@article{6454, abstract = {Adult neural stem cells and multiciliated ependymalcells are glial cells essential for neurological func-tions. Together, they make up the adult neurogenicniche. Using both high-throughput clonal analysisand single-cell resolution of progenitor division pat-terns and fate, we show that these two componentsof the neurogenic niche are lineally related: adult neu-ral stem cells are sister cells to ependymal cells,whereas most ependymal cells arise from the termi-nal symmetric divisions of the lineage. Unexpectedly,we found that the antagonist regulators of DNA repli-cation, GemC1 and Geminin, can tune the proportionof neural stem cells and ependymal cells. Our find-ings reveal the controlled dynamic of the neurogenicniche ontogeny and identify the Geminin familymembers as key regulators of the initial pool of adultneural stem cells.}, author = {Ortiz-Álvarez, G and Daclin, M and Shihavuddin, A and Lansade, P and Fortoul, A and Faucourt, M and Clavreul, S and Lalioti, ME and Taraviras, S and Hippenmeyer, Simon and Livet, J and Meunier, A and Genovesio, A and Spassky, N}, issn = {1097-4199}, journal = {Neuron}, number = {1}, pages = {159--172.e7}, publisher = {Elsevier}, title = {{Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members}}, doi = {10.1016/j.neuron.2019.01.051}, volume = {102}, year = {2019}, } @article{6979, author = {Kopf, Aglaja and Sixt, Michael K}, issn = {1879-0445}, journal = {Current Biology}, number = {20}, pages = {R1091--R1093}, publisher = {Cell Press}, title = {{Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal}}, doi = {10.1016/j.cub.2019.08.068}, volume = {29}, year = {2019}, } @article{6980, abstract = {Tissue morphogenesis in multicellular organisms is brought about by spatiotemporal coordination of mechanical and chemical signals. Extensive work on how mechanical forces together with the well‐established morphogen signalling pathways can actively shape living tissues has revealed evolutionary conserved mechanochemical features of embryonic development. More recently, attention has been drawn to the description of tissue material properties and how they can influence certain morphogenetic processes. Interestingly, besides the role of tissue material properties in determining how much tissues deform in response to force application, there is increasing theoretical and experimental evidence, suggesting that tissue material properties can abruptly and drastically change in development. These changes resemble phase transitions, pointing at the intriguing possibility that important morphogenetic processes in development, such as symmetry breaking and self‐organization, might be mediated by tissue phase transitions. In this review, we summarize recent findings on the regulation and role of tissue material properties in the context of the developing embryo. We posit that abrupt changes of tissue rheological properties may have important implications in maintaining the balance between robustness and adaptability during embryonic development.}, author = {Petridou, Nicoletta and Heisenberg, Carl-Philipp J}, issn = {1460-2075}, journal = {The EMBO Journal}, number = {20}, publisher = {EMBO}, title = {{Tissue rheology in embryonic organization}}, doi = {10.15252/embj.2019102497}, volume = {38}, year = {2019}, } @article{6554, abstract = {Due to the importance of zero-shot learning, i.e. classifying images where there is a lack of labeled training data, the number of proposed approaches has recently increased steadily. We argue that it is time to take a step back and to analyze the status quo of the area. The purpose of this paper is three-fold. First, given the fact that there is no agreed upon zero-shot learning benchmark, we first define a new benchmark by unifying both the evaluation protocols and data splits of publicly available datasets used for this task. This is an important contribution as published results are often not comparable and sometimes even flawed due to, e.g. pre-training on zero-shot test classes. Moreover, we propose a new zero-shot learning dataset, the Animals with Attributes 2 (AWA2) dataset which we make publicly available both in terms of image features and the images themselves. Second, we compare and analyze a significant number of the state-of-the-art methods in depth, both in the classic zero-shot setting but also in the more realistic generalized zero-shot setting. Finally, we discuss in detail the limitations of the current status of the area which can be taken as a basis for advancing it.}, author = {Xian, Yongqin and Lampert, Christoph and Schiele, Bernt and Akata, Zeynep}, issn = {1939-3539}, journal = {IEEE Transactions on Pattern Analysis and Machine Intelligence}, number = {9}, pages = {2251 -- 2265}, publisher = {Institute of Electrical and Electronics Engineers (IEEE)}, title = {{Zero-shot learning - A comprehensive evaluation of the good, the bad and the ugly}}, doi = {10.1109/tpami.2018.2857768}, volume = {41}, year = {2019}, } @article{6259, abstract = {The plant hormone auxin has crucial roles in almost all aspects of plant growth and development. Concentrations of auxin vary across different tissues, mediating distinct developmental outcomes and contributing to the functional diversity of auxin. However, the mechanisms that underlie these activities are poorly understood. Here we identify an auxin signalling mechanism, which acts in parallel to the canonical auxin pathway based on the transport inhibitor response1 (TIR1) and other auxin receptor F-box (AFB) family proteins (TIR1/AFB receptors)1,2, that translates levels of cellular