@article{6920, author = {Artner, Christina and Benková, Eva}, issn = {1674-2052}, journal = {Molecular Plant}, number = {10}, pages = {1312--1314}, publisher = {Cell Press}, title = {{Ethylene and cytokinin - partners in root growth regulation}}, doi = {10.1016/j.molp.2019.09.003}, volume = {12}, 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{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}, } @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{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}, } @article{6936, abstract = {A key challenge for community ecology is to understand to what extent observational data can be used to infer the underlying community assembly processes. As different processes can lead to similar or even identical patterns, statistical analyses of non‐manipulative observational data never yield undisputable causal inference on the underlying processes. Still, most empirical studies in community ecology are based on observational data, and hence understanding under which circumstances such data can shed light on assembly processes is a central concern for community ecologists. We simulated a spatial agent‐based model that generates variation in metacommunity dynamics across multiple axes, including the four classic metacommunity paradigms as special cases. We further simulated a virtual ecologist who analysed snapshot data sampled from the simulations using eighteen output metrics derived from beta‐diversity and habitat variation indices, variation partitioning and joint species distribution modelling. Our results indicated two main axes of variation in the output metrics. The first axis of variation described whether the landscape has patchy or continuous variation, and thus was essentially independent of the properties of the species community. The second axis of variation related to the level of predictability of the metacommunity. The most predictable communities were niche‐based metacommunities inhabiting static landscapes with marked environmental heterogeneity, such as metacommunities following the species sorting paradigm or the mass effects paradigm. The most unpredictable communities were neutral‐based metacommunities inhabiting dynamics landscapes with little spatial heterogeneity, such as metacommunities following the neutral or patch sorting paradigms. The output metrics from joint species distribution modelling yielded generally the highest resolution to disentangle among the simulated scenarios. Yet, the different types of statistical approaches utilized in this study carried complementary information, and thus our results suggest that the most comprehensive evaluation of metacommunity structure can be obtained by combining them. }, author = {Ovaskainen, Otso and Rybicki, Joel and Abrego, Nerea}, issn = {1600-0587}, journal = {Ecography}, number = {11}, pages = {1877--1886}, publisher = {Wiley}, title = {{What can observational data reveal about metacommunity processes?}}, doi = {10.1111/ecog.04444}, volume = {42}, year = {2019}, } @article{6857, abstract = {Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.}, author = {Giese, B and Friess, J L and Schetelig, M F and Barton, Nicholas H and Messer, Philip and Debarre, Florence and Meimberg, H and Windbichler, N and Boete, C}, issn = {1521-1878}, journal = {BioEssays}, number = {11}, publisher = {Wiley}, title = {{Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna}}, doi = {10.1002/bies.201900151}, volume = {41}, year = {2019}, } @inbook{6890, abstract = {Describing the protein interactions that form pleomorphic and asymmetric viruses represents a considerable challenge to most structural biology techniques, including X-ray crystallography and single particle cryo-electron microscopy. Obtaining a detailed understanding of these interactions is nevertheless important, considering the number of relevant human pathogens that do not follow strict icosahedral or helical symmetry. Cryo-electron tomography and subtomogram averaging methods provide structural insights into complex biological environments and are well suited to go beyond structures of perfectly symmetric viruses. This chapter discusses recent developments showing that cryo-ET and subtomogram averaging can provide high-resolution insights into hitherto unknown structural features of pleomorphic and asymmetric virus particles. It also describes how these methods have significantly added to our understanding of retrovirus capsid assemblies in immature and mature viruses. Additional examples of irregular viruses and their associated proteins, whose structures have been studied via cryo-ET and subtomogram averaging, further support the versatility of these methods.}, author = {Obr, Martin and Schur, Florian KM}, booktitle = {Complementary Strategies to Study Virus Structure and Function}, editor = {Rey, Félix A.