: (i) the size of the partitioning induced by the equivalence, and (ii) the time spent by the exploration algorithm in each class of the partitioning. In this work, we present a new equivalence, called value-happens-before and show that it has two appealing features. First, value-happens-before is always at least as coarse as the happens-before equivalence, and can be even exponentially coarser. Second, the value-happens-before partitioning is efficiently explorable when the number of threads is bounded. We present an algorithm called value-centric DPOR (VCDPOR), which explores the underlying partitioning using polynomial time per class. Finally, we perform an experimental evaluation of VCDPOR on various benchmarks, and compare it against other state-of-the-art approaches. Our results show that value-happens-before typically induces a significant reduction in the size of the underlying partitioning, which leads to a considerable reduction in the running time for exploring the whole partitioning.},
author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Toman, Viktor},
booktitle = {Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications},
issn = {2475-1421},
keywords = {safety, risk, reliability and quality, software},
location = {Athens, Greece},
publisher = {ACM},
title = {{Value-centric dynamic partial order reduction}},
doi = {10.1145/3360550},
volume = {3},
year = {2019},
}
@inproceedings{6673,
abstract = {Several classic problems in graph processing and computational geometry are solved via incremental algorithms, which split computation into a series of small tasks acting on shared state, which gets updated progressively. While the sequential variant of such algorithms usually specifies a fixed (but sometimes random) order in which the tasks should be performed, a standard approach to parallelizing such algorithms is to relax this constraint to allow for out-of-order parallel execution. This is the case for parallel implementations of Dijkstra's single-source shortest-paths (SSSP) algorithm, and for parallel Delaunay mesh triangulation. While many software frameworks parallelize incremental computation in this way, it is still not well understood whether this relaxed ordering approach can still provide any complexity guarantees. In this paper, we address this problem, and analyze the efficiency guarantees provided by a range of incremental algorithms when parallelized via relaxed schedulers. We show that, for algorithms such as Delaunay mesh triangulation and sorting by insertion, schedulers with a maximum relaxation factor of k in terms of the maximum priority inversion allowed will introduce a maximum amount of wasted work of O(Ćog n poly(k)), where n is the number of tasks to be executed. For SSSP, we show that the additional work is O(poly(k), dmax / wmin), where dmax is the maximum distance between two nodes, and wmin is the minimum such distance. In practical settings where n >> k, this suggests that the overheads of relaxation will be outweighed by the improved scalability of the relaxed scheduler. On the negative side, we provide lower bounds showing that certain algorithms will inherently incur a non-trivial amount of wasted work due to scheduler relaxation, even for relatively benign relaxed schedulers.},
author = {Alistarh, Dan-Adrian and Nadiradze, Giorgi and Koval, Nikita},
booktitle = {31st ACM Symposium on Parallelism in Algorithms and Architectures},
isbn = {9781450361842},
location = {Phoenix, AZ, United States},
pages = {145--154},
publisher = {ACM Press},
title = {{Efficiency guarantees for parallel incremental algorithms under relaxed schedulers}},
doi = {10.1145/3323165.3323201},
year = {2019},
}
@inproceedings{6590,
abstract = {Modern machine learning methods often require more data for training than a single expert can provide. Therefore, it has become a standard procedure to collect data from external sources, e.g. via crowdsourcing. Unfortunately, the quality of these sources is not always guaranteed. As additional complications, the data might be stored in a distributed way, or might even have to remain private. In this work, we address the question of how to learn robustly in such scenarios. Studying the problem through the lens of statistical learning theory, we derive a procedure that allows for learning from all available sources, yet automatically suppresses irrelevant or corrupted data. We show by extensive experiments that our method provides significant improvements over alternative approaches from robust statistics and distributed optimization. },
author = {Konstantinov, Nikola H and Lampert, Christoph},
booktitle = {Proceedings of the 36th International Conference on Machine Learning},
location = {Long Beach, CA, USA},
pages = {3488--3498},
publisher = {PMLR},
title = {{Robust learning from untrusted sources}},
volume = {97},
year = {2019},
}
@article{7396,
abstract = {The angular momentum of molecules, or, equivalently, their rotation in three-dimensional space, is ideally suited for quantum control. Molecular angular momentum is naturally quantized, time evolution is governed by a well-known Hamiltonian with only a few accurately known parameters, and transitions between rotational levels can be driven by external fields from various parts of the electromagnetic spectrum. Control over the rotational motion can be exerted in one-, two-, and many-body scenarios, thereby allowing one to probe Anderson localization, target stereoselectivity of bimolecular reactions, or encode quantum information to name just a few examples. The corresponding approaches to quantum control are pursued within separate, and typically disjoint, subfields of physics, including ultrafast science, cold collisions, ultracold gases, quantum information science, and condensed-matter physics. It is the purpose of this review to present the various control phenomena, which all rely on the same underlying physics, within a unified framework. To this end, recall the Hamiltonian for free rotations, assuming the rigid rotor approximation to be valid, and summarize the different ways for a rotor to interact with external electromagnetic fields. These interactions can be exploited for controlâfrom achieving alignment, orientation, or laser cooling in a one-body framework, steering bimolecular collisions, or realizing a quantum computer or quantum simulator in the many-body setting.},
author = {Koch, Christiane P. and Lemeshko, Mikhail and Sugny, Dominique},
issn = {1539-0756},
journal = {Reviews of Modern Physics},
number = {3},
publisher = {APS},
title = {{Quantum control of molecular rotation}},
doi = {10.1103/revmodphys.91.035005},
volume = {91},
year = {2019},
}
@article{7399,
abstract = {Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established.},
author = {Andergassen, Daniel and Muckenhuber, Markus and Bammer, Philipp C. and Kulinski, Tomasz M. and Theussl, Hans-Christian and Shimizu, Takahiko and Penninger, Josef M. and Pauler, Florian and Hudson, Quanah J.},
issn = {1553-7404},
journal = {PLOS Genetics},
number = {7},
publisher = {PLoS},
title = {{The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes}},
doi = {10.1371/journal.pgen.1008268},
volume = {15},
year = {2019},
}
@article{7398,
abstract = {Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Clâ. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Clâ in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Clâ on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Clâ. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation.},
author = {Erdem, Fatma Asli and Ilic, Marija and Koppensteiner, Peter and GoĆacki, Jakub and Lubec, Gert and Freissmuth, Michael and Sandtner, Walter},
issn = {1540-7748},
journal = {The Journal of General Physiology},
number = {8},
pages = {1035--1050},
publisher = {Rockefeller University Press},
title = {{A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2}},
doi = {10.1085/jgp.201912318},
volume = {151},
year = {2019},
}
@article{7395,
abstract = {The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Ă
in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between âclosedâ and âopenâ conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.},
author = {Letts, James A and Fiedorczuk, Karol and Degliesposti, Gianluca and Skehel, Mark and Sazanov, Leonid A},
issn = {1097-2765},
journal = {Molecular Cell},
number = {6},
pages = {1131--1146.e6},
publisher = {Cell Press},
title = {{Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk}},
doi = {10.1016/j.molcel.2019.07.022},
volume = {75},
year = {2019},
}
@article{7405,
abstract = {Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis â connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena.},
author = {Dura-Bernal, Salvador and Suter, Benjamin and Gleeson, Padraig and Cantarelli, Matteo and Quintana, Adrian and Rodriguez, Facundo and Kedziora, David J and Chadderdon, George L and Kerr, Cliff C and Neymotin, Samuel A and McDougal, Robert A and Hines, Michael and Shepherd, Gordon MG and Lytton, William W},
issn = {2050-084X},
journal = {eLife},
publisher = {eLife Sciences Publications},
title = {{NetPyNE, a tool for data-driven multiscale modeling of brain circuits}},
doi = {10.7554/elife.44494},
volume = {8},
year = {2019},
}
@article{7400,
