@article{7406,
abstract = {Background
Synaptic vesicles (SVs) are an integral part of the neurotransmission machinery, and isolation of SVs from their host neuron is necessary to reveal their most fundamental biochemical and functional properties in in vitro assays. Isolated SVs from neurons that have been genetically engineered, e.g. to introduce genetically encoded indicators, are not readily available but would permit new insights into SV structure and function. Furthermore, it is unclear if cultured neurons can provide sufficient starting material for SV isolation procedures.
New method
Here, we demonstrate an efficient ex vivo procedure to obtain functional SVs from cultured rat cortical neurons after genetic engineering with a lentivirus.
Results
We show that ∼108 plated cortical neurons allow isolation of suitable SV amounts for functional analysis and imaging. We found that SVs isolated from cultured neurons have neurotransmitter uptake comparable to that of SVs isolated from intact cortex. Using total internal reflection fluorescence (TIRF) microscopy, we visualized an exogenous SV-targeted marker protein and demonstrated the high efficiency of SV modification.
Comparison with existing methods
Obtaining SVs from genetically engineered neurons currently generally requires the availability of transgenic animals, which is constrained by technical (e.g. cost and time) and biological (e.g. developmental defects and lethality) limitations.
Conclusions
These results demonstrate the modification and isolation of functional SVs using cultured neurons and viral transduction. The ability to readily obtain SVs from genetically engineered neurons will permit linking in situ studies to in vitro experiments in a variety of genetic contexts.},
author = {Mckenzie, Catherine and Spanova, Miroslava and Johnson, Alexander J and Kainrath, Stephanie and Zheden, Vanessa and Sitte, Harald H. and Janovjak, Harald L},
issn = {0165-0270},
journal = {Journal of Neuroscience Methods},
pages = {114--121},
publisher = {Elsevier},
title = {{Isolation of synaptic vesicles from genetically engineered cultured neurons}},
doi = {10.1016/j.jneumeth.2018.11.018},
volume = {312},
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 = {Stürner, Tomke and Tatarnikova, Anastasia and Müller, 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},
}
@inbook{7410,
abstract = {Epiboly is a conserved gastrulation movement describing the thinning and spreading of a sheet or multi-layer of cells. The zebrafish embryo has emerged as a vital model system to address the cellular and molecular mechanisms that drive epiboly. In the zebrafish embryo, the blastoderm, consisting of a simple squamous epithelium (the enveloping layer) and an underlying mass of deep cells, as well as a yolk nuclear syncytium (the yolk syncytial layer) undergo epiboly to internalize the yolk cell during gastrulation. The major events during zebrafish epiboly are: expansion of the enveloping layer and the internal yolk syncytial layer, reduction and removal of the yolk membrane ahead of the advancing blastoderm margin and deep cell rearrangements between the enveloping layer and yolk syncytial layer to thin the blastoderm. Here, work addressing the cellular and molecular mechanisms as well as the sources of the mechanical forces that underlie these events is reviewed. The contribution of recent findings to the current model of epiboly as well as open questions and future prospects are also discussed.},
author = {Bruce, Ashley E.E. and Heisenberg, Carl-Philipp J},
booktitle = {Gastrulation: From Embryonic Pattern to Form},
editor = {Solnica-Krezel, Lilianna },
isbn = {9780128127988},
issn = {0070-2153},
pages = {319--341},
publisher = {Elsevier},
title = {{Mechanisms of zebrafish epiboly: A current view}},
doi = {10.1016/bs.ctdb.2019.07.001},
volume = {136},
year = {2019},
}
@inproceedings{7411,
abstract = {Proofs of sequential work (PoSW) are proof systems where a prover, upon receiving a statement χ and a time parameter T computes a proof ϕ(χ,T) which is efficiently and publicly verifiable. The proof can be computed in T sequential steps, but not much less, even by a malicious party having large parallelism. A PoSW thus serves as a proof that T units of time have passed since χ
was received.
PoSW were introduced by Mahmoody, Moran and Vadhan [MMV11], a simple and practical construction was only recently proposed by Cohen and Pietrzak [CP18].
In this work we construct a new simple PoSW in the random permutation model which is almost as simple and efficient as [CP18] but conceptually very different. Whereas the structure underlying [CP18] is a hash tree, our construction is based on skip lists and has the interesting property that computing the PoSW is a reversible computation.
The fact that the construction is reversible can potentially be used for new applications like constructing proofs of replication. We also show how to “embed” the sloth function of Lenstra and Weselowski [LW17] into our PoSW to get a PoSW where one additionally can verify correctness of the output much more efficiently than recomputing it (though recent constructions of “verifiable delay functions” subsume most of the applications this construction was aiming at).},
author = {Abusalah, Hamza M and Kamath Hosdurg, Chethan and Klein, Karen and Pietrzak, Krzysztof Z and Walter, Michael},
booktitle = {Advances in Cryptology – EUROCRYPT 2019},
isbn = {9783030176556},
issn = {0302-9743},
location = {Darmstadt, Germany},
pages = {277--291},
publisher = {Springer International Publishing},
title = {{Reversible proofs of sequential work}},
doi = {10.1007/978-3-030-17656-3_10},
volume = {11477},
year = {2019},
}
@article{7412,
abstract = {We develop a framework for the rigorous analysis of focused stochastic local search algorithms. These algorithms search a state space by repeatedly selecting some constraint that is violated in the current state and moving to a random nearby state that addresses the violation, while (we hope) not introducing many new violations. An important class of focused local search algorithms with provable performance guarantees has recently arisen from algorithmizations of the Lovász local lemma (LLL), a nonconstructive tool for proving the existence of satisfying states by introducing a background measure on the state space. While powerful, the state transitions of algorithms in this class must be, in a precise sense, perfectly compatible with the background measure. In many applications this is a very restrictive requirement, and one needs to step outside the class. Here we introduce the notion of measure distortion and develop a framework for analyzing arbitrary focused stochastic local search algorithms, recovering LLL algorithmizations as the special case of no distortion. Our framework takes as input an arbitrary algorithm of such type and an arbitrary probability measure and shows how to use the measure as a yardstick of algorithmic progress, even for algorithms designed independently of the measure.},
author = {Achlioptas, Dimitris and Iliopoulos, Fotis and Kolmogorov, Vladimir},
issn = {1095-7111},
journal = {SIAM Journal on Computing},
number = {5},
pages = {1583--1602},
publisher = {SIAM},
title = {{A local lemma for focused stochastical algorithms}},
doi = {10.1137/16m109332x},
volume = {48},
year = {2019},
}
@article{7418,
abstract = {Multiple importance sampling (MIS) has become an indispensable tool in Monte Carlo rendering, widely accepted as a near-optimal solution for combining different sampling techniques. But an MIS combination, using the common balance or power heuristics, often results in an overly defensive estimator, leading to high variance. We show that by generalizing the MIS framework, variance can be substantially reduced. Specifically, we optimize one of the combined sampling techniques so as to decrease the overall variance of the resulting MIS estimator. We apply the approach to the computation of direct illumination due to an HDR environment map and to the computation of global illumination using a path guiding algorithm. The implementation can be as simple as subtracting a constant value from the tabulated sampling density done entirely in a preprocessing step. This produces a consistent noise reduction in all our tests with no negative influence on run time, no artifacts or bias, and no failure cases.},
