@article{12190, abstract = {Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.}, author = {Lawrence, Emma J. and Gao, Hongbo and Tock, Andrew J. and Lambing, Christophe and Blackwell, Alexander R. and Feng, Xiaoqi and Henderson, Ian R.}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {16}, pages = {2676--2686.e3}, publisher = {Elsevier}, title = {{Natural variation in TBP-ASSOCIATED FACTOR 4b controls meiotic crossover and germline transcription in Arabidopsis}}, doi = {10.1016/j.cub.2019.06.084}, volume = {29}, year = {2019}, } @article{12192, abstract = {Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.}, author = {He, Shengbo and Vickers, Martin and Zhang, Jingyi and Feng, Xiaoqi}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation}}, doi = {10.7554/elife.42530}, volume = {8}, year = {2019}, } @article{27, abstract = {The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved.}, author = {Amberg, Nicole and Laukoter, Susanne and Hippenmeyer, Simon}, journal = {Journal of Neurochemistry}, number = {1}, pages = {12--26}, publisher = {Wiley}, title = {{Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex}}, doi = {10.1111/jnc.14601}, volume = {149}, year = {2019}, } @article{301, abstract = {A representation formula for solutions of stochastic partial differential equations with Dirichlet boundary conditions is proved. The scope of our setting is wide enough to cover the general situation when the backward characteristics that appear in the usual formulation are not even defined in the Itô sense.}, author = {Gerencser, Mate and Gyöngy, István}, journal = {Stochastic Processes and their Applications}, number = {3}, pages = {995--1012}, publisher = {Elsevier}, title = {{A Feynman–Kac formula for stochastic Dirichlet problems}}, doi = {10.1016/j.spa.2018.04.003}, volume = {129}, year = {2019}, } @article{138, abstract = {Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche.}, author = {Nikolic, Nela}, journal = {Current Genetics}, number = {1}, pages = {133--138}, publisher = {Springer}, title = {{Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system}}, doi = {10.1007/s00294-018-0879-8}, volume = {65}, year = {2019}, } @inproceedings{14184, abstract = {Learning disentangled representations is considered a cornerstone problem in representation learning. Recently, Locatello et al. (2019) demonstrated that unsupervised disentanglement learning without inductive biases is theoretically impossible and that existing inductive biases and unsupervised methods do not allow to consistently learn disentangled representations. However, in many practical settings, one might have access to a limited amount of supervision, for example through manual labeling of (some) factors of variation in a few training examples. In this paper, we investigate the impact of such supervision on state-of-the-art disentanglement methods and perform a large scale study, training over 52000 models under well-defined and reproducible experimental conditions. We observe that a small number of labeled examples (0.01--0.5\% of the data set), with potentially imprecise and incomplete labels, is sufficient to perform model selection on state-of-the-art unsupervised models. Further, we investigate the benefit of incorporating supervision into the training process. Overall, we empirically validate that with little and imprecise supervision it is possible to reliably learn disentangled representations.}, author = {Locatello, Francesco and Tschannen, Michael and Bauer, Stefan and Rätsch, Gunnar and Schölkopf, Bernhard and Bachem, Olivier}, booktitle = {8th International Conference on Learning Representations}, location = {Virtual}, title = {{Disentangling factors of variation using few labels}}, year = {2019}, } @inproceedings{14189, abstract = {We consider the problem of recovering a common latent source with independent components from multiple views. This applies to settings in which a variable is measured with multiple experimental modalities, and where the goal is to synthesize the disparate measurements into a single unified representation. We consider the case that the observed views are a nonlinear mixing of component-wise corruptions of the sources. When the views are considered separately, this reduces to nonlinear Independent Component Analysis (ICA) for which it is provably impossible to undo the mixing. We present novel identifiability proofs that this is possible when the multiple views are considered jointly, showing that the mixing can theoretically be undone using function approximators such as deep neural networks. In contrast to known identifiability results for nonlinear ICA, we prove that independent latent sources with arbitrary mixing can be recovered as long as multiple, sufficiently different noisy views are available.