abstract = {Suppressed recombination allows divergence between homologous sex chromosomes and the functionality of their genes. Here, we reveal patterns of the earliest stages of sex-chromosome evolution in the diploid dioecious herb Mercurialis annua on the basis of cytological analysis, de novo genome assembly and annotation, genetic mapping, exome resequencing of natural populations, and transcriptome analysis. The genome assembly contained 34,105 expressed genes, of which 10,076 were assigned to linkage groups. Genetic mapping and exome resequencing of individuals across the species range both identified the largest linkage group, LG1, as the sex chromosome. Although the sex chromosomes of M. annua are karyotypically homomorphic, we estimate that about one-third of the Y chromosome, containing 568 transcripts and spanning 22.3 cM in the corresponding female map, has ceased recombining. Nevertheless, we found limited evidence for Y-chromosome degeneration in terms of gene loss and pseudogenization, and most X- and Y-linked genes appear to have diverged in the period subsequent to speciation between M. annua and its sister species M. huetii, which shares the same sex-determining region. Taken together, our results suggest that the M. annua Y chromosome has at least two evolutionary strata: a small old stratum shared with M. huetii, and a more recent larger stratum that is probably unique to M. annua and that stopped recombining âŒ1 MYA. Patterns of gene expression within the nonrecombining region are consistent with the idea that sexually antagonistic selection may have played a role in favoring suppressed recombination.},
author = {Veltsos, Paris and Ridout, Kate E. and Toups, Melissa A and GonzĂĄlez-MartĂnez, Santiago C. and Muyle, Aline and Emery, Olivier and Rastas, Pasi and Hudzieczek, Vojtech and Hobza, Roman and Vyskot, Boris and Marais, Gabriel A. B. and Filatov, Dmitry A. and Pannell, John R.},
issn = {1943-2631},
journal = {Genetics},
number = {3},
pages = {815--835},
publisher = {Genetics Society of America},
title = {{Early sex-chromosome evolution in the diploid dioecious plant Mercurialis annua}},
doi = {10.1534/genetics.119.302045},
volume = {212},
year = {2019},
}
@article{7404,
abstract = {The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.},
author = {StĂŒrner, Tomke and Tatarnikova, Anastasia and MĂŒller, Jan and Schaffran, Barbara and Cuntz, Hermann and Zhang, Yun and Nemethova, Maria and Bogdan, Sven and Small, Vic and Tavosanis, Gaia},
issn = {1477-9129},
journal = {Development},
number = {7},
publisher = {The Company of Biologists},
title = {{Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo}},
doi = {10.1242/dev.171397},
volume = {146},
year = {2019},
}
@inproceedings{7402,
abstract = {Graph planning gives rise to fundamental algorithmic questions such as shortest path, traveling salesman problem, etc. A classical problem in discrete planning is to consider a weighted graph and construct a path that maximizes the sum of weights for a given time horizon T. However, in many scenarios, the time horizon is not fixed, but the stopping time is chosen according to some distribution such that the expected stopping time is T. If the stopping time distribution is not known, then to ensure robustness, the distribution is chosen by an adversary, to represent the worst-case scenario. A stationary plan for every vertex always chooses the same outgoing edge. For fixed horizon or fixed stopping-time distribution, stationary plans are not sufficient for optimality. Quite surprisingly we show that when an adversary chooses the stopping-time distribution with expected stopping time T, then stationary plans are sufficient. While computing optimal stationary plans for fixed horizon is NP-complete, we show that computing optimal stationary plans under adversarial stopping-time distribution can be achieved in polynomial time. Consequently, our polynomial-time algorithm for adversarial stopping time also computes an optimal plan among all possible plans.},
author = {Chatterjee, Krishnendu and Doyen, Laurent},
booktitle = {34th Annual ACM/IEEE Symposium on Logic in Computer Science},
isbn = {9781728136080},
location = {Vancouver, BC, Canada},
pages = {1--13},
publisher = {IEEE},
title = {{Graph planning with expected finite horizon}},
doi = {10.1109/lics.2019.8785706},
year = {2019},
}
@article{7451,
abstract = {We prove that the observable telegraph signal accompanying the bistability in the photon-blockade-breakdown regime of the driven and lossy JaynesâCummings model is the finite-size precursor of what in the thermodynamic limit is a genuine first-order phase transition. We construct a finite-size scaling of the system parameters to a well-defined thermodynamic limit, in which the system remains the same microscopic system, but the telegraph signal becomes macroscopic both in its timescale and intensity. The existence of such a finite-size scaling completes and justifies the classification of the photon-blockade-breakdown effect as a first-order dissipative quantum phase transition.},
author = {Vukics, A. and Dombi, A. and Fink, Johannes M and Domokos, P.},
issn = {2521-327X},
journal = {Quantum},
publisher = {Verein zur FĂ¶rderung des Open Access Publizierens in den Quantenwissenschaften},
title = {{Finite-size scaling of the photon-blockade breakdown dissipative quantum phase transition}},
doi = {10.22331/q-2019-06-03-150},
volume = {3},
year = {2019},
}
@inproceedings{7468,
abstract = {We present a new proximal bundle method for Maximum-A-Posteriori (MAP) inference in structured energy minimization problems. The method optimizes a Lagrangean relaxation of the original energy minimization problem using a multi plane block-coordinate Frank-Wolfe method that takes advantage of the specific structure of the Lagrangean decomposition. We show empirically that our method outperforms state-of-the-art Lagrangean decomposition based algorithms on some challenging Markov Random Field, multi-label discrete tomography and graph matching problems.},
author = {Swoboda, Paul and Kolmogorov, Vladimir},
booktitle = {Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition},
isbn = {9781728132938},
issn = {10636919},
location = {Long Beach, CA, United States},
publisher = {IEEE},
title = {{Map inference via block-coordinate Frank-Wolfe algorithm}},
doi = {10.1109/CVPR.2019.01140},
volume = {2019-June},
year = {2019},
}
@article{7415,
author = {Morandell, Jasmin and Nicolas, Armel and Schwarz, Lena A and Novarino, Gaia},
issn = {0924-977X},
journal = {European Neuropsychopharmacology},
number = {Supplement 6},
pages = {S11--S12},
publisher = {Elsevier},
title = {{S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism}},
doi = {10.1016/j.euroneuro.2019.09.040},
volume = {29},
year = {2019},
}
@article{7414,
author = {Knaus, Lisa and Tarlungeanu, Dora-Clara and Novarino, Gaia},
issn = {0924-977X},
journal = {European Neuropsychopharmacology},
number = {Supplement 6},
pages = {S11},
publisher = {Elsevier},
title = {{S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly}},
doi = {10.1016/j.euroneuro.2019.09.039},
volume = {29},
year = {2019},
}
@article{7394,
author = {BenkovĂĄ, Eva and Dagdas, Yasin},
issn = {1369-5266},
journal = {Current Opinion in Plant Biology},
number = {12},
pages = {A1--A2},
publisher = {Elsevier},
title = {{Editorial overview: Cell biology in the era of omics?}},
doi = {10.1016/j.pbi.2019.11.002},
volume = {52},
year = {2019},
}
@inproceedings{7479,
abstract = {Multi-exit architectures, in which a stack of processing layers is interleaved with early output layers, allow the processing of a test example to stop early and thus save computation time and/or energy. In this work, we propose a new training procedure for multi-exit architectures based on the principle of knowledge distillation. The method encourage searly exits to mimic later, more accurate exits, by matching their output probabilities.
Experiments on CIFAR100 and ImageNet show that distillation-based training significantly improves the accuracy of early exits while maintaining state-of-the-art accuracy for late ones. The method is particularly beneficial when training data is limited and it allows a straightforward extension to semi-supervised learning,i.e. making use of unlabeled data at training time. Moreover, it takes only afew lines to implement and incurs almost no computational overhead at training time, and none at all at test time.},
author = {Bui Thi Mai, Phuong and Lampert, Christoph},
booktitle = {IEEE International Conference on Computer Vision},
isbn = {9781728148038},
issn = {15505499},
location = {Seoul, Korea},
pages = {1355--1364},
publisher = {IEEE},
title = {{Distillation-based training for multi-exit architectures}},
doi = {10.1109/ICCV.2019.00144},
volume = {2019-October},
year = {2019},
}
@inproceedings{7542,
abstract = {We present a novel class of convolutional neural networks (CNNs) for set functions,i.e., data indexed with the powerset of a finite set. The convolutions are derivedas linear, shift-equivariant functions for various notions of shifts on set functions.The framework is fundamentally different from graph convolutions based on theLaplacian, as it provides not one but several basic shifts, one for each element inthe ground set. Prototypical experiments with several set function classificationtasks on synthetic datasets and on datasets derived from real-world hypergraphsdemonstrate the potential of our new powerset CNNs.},
author = {Wendler, Chris and Alistarh, Dan-Adrian and PĂŒschel, Markus},
issn = {1049-5258},
location = {Vancouver, Canada},
pages = {927--938},
publisher = {Neural Information Processing Systems Foundation},
title = {{Powerset convolutional neural networks}},
volume = {32},
year = {2019},
}
@inbook{7513,