author = {Karlík, Ondřej and Šik, Martin and Vévoda, Petr and Skrivan, Tomas and Křivánek, Jaroslav},
issn = {0730-0301},
journal = {ACM Transactions on Graphics},
number = {6},
publisher = {ACM},
title = {{MIS compensation: Optimizing sampling techniques in multiple importance sampling}},
doi = {10.1145/3355089.3356565},
volume = {38},
year = {2019},
}
@article{7413,
abstract = {We consider Bose gases consisting of N particles trapped in a box with volume one and interacting through a repulsive potential with scattering length of order N−1 (Gross–Pitaevskii regime). We determine the ground state energy and the low-energy excitation spectrum, up to errors vanishing as N→∞. Our results confirm Bogoliubov’s predictions.},
author = {Boccato, Chiara and Brennecke, Christian and Cenatiempo, Serena and Schlein, Benjamin},
issn = {0001-5962},
journal = {Acta Mathematica},
number = {2},
pages = {219--335},
publisher = {International Press of Boston},
title = {{Bogoliubov theory in the Gross–Pitaevskii limit}},
doi = {10.4310/acta.2019.v222.n2.a1},
volume = {222},
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{7422,
abstract = {Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions.},
author = {Sokolowski, Thomas R and Paijmans, Joris and Bossen, Laurens and Miedema, Thomas and Wehrens, Martijn and Becker, Nils B. and Kaizu, Kazunari and Takahashi, Koichi and Dogterom, Marileen and ten Wolde, Pieter Rein},
issn = {0021-9606},
journal = {The Journal of Chemical Physics},
number = {5},
publisher = {AIP Publishing},
title = {{eGFRD in all dimensions}},
doi = {10.1063/1.5064867},
volume = {150},
year = {2019},
}
@article{7420,
abstract = {β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.},
author = {Sahgal, Pranshu and Alanko, Jonna H and Icha, Jaroslav and Paatero, Ilkka and Hamidi, Hellyeh and Arjonen, Antti and Pietilä, Mika and Rokka, Anne and Ivaska, Johanna},
issn = {0021-9533},
journal = {Journal of Cell Science},
number = {11},
publisher = {The Company of Biologists},
title = {{GGA2 and RAB13 promote activity-dependent β1-integrin recycling}},
doi = {10.1242/jcs.233387},
volume = {132},
year = {2019},
}
@article{7423,
abstract = {We compare finite rank perturbations of the following three ensembles of complex rectangular random matrices: First, a generalised Wishart ensemble with one random and two fixed correlation matrices introduced by Borodin and Péché, second, the product of two independent random matrices where one has correlated entries, and third, the case when the two random matrices become also coupled through a fixed matrix. The singular value statistics of all three ensembles is shown to be determinantal and we derive double contour integral representations for their respective kernels. Three different kernels are found in the limit of infinite matrix dimension at the origin of the spectrum. They depend on finite rank perturbations of the correlation and coupling matrices and are shown to be integrable. The first kernel (I) is found for two independent matrices from the second, and two weakly coupled matrices from the third ensemble. It generalises the Meijer G-kernel for two independent and uncorrelated matrices. The third kernel (III) is obtained for the generalised Wishart ensemble and for two strongly coupled matrices. It further generalises the perturbed Bessel kernel of Desrosiers and Forrester. Finally, kernel (II), found for the ensemble of two coupled matrices, provides an interpolation between the kernels (I) and (III), generalising previous findings of part of the authors.},
author = {Akemann, Gernot and Checinski, Tomasz and Liu, Dangzheng and Strahov, Eugene},
issn = {0246-0203},
journal = {Annales de l'Institut Henri Poincaré, Probabilités et Statistiques},
number = {1},
pages = {441--479},
publisher = {Institute of Mathematical Statistics},
title = {{Finite rank perturbations in products of coupled random matrices: From one correlated to two Wishart ensembles}},
doi = {10.1214/18-aihp888},
volume = {55},
year = {2019},
}
@article{7421,
abstract = {X and Y chromosomes can diverge when rearrangements block recombination between them. Here we present the first genomic view of a reciprocal translocation that causes two physically unconnected pairs of chromosomes to be coinherited as sex chromosomes. In a population of the common frog (Rana temporaria), both pairs of X and Y chromosomes show extensive sequence differentiation, but not degeneration of the Y chromosomes. A new method based on gene trees shows both chromosomes are sex‐linked. Furthermore, the gene trees from the two Y chromosomes have identical topologies, showing they have been coinherited since the reciprocal translocation occurred. Reciprocal translocations can thus reshape sex linkage on a much greater scale compared with inversions, the type of rearrangement that is much better known in sex chromosome evolution, and they can greatly amplify the power of sexually antagonistic selection to drive genomic rearrangement. Two more populations show evidence of other rearrangements, suggesting that this species has unprecedented structural polymorphism in its sex chromosomes.},
author = {Toups, Melissa A and Rodrigues, Nicolas and Perrin, Nicolas and Kirkpatrick, Mark},
issn = {0962-1083},
journal = {Molecular Ecology},
number = {8},
pages = {1877--1889},
publisher = {Wiley},
title = {{A reciprocal translocation radically reshapes sex‐linked inheritance in the common frog}},
doi = {10.1111/mec.14990},
volume = {28},
year = {2019},
}
@article{7436,
abstract = {For an ordinary K3 surface over an algebraically closed field of positive characteristic we show that every automorphism lifts to characteristic zero. Moreover, we show that the Fourier-Mukai partners of an ordinary K3 surface are in one-to-one correspondence with the Fourier-Mukai partners of the geometric generic fiber of its canonical lift. We also prove that the explicit counting formula for Fourier-Mukai partners of the K3 surfaces with Picard rank two and with discriminant equal to minus of a prime number, in terms of the class number of the prime, holds over a field of positive characteristic as well. We show that the image of the derived autoequivalence group of a K3 surface of finite height in the group of isometries of its crystalline cohomology has index at least two. Moreover, we provide a conditional upper bound on the kernel of this natural cohomological descent map. Further, we give an extended remark in the appendix on the possibility of an F-crystal structure on the crystalline cohomology of a K3 surface over an algebraically closed field of positive characteristic and show that the naive F-crystal structure fails in being compatible with inner product. },
author = {Srivastava, Tanya K},
issn = {14310643},
journal = {Documenta Mathematica},
pages = {1135--1177},
publisher = {Deutsche Mathematiker-Vereinigung},
title = {{On derived equivalences of k3 surfaces in positive characteristic}},
doi = {10.25537/dm.2019v24.1135-1177},
volume = {24},
year = {2019},
}
@inproceedings{7437,
