@article{1309, abstract = {We show that weak solutions of the Derrida-Lebowitz-Speer-Spohn (DLSS) equation display infinite speed of support propagation. We apply our method to the case of the quantum drift-diffusion equation which augments the DLSS equation with a drift term and possibly a second-order diffusion term. The proof is accomplished using weighted entropy estimates, Hardy's inequality and a family of singular weight functions to derive a differential inequality; the differential inequality shows exponential growth of the weighted entropy, with the growth constant blowing up very fast as the singularity of the weight becomes sharper. To the best of our knowledge, this is the first example of a nonnegativity-preserving higher-order parabolic equation displaying infinite speed of support propagation.}, author = {Julian Fischer}, journal = {Nonlinear Differential Equations and Applications}, number = {1}, pages = {27 -- 50}, publisher = {Birkhäuser}, title = {{Infinite speed of support propagation for the Derrida-Lebowitz-Speer-Spohn equation and quantum drift-diffusion models}}, doi = {10.1007/s00030-013-0235-0}, volume = {21}, year = {2014}, } @article{1312, abstract = {We derive upper bounds on the waiting time of solutions to the thin-film equation in the regime of weak slippage n ∈ [2, 32\11). In particular, we give sufficient conditions on the initial data for instantaneous forward motion of the free boundary. For n ∈ (2, 32\11), our estimates are sharp, for n = 2, they are sharp up to a logarithmic correction term. Note that the case n = 2 corresponds-with a grain of salt-to the assumption of the Navier slip condition at the fluid-solid interface. We also obtain results in the regime of strong slippage n ∈ (1,2); however, in this regime we expect them not to be optimal. Our method is based on weighted backward entropy estimates, Hardy's inequality and singular weight functions; we deduce a differential inequality which would enforce blowup of the weighted entropy if the contact line were to remain stationary for too long.}, author = {Julian Fischer}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {771 -- 818}, publisher = {Springer}, title = {{Upper bounds on waiting times for the Thin-film equation: The case of weak slippage}}, doi = {10.1007/s00205-013-0690-0}, volume = {211}, year = {2014}, } @article{1979, abstract = {NADH-ubiquinone oxidoreductase (complex I) is the first and largest enzyme in the respiratory chain of mitochondria and many bacteria. It couples the transfer of two electrons between NADH and ubiquinone to the translocation of four protons across the membrane. Complex I is an L-shaped assembly formed by the hydrophilic (peripheral) arm, containing all the redox centres performing electron transfer and the membrane arm, containing proton-translocating machinery. Mitochondrial complex I consists of 44 subunits of about 1 MDa in total, whilst the prokaryotic enzyme is simpler and generally consists of 14 conserved “core” subunits. Recently we have determined the first atomic structure of the entire complex I, using the enzyme from Thermus thermophilus (536 kDa, 16 subunits, 9 Fe-S clusters, 64 TM helices). Structure suggests a unique coupling mechanism, with redox energy of electron transfer driving proton translocation via long-range (up to ~200 Å) conformational changes. It resembles a steam engine, with coupling elements (akin to coupling rods) linking parts of this molecular machine.}, author = {Leonid Sazanov}, journal = {Journal of Bioenergetics and Biomembranes}, number = {4}, pages = {247 -- 253}, publisher = {Springer}, title = {{The mechanism of coupling between electron transfer and proton translocation in respiratory complex I}}, doi = {10.1007/s10863-014-9554-z}, volume = {46}, year = {2014}, } @article{1980, abstract = {Non-proton pumping type II NADH dehydrogenase (NDH-2) plays a central role in the respiratory metabolism of bacteria, and in the mitochondria of fungi, plants and protists. The lack of NDH-2 in mammalian mitochondria and its essentiality in important bacterial pathogens suggests these enzymes may represent a potential new drug target to combat microbial pathogens. Here, we report the first crystal structure of a bacterial NDH-2 enzyme at 2.5Å resolution from Caldalkalibacillus thermarum. The NDH-2 structure reveals a homodimeric organization that has a unique dimer interface. NDH-2 is localized to the cytoplasmic membrane by two separated C-terminal membrane-anchoring regions that are essential for membrane localization and FAD binding, but not NDH-2 dimerization. Comparison of bacterial NDH-2 with the yeast NADH dehydrogenase (Ndi1) structure revealed non-overlapping binding sites for quinone and NADH in the bacterial enzyme. The bacterial NDH-2 structure establishes a framework for the structure-based design of small-molecule inhibitors.