}, isbn = {9780128184561}, issn = {0065-3527}, pages = {117--159}, publisher = {Elsevier}, title = {{Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging}}, doi = {10.1016/bs.aivir.2019.07.008}, volume = {105}, year = {2019}, } @article{6940, abstract = {We study the effect of a linear tunneling coupling between two-dimensional systems, each separately exhibiting the topological Berezinskii-Kosterlitz-Thouless (BKT) transition. In the uncoupled limit, there are two phases: one where the one-body correlation functions are algebraically decaying and the other with exponential decay. When the linear coupling is turned on, a third BKT-paired phase emerges, in which one-body correlations are exponentially decaying, while two-body correlation functions exhibit power-law decay. We perform numerical simulations in the paradigmatic case of two coupled XY models at finite temperature, finding evidences that for any finite value of the interlayer coupling, the BKT-paired phase is present. We provide a picture of the phase diagram using a renormalization group approach.}, author = {Bighin, Giacomo and Defenu, Nicolò and Nándori, István and Salasnich, Luca and Trombettoni, Andrea}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {10}, publisher = {American Physical Society}, title = {{Berezinskii-Kosterlitz-Thouless paired phase in coupled XY models}}, doi = {10.1103/physrevlett.123.100601}, volume = {123}, year = {2019}, } @article{6919, author = {Qi, Chao and Minin, Giulio Di and Vercellino, Irene and Wutz, Anton and Korkhov, Volodymyr M.}, issn = {23752548}, journal = {Science Advances}, number = {9}, publisher = {American Association for the Advancement of Science}, title = {{Structural basis of sterol recognition by human hedgehog receptor PTCH1}}, doi = {10.1126/sciadv.aaw6490}, volume = {5}, year = {2019}, } @article{6983, abstract = {Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness” of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to the clusters, we found no evidence that non-specific CD8 T cells play a role in cluster formation. Third and finally, mathematical modeling suggested that formation of clusters occurs rapidly, within few hours after adoptive transfer of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their targets in complex peripheral organs, such as the liver. Taken together, our analysis provides novel insights into and attempts to discriminate between alternative mechanisms driving the formation of clusters of antigen-specific CD8 T cells in the liver.}, author = {Kelemen, Réka K and Rajakaruna, H and Cockburn, IA and Ganusov, VV}, issn = {1664-3224}, journal = {Frontiers in Immunology}, publisher = {Frontiers}, title = {{Clustering of activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific cells}}, doi = {10.3389/fimmu.2019.02153}, volume = {10}, year = {2019}, } @article{6972, abstract = {We give fault-tolerant algorithms for establishing synchrony in distributed systems in which each of thennodes has its own clock. Our algorithms operate in a very strong fault model: we require self-stabilisation, i.e.,the initial state of the system may be arbitrary, and there can be up to f> r eff and show that these systems obey universal scaling laws different from neutral particles. An accurate description of these states requires both the Coulomb-modified scattering length and the effective range unless the Coulomb interaction is very weak (D -> ). Our findings are relevant for bound states whose spatial extent is significantly larger than the range of the attractive potential. These states enjoy universality – their character is independent of the shape of the short-range potential.}, author = {Schmickler, C.H. and Hammer, H.-W. and Volosniev, Artem}, issn = {0370-2693}, journal = {Physics Letters B}, publisher = {Elsevier}, title = {{Universal physics of bound states of a few charged particles}}, doi = {10.1016/j.physletb.2019.135016}, volume = {798}, year = {2019}, } @article{7005, abstract = {Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes.}, author = {Cheung, Giselle T and Cousin, Michael A.}, issn = {1471-4159}, journal = {Journal of Neurochemistry}, number = {5}, pages = {570--583}, publisher = {Wiley}, title = {{Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction}}, doi = {10.1111/jnc.14862}, volume = {151}, year = {2019}, } @article{7000, abstract = {The main contributions of this paper are the proposition and the convergence analysis of a class of inertial projection-type algorithm for solving variational inequality problems in real Hilbert spaces where the underline operator is monotone and uniformly continuous. We carry out a unified analysis of the proposed method under very mild assumptions. In particular, weak convergence of the generated sequence is established and nonasymptotic O(1 / n) rate of convergence is established, where n denotes the iteration counter. We also present some experimental results to illustrate the profits gained by introducing the inertial extrapolation steps.