abstract = {Most of today's distributed machine learning systems assume reliable networks: whenever two machines exchange information (e.g., gradients or models), the network should guarantee the delivery of the message. At the same time, recent work exhibits the impressive tolerance of machine learning algorithms to errors or noise arising from relaxed communication or synchronization. In this paper, we connect these two trends, and consider the following question: Can we design machine learning systems that are tolerant to network unreliability during training? With this motivation, we focus on a theoretical problem of independent interest-given a standard distributed parameter server architecture, if every communication between the worker and the server has a non-zero probability p of being dropped, does there exist an algorithm that still converges, and at what speed? The technical contribution of this paper is a novel theoretical analysis proving that distributed learning over unreliable network can achieve comparable convergence rate to centralized or distributed learning over reliable networks. Further, we prove that the influence of the packet drop rate diminishes with the growth of the number of parameter servers. We map this theoretical result onto a real-world scenario, training deep neural networks over an unreliable network layer, and conduct network simulation to validate the system improvement by allowing the networks to be unreliable.},
author = {Yu, Chen and Tang, Hanlin and Renggli, Cedric and Kassing, Simon and Singla, Ankit and Alistarh, Dan-Adrian and Zhang, Ce and Liu, Ji},
booktitle = {36th International Conference on Machine Learning, ICML 2019},
isbn = {9781510886988},
location = {Long Beach, CA, United States},
pages = {12481--12512},
publisher = {IMLS},
title = {{Distributed learning over unreliable networks}},
volume = {2019-June},
year = {2019},
}
@inbook{7453,
abstract = {We illustrate the ingredients of the state-of-the-art of model-based approach for the formal design and verification of cyber-physical systems. To capture the interaction between a discrete controller and its continuously evolving environment, we use the formal models of timed and hybrid automata. We explain the steps of modeling and verification in the tools Uppaal and SpaceEx using a case study based on a dual-chamber implantable pacemaker monitoring a human heart. We show how to design a model as a composition of components, how to construct models at varying levels of detail, how to establish that one model is an abstraction of another, how to specify correctness requirements using temporal logic, and how to verify that a model satisfies a logical requirement.},
author = {Alur, Rajeev and Giacobbe, Mirco and Henzinger, Thomas A and Larsen, Kim G. and Mikučionis, Marius},
booktitle = {Computing and Software Science},
editor = {Steffen, Bernhard and Woeginger, Gerhard},
isbn = {9783319919072},
issn = {0302-9743},
pages = {452--477},
publisher = {Springer Nature},
title = {{Continuous-time models for system design and analysis}},
doi = {10.1007/978-3-319-91908-9_22},
volume = {10000},
year = {2019},
}
@article{7451,
abstract = {We prove that the observable telegraph signal accompanying the bistability in the photon-blockade-breakdown regime of the driven and lossy Jaynes–Cummings 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 Förderung 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},
}
@article{6608,
abstract = {We use the canonical bases produced by the tri-partition algorithm in (Edelsbrunner and Ölsböck, 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 Ölsböck, 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{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},
}
@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{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 Püschel, Markus},
location = {Vancouver, Canada},
pages = {927--938},
publisher = {Neural Information Processing Systems Foundation},
title = {{Powerset convolutional neural networks}},
volume = {32},
year = {2019},
}
@article{7550,
abstract = {We consider an optimal control problem for an abstract nonlinear dissipative evolution equation. The differential constraint is penalized by augmenting the target functional by a nonnegative global-in-time functional which is null-minimized in the evolution equation is satisfied. Different variational settings are presented, leading to the convergence of the penalization method for gradient flows, noncyclic and semimonotone flows, doubly nonlinear evolutions, and GENERIC systems. },
author = {Portinale, Lorenzo and Stefanelli, Ulisse},
issn = {1343-4373},
journal = {Advances in Mathematical Sciences and Applications},
number = {2},
pages = {425--447},
publisher = {Gakko Tosho},
title = {{Penalization via global functionals of optimal-control problems for dissipative evolution}},
volume = {28},
year = {2019},
}
@unpublished{7552,
abstract = {There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests. },
author = {Bialek, William and Gregor, Thomas and Tkačik, Gašper},
booktitle = {arXiv:1912.08579},
pages = {5},
publisher = {ArXiv},
title = {{Action at a distance in transcriptional regulation}},
year = {2019},
}
@inproceedings{7576,
abstract = {We present the results of a friendly competition for formal verification of continuous and hybrid systems with nonlinear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In this year, 6 tools Ariadne, CORA, DynIbex, Flow*, Isabelle/HOL, and JuliaReach (in alphabetic order) participated. They are applied to solve reachability analysis problems on four benchmark problems, one of them with hybrid dynamics. We do not rank the tools based on the results, but show the current status and discover the potential advantages of different tools.},
author = {Immler, Fabian and Althoff, Matthias and Benet, Luis and Chapoutot, Alexandre and Chen, Xin and Forets, Marcelo and Geretti, Luca and Kochdumper, Niklas and Sanders, David P. and Schilling, Christian},
booktitle = {EPiC Series in Computing},
issn = {23987340},
location = {Montreal, Canada},
pages = {41--61},
publisher = {EasyChair Publications},
title = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with nonlinear dynamics}},
doi = {10.29007/m75b},
volume = {61},
year = {2019},
}
@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 Tkačik, Gašper},
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{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{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},
}
@misc{7016,
abstract = {Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.},
author = {Tomanek, Isabella},
keywords = {Escherichia coli, gene amplification, galactose, DOG, experimental evolution, Illumina sequence data, FACS data, microfluidics data},
publisher = {IST Austria},
title = {{Data for the paper "Gene amplification as a form of population-level gene expression regulation"}},
doi = {10.15479/AT:ISTA:7016},
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},
}
@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 protocol’s 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 END−OF−METERED−LINE 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 Hubáček, 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},
}
@inproceedings{6933,
abstract = {We design fast deterministic algorithms for distance computation in the CONGESTED CLIQUE model. Our key contributions include:
- A (2+ε)-approximation for all-pairs shortest paths problem in O(log²n / ε) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model.
- A (1+ε)-approximation for multi-source shortest paths problem from O(√n) sources in O(log² n / ε) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size.
Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in Õ(n^{1/6}) rounds.},
author = {Censor-Hillel, Keren and Dory, Michal and Korhonen, Janne and Leitersdorf, Dean},
booktitle = {Proceedings of the 2019 ACM Symposium on Principles of Distributed Computin},
isbn = {9781450362177},
location = {Toronto, ON, Canada},
pages = {74--83},
publisher = {ACM},
title = {{Fast approximate shortest paths in the congested clique}},
doi = {10.1145/3293611.3331633},
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 𝑂(𝑛8) 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 𝑂(𝑛7) 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 Masárová, Zuzana and Wagner, Uli},
issn = {0179-5376},
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},
}
@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 “sorting with a transposition tree,” 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 “happy leaf”), disproving a conjecture of Vaughan.