auxin to mediate differential growth during apical-hook development. This signalling mechanism operates at the concave side of the apical hook, and involves auxin-mediated C-terminal cleavage of transmembrane kinase 1 (TMK1). The cytosolic and nucleus-translocated C terminus of TMK1 specifically interacts with and phosphorylates two non-canonical transcriptional repressors of the auxin or indole-3-acetic acid (Aux/IAA) family (IAA32 and IAA34), thereby regulating ARF transcription factors. In contrast to the degradation of Aux/IAA transcriptional repressors in the canonical pathway, the newly identified mechanism stabilizes the non-canonical IAA32 and IAA34 transcriptional repressors to regulate gene expression and ultimately inhibit growth. The auxin–TMK1 signalling pathway originates at the cell surface, is triggered by high levels of auxin and shares a partially overlapping set of transcription factors with the TIR1/AFB signalling pathway. This allows distinct interpretations of different concentrations of cellular auxin, and thus enables this versatile signalling molecule to mediate complex developmental outcomes.}, author = {Cao, Min and Chen, Rong and Li, Pan and Yu, Yongqiang and Zheng, Rui and Ge, Danfeng and Zheng, Wei and Wang, Xuhui and Gu, Yangtao and Gelová, Zuzana and Friml, Jiří and Zhang, Heng and Liu, Renyi and He, Jun and Xu, Tongda}, issn = {1476-4687}, journal = {Nature}, pages = {240--243}, publisher = {Springer Nature}, title = {{TMK1-mediated auxin signalling regulates differential growth of the apical hook}}, doi = {10.1038/s41586-019-1069-7}, volume = {568}, year = {2019}, } @inbook{6987, abstract = {Cells are arranged into species-specific patterns during early embryogenesis. Such cell division patterns are important since they often reflect the distribution of localized cortical factors from eggs/fertilized eggs to specific cells as well as the emergence of organismal form. However, it has proven difficult to reveal the mechanisms that underlie the emergence of cell positioning patterns that underlie embryonic shape, likely because a systems-level approach is required that integrates cell biological, genetic, developmental, and mechanical parameters. The choice of organism to address such questions is also important. Because ascidians display the most extreme form of invariant cleavage pattern among the metazoans, we have been analyzing the cell biological mechanisms that underpin three aspects of cell division (unequal cell division (UCD), oriented cell division (OCD), and asynchronous cell cycles) which affect the overall shape of the blastula-stage ascidian embryo composed of 64 cells. In ascidians, UCD creates two small cells at the 16-cell stage that in turn undergo two further successive rounds of UCD. Starting at the 16-cell stage, the cell cycle becomes asynchronous, whereby the vegetal half divides before the animal half, thus creating 24-, 32-, 44-, and then 64-cell stages. Perturbing either UCD or the alternate cell division rhythm perturbs cell position. We propose that dynamic cell shape changes propagate throughout the embryo via cell-cell contacts to create the ascidian-specific invariant cleavage pattern.}, author = {McDougall, Alex and Chenevert, Janet and Godard, Benoit G and Dumollard, Remi}, booktitle = {Evo-Devo: Non-model species in cell and developmental biology}, editor = {Tworzydlo, Waclaw and Bilinski, Szczepan M.}, isbn = {9783030234584}, issn = {1861-0412}, pages = {127--154}, publisher = {Springer Nature}, title = {{Emergence of embryo shape during cleavage divisions}}, doi = {10.1007/978-3-030-23459-1_6}, volume = {68}, year = {2019}, } @article{6762, abstract = {We present and study novel optimal control problems motivated by the search for photovoltaic materials with high power-conversion efficiency. The material must perform the first step: convert light (photons) into electronic excitations. We formulate various desirable properties of the excitations as mathematical control goals at the Kohn-Sham-DFT level of theory, with the control being given by the nuclear charge distribution. We prove that nuclear distributions exist which give rise to optimal HOMO-LUMO excitations, and present illustrative numerical simulations for 1D finite nanocrystals. We observe pronounced goal-dependent features such as large electron-hole separation, and a hierarchy of length scales: internal HOMO and LUMO wavelengths < atomic spacings < (irregular) fluctuations of the doping profiles < system size.}, author = {Friesecke, Gero and Kniely, Michael}, issn = {15403467}, journal = {Multiscale Modeling and Simulation}, number = {3}, pages = {926--947}, publisher = {SIAM}, title = {{New optimal control problems in density functional theory motivated by photovoltaics}}, doi = {10.1137/18M1207272}, volume = {17}, 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}, } @article{7100, abstract = {We present microscopic derivations of the defocusing two-dimensional cubic nonlinear Schrödinger equation and the Gross–Pitaevskii equation starting froman interacting N-particle system of bosons. We consider the interaction potential to be given either by Wβ(x)=N−1+2βW(Nβx), for any β>0, or to be given by VN(x)=e2NV(eNx), for some spherical symmetric, nonnegative and compactly supported W,V∈L∞(R2,R). In both cases we prove the convergence of the reduced density corresponding to the exact time evolution to the projector onto the solution of the corresponding nonlinear Schrödinger equation in trace norm. For the latter potential VN we show that it is crucial to take the microscopic structure of the condensate into account in order to obtain the correct dynamics.