}, author = {Shehu, Yekini and Iyiola, Olaniyi S. and Li, Xiao-Huan and Dong, Qiao-Li}, issn = {1807-0302}, journal = {Computational and Applied Mathematics}, number = {4}, publisher = {Springer Nature}, title = {{Convergence analysis of projection method for variational inequalities}}, doi = {10.1007/s40314-019-0955-9}, volume = {38}, year = {2019}, } @article{7009, abstract = {Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non- muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration.}, author = {Yamada, KM and Sixt, Michael K}, issn = {1471-0080}, journal = {Nature Reviews Molecular Cell Biology}, number = {12}, pages = {738–752}, publisher = {Springer Nature}, title = {{Mechanisms of 3D cell migration}}, doi = {10.1038/s41580-019-0172-9}, volume = {20}, year = {2019}, } @article{6988, abstract = {Platelets are central players in thrombosis and hemostasis but are increasingly recognized as key components of the immune system. They shape ensuing immune responses by recruiting leukocytes, and support the development of adaptive immunity. Recent data shed new light on the complex role of platelets in immunity. Here, we summarize experimental and clinical data on the role of platelets in host defense against bacteria. Platelets bind, contain, and kill bacteria directly; however, platelet proinflammatory effector functions and cross-talk with the coagulation system, can also result in damage to the host (e.g., acute lung injury and sepsis). Novel clinical insights support this dichotomy: platelet inhibition/thrombocytopenia can be either harmful or protective, depending on pathophysiological context. Clinical studies are currently addressing this aspect in greater depth.}, author = {Nicolai, Leo and Gärtner, Florian R and Massberg, Steffen}, issn = {1471-4906}, journal = {Trends in Immunology}, number = {10}, pages = {922--938}, publisher = {Cell Press}, title = {{Platelets in host defense: Experimental and clinical insights}}, doi = {10.1016/j.it.2019.08.004}, volume = {40}, year = {2019}, } @article{7002, abstract = {Multiple Importance Sampling (MIS) is a key technique for achieving robustness of Monte Carlo estimators in computer graphics and other fields. We derive optimal weighting functions for MIS that provably minimize the variance of an MIS estimator, given a set of sampling techniques. We show that the resulting variance reduction over the balance heuristic can be higher than predicted by the variance bounds derived by Veach and Guibas, who assumed only non-negative weights in their proof. We theoretically analyze the variance of the optimal MIS weights and show the relation to the variance of the balance heuristic. Furthermore, we establish a connection between the new weighting functions and control variates as previously applied to mixture sampling. We apply the new optimal weights to integration problems in light transport and show that they allow for new design considerations when choosing the appropriate sampling techniques for a given integration problem.}, author = {Kondapaneni, Ivo and Vevoda, Petr and Grittmann, Pascal and Skrivan, Tomas and Slusallek, Philipp and Křivánek, Jaroslav}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Optimal multiple importance sampling}}, doi = {10.1145/3306346.3323009}, volume = {38}, year = {2019}, } @article{6978, abstract = {In pipes and channels, the onset of turbulence is initially dominated by localizedtransients, which lead to sustained turbulence through their collective dynamics. In thepresent work, we study numerically the localized turbulence in pipe flow and elucidate astate space structure that gives rise to transient chaos. Starting from the basin boundaryseparating laminar and turbulent flow, we identify transverse homoclinic orbits, thepresence of which necessitates a homoclinic tangle and chaos. A direct consequence ofthe homoclinic tangle is the fractal nature of the laminar-turbulent boundary, which wasconjectured in various earlier studies. By mapping the transverse intersections between thestable and unstable manifold of a periodic orbit, we identify the gateways that promote anescape from turbulence.}, author = {Budanur, Nazmi B and Dogra, Akshunna and Hof, Björn}, journal = {Physical Review Fluids}, number = {10}, pages = {102401}, publisher = {American Physical Society}, title = {{Geometry of transient chaos in streamwise-localized pipe flow turbulence}}, doi = {10.1103/PhysRevFluids.4.102401}, volume = {4}, year = {2019}, } @article{7026, abstract = {Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information.}, author = {Lukacisin, Martin and Bollenbach, Tobias}, issn = {2405-4712}, journal = {Cell Systems}, number = {5}, pages = {423--433.e1--e3}, publisher = {Cell Press}, title = {{Emergent gene expression responses to drug combinations predict higher-order drug interactions}}, doi = {10.1016/j.cels.2019.10.004}, volume = {9}, year = {2019}, } @article{7034, abstract = {We find a graph of genus 5 and its drawing on the orientable surface of genus 4 with every pair of independent edges crossing an even number of times. This shows that the strong Hanani–Tutte theorem cannot be extended to the orientable surface of genus 4. As a base step in the construction we use a counterexample to an extension of the unified Hanani–Tutte theorem on the torus.