2. Any algorithm that fixes happy leaves—as all known approximation algorithms for the problem do—has approximation factor at least 4/3. Furthermore, the two best-known 2-approximation algorithms have approximation factor exactly 2.
3. A generalized problem—weighted coloured token swapping—is 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 Masárová, 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},
}
@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 = {Trébuchet, Guillaume and Cattenoz, Pierre B and Zsámboki, János 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{80,
abstract = {We consider an interacting, dilute Bose gas trapped in a harmonic potential at a positive temperature. The system is analyzed in a combination of a thermodynamic and a Gross–Pitaevskii (GP) limit where the trap frequency ω, the temperature T, and the particle number N are related by N∼ (T/ ω) 3→ ∞ while the scattering length is so small that the interaction energy per particle around the center of the trap is of the same order of magnitude as the spectral gap in the trap. We prove that the difference between the canonical free energy of the interacting gas and the one of the noninteracting system can be obtained by minimizing the GP energy functional. We also prove Bose–Einstein condensation in the following sense: The one-particle density matrix of any approximate minimizer of the canonical free energy functional is to leading order given by that of the noninteracting gas but with the free condensate wavefunction replaced by the GP minimizer.},
author = {Deuchert, Andreas and Seiringer, Robert and Yngvason, Jakob},
journal = {Communications in Mathematical Physics},
number = {2},
pages = {723--776},
publisher = {Springer},
title = {{Bose–Einstein condensation in a dilute, trapped gas at positive temperature}},
doi = {10.1007/s00220-018-3239-0},
volume = {368},
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 = {Huszár, Kristóf 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 für 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 = {Huszár, Kristóf and Spreer, Jonathan and Wagner, Uli},
issn = {1920-180X},
journal = {Journal of Computational Geometry},
number = {2},
pages = {70–98},
publisher = {Computational Geometry Laborartoy},
title = {{On the treewidth of triangulated 3-manifolds}},
doi = {10.20382/JOGC.V10I2A5},
volume = {10},
year = {2019},
}
@inproceedings{8175,
abstract = {We study edge asymptotics of poissonized Plancherel-type measures on skew Young diagrams (integer partitions). These measures can be seen as generalizations of those studied by Baik--Deift--Johansson and Baik--Rains in resolving Ulam's problem on longest increasing subsequences of random permutations and the last passage percolation (corner growth) discrete versions thereof. Moreover they interpolate between said measures and the uniform measure on partitions. In the new KPZ-like 1/3 exponent edge scaling limit with logarithmic corrections, we find new probability distributions generalizing the classical Tracy--Widom GUE, GOE and GSE distributions from the theory of random matrices.},
author = {Betea, Dan and Bouttier, Jérémie and Nejjar, Peter and Vuletíc, Mirjana},
booktitle = {Proceedings on the 31st International Conference on Formal Power Series and Algebraic Combinatorics},
location = {Ljubljana, Slovenia},
publisher = {Formal Power Series and Algebraic Combinatorics},
title = {{New edge asymptotics of skew Young diagrams via free boundaries}},
year = {2019},
}
@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{8184,
abstract = {Denote by ∆N the N-dimensional simplex. A map f : ∆N → Rd is an almost r-embedding if fσ1∩. . .∩fσr = ∅ whenever σ1, . . . , σr are pairwise disjoint faces. A counterexample to the topological Tverberg conjecture asserts that if r is not a prime power and d ≥ 2r + 1, then there is an almost r-embedding ∆(d+1)(r−1) → Rd. This was improved by Blagojevi´c–Frick–Ziegler 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)r−r l
d + 2 r + 1 m−2, then there is an almost r-embedding ∆N → Rd. For the r-fold van Kampen–Flores conjecture we also produce counterexamples which are stronger than previously known. Our proof is based on generalizations of the Mabillard–Wagner 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},
}
@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}},
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},
}
@inproceedings{6989,
abstract = {When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with hole(s) to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special simple holes guarantee foldability. },
author = {Aichholzer, Oswin and Akitaya, Hugo A and Cheung, Kenneth C and Demaine, Erik D and Demaine, Martin L and Fekete, Sandor P and Kleist, Linda and Kostitsyna, Irina and Löffler, Maarten and Masárová, Zuzana and Mundilova, Klara and Schmidt, Christiane},
booktitle = {Proceedings of the 31st Canadian Conference on Computational Geometry},
location = {Edmonton, Canada},
pages = {164--170},
publisher = {Canadian Conference on Computational Geometry},
title = {{Folding polyominoes with holes into a cube}},
year = {2019},
}
@inproceedings{8324,
abstract = {The notion of program sensitivity (aka Lipschitz continuity) specifies that changes in the program input result in proportional changes to the program output. For probabilistic programs the notion is naturally extended to expected sensitivity. A previous approach develops a relational program logic framework for proving expected sensitivity of probabilistic while loops, where the number of iterations is fixed and bounded. In this work, we consider probabilistic while loops where the number of iterations is not fixed, but randomized and depends on the initial input values. We present a sound approach for proving expected sensitivity of such programs. Our sound approach is martingale-based and can be automated through existing martingale-synthesis algorithms. Furthermore, our approach is compositional for sequential composition of while loops under a mild side condition. We demonstrate the effectiveness of our approach on several classical examples from Gambler's Ruin, stochastic hybrid systems and stochastic gradient descent. We also present experimental results showing that our automated approach can handle various probabilistic programs in the literature.},
author = {Wang, Peixin and Fu, Hongfei and Chatterjee, Krishnendu and Deng, Yuxin and Xu, Ming},
booktitle = {Proceedings of the ACM on Programming Languages},
issn = {2475-1421},
number = {POPL},
publisher = {ACM},
title = {{Proving expected sensitivity of probabilistic programs with randomized variable-dependent termination time}},
doi = {10.1145/3371093},
volume = {4},
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 Brugués, 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{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},
}
@inproceedings{8570,
abstract = {This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with linear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In its third edition, seven tools have been applied to solve six different benchmark problems in the category for linear continuous dynamics (in alphabetical order): CORA, CORA/SX, HyDRA, Hylaa, JuliaReach, SpaceEx, and XSpeed. This report is a snapshot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results provide one of the most complete assessments of tools for the safety verification of continuous and hybrid systems with linear continuous dynamics up to this date.},
author = {Althoff, Matthias and Bak, Stanley and Forets, Marcelo and Frehse, Goran and Kochdumper, Niklas and Ray, Rajarshi and Schilling, Christian and Schupp, Stefan},
booktitle = {EPiC Series in Computing},
issn = {23987340},
location = {Montreal, Canada},
pages = {14--40},
publisher = {EasyChair},
title = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with linear continuous dynamics}},
doi = {10.29007/bj1w},
volume = {61},
year = {2019},
}
@article{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 Fröhlich polaron–a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon–a 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 Fröhlich polaron to the angulon}},
doi = {10.1080/00268976.2019.1567852},
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},
}
@article{6784,
abstract = {Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems.},