abstract = {Social insects (i.e., ants, termites and the social bees and wasps) protect their colonies from disease using a combination of individual immunity and collectively performed defenses, termed social immunity. The first line of social immune defense is sanitary care, which is performed by colony members to protect their pathogen-exposed nestmates from developing an infection. If sanitary care fails and an infection becomes established, a second line of social immune defense is deployed to stop disease transmission within the colony and to protect the valuable queens, which together with the males are the reproductive individuals of the colony. Insect colonies are separated into these reproductive individuals and the sterile worker force, forming a superorganismal reproductive unit reminiscent of the differentiated germline and soma in a multicellular organism. Ultimately, the social immune response preserves the germline of the superorganism insect colony and increases overall fitness of the colony in case of disease. },
author = {Cremer, Sylvia and Kutzer, Megan},
booktitle = {Encyclopedia of Animal Behavior},
editor = {Choe, Jae},
isbn = {9780128132517},
pages = {747--755},
publisher = {Elsevier},
title = {{Social immunity}},
doi = {10.1016/B978-0-12-809633-8.90721-0},
year = {2019},
}
@inproceedings{9261,
abstract = {Bending-active structures are able to efficiently produce complex curved shapes starting from flat panels. The desired deformation of the panels derives from the proper selection of their elastic properties. Optimized panels, called FlexMaps, are designed such that, once they are bent and assembled, the resulting static equilibrium configuration matches a desired input 3D shape. The FlexMaps elastic properties are controlled by locally varying spiraling geometric mesostructures, which are optimized in size and shape to match the global curvature (i.e., bending requests) of the target shape. The design pipeline starts from a quad mesh representing the input 3D shape, which defines the edge size and the total amount of spirals: every quad will embed one spiral. Then, an optimization algorithm tunes the geometry of the spirals by using a simplified pre-computed rod model. This rod model is derived from a non-linear regression algorithm which approximates the non-linear behavior of solid FEM spiral models subject to hundreds of load combinations. This innovative pipeline has been applied to the project of a lightweight plywood pavilion named FlexMaps Pavilion, which is a single-layer piecewise twisted arc that fits a bounding box of 3.90x3.96x3.25 meters.},
author = {Laccone, Francesco and Malomo, Luigi and Perez Rodriguez, Jesus and Pietroni, Nico and Ponchio, Federico and Bickel, Bernd and Cignoni, Paolo},
booktitle = {IASS Symposium 2019 - 60th Anniversary Symposium of the International Association for Shell and Spatial Structures; Structural Membranes 2019 - 9th International Conference on Textile Composites and Inflatable Structures, FORM and FORCE},
isbn = {9788412110104},
issn = {2518-6582},
location = {Barcelona, Spain},
pages = {509--515},
publisher = {International Center for Numerical Methods in Engineering},
title = {{FlexMaps Pavilion: A twisted arc made of mesostructured flat flexible panels}},
year = {2019},
}
@inproceedings{7640,
abstract = {We propose a new model for detecting visual relationships, such as "person riding motorcycle" or "bottle on table". This task is an important step towards comprehensive structured mage understanding, going beyond detecting individual objects. Our main novelty is a Box Attention mechanism that allows to model pairwise interactions between objects using standard object detection pipelines. The resulting model is conceptually clean, expressive and relies on well-justified training and prediction procedures. Moreover, unlike previously proposed approaches, our model does not introduce any additional complex components or hyperparameters on top of those already required by the underlying detection model. We conduct an experimental evaluation on two datasets, V-COCO and Open Images, demonstrating strong quantitative and qualitative results.},
author = {Kolesnikov, Alexander and Kuznetsova, Alina and Lampert, Christoph and Ferrari, Vittorio},
booktitle = {Proceedings of the 2019 International Conference on Computer Vision Workshop},
isbn = {9781728150239},
location = {Seoul, South Korea},
publisher = {IEEE},
title = {{Detecting visual relationships using box attention}},
doi = {10.1109/ICCVW.2019.00217},
year = {2019},
}
@inproceedings{7606,
abstract = {We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound.},
author = {Hledik, Michal and Sokolowski, Thomas R and TkaÄik, GaĆĄper},
booktitle = {IEEE Information Theory Workshop, ITW 2019},
isbn = {9781538669006},
location = {Visby, Sweden},
publisher = {IEEE},
title = {{A tight upper bound on mutual information}},
doi = {10.1109/ITW44776.2019.8989292},
year = {2019},
}
@inproceedings{7639,
abstract = {Deep neural networks (DNNs) have become increasingly important due to their excellent empirical performance on a wide range of problems. However, regularization is generally achieved by indirect means, largely due to the complex set of functions defined by a network and the difficulty in measuring function complexity. There exists no method in the literature for additive regularization based on a norm of the function, as is classically considered in statistical learning theory. In this work, we study the tractability of function norms for deep neural networks with ReLU activations. We provide, to the best of our knowledge, the first proof in the literature of the NP-hardness of computing function norms of DNNs of 3 or more layers. We also highlight a fundamental difference between shallow and deep networks. In the light on these results, we propose a new regularization strategy based on approximate function norms, and show its efficiency on a segmentation task with a DNN.},
author = {Rannen-Triki, Amal and Berman, Maxim and Kolmogorov, Vladimir and Blaschko, Matthew B.},
booktitle = {Proceedings of the 2019 International Conference on Computer Vision Workshop},
isbn = {9781728150239},
location = {Seoul, South Korea},
publisher = {IEEE},
title = {{Function norms for neural networks}},
doi = {10.1109/ICCVW.2019.00097},
year = {2019},
}
@inbook{8281,
abstract = {We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it.},
author = {Barton, Nicholas H and Etheridge, Alison},
booktitle = {Handbook of statistical genomics},
editor = {Balding, David and Moltke, Ida and Marioni, John},
isbn = {9781119429142},
pages = {115--144},
publisher = {Wiley},
title = {{Mathematical models in population genetics}},
doi = {10.1002/9781119487845.ch4},
year = {2019},
}
@unpublished{8184,
abstract = {Denote by âN the N-dimensional simplex. A map f : âN â Rd is an almost r-embedding if fÏ1â©. . .â©fÏr = â
whenever Ï1, . . . , Ïr are pairwise disjoint faces. A counterexample to the topological Tverberg conjecture asserts that if r is not a prime power and d â„ 2r + 1, then there is an almost r-embedding â(d+1)(râ1) â Rd. This was improved by BlagojeviÂŽcâFrickâZiegler using a simple construction of higher-dimensional counterexamples by taking k-fold join power of lower-dimensional ones. We improve this further (for d large compared to r): If r is not a prime power and N := (d+ 1)râr l
d + 2 r + 1 mâ2, then there is an almost r-embedding âN â Rd. For the r-fold van KampenâFlores conjecture we also produce counterexamples which are stronger than previously known. Our proof is based on generalizations of the MabillardâWagner theorem on construction of almost r-embeddings from equivariant maps, and of the Ozaydin theorem on existence of equivariant maps. },
author = {Avvakumov, Sergey and Karasev, R. and Skopenkov, A.},
booktitle = {arXiv},
publisher = {arXiv},
title = {{Stronger counterexamples to the topological Tverberg conjecture}},
year = {2019},
}
@inproceedings{6430,
abstract = {A proxy re-encryption (PRE) scheme is a public-key encryption scheme that allows the holder of a key pk to derive a re-encryption key for any other key đđâČ. This re-encryption key lets anyone transform ciphertexts under pk into ciphertexts under đđâČ without having to know the underlying message, while transformations from đđâČ to pk should not be possible (unidirectional). Security is defined in a multi-user setting against an adversary that gets the usersâ public keys and can ask for re-encryption keys and can corrupt users by requesting their secret keys. Any ciphertext that the adversary cannot trivially decrypt given the obtained secret and re-encryption keys should be secure.
All existing security proofs for PRE only show selective security, where the adversary must first declare the users it wants to corrupt. This can be lifted to more meaningful adaptive security by guessing the set of corrupted users among the n users, which loses a factor exponential in Open image in new window , rendering the result meaningless already for moderate Open image in new window .
Jafargholi et al. (CRYPTOâ17) proposed a framework that in some cases allows to give adaptive security proofs for schemes which were previously only known to be selectively secure, while avoiding the exponential loss that results from guessing the adaptive choices made by an adversary. We apply their framework to PREs that satisfy some natural additional properties. Concretely, we give a more fine-grained reduction for several unidirectional PREs, proving adaptive security at a much smaller loss. The loss depends on the graph of users whose edges represent the re-encryption keys queried by the adversary. For trees and chains the loss is quasi-polynomial in the size and for general graphs it is exponential in their depth and indegree (instead of their size as for previous reductions). Fortunately, trees and low-depth graphs cover many, if not most, interesting applications.