}, author = {Jeblick, Maximilian and Leopold, Nikolai K and Pickl, Peter}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {1--69}, publisher = {Springer Nature}, title = {{Derivation of the time dependent Gross–Pitaevskii equation in two dimensions}}, doi = {10.1007/s00220-019-03599-x}, volume = {372}, year = {2019}, } @article{7106, abstract = {PIN-FORMED (PIN) transporters mediate directional, intercellular movement of the phytohormone auxin in land plants. To elucidate the evolutionary origins of this developmentally crucial mechanism, we analysed the single PIN homologue of a simple green alga Klebsormidium flaccidum. KfPIN functions as a plasma membrane-localized auxin exporter in land plants and heterologous models. While its role in algae remains unclear, PIN-driven auxin export is probably an ancient and conserved trait within streptophytes.}, author = {Skokan, Roman and Medvecká, Eva and Viaene, Tom and Vosolsobě, Stanislav and Zwiewka, Marta and Müller, Karel and Skůpa, Petr and Karady, Michal and Zhang, Yuzhou and Janacek, Dorina P. and Hammes, Ulrich Z. and Ljung, Karin and Nodzyński, Tomasz and Petrášek, Jan and Friml, Jiří}, issn = {2055-0278}, journal = {Nature Plants}, number = {11}, pages = {1114--1119}, publisher = {Springer Nature}, title = {{PIN-driven auxin transport emerged early in streptophyte evolution}}, doi = {10.1038/s41477-019-0542-5}, volume = {5}, year = {2019}, } @article{7105, abstract = {Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.}, author = {Yolland, Lawrence and Burki, Mubarik and Marcotti, Stefania and Luchici, Andrei and Kenny, Fiona N. and Davis, John Robert and Serna-Morales, Eduardo and Müller, Jan and Sixt, Michael K and Davidson, Andrew and Wood, Will and Schumacher, Linus J. and Endres, Robert G. and Miodownik, Mark and Stramer, Brian M.}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {11}, pages = {1370--1381}, publisher = {Springer Nature}, title = {{Persistent and polarized global actin flow is essential for directionality during cell migration}}, doi = {10.1038/s41556-019-0411-5}, volume = {21}, year = {2019}, } @article{7109, abstract = {We show how to construct temporal testers for the logic MITL, a prominent linear-time logic for real-time systems. A temporal tester is a transducer that inputs a signal holding the Boolean value of atomic propositions and outputs the truth value of a formula along time. Here we consider testers over continuous-time Boolean signals that use clock variables to enforce duration constraints, as in timed automata. We first rewrite the MITL formula into a “simple” formula using a limited set of temporal modalities. We then build testers for these specific modalities and show how to compose testers for simple formulae into complex ones. Temporal testers can be turned into acceptors, yielding a compositional translation from MITL to timed automata. This construction is much simpler than previously known and remains asymptotically optimal. It supports both past and future operators and can easily be extended.}, author = {Ferrere, Thomas and Maler, Oded and Ničković, Dejan and Pnueli, Amir}, issn = {0004-5411}, journal = {Journal of the ACM}, number = {3}, publisher = {ACM}, title = {{From real-time logic to timed automata}}, doi = {10.1145/3286976}, volume = {66}, year = {2019}, } @article{7108, abstract = {We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes. Another simple corollary of our result is that it is NP-hard to decide whether a given poset is CL-shellable.}, author = {Goaoc, Xavier and Patak, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli}, issn = {0004-5411}, journal = {Journal of the ACM}, number = {3}, publisher = {ACM}, title = {{Shellability is NP-complete}}, doi = {10.1145/3314024}, volume = {66}, year = {2019}, } @inproceedings{7147, abstract = {The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets. In this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest. The behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions.}, author = {Guet, Calin C and Henzinger, Thomas A and Igler, Claudia and Petrov, Tatjana and Sezgin, Ali}, booktitle = {17th International Conference on Computational Methods in Systems Biology}, isbn = {9783030313036}, issn = {1611-3349}, location = {Trieste, Italy}, pages = {155--187}, publisher = {Springer Nature}, title = {{Transient memory in gene regulation}}, doi = {10.1007/978-3-030-31304-3_9}, volume = {11773}, year = {2019}, } @inproceedings{7136, abstract = {It is well established that the notion of min-entropy fails to satisfy the \emph{chain rule} of the form H(X,Y)=H(X|Y)+H(Y), known for Shannon Entropy. Such a property would help to analyze how min-entropy is split among smaller blocks. Problems of this kind arise for example when constructing extractors and dispersers. We show that any sequence of variables exhibits a very strong strong block-source structure (conditional distributions of blocks are nearly flat) when we \emph{spoil few correlated bits}. This implies, conditioned on the spoiled bits, that \emph{splitting-recombination properties} hold. In particular, we have many nice properties that min-entropy doesn't obey in general, for example strong chain rules, "information can't hurt" inequalities, equivalences of average and worst-case conditional entropy definitions and others. Quantitatively, for any sequence X1,…,Xt of random variables over an alphabet X we prove that, when conditioned on m=t⋅O(loglog|X|+loglog(1/ϵ)+logt) bits of auxiliary information, all conditional distributions of the form Xi|X