}, author = {Fulek, Radoslav and Kynčl, Jan}, issn = {1439-6912}, journal = {Combinatorica}, number = {6}, pages = {1267--1279}, publisher = {Springer Nature}, title = {{Counterexample to an extension of the Hanani-Tutte theorem on the surface of genus 4}}, doi = {10.1007/s00493-019-3905-7}, volume = {39}, year = {2019}, } @inproceedings{7032, abstract = {Optical frequency combs (OFCs) are light sources whose spectra consists of equally spaced frequency lines in the optical domain [1]. They have great potential for improving high-capacity data transfer, all-optical atomic clocks, spectroscopy, and high-precision measurements [2].}, author = {Rueda Sanchez, Alfredo R and Sedlmeir, Florian and Leuchs, Gerd and Kuamri, Madhuri and Schwefel, Harald G. L.}, booktitle = {2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference}, isbn = {9781728104690}, location = {Munich, Germany}, publisher = {IEEE}, title = {{Electro-optic frequency comb generation in lithium niobate whispering gallery mode resonators}}, doi = {10.1109/cleoe-eqec.2019.8873300}, year = {2019}, } @article{7095, abstract = {BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells.}, author = {Maes, Margaret E and Grosser, J. A. and Fehrman, R. L. and Schlamp, C. L. and Nickells, R. W.}, issn = {2045-2322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{Completion of BAX recruitment correlates with mitochondrial fission during apoptosis}}, doi = {10.1038/s41598-019-53049-w}, volume = {9}, year = {2019}, } @article{7097, abstract = {Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway.}, author = {Nagano, Makoto and Toshima, Junko Y. and Siekhaus, Daria E and Toshima, Jiro}, issn = {2399-3642}, journal = {Communications Biology}, number = {1}, publisher = {Springer Nature}, title = {{Rab5-mediated endosome formation is regulated at the trans-Golgi network}}, doi = {10.1038/s42003-019-0670-5}, volume = {2}, year = {2019}, } @article{7099, author = {Kasugai, Yu and Vogel, Elisabeth and Hörtnagl, Heide and Schönherr, Sabine and Paradiso, Enrica and Hauschild, Markus and Göbel, Georg and Milenkovic, Ivan and Peterschmitt, Yvan and Tasan, Ramon and Sperk, Günther and Shigemoto, Ryuichi and Sieghart, Werner and Singewald, Nicolas and Lüthi, Andreas and Ferraguti, Francesco}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {781--794.e4}, publisher = {Elsevier}, title = {{Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning}}, doi = {10.1016/j.neuron.2019.08.013}, volume = {104}, year = {2019}, } @article{6455, abstract = {During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age–dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity.}, author = {Telley, L and Agirman, G and Prados, J and Amberg, Nicole and Fièvre, S and Oberst, P and Bartolini, G and Vitali, I and Cadilhac, C and Hippenmeyer, Simon and Nguyen, L and Dayer, A and Jabaudon, D}, issn = {1095-9203}, journal = {Science}, number = {6440}, publisher = {AAAS}, title = {{Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex}}, doi = {10.1126/science.aav2522}, volume = {364}, year = {2019}, } @article{6586, abstract = {The bottom-up assembly of colloidal nanocrystals is a versatile methodology to produce composite nanomaterials with precisely tuned electronic properties. Beyond the synthetic control over crystal domain size, shape, crystal phase, and composition, solution-processed nanocrystals allow exquisite surface engineering. This provides additional means to modulate the nanomaterial characteristics and particularly its electronic transport properties. For instance, inorganic surface ligands can be used to tune the type and concentration of majority carriers or to modify the electronic band structure. Herein, we report the thermoelectric properties of SnTe nanocomposites obtained from the consolidation of surface-engineered SnTe nanocrystals into macroscopic pellets. A CdSe-based ligand is selected to (i) converge the light and heavy bands through partial Cd alloying and (ii) generate CdSe nanoinclusions as a secondary phase within the SnTe matrix, thereby reducing the thermal conductivity. These SnTe-CdSe nanocomposites possess thermoelectric figures of merit of up to 1.3 at 850 K, which is, to the best of our knowledge, the highest thermoelectric figure of merit reported for solution-processed SnTe.}, author = {Ibáñez, Maria and Hasler, Roger and Genç, Aziz and Liu, Yu and Kuster, Beatrice and Schuster, Maximilian and Dobrozhan, Oleksandr and Cadavid, Doris and Arbiol, Jordi and Cabot, Andreu and Kovalenko, Maksym V.