}, author = {Gresele, Luigi and Rubenstein, Paul K. and Mehrjou, Arash and Locatello, Francesco and Schölkopf, Bernhard}, booktitle = {Proceedings of the 35th Conference on Uncertainty in Artificial Intelligence}, location = {Tel Aviv, Israel}, pages = {217--227}, publisher = {ML Research Press}, title = {{The incomplete Rosetta Stone problem: Identifiability results for multi-view nonlinear ICA}}, volume = {115}, year = {2019}, } @inproceedings{14190, abstract = {Learning meaningful and compact representations with disentangled semantic aspects is considered to be of key importance in representation learning. Since real-world data is notoriously costly to collect, many recent state-of-the-art disentanglement models have heavily relied on synthetic toy data-sets. In this paper, we propose a novel data-set which consists of over one million images of physical 3D objects with seven factors of variation, such as object color, shape, size and position. In order to be able to control all the factors of variation precisely, we built an experimental platform where the objects are being moved by a robotic arm. In addition, we provide two more datasets which consist of simulations of the experimental setup. These datasets provide for the first time the possibility to systematically investigate how well different disentanglement methods perform on real data in comparison to simulation, and how simulated data can be leveraged to build better representations of the real world. We provide a first experimental study of these questions and our results indicate that learned models transfer poorly, but that model and hyperparameter selection is an effective means of transferring information to the real world.}, author = {Gondal, Muhammad Waleed and Wüthrich, Manuel and Miladinović, Đorđe and Locatello, Francesco and Breidt, Martin and Volchkov, Valentin and Akpo, Joel and Bachem, Olivier and Schölkopf, Bernhard and Bauer, Stefan}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713807933}, location = {Vancouver, Canada}, title = {{On the transfer of inductive bias from simulation to the real world: a new disentanglement dataset}}, volume = {32}, year = {2019}, } @inproceedings{14191, abstract = {A broad class of convex optimization problems can be formulated as a semidefinite program (SDP), minimization of a convex function over the positive-semidefinite cone subject to some affine constraints. The majority of classical SDP solvers are designed for the deterministic setting where problem data is readily available. In this setting, generalized conditional gradient methods (aka Frank-Wolfe-type methods) provide scalable solutions by leveraging the so-called linear minimization oracle instead of the projection onto the semidefinite cone. Most problems in machine learning and modern engineering applications, however, contain some degree of stochasticity. In this work, we propose the first conditional-gradient-type method for solving stochastic optimization problems under affine constraints. Our method guarantees O(k−1/3) convergence rate in expectation on the objective residual and O(k−5/12) on the feasibility gap.}, author = {Locatello, Francesco and Yurtsever, Alp and Fercoq, Olivier and Cevher, Volkan}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713807933}, location = {Vancouver, Canada}, pages = {14291–14301}, title = {{Stochastic Frank-Wolfe for composite convex minimization}}, volume = {32}, year = {2019}, } @inproceedings{14193, abstract = {A disentangled representation encodes information about the salient factors of variation in the data independently. Although it is often argued that this representational format is useful in learning to solve many real-world down-stream tasks, there is little empirical evidence that supports this claim. In this paper, we conduct a large-scale study that investigates whether disentangled representations are more suitable for abstract reasoning tasks. Using two new tasks similar to Raven's Progressive Matrices, we evaluate the usefulness of the representations learned by 360 state-of-the-art unsupervised disentanglement models. Based on these representations, we train 3600 abstract reasoning models and observe that disentangled representations do in fact lead to better down-stream performance. In particular, they enable quicker learning using fewer samples.}, author = {Steenkiste, Sjoerd van and Locatello, Francesco and Schmidhuber, Jürgen and Bachem, Olivier}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713807933}, location = {Vancouver, Canada}, title = {{Are disentangled representations helpful for abstract visual reasoning?}}, volume = {32}, year = {2019}, } @inproceedings{14197, abstract = {Recently there has been a significant interest in learning disentangled representations, as they promise increased interpretability, generalization to unseen scenarios and faster learning on downstream tasks. In this paper, we investigate the usefulness of different notions of disentanglement for improving the fairness of downstream prediction tasks based on representations. We consider the setting where the goal is to predict a target variable based on the learned representation of high-dimensional observations (such as images) that depend on both the target variable and an \emph{unobserved} sensitive variable. We show that in this setting both the optimal and empirical predictions can be unfair, even if the target variable and the sensitive variable are independent. Analyzing the representations of more than \num{12600} trained state-of-the-art disentangled models, we observe that several disentanglement scores are consistently correlated with increased fairness, suggesting that disentanglement may be a useful property to encourage fairness when sensitive variables are not observed.