author = {Ruess, Jakob and Pleska, Maros and Guet, Calin C and Tkačik, Gašper},
issn = {1553-7358},
journal = {PLoS Computational Biology},
number = {7},
publisher = {Public Library of Science},
title = {{Molecular noise of innate immunity shapes bacteria-phage ecologies}},
doi = {10.1371/journal.pcbi.1007168},
volume = {15},
year = {2019},
}
@article{6819,
abstract = {Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome.},
author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez},
issn = {1756-0500},
journal = {BMC Research Notes},
publisher = {BioMed Central},
title = {{Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}},
doi = {10.1186/s13104-019-4534-3},
volume = {12},
year = {2019},
}
@misc{9783,
abstract = {Predicted frameshift and nonsense mutations in Chlamydial pan-genome. For the analysis of putative pseudogenes, events located less than 60 bp. away from gene end or present in a single genome from the corresponding OG were excluded. (CSV 600 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 10 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808760.v1},
year = {2019},
}
@misc{9784,
abstract = {Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1 of seeding flasks and following 6-days of continuous culture. Note: no differences in cell numbers were observed between negative control and glyphosate treated cultures.},
author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez},
publisher = {Springer Nature},
title = {{MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}},
doi = {10.6084/m9.figshare.9411761.v1},
year = {2019},
}
@misc{9786,
author = {Ruess, Jakob and Pleska, Maros and Guet, Calin C and Tkačik, Gašper},
publisher = {Public Library of Science},
title = {{Supporting text and results}},
doi = {10.1371/journal.pcbi.1007168.s001},
year = {2019},
}
@article{6419,
abstract = {Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.},
author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor},
issn = {15537404},
journal = {PLoS Genetics},
number = {4},
publisher = {Public Library of Science},
title = {{An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape}},
doi = {10.1371/journal.pgen.1008079},
volume = {15},
year = {2019},
}
@article{6467,
abstract = {Fitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from a class of simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effect sizes, mutational bias and maladaptation of the wild type. We illustrate our approach by reanalysing a large dataset of mutant effects in a yeast snoRNA (small nucleolar RNA). Though characterized by some large epistatic effects, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have limited influence on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape and the distribution of mutations, and so is expected to vary in consistent ways between new mutations, standing variation and fixed mutations.},
author = {Fraisse, Christelle and Welch, John J.},
issn = {1744957X},
journal = {Biology Letters},
number = {4},
publisher = {Royal Society of London},
title = {{The distribution of epistasis on simple fitness landscapes}},
doi = {10.1098/rsbl.2018.0881},
volume = {15},
year = {2019},
}
@misc{9797,
author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor},
publisher = {Public Library of Science},
title = {{A statistical summary of segment libraries and sequencing results}},
doi = {10.1371/journal.pgen.1008079.s011},
year = {2019},
}
@article{6105,
abstract = { Hosts can alter their strategy towards pathogens during their lifetime; that is, they can show phenotypic plasticity in immunity or life history. Immune priming is one such example, where a previous encounter with a pathogen confers enhanced protection upon secondary challenge, resulting in reduced pathogen load (i.e., resistance) and improved host survival. However, an initial encounter might also enhance tolerance, particularly to less virulent opportunistic pathogens that establish persistent infections. In this scenario, individuals are better able to reduce the negative fecundity consequences that result from a high pathogen burden. Finally, previous exposure may also lead to life‐history adjustments, such as terminal investment into reproduction.
Using different Drosophila melanogaster host genotypes and two bacterial pathogens, Lactococcus lactis and Pseudomonas entomophila, we tested whether previous exposure results in resistance or tolerance and whether it modifies immune gene expression during an acute‐phase infection (one day post‐challenge). We then asked whether previous pathogen exposure affects chronic‐phase pathogen persistence and longer‐term survival (28 days post‐challenge).
We predicted that previous exposure would increase host resistance to an early stage bacterial infection while it might come at a cost to host fecundity tolerance. We reasoned that resistance would be due in part to stronger immune gene expression after challenge. We expected that previous exposure would improve long‐term survival, that it would reduce infection persistence, and we expected to find genetic variation in these responses.
We found that previous exposure to P. entomophila weakened host resistance to a second infection independent of genotype and had no effect on immune gene expression. Fecundity tolerance showed genotypic variation but was not influenced by previous exposure. However, L. lactis persisted as a chronic infection, whereas survivors cleared the more pathogenic P. entomophila infection.
To our knowledge, this is the first study that addresses host tolerance to bacteria in relation to previous exposure, taking a multi‐faceted approach to address the topic. Our results suggest that previous exposure comes with transient costs to resistance during the early stage of infection in this host–pathogen system and that infection persistence may be bacterium‐specific.
},
author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie A.O.},
issn = {13652656},
journal = {Journal of Animal Ecology},
number = {4},
pages = {566--578},
publisher = {Wiley},
title = {{A multi-faceted approach testing the effects of previous bacterial exposure on resistance and tolerance}},
doi = {10.1111/1365-2656.12953},
volume = {88},
year = {2019},
}
@misc{9806,
abstract = {1. Hosts can alter their strategy towards pathogens during their lifetime, i.e., they can show phenotypic plasticity in immunity or life history. Immune priming is one such example, where a previous encounter with a pathogen confers enhanced protection upon secondary challenge, resulting in reduced pathogen load (i.e. resistance) and improved host survival. However, an initial encounter might also enhance tolerance, particularly to less virulent opportunistic pathogens that establish persistent infections. In this scenario, individuals are better able to reduce the negative fitness consequences that result from a high pathogen load. Finally, previous exposure may also lead to life history adjustments, such as terminal investment into reproduction. 2. Using different Drosophila melanogaster host genotypes and two bacterial pathogens, Lactococcus lactis and Pseudomonas entomophila, we tested if previous exposure results in resistance or tolerance and whether it modifies immune gene expression during an acute-phase infection (one day post-challenge). We then asked if previous pathogen exposure affects chronic-phase pathogen persistence and longer-term survival (28 days post-challenge). 3. We predicted that previous exposure would increase host resistance to an early stage bacterial infection while it might come at a cost to host fecundity tolerance. We reasoned that resistance would be due in part to stronger immune gene expression after challenge. We expected that previous exposure would improve long-term survival, that it would reduce infection persistence, and we expected to find genetic variation in these responses. 4. We found that previous exposure to P. entomophila weakened host resistance to a second infection independent of genotype and had no effect on immune gene expression. Fecundity tolerance showed genotypic variation but was not influenced by previous exposure. However, L. lactis persisted as a chronic infection, whereas survivors cleared the more pathogenic P. entomophila infection. 5. To our knowledge, this is the first study that addresses host tolerance to bacteria in relation to previous exposure, taking a multi-faceted approach to address the topic. Our results suggest that previous exposure comes with transient costs to resistance during the early stage of infection in this host-pathogen system and that infection persistence may be bacterium-specific.},