}, issn = {1520-5126}, journal = {Journal of the American Chemical Society}, number = {20}, pages = {8025--8029}, publisher = {American Chemical Society}, title = {{Ligand-mediated band engineering in bottom-up assembled SnTe nanocomposites for thermoelectric energy conversion}}, doi = {10.1021/jacs.9b01394}, volume = {141}, year = {2019}, } @article{6174, abstract = {We propose a scaling theory for the many-body localization (MBL) phase transition in one dimension, building on the idea that it proceeds via a “quantum avalanche.” We argue that the critical properties can be captured at a coarse-grained level by a Kosterlitz-Thouless (KT) renormalization group (RG) flow. On phenomenological grounds, we identify the scaling variables as the density of thermal regions and the length scale that controls the decay of typical matrix elements. Within this KT picture, the MBL phase is a line of fixed points that terminates at the delocalization transition. We discuss two possible scenarios distinguished by the distribution of rare, fractal thermal inclusions within the MBL phase. In the first scenario, these regions have a stretched exponential distribution in the MBL phase. In the second scenario, the near-critical MBL phase hosts rare thermal regions that are power-law-distributed in size. This points to the existence of a second transition within the MBL phase, at which these power laws change to the stretched exponential form expected at strong disorder. We numerically simulate two different phenomenological RGs previously proposed to describe the MBL transition. Both RGs display a universal power-law length distribution of thermal regions at the transition with a critical exponent αc=2, and continuously varying exponents in the MBL phase consistent with the KT picture.}, author = {Dumitrescu, Philipp T. and Goremykina, Anna and Parameswaran, Siddharth A. and Serbyn, Maksym and Vasseur, Romain}, issn = {2469-9969}, journal = {Physical Review B}, number = {9}, publisher = {American Physical Society}, title = {{Kosterlitz-Thouless scaling at many-body localization phase transitions}}, doi = {10.1103/physrevb.99.094205}, volume = {99}, year = {2019}, } @article{6366, abstract = {Plants have a remarkable capacity to adjust their growth and development to elevated ambient temperatures. Increased elongation growth of roots, hypocotyls and petioles in warm temperatures are hallmarks of seedling thermomorphogenesis. In the last decade, significant progress has been made to identify the molecular signaling components regulating these growth responses. Increased ambient temperature utilizes diverse components of the light sensing and signal transduction network to trigger growth adjustments. However, it remains unknown whether temperature sensing and responses are universal processes that occur uniformly in all plant organs. Alternatively, temperature sensing may be confined to specific tissues or organs, which would require a systemic signal that mediates responses in distal parts of the plant. Here we show that Arabidopsis (Arabidopsis thaliana) seedlings show organ-specific transcriptome responses to elevated temperatures, and that thermomorphogenesis involves both autonomous and organ-interdependent temperature sensing and signaling. Seedling roots can sense and respond to temperature in a shoot-independent manner, whereas shoot temperature responses require both local and systemic processes. The induction of cell elongation in hypocotyls requires temperature sensing in cotyledons, followed by generation of a mobile auxin signal. Subsequently, auxin travels to the hypocotyl where it triggers local brassinosteroid-induced cell elongation in seedling stems, which depends upon a distinct, permissive temperature sensor in the hypocotyl.}, author = {Bellstaedt, Julia and Trenner, Jana and Lippmann, Rebecca and Poeschl, Yvonne and Zhang, Xixi and Friml, Jiří and Quint, Marcel and Delker, Carolin}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {757--766}, publisher = {ASPB}, title = {{A mobile auxin signal connects temperature sensing in cotyledons with growth responses in hypocotyls}}, doi = {10.1104/pp.18.01377}, volume = {180}, year = {2019}, } @article{6986, abstract = {Li-Nadler proposed a conjecture about traces of Hecke categories, which implies the semistable part of the Betti geometric Langlands conjecture of Ben-Zvi-Nadler in genus 1. We prove a Weyl group analogue of this conjecture. Our theorem holds in the natural generality of reflection groups in Euclidean or hyperbolic space. As a corollary, we give an expression of the centralizer of a finite order element in a reflection group using homotopy theory. }, author = {Li, Penghui}, issn = {1088-6826}, journal = {Proceedings of the American Mathematical Society}, number = {11}, pages = {4597--4604}, publisher = {AMS}, title = {{A colimit of traces of reflection groups}}, doi = {10.1090/proc/14586}, volume = {147}, year = {2019}, } @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