}, author = {Locatello, Francesco and Abbati, Gabriele and Rainforth, Tom and Bauer, Stefan and Schölkopf, Bernhard and Bachem, Olivier}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713807933}, location = {Vancouver, Canada}, pages = {14611–14624}, title = {{On the fairness of disentangled representations}}, volume = {32}, year = {2019}, } @inproceedings{14200, abstract = {The key idea behind the unsupervised learning of disentangled representations is that real-world data is generated by a few explanatory factors of variation which can be recovered by unsupervised learning algorithms. In this paper, we provide a sober look at recent progress in the field and challenge some common assumptions. We first theoretically show that the unsupervised learning of disentangled representations is fundamentally impossible without inductive biases on both the models and the data. Then, we train more than 12000 models covering most prominent methods and evaluation metrics in a reproducible large-scale experimental study on seven different data sets. We observe that while the different methods successfully enforce properties ``encouraged'' by the corresponding losses, well-disentangled models seemingly cannot be identified without supervision. Furthermore, increased disentanglement does not seem to lead to a decreased sample complexity of learning for downstream tasks. Our results suggest that future work on disentanglement learning should be explicit about the role of inductive biases and (implicit) supervision, investigate concrete benefits of enforcing disentanglement of the learned representations, and consider a reproducible experimental setup covering several data sets.}, author = {Locatello, Francesco and Bauer, Stefan and Lucic, Mario and Rätsch, Gunnar and Gelly, Sylvain and Schölkopf, Bernhard and Bachem, Olivier}, booktitle = {Proceedings of the 36th International Conference on Machine Learning}, location = {Long Beach, CA, United States}, pages = {4114--4124}, publisher = {ML Research Press}, title = {{Challenging common assumptions in the unsupervised learning of disentangled representations}}, volume = {97}, year = {2019}, } @inproceedings{12901, author = {Schlögl, Alois and Kiss, Janos and Elefante, Stefano}, booktitle = {AHPC19 - Austrian HPC Meeting 2019 }, location = {Grundlsee, Austria}, pages = {25}, publisher = {Institut für Mathematik und wissenschaftliches Rechnen der Universität Graz}, title = {{Is Debian suitable for running an HPC Cluster?}}, year = {2019}, } @misc{13067, abstract = {Genetic incompatibilities contribute to reproductive isolation between many diverging populations, but it is still unclear to what extent they play a role if divergence happens with gene flow. In contact zones between the "Crab" and "Wave" ecotypes of the snail Littorina saxatilis divergent selection forms strong barriers to gene flow, while the role of postzygotic barriers due to selection against hybrids remains unclear. High embryo abortion rates in this species could indicate the presence of such barriers. Postzygotic barriers might include genetic incompatibilities (e.g. Dobzhansky-Muller incompatibilities) but also maladaptation, both expected to be most pronounced in contact zones. In addition, embryo abortion might reflect physiological stress on females and embryos independent of any genetic stress. We examined all embryos of >500 females sampled outside and inside contact zones of three populations in Sweden. Females' clutch size ranged from 0 to 1011 embryos (mean 130±123) and abortion rates varied between 0 and100% (mean 12%). We described female genotypes by using a hybrid index based on hundreds of SNPs differentiated between ecotypes with which we characterised female genotypes. We also calculated female SNP heterozygosity and inversion karyotype. Clutch size did not vary with female hybrid index and abortion rates were only weakly related to hybrid index in two sites but not at all in a third site. No additional variation in abortion rate was explained by female SNP heterozygosity, but increased female inversion heterozygosity added slightly to increased abortion. Our results show only weak and probably biologically insignificant postzygotic barriers contributing to ecotype divergence and the high and variable abortion rates were marginally, if at all, explained by hybrid index of females.}, author = {Johannesson, Kerstin and Zagrodzka, Zuzanna and Faria, Rui and Westram, Anja M and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Is embryo abortion a postzygotic barrier to gene flow between Littorina ecotypes?}}, doi = {10.5061/DRYAD.TB2RBNZWK}, year = {2019}, } @inbook{19987, abstract = {These lecture notes are based on Yang’s talk at the MATRIX program Geometric R-Matrices: from Geometry to Probability, at the University of Melbourne, Dec. 18–22, 2017, and Zhao’s talk at Perimeter Institute for Theoretical Physics in January 2018. We give an introductory survey of the results in Yang and Zhao (Quiver varieties and elliptic quantum groups, 2017. arxiv1708.01418). We discuss a sheafified elliptic quantum group associated to any symmetric Kac-Moody Lie algebra. The sheafification is obtained by applying the equivariant elliptic cohomological theory to the moduli space of representations of a preprojective algebra. By construction, the elliptic quantum group naturally acts on the equivariant elliptic cohomology of Nakajima quiver varieties. As an application, we obtain a relation between the sheafified elliptic quantum group and the global affine Grassmannian over an elliptic curve.