Our results apply e.g. to the bilinear-map based PRE schemes by Ateniese et al. (NDSSâ05 and CT-RSAâ09), Gentryâs FHE-based scheme (STOCâ09) and the LWE-based scheme by Chandran et al. (PKCâ14).},
author = {Fuchsbauer, Georg and Kamath Hosdurg, Chethan and Klein, Karen and Pietrzak, Krzysztof Z},
isbn = {9783030172589},
issn = {16113349},
location = {Beijing, China},
pages = {317--346},
publisher = {Springer Nature},
title = {{Adaptively secure proxy re-encryption}},
doi = {10.1007/978-3-030-17259-6_11},
volume = {11443},
year = {2019},
}
@article{6069,
abstract = {Electron transport in two-dimensional conducting materials such as graphene, with dominant electronâelectron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohmâs law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressureâspeed relation is Stokeâs law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavityâanalogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments.},
author = {Mayzel, Jonathan and Steinberg, Victor and Varshney, Atul},
issn = {2041-1723},
journal = {Nature Communications},
publisher = {Springer Nature},
title = {{Stokes flow analogous to viscous electron current in graphene}},
doi = {10.1038/s41467-019-08916-5},
volume = {10},
year = {2019},
}
@article{6014,
abstract = {Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity.},
author = {Varshney, Atul and Steinberg, Victor},
issn = {2041-1723},
journal = {Nature Communications},
publisher = {Springer Nature},
title = {{Elastic alfven waves in elastic turbulence}},
doi = {10.1038/s41467-019-08551-0},
volume = {10},
year = {2019},
}
@article{6451,
abstract = {Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis.},
author = {Amberg, Nicole and Sotiropoulou, Panagiota A. and Heller, Gerwin and Lichtenberger, Beate M. and Holcmann, Martin and Camurdanoglu, Bahar and Baykuscheva-Gentscheva, Temenuschka and Blanpain, Cedric and Sibilia, Maria},
issn = {2589-0042},
journal = {iScience},
pages = {243--256},
publisher = {Elsevier},
title = {{EGFR controls hair shaft differentiation in a p53-independent manner}},
doi = {10.1016/j.isci.2019.04.018},
volume = {15},
year = {2019},
}
@article{10879,
abstract = {We study effects of a bounded and compactly supported perturbation on multidimensional continuum random SchrĂ¶dinger operators in the region of complete localisation. Our main emphasis is on Anderson orthogonality for random SchrĂ¶dinger operators. Among others, we prove that Anderson orthogonality does occur for Fermi energies in the region of complete localisation with a non-zero probability. This partially confirms recent non-rigorous findings [V. Khemani et al., Nature Phys. 11 (2015), 560â565]. The spectral shift function plays an important role in our analysis of Anderson orthogonality. We identify it with the index of the corresponding pair of spectral projections and explore the consequences thereof. All our results rely on the main technical estimate of this paper which guarantees separate exponential decay of the disorder-averaged Schatten p-norm of Ïa(f(H)âf(HÏ))Ïb in a and b. Here, HÏ is a perturbation of the random SchrĂ¶dinger operator H, Ïa is the multiplication operator corresponding to the indicator function of a unit cube centred about aâRd, and f is in a suitable class of functions of bounded variation with distributional derivative supported in the region of complete localisation for H.},
author = {Dietlein, Adrian M and Gebert, Martin and MĂŒller, Peter},
issn = {1664-039X},
journal = {Journal of Spectral Theory},
keywords = {Random SchrĂ¶dinger operators, spectral shift function, Anderson orthogonality},
number = {3},
pages = {921--965},
publisher = {European Mathematical Society Publishing House},
title = {{Perturbations of continuum random SchrĂ¶dinger operators with applications to Anderson orthogonality and the spectral shift function}},
doi = {10.4171/jst/267},
volume = {9},
year = {2019},
}
@article{10878,
abstract = {Starting from a microscopic model for a system of neurons evolving in time which individually follow a stochastic integrate-and-fire type model, we study a mean-field limit of the system. Our model is described by a system of SDEs with discontinuous coefficients for the action potential of each neuron and takes into account the (random) spatial configuration of neurons allowing the interaction to depend on it. In the limit as the number of particles tends to infinity, we obtain a nonlinear Fokker-Planck type PDE in two variables, with derivatives only with respect to one variable and discontinuous coefficients. We also study strong well-posedness of the system of SDEs and prove the existence and uniqueness of a weak measure-valued solution to the PDE, obtained as the limit of the laws of the empirical measures for the system of particles.},
author = {Flandoli, Franco and Priola, Enrico and Zanco, Giovanni A},
issn = {1553-5231},
journal = {Discrete and Continuous Dynamical Systems},
keywords = {Applied Mathematics, Discrete Mathematics and Combinatorics, Analysis},
number = {6},
pages = {3037--3067},
publisher = {American Institute of Mathematical Sciences},
title = {{A mean-field model with discontinuous coefficients for neurons with spatial interaction}},
doi = {10.3934/dcds.2019126},
volume = {39},
year = {2019},
}
@inproceedings{6935,
abstract = {This paper investigates the power of preprocessing in the CONGEST model. Schmid and Suomela (ACM HotSDN 2013) introduced the SUPPORTED CONGEST model to study the application of distributed algorithms in Software-Defined Networks (SDNs). In this paper, we show that a large class of lower bounds in the CONGEST model still hold in the SUPPORTED model, highlighting the robustness of these bounds. This also raises the question how much does
preprocessing help in the CONGEST model.},
author = {Foerster, Klaus-Tycho and Korhonen, Janne and Rybicki, Joel and Schmid, Stefan},
booktitle = {Proceedings of the 2019 ACM Symposium on Principles of Distributed Computing},
isbn = {9781450362177},
location = {Toronto, ON, Canada},
pages = {259--261},
publisher = {ACM},
title = {{Does preprocessing help under congestion?}},
doi = {10.1145/3293611.3331581},
year = {2019},
}
@article{138,
abstract = {Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxinâantitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxinâantitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxinâantitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche.},
author = {Nikolic, Nela},
journal = {Current Genetics},
number = {1},
pages = {133--138},
publisher = {Springer},
title = {{Autoregulation of bacterial gene expression: lessons from the MazEF toxinâantitoxin system}},
doi = {10.1007/s00294-018-0879-8},
volume = {65},
year = {2019},
}
@article{151,
abstract = {We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function fâLp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for fâLâ, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, CsĂ¶rnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide.},
author = {Fischer, Julian L and Kneuss, Olivier},
journal = {Journal of Differential Equations},
number = {1},
pages = {257 -- 311},
publisher = {Elsevier},
title = {{Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity}},
doi = {10.1016/j.jde.2018.07.045},
volume = {266},
year = {2019},
}
@article{27,
abstract = {The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved.},
author = {Amberg, Nicole and Laukoter, Susanne and Hippenmeyer, Simon},
journal = {Journal of Neurochemistry},
number = {1},
pages = {12--26},
publisher = {Wiley},
title = {{Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex}},
doi = {10.1111/jnc.14601},
volume = {149},
year = {2019},
}
@article{5789,
abstract = {Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cellâcell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis.},
author = {Petridou, Nicoletta and Grigolon, Silvia and Salbreux, Guillaume and Hannezo, Edouard B and Heisenberg, Carl-Philipp J},
issn = {14657392},
journal = {Nature Cell Biology},
pages = {169â178},
publisher = {Nature Publishing Group},
title = {{Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling}},
doi = {10.1038/s41556-018-0247-4},
volume = {21},
year = {2019},
}
@article{196,
abstract = {The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. },
author = {Lang, Moritz and Shkolnikov, Mikhail},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences},
number = {8},
pages = {2821--2830},
publisher = {National Academy of Sciences},
title = {{Harmonic dynamics of the Abelian sandpile}},
doi = {10.1073/pnas.1812015116},
volume = {116},
year = {2019},
}
@misc{6074,
abstract = {This dataset contains the supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition".
The contained files have the following content:
'Supplementary Figures.pdf'
Additional figures (as referenced in the paper).
'Supplementary Table 1. Statistics.xlsx'
Details on statistical tests performed in the paper.
'Supplementary Table 2. Differentially expressed gene analysis.xlsx'
Results for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples.
'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx'
Results for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down).
'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx'
Results for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant.
'Supplementary Table 5. Cluster identification.xlsx'
Results for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories).
'Supplementary Table 6. GO term cluster analysis.xlsx'
Results for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1).
'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'
Results showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma.
'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'
Results for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS.},
author = {Dotter, Christoph and Novarino, Gaia},
publisher = {IST Austria},
title = {{Supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition"}},
doi = {10.15479/AT:ISTA:6074},
year = {2019},
}
@inproceedings{14184,
abstract = {Learning disentangled representations is considered a cornerstone problem in
representation learning. Recently, Locatello et al. (2019) demonstrated that
unsupervised disentanglement learning without inductive biases is theoretically
impossible and that existing inductive biases and unsupervised methods do not
allow to consistently learn disentangled representations. However, in many
practical settings, one might have access to a limited amount of supervision,
for example through manual labeling of (some) factors of variation in a few
training examples. In this paper, we investigate the impact of such supervision
on state-of-the-art disentanglement methods and perform a large scale study,
training over 52000 models under well-defined and reproducible experimental
conditions. We observe that a small number of labeled examples (0.01--0.5\% of
the data set), with potentially imprecise and incomplete labels, is sufficient
to perform model selection on state-of-the-art unsupervised models. Further, we
investigate the benefit of incorporating supervision into the training process.
Overall, we empirically validate that with little and imprecise supervision it
is possible to reliably learn disentangled representations.},
author = {Locatello, Francesco and Tschannen, Michael and Bauer, Stefan and RĂ€tsch, Gunnar and SchĂ¶lkopf, Bernhard and Bachem, Olivier},
booktitle = {8th International Conference on Learning Representations},
location = {Virtual},
title = {{Disentangling factors of variation using few labels}},
year = {2019},
}
@inproceedings{14189,
abstract = {We consider the problem of recovering a common latent source with independent
components from multiple views. This applies to settings in which a variable is
measured with multiple experimental modalities, and where the goal is to
synthesize the disparate measurements into a single unified representation. We
consider the case that the observed views are a nonlinear mixing of
component-wise corruptions of the sources. When the views are considered
separately, this reduces to nonlinear Independent Component Analysis (ICA) for
which it is provably impossible to undo the mixing. We present novel
identifiability proofs that this is possible when the multiple views are
considered jointly, showing that the mixing can theoretically be undone using
function approximators such as deep neural networks. In contrast to known
identifiability results for nonlinear ICA, we prove that independent latent
sources with arbitrary mixing can be recovered as long as multiple,
sufficiently different noisy views are available.},
author = {Gresele, Luigi and Rubenstein, Paul K. and Mehrjou, Arash and Locatello, Francesco and SchĂ¶lkopf, Bernhard},
booktitle = {Proceedings of the 35th Conference on Uncertainty in Artificial Intelligence},
location = {Tel Aviv, Israel},
pages = {217--227},
publisher = {ML Research Press},
title = {{The incomplete Rosetta Stone problem: Identifiability results for multi-view nonlinear ICA}},
volume = {115},
year = {2019},
}
@inproceedings{14197,
abstract = {Recently there has been a significant interest in learning disentangled
representations, as they promise increased interpretability, generalization to
unseen scenarios and faster learning on downstream tasks. In this paper, we
investigate the usefulness of different notions of disentanglement for
improving the fairness of downstream prediction tasks based on representations.