author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie A.O.},
publisher = {Dryad},
title = {{Data from: A multi-faceted approach testing the effects of previous bacterial exposure on resistance and tolerance}},
doi = {10.5061/dryad.9kj41f0},
year = {2019},
}
@misc{9805,
abstract = {The spread of adaptive alleles is fundamental to evolution, and in theory, this process is well‐understood. However, only rarely can we follow this process—whether 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 25‐year long study of the mosquitoes Anopheles gambiae (Figure 1) and Anopheles coluzzi in Mali, based on genotypes at 15 single‐nucleotide 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 near‐fixation 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{6095,
abstract = {Both classical and recent studies suggest that chromosomal inversion polymorphisms are important in adaptation and speciation. However, biases in discovery and reporting of inversions make it difficult to assess their prevalence and biological importance. Here, we use an approach based on linkage disequilibrium among markers genotyped for samples collected across a transect between contrasting habitats to detect chromosomal rearrangements de novo. We report 17 polymorphic rearrangements in a single locality for the coastal marine snail, Littorina saxatilis. Patterns of diversity in the field and of recombination in controlled crosses provide strong evidence that at least the majority of these rearrangements are inversions. Most show clinal changes in frequency between habitats, suggestive of divergent selection, but only one appears to be fixed for different arrangements in the two habitats. Consistent with widespread evidence for balancing selection on inversion polymorphisms, we argue that a combination of heterosis and divergent selection can explain the observed patterns and should be considered in other systems spanning environmental gradients.},
author = {Faria, Rui and Chaube, Pragya and Morales, Hernán E. and Larsson, Tomas and Lemmon, Alan R. and Lemmon, Emily M. and Rafajlović, Marina and Panova, Marina and Ravinet, Mark and Johannesson, Kerstin and Westram, Anja M and Butlin, Roger K.},
issn = {1365-294X},
journal = {Molecular Ecology},
number = {6},
pages = {1375--1393},
publisher = {Wiley},
title = {{Multiple chromosomal rearrangements in a hybrid zone between Littorina saxatilis ecotypes}},
doi = {10.1111/mec.14972},
volume = {28},
year = {2019},
}
@misc{9839,
abstract = {More than 100 years after Grigg’s influential analysis of species’ borders, the causes of limits to species’ ranges still represent a puzzle that has never been understood with clarity. The topic has become especially important recently as many scientists have become interested in the potential for species’ ranges to shift in response to climate change—and yet nearly all of those studies fail to recognise or incorporate evolutionary genetics in a way that relates to theoretical developments. I show that range margins can be understood based on just two measurable parameters: (i) the fitness cost of dispersal—a measure of environmental heterogeneity—and (ii) the strength of genetic drift, which reduces genetic diversity. Together, these two parameters define an ‘expansion threshold’: adaptation fails when genetic drift reduces genetic diversity below that required for adaptation to a heterogeneous environment. When the key parameters drop below this expansion threshold locally, a sharp range margin forms. When they drop below this threshold throughout the species’ range, adaptation collapses everywhere, resulting in either extinction or formation of a fragmented metapopulation. Because the effects of dispersal differ fundamentally with dimension, the second parameter—the strength of genetic drift—is qualitatively different compared to a linear habitat. In two-dimensional habitats, genetic drift becomes effectively independent of selection. It decreases with ‘neighbourhood size’—the number of individuals accessible by dispersal within one generation. Moreover, in contrast to earlier predictions, which neglected evolution of genetic variance and/or stochasticity in two dimensions, dispersal into small marginal populations aids adaptation. This is because the reduction of both genetic and demographic stochasticity has a stronger effect than the cost of dispersal through increased maladaptation. The expansion threshold thus provides a novel, theoretically justified, and testable prediction for formation of the range margin and collapse of the species’ range.},
author = {Polechova, Jitka},
publisher = {Dryad},
title = {{Data from: Is the sky the limit? On the expansion threshold of a species' range}},
doi = {10.5061/dryad.5vv37},
year = {2019},
}
@misc{9892,
abstract = {Distribution of OGs with mosaic phyletic patterns across species (all genomes). (CSV 10 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 16 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808814.v1},
year = {2019},
}
@misc{9890,
abstract = {Distribution of OGs with mosaic phyletic patterns across species (complete genomes only). (CSV 7 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 15 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808802.v1},
year = {2019},
}
@misc{9894,
abstract = {Orthologous families (OFs) derived by MCL clustering of OGs. (CSV 189 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 18 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808826.v1},
year = {2019},
}
@misc{9893,
abstract = {Summary of peripheral genesa phyletic patterns and tree concordance. (CSV 26 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 17 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808820.v1},
year = {2019},
}
@misc{9898,
abstract = {All polyN tracts of length 5 or more nucleotides in sequences of genes from OG1. Sequences were extracted and scanned prior to automatic correction for frameshifts implemented in the RAST pipeline. (CSV 133 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 21 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808859.v1},
year = {2019},
}
@misc{9897,
abstract = {Frameshift and nonsense mutations near homopolymeric tracts of OG1 genes. Only 374 genes with typical length and domain composition were considered. (CSV 6 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 20 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808850.v1},
year = {2019},
}
@misc{9899,
abstract = {Summary of orthologous groups (OGs) for 227 genomes of genus Chlamydia. (CSV 362 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 2 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808865.v1},
year = {2019},
}
@misc{9895,
abstract = {Additional information on proteins from OG1. (CSV 30 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 19 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808835.v1},
year = {2019},
}
@misc{9900,
abstract = {Pan-genome statistics by species. (CSV 3 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 5 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808886.v1},
year = {2019},
}
@misc{9896,
abstract = {Summary of the analysed genomes. (CSV 24 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 1 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808841.v1},
year = {2019},
}
@article{6898,
abstract = {Background
Chlamydia are ancient intracellular pathogens with reduced, though strikingly conserved genome. Despite their parasitic lifestyle and isolated intracellular environment, these bacteria managed to avoid accumulation of deleterious mutations leading to subsequent genome degradation characteristic for many parasitic bacteria.
Results
We report pan-genomic analysis of sixteen species from genus Chlamydia including identification and functional annotation of orthologous genes, and characterization of gene gains, losses, and rearrangements. We demonstrate the overall genome stability of these bacteria as indicated by a large fraction of common genes with conserved genomic locations. On the other hand, extreme evolvability is confined to several paralogous gene families such as polymorphic membrane proteins and phospholipase D, and likely is caused by the pressure from the host immune system.