}, author = {Yang, Yaping and Zhao, Gufang}, booktitle = {2017 MATRIX Annals}, isbn = {9783030041601}, issn = {2523-305X}, pages = {675--691}, publisher = {Springer International Publishing}, title = {{How to Sheafify an Elliptic Quantum Group}}, doi = {10.1007/978-3-030-04161-8_54}, volume = {2}, year = {2019}, } @inbook{19988, abstract = {Quantitative studies of cell metabolism are often based on large chemical reaction network models. A steady-state approach is suited to analyze phenomena on the timescale of cell growth and circumvents the problem of incomplete experimental knowledge on kinetic laws and parameters, but it should be supported by a correct implementation of thermodynamic constraints. In this chapter, we review the latter aspect, highlighting its computational challenges and physical insights. The simple introduction of Gibbs inequalities avoids the presence of unfeasible loops allowing for correct timescale analysis, but leads to possibly non-convex feasible flux spaces whose exploration needs efficient algorithms. We briefly review the implementation of thermodynamics through variational principles in constraint-based models of metabolic networks.}, author = {De Martino, A and De Martino, Daniele and Marinari, E}, booktitle = {Chemical Kinetics}, isbn = {9781786347008}, pages = {455--471}, publisher = {World Scientific Publishing}, title = {{The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges}}, doi = {10.1142/9781786347015_0018}, year = {2019}, } @inbook{19989, abstract = {Neurone empfangen Eingangssignale, konvertieren diese in Aktionspotenziale und generieren schließlich Ausgangssignale auf ihren Zielzellen. Dabei sind die zu überwindenden räumlichen Distanzen oft groß. Daher ist entscheidend, dass elektrische Signale in Nervenzellen schnell von einem zum anderen Ort geleitet werden können. Diese wichtige Aufgabe erfüllt das Axon, der „Ausgangsfortsatz“ der Nervenzelle. Für die schnelle Leitung des Aktionspotenzials sind sowohl die passiven Eigenschaften des axonalen Kabels als auch die aktiven Eigenschaften der Zellmembran von entscheidender Bedeutung. Die Evolution bedient sich zweier Tricks, um die Leitungsgeschwindigkeit des Aktionspotenzials zu maximieren. Der eine Trick ist die Zunahme des Axondurchmessers. Der andere Trick ist die Ausbildung von Markscheiden. Dies führt bei nahezu gleichem Platzbedarf zu einer Zunahme der Leistungsgeschwindigkeit um fast zwei Größenordnungen. Die Aktionspotenzialleitung an myelinisierten Axonen erfolgt „saltatorisch“.}, author = {Jonas, Peter M}, booktitle = {Physiologie des Menschen}, isbn = {9783662564677}, issn = {2512-5214}, pages = {72--82}, publisher = {Springer Nature}, title = {{Aktionspotenzial: Fortleitung im Axon}}, doi = {10.1007/978-3-662-56468-4_7}, year = {2019}, } @article{196, abstract = {The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. }, author = {Lang, Moritz and Shkolnikov, Mikhail}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, pages = {2821--2830}, publisher = {National Academy of Sciences}, title = {{Harmonic dynamics of the Abelian sandpile}}, doi = {10.1073/pnas.1812015116}, volume = {116}, year = {2019}, } @article{151, abstract = {We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function f∈Lp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for f∈L∞, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide.}, author = {Fischer, Julian L and Kneuss, Olivier}, journal = {Journal of Differential Equations}, number = {1}, pages = {257 -- 311}, publisher = {Elsevier}, title = {{Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity}}, doi = {10.1016/j.jde.2018.07.045}, volume = {266}, year = {2019}, } @article{10874, abstract = {In this article we prove an analogue of a theorem of Lachaud, Ritzenthaler, and Zykin, which allows us to connect invariants of binary octics to Siegel modular forms of genus 3. We use this connection to show that certain modular functions, when restricted to the hyperelliptic locus, assume values whose denominators are products of powers of primes of bad reduction for the associated hyperelliptic curves. We illustrate our theorem with explicit computations. This work is motivated by the study of the values of these modular functions at CM points of the Siegel upper half-space, which, if their denominators are known, can be used to effectively compute models of (hyperelliptic, in our case) curves with CM.}, author = {Ionica, Sorina and Kılıçer, Pınar and Lauter, Kristin and Lorenzo García, Elisa and Manzateanu, Maria-Adelina and Massierer, Maike and Vincent, Christelle}, issn = {2363-9555}, journal = {Research in Number Theory}, keywords = {Algebra and Number Theory}, publisher = {Springer Nature}, title = {{Modular invariants for genus 3 hyperelliptic curves}}, doi = {10.1007/s40993-018-0146-6}, volume = {5}, year = {2019}, }