We consider the setting where the goal is to predict a target variable based on
the learned representation of high-dimensional observations (such as images)
that depend on both the target variable and an \emph{unobserved} sensitive
variable. We show that in this setting both the optimal and empirical
predictions can be unfair, even if the target variable and the sensitive
variable are independent. Analyzing the representations of more than
\num{12600} trained state-of-the-art disentangled models, we observe that
several disentanglement scores are consistently correlated with increased
fairness, suggesting that disentanglement may be a useful property to encourage
fairness when sensitive variables are not observed.},
author = {Locatello, Francesco and Abbati, Gabriele and Rainforth, Tom and Bauer, Stefan and SchĂ¶lkopf, Bernhard and Bachem, Olivier},
booktitle = {Advances in Neural Information Processing Systems},
isbn = {9781713807933},
location = {Vancouver, Canada},
pages = {14611â14624},
title = {{On the fairness of disentangled representations}},
volume = {32},
year = {2019},
}
@inproceedings{14191,
abstract = {A broad class of convex optimization problems can be formulated as a semidefinite program (SDP), minimization of a convex function over the positive-semidefinite cone subject to some affine constraints. The majority of classical SDP solvers are designed for the deterministic setting where problem data is readily available. In this setting, generalized conditional gradient methods (aka Frank-Wolfe-type methods) provide scalable solutions by leveraging the so-called linear minimization oracle instead of the projection onto the semidefinite cone. Most problems in machine learning and modern engineering applications, however, contain some degree of stochasticity. In this work, we propose the first conditional-gradient-type method for solving stochastic optimization problems under affine constraints. Our method guarantees O(kâ1/3) convergence rate in expectation on the objective residual and O(kâ5/12) on the feasibility gap.},
author = {Locatello, Francesco and Yurtsever, Alp and Fercoq, Olivier and Cevher, Volkan},
booktitle = {Advances in Neural Information Processing Systems},
isbn = {9781713807933},
location = {Vancouver, Canada},
pages = {14291â14301},
title = {{Stochastic Frank-Wolfe for composite convex minimization}},
volume = {32},
year = {2019},
}
@inproceedings{14193,
abstract = {A disentangled representation encodes information about the salient factors
of variation in the data independently. Although it is often argued that this
representational format is useful in learning to solve many real-world
down-stream tasks, there is little empirical evidence that supports this claim.
In this paper, we conduct a large-scale study that investigates whether
disentangled representations are more suitable for abstract reasoning tasks.
Using two new tasks similar to Raven's Progressive Matrices, we evaluate the
usefulness of the representations learned by 360 state-of-the-art unsupervised
disentanglement models. Based on these representations, we train 3600 abstract
reasoning models and observe that disentangled representations do in fact lead
to better down-stream performance. In particular, they enable quicker learning
using fewer samples.},
author = {Steenkiste, Sjoerd van and Locatello, Francesco and Schmidhuber, JĂŒrgen and Bachem, Olivier},
booktitle = {Advances in Neural Information Processing Systems},
isbn = {9781713807933},
location = {Vancouver, Canada},
title = {{Are disentangled representations helpful for abstract visual reasoning?}},
volume = {32},
year = {2019},
}
@inproceedings{14200,
abstract = {The key idea behind the unsupervised learning of disentangled representations
is that real-world data is generated by a few explanatory factors of variation
which can be recovered by unsupervised learning algorithms. In this paper, we
provide a sober look at recent progress in the field and challenge some common
assumptions. We first theoretically show that the unsupervised learning of
disentangled representations is fundamentally impossible without inductive
biases on both the models and the data. Then, we train more than 12000 models
covering most prominent methods and evaluation metrics in a reproducible
large-scale experimental study on seven different data sets. We observe that
while the different methods successfully enforce properties ``encouraged'' by
the corresponding losses, well-disentangled models seemingly cannot be
identified without supervision. Furthermore, increased disentanglement does not
seem to lead to a decreased sample complexity of learning for downstream tasks.
Our results suggest that future work on disentanglement learning should be
explicit about the role of inductive biases and (implicit) supervision,
investigate concrete benefits of enforcing disentanglement of the learned
representations, and consider a reproducible experimental setup covering
several data sets.},
author = {Locatello, Francesco and Bauer, Stefan and Lucic, Mario and RĂ€tsch, Gunnar and Gelly, Sylvain and SchĂ¶lkopf, Bernhard and Bachem, Olivier},
booktitle = {Proceedings of the 36th International Conference on Machine Learning},
location = {Long Beach, CA, United States},
pages = {4114--4124},
publisher = {ML Research Press},
title = {{Challenging common assumptions in the unsupervised learning of disentangled representations}},
volume = {97},
year = {2019},
}
@article{5817,
abstract = {We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion.},
author = {Kavcic, Bor and Sakashita, A. and Noguchi, H. and Ziherl, P.},
issn = {1744-6848},
journal = {Soft Matter},
number = {4},
pages = {602--614},
publisher = {Royal Society of Chemistry},
title = {{Limiting shapes of confined lipid vesicles}},
doi = {10.1039/c8sm01956h},
volume = {15},
year = {2019},
}
@article{73,
abstract = {We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset YâX, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest.},
author = {Erbar, Matthias and Maas, Jan and Wirth, Melchior},
issn = {09442669},
journal = {Calculus of Variations and Partial Differential Equations},
number = {1},
publisher = {Springer},
title = {{On the geometry of geodesics in discrete optimal transport}},
doi = {10.1007/s00526-018-1456-1},
volume = {58},
year = {2019},
}
@inproceedings{14190,
abstract = {Learning meaningful and compact representations with disentangled semantic
aspects is considered to be of key importance in representation learning. Since
real-world data is notoriously costly to collect, many recent state-of-the-art
disentanglement models have heavily relied on synthetic toy data-sets. In this
paper, we propose a novel data-set which consists of over one million images of
physical 3D objects with seven factors of variation, such as object color,
shape, size and position. In order to be able to control all the factors of
variation precisely, we built an experimental platform where the objects are
being moved by a robotic arm. In addition, we provide two more datasets which
consist of simulations of the experimental setup. These datasets provide for
the first time the possibility to systematically investigate how well different
disentanglement methods perform on real data in comparison to simulation, and
how simulated data can be leveraged to build better representations of the real
world. We provide a first experimental study of these questions and our results
indicate that learned models transfer poorly, but that model and hyperparameter
selection is an effective means of transferring information to the real world.},
author = {Gondal, Muhammad Waleed and WĂŒthrich, Manuel and MiladinoviÄ, ÄorÄe and Locatello, Francesco and Breidt, Martin and Volchkov, Valentin and Akpo, Joel and Bachem, Olivier and SchĂ¶lkopf, Bernhard and Bauer, Stefan},
booktitle = {Advances in Neural Information Processing Systems},
isbn = {9781713807933},
location = {Vancouver, Canada},
title = {{On the transfer of inductive bias from simulation to the real world: a new disentanglement dataset}},
volume = {32},
year = {2019},
}
@article{6982,
abstract = {We present an efficient algorithm for a problem in the interface between clustering and graph embeddings. An embedding Ï : G â M of a graph G into a 2-manifold M maps the vertices in V(G) to distinct points and the edges in E(G) to interior-disjoint Jordan arcs between the corresponding vertices. In applications in clustering, cartography, and visualization, nearby vertices and edges are often bundled to the same point or overlapping arcs due to data compression or low resolution. This raises the computational problem of deciding whether a given map Ï : G â M comes from an embedding. A map Ï : G â M is a weak embedding if it can be perturbed into an embedding Ï Ï” : G â M with â Ï â Ï Ï” â < Ï” for every Ï” > 0, where â.â is the unform norm.
A polynomial-time algorithm for recognizing weak embeddings has recently been found by Fulek and KynÄl. It reduces the problem to solving a system of linear equations over Z2. It runs in O(n2Ï)â€ O(n4.75) time, where Ï â [2,2.373) is the matrix multiplication exponent and n is the number of vertices and edges of G. We improve the running time to O(n log n). Our algorithm is also conceptually simpler: We perform a sequence of local operations that gradually âuntanglesâ the image Ï(G) into an embedding Ï(G) or reports that Ï is not a weak embedding. It combines local constraints on the orientation of subgraphs directly, thereby eliminating the need for solving large systems of linear equations.
},
author = {Akitaya, Hugo and Fulek, Radoslav and TĂłth, Csaba},
journal = {ACM Transactions on Algorithms},
number = {4},
publisher = {ACM},
title = {{Recognizing weak embeddings of graphs}},
doi = {10.1145/3344549},
volume = {15},
year = {2019},
}
@phdthesis{6894,
abstract = {Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving.
Nevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions.