Conclusions
This combination of a large, conserved core genome and a small, evolvable periphery likely reflect the balance between the selective pressure towards genome reduction and the need to adapt to escape from the host immunity.},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
issn = {14712164},
journal = {BMC Genomics},
number = {1},
publisher = {BioMed Central},
title = {{Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.1186/s12864-019-6059-5},
volume = {20},
year = {2019},
}
@misc{9901,
abstract = {Clusters of Orthologous Genes (COGs) and corresponding functional categories assigned to OGs. (CSV 117 kb)},
author = {Sigalova, Olga M. and Chaplin, Andrei V. and Bochkareva, Olga and Shelyakin, Pavel V. and Filaretov, Vsevolod A. and Akkuratov, Evgeny E. and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 9 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808907.v1},
year = {2019},
}
@inproceedings{6884,
abstract = {In two-player games on graphs, the players move a token through a graph to produce a finite or infinite path, which determines the qualitative winner or quantitative payoff of the game. We study bidding games in which the players bid for the right to move the token. Several bidding rules were studied previously. In Richman bidding, in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Poorman bidding is similar except that the winner of the bidding pays the "bank" rather than the other player. Taxman bidding spans the spectrum between Richman and poorman bidding. They are parameterized by a constant tau in [0,1]: portion tau of the winning bid is paid to the other player, and portion 1-tau to the bank. While finite-duration (reachability) taxman games have been studied before, we present, for the first time, results on infinite-duration taxman games. It was previously shown that both Richman and poorman infinite-duration games with qualitative objectives reduce to reachability games, and we show a similar result here. Our most interesting results concern quantitative taxman games, namely mean-payoff games, where poorman and Richman bidding differ significantly. A central quantity in these games is the ratio between the two players' initial budgets. While in poorman mean-payoff games, the optimal payoff of a player depends on the initial ratio, in Richman bidding, the payoff depends only on the structure of the game. In both games the optimal payoffs can be found using (different) probabilistic connections with random-turn games in which in each turn, instead of bidding, a coin is tossed to determine which player moves. While the value with Richman bidding equals the value of a random-turn game with an un-biased coin, with poorman bidding, the bias in the coin is the initial ratio of the budgets. We give a complete classification of mean-payoff taxman games that is based on a probabilistic connection: the value of a taxman bidding game with parameter tau and initial ratio r, equals the value of a random-turn game that uses a coin with bias F(tau, r) = (r+tau * (1-r))/(1+tau). Thus, we show that Richman bidding is the exception; namely, for every tau <1, the value of the game depends on the initial ratio. Our proof technique simplifies and unifies the previous proof techniques for both Richman and poorman bidding. },
author = {Avni, Guy and Henzinger, Thomas A and Zikelic, Dorde},
location = {Aachen, Germany},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Bidding mechanisms in graph games}},
doi = {10.4230/LIPICS.MFCS.2019.11},
volume = {138},
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},
}
@article{6752,
abstract = {Two-player games on graphs are widely studied in formal methods, as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. The following bidding rule was previously defined and called Richman bidding. Both players have separate budgets, which sum up to 1. In each turn, a bidding takes place: Both players submit bids simultaneously, where a bid is legal if it does not exceed the available budget, and the higher bidder pays his bid to the other player and moves the token. The central question studied in bidding games is a necessary and sufficient initial budget for winning the game: a threshold budget in a vertex is a value t ∈ [0, 1] such that if Player 1’s budget exceeds t, he can win the game; and if Player 2’s budget exceeds 1 − t, he can win the game. Threshold budgets were previously shown to exist in every vertex of a reachability game, which have an interesting connection with random-turn games—a sub-class of simple stochastic games in which the player who moves is chosen randomly. We show the existence of threshold budgets for a qualitative class of infinite-duration games, namely parity games, and a quantitative class, namely mean-payoff games. The key component of the proof is a quantitative solution to strongly connected mean-payoff bidding games in which we extend the connection with random-turn games to these games, and construct explicit optimal strategies for both players.},
author = {Avni, Guy and Henzinger, Thomas A and Chonev, Ventsislav K},
issn = {1557735X},
journal = {Journal of the ACM},
number = {4},
publisher = {ACM},
title = {{Infinite-duration bidding games}},
doi = {10.1145/3340295},
volume = {66},
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},
pages = {189},
publisher = {IST Austria},
title = {{Coevolution of transcription factors and their binding sites in sequence space}},
doi = {10.15479/at:ista:th6071},
year = {2019},
}
@misc{9731,
abstract = {OGs with putative pseudogenes by the number of affected genomes in different chlamydial species. Frameshift and nonsense mutations located less than 60 bp upstreamof the gene end or present in a single genome from the corresponding OG were excluded. (CSV 31 kb)},
author = {Sigalova, Olga and Chaplin, Andrei and Bochkareva, Olga and Shelyakin, Pavel and Filaretov, Vsevolod and Akkuratov, Evgeny and Burskaia, Valentina and Gelfand, Mikhail S.},
publisher = {Springer Nature},
title = {{Additional file 11 of Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction}},
doi = {10.6084/m9.figshare.9808772.v1},
year = {2019},
}
@misc{9726,
abstract = {A detailed description of the two stochastic models, table of parameters, supplementary data for Figures 4 and 5, parameter dependence of the results, and an analysis on motors with different force–velocity functions (PDF)},
author = {Ucar, Mehmet C and Lipowsky, Reinhard},
publisher = {American Chemical Society },
title = {{Supplementary information - Collective force generation by molecular motors is determined by strain-induced unbinding}},
doi = {10.1021/acs.nanolett.9b04445.s001},
year = {2019},
}
@misc{9790,
author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor},
publisher = {Public Library of Science},
title = {{A statistical summary of segment libraries and sequencing results}},
doi = {10.1371/journal.pgen.1008079.s011},
year = {2019},
}
@misc{9789,
author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor},
publisher = {Public Library of Science},
title = {{Multiple alignment of His3 orthologues}},
doi = {10.1371/journal.pgen.1008079.s010},
year = {2019},
}
@article{6831,
abstract = {* Understanding the mechanisms causing phenotypic differences between females and males has long fascinated evolutionary biologists. An extensive literature exists on animal sexual dimorphism but less information is known about sex differences in plants, particularly the extent of geographical variation in sexual dimorphism and its life‐cycle dynamics.
* Here, we investigated patterns of genetically based sexual dimorphism in vegetative and reproductive traits of a wind‐pollinated dioecious plant, Rumex hastatulus, across three life‐cycle stages using open‐pollinated families from 30 populations spanning the geographic range and chromosomal variation (XY and XY1Y2) of the species.
* The direction and degree of sexual dimorphism was highly variable among populations and life‐cycle stages. Sex‐specific differences in reproductive function explained a significant amount of temporal change in sexual dimorphism. For several traits, geographical variation in sexual dimorphism was associated with bioclimatic parameters, likely due to the differential responses of the sexes to climate. We found no systematic differences in sexual dimorphism between chromosome races.