While, previously, directions were given by the user, we introduce (1) the first method
for computing template directions from spurious counterexamples, so as to generalize and
eliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid
automata with (possibly non-linear) convex constraints on derivatives only, while for linear
ODE requires further abstraction. Specifically, we introduce (2) the conic abstractions,
which, partitioning the state space into appropriate (possibly non-uniform) cones, divide
curvy trajectories into relatively straight sections, suitable for polyhedral abstractions.
Finally, we introduce (3) space-time interpolation, which, combining interval arithmetic
and template refinement, computes appropriate (possibly non-uniform) time partitioning
and template directions along spurious trajectories, so as to eliminate them.
We obtain sound and automatic methods for the reachability analysis over dense
and unbounded time of convex hybrid automata and hybrid automata with linear ODE.
We build prototype tools and compareâfavorablyâour methods against the respective
state-of-the-art tools, on several benchmarks.},
author = {Giacobbe, Mirco},
issn = {2663-337X},
pages = {132},
publisher = {Institute of Science and Technology Austria},
title = {{Automatic time-unbounded reachability analysis of hybrid systems}},
doi = {10.15479/AT:ISTA:6894},
year = {2019},
}
@misc{9805,
abstract = {The spread of adaptive alleles is fundamental to evolution, and in theory, this process is wellâunderstood. However, only rarely can we follow this processâwhether it originates from the spread of a new mutation, or by introgression from another population. In this issue of Molecular Ecology, Hanemaaijer et al. (2018) report on a 25âyear long study of the mosquitoes Anopheles gambiae (Figure 1) and Anopheles coluzzi in Mali, based on genotypes at 15 singleânucleotide polymorphism (SNP). The species are usually reproductively isolated from each other, but in 2002 and 2006, bursts of hybridization were observed, when F1 hybrids became abundant. Alleles backcrossed from A. gambiae into A. coluzzi, but after the first event, these declined over the following years. In contrast, after 2006, an insecticide resistance allele that had established in A. gambiae spread into A. coluzzi, and rose to high frequency there, over 6 years (~75 generations). Whole genome sequences of 74 individuals showed that A. gambiae SNP from across the genome had become common in the A. coluzzi population, but that most of these were clustered in 34 genes around the resistance locus. A new set of SNP from 25 of these genes were assayed over time; over the 4 years since nearâfixation of the resistance allele; some remained common, whereas others declined. What do these patterns tell us about this introgression event?},
author = {Barton, Nicholas H},
publisher = {Dryad},
title = {{Data from: The consequences of an introgression event}},
doi = {10.5061/dryad.2kb6fh4},
year = {2019},
}
@article{8,
abstract = {Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification.},
author = {TrĂ©buchet, Guillaume and Cattenoz, Pierre B and ZsĂĄmboki, JĂĄnos and Mazaud, David and Siekhaus, Daria E and Fanto, Manolis and Giangrande, Angela},
journal = {Journal of Neuroscience},
number = {2},
pages = {238--255},
publisher = {Society for Neuroscience},
title = {{The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate}},
doi = {10.1523/JNEUROSCI.1059-18.2018},
volume = {39},
year = {2019},
}
@article{5,
abstract = {In this paper, we introduce a quantum version of the wonderful compactification of a group as a certain noncommutative projective scheme. Our approach stems from the fact that the wonderful compactification encodes the asymptotics of matrix coefficients, and from its realization as a GIT quotient of the Vinberg semigroup. In order to define the wonderful compactification for a quantum group, we adopt a generalized formalism of Proj categories in the spirit of Artin and Zhang. Key to our construction is a quantum version of the Vinberg semigroup, which we define as a q-deformation of a certain Rees algebra, compatible with a standard Poisson structure. Furthermore, we discuss quantum analogues of the stratification of the wonderful compactification by orbits for a certain group action, and provide explicit computations in the case of SL2.},
author = {Ganev, Iordan V},
journal = {Journal of the London Mathematical Society},
number = {3},
pages = {778--806},
publisher = {Wiley},
title = {{The wonderful compactification for quantum groups}},
doi = {10.1112/jlms.12193},
volume = {99},
year = {2019},
}
@phdthesis{7172,
abstract = {The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers.
The first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone.
The second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition.
The third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24.
In the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis.
In the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results.
In the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes.},
author = {Vasileva, Mina K},
issn = {2663-337X},
pages = {192},
publisher = {Institute of Science and Technology Austria},
title = {{Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana}},
doi = {10.15479/AT:ISTA:7172},
year = {2019},
}
@article{6093,
abstract = {Blebs are cellular protrusions observed in migrating cells and in cells undergoing spreading, cytokinesis, and apoptosis. Here we investigate the flow of cytoplasm during bleb formation and the concurrent changes in cell volume using zebrafish primordial germ cells (PGCs) as an in vivo model. We show that bleb inflation occurs concomitantly with cytoplasmic inflow into it and that during this process the total cell volume does not change. We thus show that bleb formation in primordial germ cells results primarily from redistribution of material within the cell rather than being driven by flow of water from an external source.},
author = {Goudarzi, Mohammad and Boquet-Pujadas, Aleix and Olivo-Marin, Jean Christophe and Raz, Erez},
journal = {PLOS ONE},
number = {2},
publisher = {Public Library of Science},
title = {{Fluid dynamics during bleb formation in migrating cells in vivo}},
doi = {10.1371/journal.pone.0212699},
volume = {14},
year = {2019},
}
@phdthesis{6179,
abstract = {In the first part of this thesis we consider large random matrices with arbitrary expectation and a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent in the bulk and edge regime. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion.
In the second part we consider Wigner-type matrices and show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are uni- versal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner- Dyson-Mehta universality conjecture for the last remaining universality type. Our analysis holds not only for exact cusps, but approximate cusps as well, where an ex- tended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp, and extend the fast relaxation to equilibrium of the Dyson Brow- nian motion to the cusp regime.
In the third and final part we explore the entrywise linear statistics of Wigner ma- trices and identify the fluctuations for a large class of test functions with little regularity. This enables us to study the rectangular Young diagram obtained from the interlacing eigenvalues of the random matrix and its minor, and we find that, despite having the same limit, the fluctuations differ from those of the algebraic Young tableaux equipped with the Plancharel measure.},
author = {SchrĂ¶der, Dominik J},
issn = {2663-337X},
pages = {375},
publisher = {Institute of Science and Technology Austria},
title = {{From Dyson to Pearcey: Universal statistics in random matrix theory}},
doi = {10.15479/AT:ISTA:th6179},
year = {2019},
}
@phdthesis{6473,
abstract = {Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory.
The recent availability of realâtime dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the timeâseries. However, efficient estimation of the information transmitted by these signals has been a dataâanalysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decodingâbased estimation methods to lower bound the mutual information and derive modelâbased precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes.
Finally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This âcrosstalkâ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. },
author = {Cepeda Humerez, Sarah A},
issn = {2663-337X},
keywords = {Information estimation, Time-series, data analysis},
pages = {135},
publisher = {Institute of Science and Technology Austria},
title = {{Estimating information flow in single cells}},
doi = {10.15479/AT:ISTA:6473},
year = {2019},
}
@phdthesis{6392,
abstract = {The regulation of gene expression is one of the most fundamental processes in living systems. In recent years, thanks to advances in sequencing technology and automation, it has become possible to study gene expression quantitatively, genome-wide and in high-throughput. This leads to the possibility of exploring changes in gene expression in the context of many external perturbations and their combinations, and thus of characterising the basic principles governing gene regulation. In this thesis, I present quantitative experimental approaches to studying transcriptional and protein level changes in response to combinatorial drug treatment, as well as a theoretical data-driven approach to analysing thermodynamic principles guiding transcription of protein coding genes.
In the first part of this work, I present a novel methodological framework for quantifying gene expression changes in drug combinations, termed isogrowth profiling. External perturbations through small molecule drugs influence the growth rate of the cell, leading to wide-ranging changes in cellular physiology and gene expression. This confounds the gene expression changes specifically elicited by the particular drug. Combinatorial perturbations, owing to the increased stress they exert, influence the growth rate even more strongly and hence suffer the convolution problem to a greater extent when measuring gene expression changes. Isogrowth profiling is a way to experimentally abstract non-specific, growth rate related changes, by performing the measurement using varying ratios of two drugs at such concentrations that the overall inhibition rate is constant. Using a robotic setup for automated high-throughput re-dilution culture of Saccharomyces cerevisiae, the budding yeast, I investigate all pairwise interactions of four small molecule drugs through sequencing RNA along a growth isobole. Through principal component analysis, I demonstrate here that isogrowth profiling can uncover drug-specific as well as drug-interaction-specific gene expression changes. I show that drug-interaction-specific gene expression changes can be used for prediction of higher-order drug interactions. I propose a simplified generalised framework of isogrowth profiling, with few measurements needed for each drug pair, enabling the broad application of isogrowth profiling to high-throughput screening of inhibitors of cellular growth and beyond. Such high-throughput screenings of gene expression changes specific to pairwise drug interactions will be instrumental for predicting the higher-order interactions of the drugs.