* Sex‐specific trait differences in dioecious plants largely result from a balance between sexual and natural selection on resource allocation. Our results indicate that abiotic factors associated with geographical context also play a role in modifying sexual dimorphism during the plant life‐cycle.},
author = {Puixeu Sala, Gemma and Pickup, Melinda and Field, David and Barrett, Spencer C.H.},
issn = {1469-8137},
journal = {New Phytologist},
number = {3},
pages = {1108--1120},
publisher = {Wiley},
title = {{Variation in sexual dimorphism in a wind-pollinated plant: The influence of geographical context and life-cycle dynamics}},
doi = {10.1111/nph.16050},
volume = {224},
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, João Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and Kučka, 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},
}
@article{6022,
abstract = {The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution or more generally about the genetic basis for assortative mating behaviors. Both tight physical linkage and the existence of large-effect preference loci will strengthen genetic associations between behavioral and ecological barriers, promoting the evolution of assortative mating. The warning patterns of Heliconius melpomene and H. cydno are under disruptive selection due to increased predation of nonmimetic hybrids and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. We identify three QTLs that together explain a large proportion (approximately 60%) of the difference in preference behavior observed between the parental species. One of these QTLs is just 1.2 (0-4.8) centiMorgans (cM) from the major color pattern gene optix, and, individually, all three have a large effect on the preference phenotype. Genomic divergence between H. cydno and H. melpomene is high but broadly heterogenous, and admixture is reduced at the preference-optix color pattern locus but not the other preference QTLs. The simple genetic architecture we reveal will facilitate the evolution and maintenance of new species despite ongoing gene flow by coupling behavioral and ecological aspects of reproductive isolation.},
author = {Merrill, Richard M. and Rastas, Pasi and Martin, Simon H. and Melo Hurtado, Maria C and Barker, Sarah and Davey, John and Mcmillan, W. Owen and Jiggins, Chris D.},
journal = {PLoS Biology},
number = {2},
publisher = {Public Library of Science},
title = {{Genetic dissection of assortative mating behavior}},
doi = {10.1371/journal.pbio.2005902},
volume = {17},
year = {2019},
}
@article{6680,
abstract = {This paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation‐selection balance in a large, partially selfing source population under selection involving multiple non‐identical loci. I then use individual‐based simulations to study the eco‐evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long‐term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.},
author = {Sachdeva, Himani},
issn = {1558-5646},
journal = {Evolution},
number = {9},
pages = {1729--1745},
publisher = {Wiley},
title = {{Effect of partial selfing and polygenic selection on establishment in a new habitat}},
doi = {10.1111/evo.13812},
volume = {73},
year = {2019},
}
@misc{9804,
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, João Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and Kučka, 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},
publisher = {Dryad},
title = {{Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice}},
doi = {10.5061/dryad.0q2h6tk},
year = {2019},
}
@misc{9803,
abstract = {Understanding the mechanisms causing phenotypic differences between females and males has long fascinated evolutionary biologists. An extensive literature exists on animal sexual dimorphism but less is known about sex differences in plants, particularly the extent of geographical variation in sexual dimorphism and its life-cycle dynamics. Here, we investigate patterns of genetically-based sexual dimorphism in vegetative and reproductive traits of a wind-pollinated dioecious plant, Rumex hastatulus, across three life-cycle stages using open-pollinated families from 30 populations spanning the geographic range and chromosomal variation (XY and XY1Y2) of the species. The direction and degree of sexual dimorphism was highly variable among populations and life-cycle stages. Sex-specific differences in reproductive function explained a significant amount of temporal change in sexual dimorphism. For several traits, geographical variation in sexual dimorphism was associated with bioclimatic parameters, likely due to the differential responses of the sexes to climate. We found no systematic differences in sexual dimorphism between chromosome races. Sex-specific trait differences in dioecious plants largely result from a balance between sexual and natural selection on resource allocation. Our results indicate that abiotic factors associated with geographical context also play a role in modifying sexual dimorphism during the plant life cycle.},
author = {Puixeu Sala, Gemma and Pickup, Melinda and Field, David and Barrett, Spencer C.H.},
publisher = {Dryad},
title = {{Data from: Variation in sexual dimorphism in a wind-pollinated plant: the influence of geographical context and life-cycle dynamics}},
doi = {10.5061/dryad.n1701c9},
year = {2019},
}
@misc{9802,
abstract = {This paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation-selection balance in a large, partially selfing source population under selection involving multiple non-identical loci. I then use individual-based simulations to study the eco-evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long-term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.},
author = {Sachdeva, Himani},
publisher = {Dryad},
title = {{Data from: Effect of partial selfing and polygenic selection on establishment in a new habitat}},
doi = {10.5061/dryad.8tp0900},
year = {2019},
}
@misc{9801,
author = {Merrill, Richard M. and Rastas, Pasi and Martin, Simon H. and Melo Hurtado, Maria C and Barker, Sarah and Davey, John and Mcmillan, W. Owen and Jiggins, Chris D.},
publisher = {Public Library of Science},
title = {{Raw behavioral data}},
doi = {10.1371/journal.pbio.2005902.s006},
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 = {IST Austria},
title = {{Collective defenses of garden ants against a fungal pathogen}},
doi = {10.15479/AT:ISTA:6435},
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 – 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 ‘Constant curvature model’; 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 – Sequential multi-step process – functions in the cell. Finally we also looked at one of the important physiological stimuli modulating the process – 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},
pages = {138},
publisher = {IST Austria},
title = {{Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants }},
doi = {10.15479/at:ista:th1075},
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 = {IST 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 some—but not all—cancer 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, Jörg 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},
}
@article{6877,
author = {Kopf, Aglaja and Sixt, Michael K},
issn = {10974172},
journal = {Cell},
number = {1},
pages = {51--53},
title = {{The neural crest pitches in to remove apoptotic debris}},
doi = {10.1016/j.cell.2019.08.047},
volume = {179},
year = {2019},
}
@phdthesis{6849,
abstract = {Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. },
author = {Rangel Guerrero, Dámaris K},
isbn = {9783990780039},
issn = {2663-337X},
pages = {97},
publisher = {IST Austria},
title = {{The role of CCK-interneurons in regulating hippocampal network dynamics}},
doi = {10.15479/AT:ISTA:6849},
year = {2019},
}
@phdthesis{6546,
abstract = {Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation.
Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify
a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate
a program governing migration steps important for both development and cancer metastasis.
},
author = {Valosková, Katarina},
issn = {2663-337X},
pages = {141},
publisher = {IST Austria},
title = {{The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration}},
doi = {10.15479/AT:ISTA:6546},
year = {2019},
}
@phdthesis{6947,
abstract = {Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues.},
author = {Assen, Frank P},
issn = {2663-337X},
pages = {142},
publisher = {IST Austria},
title = {{Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking}},
doi = {10.15479/AT:ISTA:6947},
year = {2019},
}
@phdthesis{6371,
abstract = {Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation.
i) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model.
ii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites.
iii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background.
iv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter.
We demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation.
},
author = {Igler, Claudia},
issn = {2663-337X},
keywords = {gene regulation, biophysics, transcription factor binding, bacteria},
pages = {152},
publisher = {IST Austria},
title = {{On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation}},
doi = {10.15479/AT:ISTA:6371},
year = {2019},
}