In the second part of this work, I extend isogrowth profiling to single-cell measurements of gene expression, characterising population heterogeneity in the budding yeast in response to combinatorial drug perturbation while controlling for non-specific growth rate effects. Through flow cytometry of strains with protein products fused to green fluorescent protein, I discover multiple proteins with bi-modally distributed expression levels in the population in response to drug treatment. I characterize more closely the effect of an ionic stressor, lithium chloride, and find that it inhibits the splicing of mRNA, most strongly affecting ribosomal protein transcripts and leading to a bi-stable behaviour of a small ribosomal subunit protein Rps22B. Time-lapse microscopy of a microfluidic culture system revealed that the induced Rps22B heterogeneity leads to preferential survival of Rps22B-low cells after long starvation, but to preferential proliferation of Rps22B-high cells after short starvation. Overall, this suggests that yeast cells might use splicing of ribosomal genes for bet-hedging in fluctuating environments. I give specific examples of how further exploration of cellular heterogeneity in yeast in response to external perturbation has the potential to reveal yet-undiscovered gene regulation circuitry.
In the last part of this thesis, a re-analysis of a published sequencing dataset of nascent elongating transcripts is used to characterise the thermodynamic constraints for RNA polymerase II (RNAP) elongation. Population-level data on RNAP position throughout the transcribed genome with single nucleotide resolution are used to infer the sequence specific thermodynamic determinants of RNAP pausing and backtracking. This analysis reveals that the basepairing strength of the eight nucleotide-long RNA:DNA duplex relative to the basepairing strength of the same sequence when in DNA:DNA duplex, and the change in this quantity during RNA polymerase movement, is the key determinant of RNAP pausing. This is true for RNAP pausing while elongating, but also of RNAP pausing while backtracking and of the backtracking length. The quantitative dependence of RNAP pausing on basepairing energetics is used to infer the increase in pausing due to transcriptional mismatches, leading to a hypothesis that pervasive RNA polymerase II pausing is due to basepairing energetics, as an evolutionary cost for increased RNA polymerase II fidelity.
This work advances our understanding of the general principles governing gene expression, with the goal of making computational predictions of single-cell gene expression responses to combinatorial perturbations based on the individual perturbations possible. This ability would substantially facilitate the design of drug combination treatments and, in the long term, lead to our increased ability to more generally design targeted manipulations to any biological system. },
author = {Lukacisin, Martin},
isbn = {978-3-99078-001-5},
issn = {2663-337X},
pages = {103},
publisher = {IST Austria},
title = {{Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory}},
doi = {10.15479/AT:ISTA:6392},
year = {2019},
}
@inproceedings{11222,
author = {Kim, Olena and Borges Merjane, Carolina and Jonas, Peter M},
booktitle = {Intrinsic Activity},
issn = {2309-8503},
keywords = {hippocampus, mossy fibers, readily releasable pool, electron microscopy},
location = {Innsbruck, Austria},
number = {Suppl. 1},
publisher = {Austrian Pharmacological Society},
title = {{Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy}},
doi = {10.25006/ia.7.s1-a3.27},
volume = {7},
year = {2019},
}
@article{6194,
abstract = {Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space.},
author = {Boccara, Charlotte N. and Nardin, Michele and Stella, Federico and O'Neill, Joseph and Csicsvari, Jozsef L},
issn = {1095-9203},
journal = {Science},
number = {6434},
pages = {1443--1447},
publisher = {American Association for the Advancement of Science},
title = {{The entorhinal cognitive map is attracted to goals}},
doi = {10.1126/science.aav4837},
volume = {363},
year = {2019},
}
@article{6713,
abstract = {Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.},
author = {Castro, JoĂŁo Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and KuÄka, Marek and Beluch, William H. and Naumann, Ronald and Skuplik, Isabella and Cobb, John and Barton, Nicholas H and Rolian, Campbell and Chan, Yingguang Frank},
journal = {eLife},
publisher = {eLife Sciences Publications},
title = {{An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice}},
doi = {10.7554/eLife.42014},
volume = {8},
year = {2019},
}
@phdthesis{6435,
abstract = {Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ
cells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are
in charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units
(i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''.
Social immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social
immunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop
the collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of
social immune responses have been dissected, but many more questions remain open.
I present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals
carrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate.
The second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive
and challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation.
In addition to the two experimental chapters, this thesis includes a co-authored published review on organisational
immunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built,
identify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in
two collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant
behaviour.},
author = {Casillas Perez, Barbara E},
issn = {2663-337X},
keywords = {Social Immunity, Sanitary care, Social Insects, Organisational Immunity, Colony development, Multi-target tracking},
pages = {183},
publisher = {Institute of Science and Technology Austria},
title = {{Collective defenses of garden ants against a fungal pathogen}},
doi = {10.15479/AT:ISTA:6435},
year = {2019},
}
@article{6848,
abstract = {Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180Â° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9.},
author = {Kampjut, Domen and Sazanov, Leonid A},
issn = {1476-4687},
journal = {Nature},
number = {7773},
pages = {291â295},
publisher = {Springer Nature},
title = {{Structure and mechanism of mitochondrial proton-translocating transhydrogenase}},
doi = {10.1038/s41586-019-1519-2},
volume = {573},
year = {2019},
}
@article{6508,
abstract = {Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation.},
author = {Shamipour, Shayan and Kardos, Roland and Xue, Shi-lei and Hof, BjĂ¶rn and Hannezo, Edouard B and Heisenberg, Carl-Philipp J},
issn = {10974172},
journal = {Cell},
number = {6},
pages = {1463--1479.e18},
publisher = {Elsevier},
title = {{Bulk actin dynamics drive phase segregation in zebrafish oocytes}},
doi = {10.1016/j.cell.2019.04.030},
volume = {177},
year = {2019},
}
@article{5949,
abstract = {Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.},
author = {KĂ€fer, Karola and Malagon-Vina, Hugo and Dickerson, Desiree and O'Neill, Joseph and Trossbach, Svenja V. and Korth, Carsten and Csicsvari, Jozsef L},
journal = {Hippocampus},
number = {9},
pages = {802--816},
publisher = {Wiley},
title = {{Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization}},
doi = {10.1002/hipo.23076},
volume = {29},
year = {2019},
}
@phdthesis{6825,
abstract = {The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions.
With tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay.
We found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by
maze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between
cell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC
trajectory-replay at the goal positively correlated with rule-switching performance.
Finally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. },
author = {KĂ€fer, Karola},
issn = {2663-337X},
pages = {89},
publisher = {Institute of Science and Technology Austria},
title = {{The hippocampus and medial prefrontal cortex during flexible behavior}},
doi = {10.15479/AT:ISTA:6825},
year = {2019},
}
@article{7001,
author = {Schwayer, Cornelia and Shamipour, Shayan and Pranjic-Ferscha, Kornelija and Schauer, Alexandra and Balda, M and Tada, M and Matter, K and Heisenberg, Carl-Philipp J},
issn = {1097-4172},
journal = {Cell},
number = {4},
pages = {937--952.e18},
publisher = {Cell Press},
title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}},
doi = {10.1016/j.cell.2019.10.006},
volume = {179},
year = {2019},
}
@phdthesis{7132,
abstract = {A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta.
Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing.},
author = {Mckenzie, Catherine},
issn = {2663-337X},
pages = {95},
publisher = {Institute of Science and Technology Austria},
title = {{Design and characterization of methods and biological components to realize synthetic neurotransmission}},
doi = {10.15479/at:ista:7132},
year = {2019},
}
@article{6189,
abstract = {Suspended particles can alter the properties of fluids and in particular also affect the transition fromlaminar to turbulent flow. An earlier study [Mataset al.,Phys. Rev. Lett.90, 014501 (2003)] reported howthe subcritical (i.e., hysteretic) transition to turbulent puffs is affected by the addition of particles. Here weshow that in addition to this known transition, with increasing concentration a supercritical (i.e.,continuous) transition to a globally fluctuating state is found. At the same time the Newtonian-typetransition to puffs is delayed to larger Reynolds numbers. At even higher concentration only the globallyfluctuating state is found. The dynamics of particle laden flows are hence determined by two competinginstabilities that give rise to three flow regimes: Newtonian-type turbulence at low, a particle inducedglobally fluctuating state at high, and a coexistence state at intermediate concentrations.},
author = {Agrawal, Nishchal and Choueiri, George H and Hof, BjĂ¶rn},
issn = {10797114},
journal = {Physical Review Letters},
number = {11},
publisher = {APS},
title = {{Transition to turbulence in particle laden flows}},
doi = {10.1103/PhysRevLett.122.114502},
volume = {122},
year = {2019},
}
@article{6627,
abstract = {Cortical microtubule arrays in elongating epidermal cells in both the root and stem of plants have the propensity of dynamic reorientations that are correlated with the activation or inhibition of growth. Factors regulating plant growth, among them the hormone auxin, have been recognized as regulators of microtubule array orientations. Some previous work in the field has aimed at elucidating the causal relationship between cell growth, the signaling of auxin or other growth-regulating factors, and microtubule array reorientations, with various conclusions. Here, we revisit this problem of causality with a comprehensive set of experiments in Arabidopsis thaliana, using the now available pharmacological and genetic tools. We use isolated, auxin-depleted hypocotyls, an experimental system allowing for full control of both growth and auxin signaling. We demonstrate that reorientation of microtubules is not directly triggered by an auxin signal during growth activation. Instead, reorientation is triggered by the activation of the growth process itself and is auxin-independent in its nature. We discuss these findings in the context of previous relevant work, including that on the mechanical regulation of microtubule array orientation.},
author = {Adamowski, Maciek and Li, Lanxin and Friml, JiĆĂ},
issn = {1422-0067},
journal = {International Journal of Molecular Sciences},
number = {13},
publisher = {MDPI},
title = {{Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling}},
doi = {10.3390/ijms20133337},
volume = {20},
year = {2019},
}
@phdthesis{6269,
abstract = {Clathrin-Mediated Endocytosis (CME) is an aspect of cellular trafficking that is constantly regulated for mediating developmental and physiological responses. The main aim of my thesis is to decipher the basic mechanisms of CME and post-endocytic trafficking in the whole multicellular organ systems of Arabidopsis. The first chapter of my thesis describes the search for new components involved in CME. Tandem affinity purification was conducted using CLC and its interacting partners were identified. Amongst the identified proteins were the Auxilin-likes1 and 2 (Axl1/2), putative uncoating factors, for which we made a full functional analysis. Over-expression of Axl1/2 causes extreme modifications in the dynamics of the machinery proteins and inhibition of endocytosis altogether. However the loss of function of the axl1/2 did not present any cellular or physiological phenotype, meaning Auxilin-likes do not form the major uncoating machinery. The second chapter of my thesis describes the establishment/utilisation of techniques to capture the dynamicity and the complexity of CME and post-endocytic trafficking. We have studied the development of endocytic pits at the PM â specifically, the mode of membrane remodeling during pit development and the role of actin in it, given plant cells possess high turgor pressure. Utilizing the improved z-resolution of TIRF and VAEM techniques, we captured the time-lapse of the endocytic events at the plasma membrane; and using particle detection software, we quantitatively analysed all the endocytic trajectories in an unbiased way to obtain the endocytic rate of the system. This together with the direct analysis of cargo internalisation from the PM provided an estimate on the endocytic potential of the cell. We also developed a methodology for ultrastructural analysis of different populations of Clathrin-Coated Structures (CCSs) in both PM and endomembranes in unroofed protoplasts. Structural analysis, together with the intensity profile of CCSs at the PM show that the mode of CCP development at the PM follows âConstant curvature modelâ; meaning that clathrin polymerisation energy is a major contributing factor of membrane remodeling. In addition, other analyses clearly show that actin is not required for membrane remodeling during invagination or any other step of CCP development, despite the prevalent high turgor pressure. However, actin is essential in orchestrating the post-endocytic trafficking of CCVs facilitating the EE formation. We also observed that the uncoating process post-endocytosis is not immediate; an alternative mechanism of uncoating â Sequential multi-step process â functions in the cell. Finally we also looked at one of the important physiological stimuli modulating the process â hormone, auxin. auxin has been known to influence CME before. We have made a detailed study on the concentration-time based effect of auxin on the machinery proteins, CCP development, and the specificity of cargoes endocytosed. To this end, we saw no general effect of auxin on CME at earlier time points. However, very low concentration of IAA, such as 50nM, accelerates endocytosis of specifically PIN2 through CME. Such a tight regulatory control with high specificity to PIN2 could be essential in modulating its polarity. },
author = {Narasimhan, Madhumitha},
issn = {2663-337X},
pages = {138},
publisher = {Institute of Science and Technology Austria},
title = {{Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants }},
doi = {10.15479/at:ista:th1075},
year = {2019},
}
@article{6351,
abstract = {A process of restorative patterning in plant roots correctly replaces eliminated cells to heal local injuries despite the absence of cell migration, which underpins wound healing in animals.
Patterning in plants relies on oriented cell divisions and acquisition of specific cell identities. Plants regularly endure wounds caused by abiotic or biotic environmental stimuli and have developed extraordinary abilities to restore their tissues after injuries. Here, we provide insight into a mechanism of restorative patterning that repairs tissues after wounding. Laser-assisted elimination of different cells in Arabidopsis root combined with live-imaging tracking during vertical growth allowed analysis of the regeneration processes in vivo. Specifically, the cells adjacent to the inner side of the injury re-activated their stem cell transcriptional programs. They accelerated their progression through cell cycle, coordinately changed the cell division orientation, and ultimately acquired de novo the correct cell fates to replace missing cells. These observations highlight existence of unknown intercellular positional signaling and demonstrate the capability of specified cells to re-acquire stem cell programs as a crucial part of the plant-specific mechanism of wound healing.},
author = {MarhavĂĄ, Petra and HĂ¶rmayer, Lukas and Yoshida, Saiko and Marhavy, Peter and BenkovĂĄ, Eva and Friml, JiĆĂ},
issn = {10974172},
journal = {Cell},
number = {4},
pages = {957--969.e13},
publisher = {Elsevier},
title = {{Re-activation of stem cell pathways for pattern restoration in plant wound healing}},
doi = {10.1016/j.cell.2019.04.015},
volume = {177},
year = {2019},
}
@article{7391,
abstract = {Electron microscopy (EM) is a technology that enables visualization of single proteins at a nanometer resolution. However, current protein analysis by EM mainly relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised by large size of antibody, precluding precise detection of protein location in biological samples. Here, we develop a specific chemical labeling method for EM detection of proteins at single-molecular level. Rational design of Î±-helical peptide tag and probe structure provided a complementary reaction pair that enabled specific cysteine conjugation of the tag. The developed chemical labeling with gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency and detectability of high-density clusters of tag-fused G protein-coupled receptors in freeze-fracture replicas compared with immunogold labeling. Furthermore, in ultrathin sections, the spatial resolution of the chemical labeling was significantly higher than that of antibody-mediated labeling. These results demonstrate substantial advantages of the chemical labeling approach for single protein visualization by EM.},
author = {Tabata, Shigekazu and Jevtic, Marijo and Kurashige, Nobutaka and Fuchida, Hirokazu and Kido, Munetsugu and Tani, Kazushi and Zenmyo, Naoki and Uchinomiya, Shohei and Harada, Harumi and Itakura, Makoto and Hamachi, Itaru and Shigemoto, Ryuichi and Ojida, Akio},
issn = {2589-0042},
journal = {iScience},
number = {12},
pages = {256--268},
publisher = {Elsevier},
title = {{Electron microscopic detection of single membrane proteins by a specific chemical labeling}},
doi = {10.1016/j.isci.2019.11.025},
volume = {22},
year = {2019},
}
@article{6943,
abstract = {Plants as sessile organisms are constantly under attack by herbivores, rough environmental situations, or mechanical pressure. These challenges often lead to the induction of wounds or destruction of already specified and developed tissues. Additionally, wounding makes plants vulnerable to invasion by pathogens, which is why wound signalling often triggers specific defence responses. To stay competitive or, eventually, survive under these circumstances, plants need to regenerate efficiently, which in rigid, tissue migration-incompatible plant tissues requires post-embryonic patterning and organogenesis. Now, several studies used laser-assisted single cell ablation in the Arabidopsis root tip as a minimal wounding proxy. Here, we discuss their findings and put them into context of a broader spectrum of wound signalling, pathogen responses and tissue as well as organ regeneration.},
author = {HĂ¶rmayer, Lukas and Friml, JiĆĂ},
issn = {1369-5266},
journal = {Current Opinion in Plant Biology},
pages = {124--130},
publisher = {Elsevier},
title = {{Targeted cell ablation-based insights into wound healing and restorative patterning}},
doi = {10.1016/j.pbi.2019.08.006},
volume = {52},
year = {2019},
}
@unpublished{10065,
abstract = {We study double quantum dots in a Ge/SiGe heterostructure and test their maturity towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability, from two single quantum dots to a double quantum dot. We measure Pauli spin blockade and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for sensing charge transitions in the double quantum dot at interest. In conclusion, Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit.},
author = {Hofmann, Andrea C and Jirovec, Daniel and Borovkov, Maxim and Prieto Gonzalez, Ivan and Ballabio, Andrea and Frigerio, Jacopo and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios},
booktitle = {arXiv},
title = {{Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits}},
doi = {10.48550/arXiv.1910.05841},
year = {2019},
}
@phdthesis{6891,
abstract = {While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance.
Cells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients.
Nevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner.
Therefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments.
The results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate.
Thus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration.
Thereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.
},
author = {Kopf, Aglaja},
isbn = {978-3-99078-002-2},
issn = {2663-337X},
keywords = {cell biology, immunology, leukocyte, migration, microfluidics},
pages = {171},
publisher = {Institute of Science and Technology Austria},
title = {{The implication of cytoskeletal dynamics on leukocyte migration}},
doi = {10.15479/AT:ISTA:6891},
year = {2019},
}
@article{6328,
abstract = {During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and someâbut not allâcancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.},
author = {Renkawitz, JĂ¶rg and Kopf, Aglaja and Stopp, Julian A and de Vries, Ingrid and Driscoll, Meghan K. and Merrin, Jack and Hauschild, Robert and Welf, Erik S. and Danuser, Gaudenz and Fiolka, Reto and Sixt, Michael K},
journal = {Nature},
pages = {546--550},
publisher = {Springer Nature},
title = {{Nuclear positioning facilitates amoeboid migration along the path of least resistance}},
doi = {10.1038/s41586-019-1087-5},
volume = {568},
year = {2019},
}