}, author = {Heikal, Adam and Nakatani, Yoshio and Dunn, Elyse A and Weimar, Marion R and Day, Catherine and Baker, Edward N and Lott, Shaun J and Leonid Sazanov and Cook, Gregory}, journal = {Molecular Microbiology}, number = {5}, pages = {950 -- 964}, publisher = {Wiley-Blackwell}, title = {{Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation}}, doi = {10.1111/mmi.12507}, volume = {91}, year = {2014}, } @article{1989, abstract = {During animal cell division, the cleavage furrow is positioned by microtubules that signal to the actin cortex at the cell midplane. We developed a cell-free system to recapitulate cytokinesis signaling using cytoplasmic extract from Xenopus eggs. Microtubules grew out as asters from artificial centrosomes and met to organize antiparallel overlap zones. These zones blocked the interpenetration of neighboring asters and recruited cytokinesis midzone proteins, including the chromosomal passenger complex (CPC) and centralspindlin. The CPC was transported to overlap zones, which required two motor proteins, Kif4A and a Kif20A paralog. Using supported lipid bilayers to mimic the plasma membrane, we observed the recruitment of cleavage furrow markers, including an active RhoA reporter, at microtubule overlaps. This system opens further approaches to understanding the biophysics of cytokinesis signaling.}, author = {Nguyen, Phuong and Groen, Aaron and Loose, Martin and Ishihara, Keisuke and Wühr, Martin and Field, Christine and Mitchison, Timothy}, journal = {Science}, number = {6206}, pages = {244 -- 247}, publisher = {American Association for the Advancement of Science}, title = {{Spatial organization of cytokinesis signaling reconstituted in a cell-free system}}, doi = {10.1126/science.1256773}, volume = {346}, year = {2014}, } @article{1990, abstract = {Bacterial cytokinesis is commonly initiated by the Z-ring, a cytoskeletal structure that assembles at the site of division. Its primary component is FtsZ, a tubulin superfamily GTPase, which is recruited to the membrane by the actin-related protein FtsA. Both proteins are required for the formation of the Z-ring, but if and how they influence each other's assembly dynamics is not known. Here, we reconstituted FtsA-dependent recruitment of FtsZ polymers to supported membranes, where both proteins self-organize into complex patterns, such as fast-moving filament bundles and chirally rotating rings. Using fluorescence microscopy and biochemical perturbations, we found that these large-scale rearrangements of FtsZ emerge from its polymerization dynamics and a dual, antagonistic role of FtsA: recruitment of FtsZ filaments to the membrane and negative regulation of FtsZ organization. Our findings provide a model for the initial steps of bacterial cell division and illustrate how dynamic polymers can self-organize into large-scale structures.}, author = {Loose, Martin and Mitchison, Timothy}, journal = {Nature Cell Biology}, pages = {38 -- 46}, publisher = {Nature Publishing Group}, title = {{The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns}}, doi = {10.1038/ncb2885}, volume = {16}, year = {2014}, } @article{1994, abstract = {The emergence and radiation of multicellular land plants was driven by crucial innovations to their body plans [1]. The directional transport of the phytohormone auxin represents a key, plant-specific mechanism for polarization and patterning in complex seed plants [2-5]. Here, we show that already in the early diverging land plant lineage, as exemplified by the moss Physcomitrella patens, auxin transport by PIN transporters is operational and diversified into ER-localized and plasma membrane-localized PIN proteins. Gain-of-function and loss-of-function analyses revealed that PIN-dependent intercellular auxin transport in Physcomitrella mediates crucial developmental transitions in tip-growing filaments and waves of polarization and differentiation in leaf-like structures. Plasma membrane PIN proteins localize in a polar manner to the tips of moss filaments, revealing an unexpected relation between polarization mechanisms in moss tip-growing cells and multicellular tissues of seed plants. Our results trace the origins of polarization and auxin-mediated patterning mechanisms and highlight the crucial role of polarized auxin transport during the evolution of multicellular land plants.}, author = {Viaene, Tom and Landberg, Katarina and Thelander, Mattias and Medvecka, Eva and Pederson, Eric and Feraru, Elena and Cooper, Endymion and Karimi, Mansour and Delwiche, Charles and Ljung, Karin and Geisler, Markus and Sundberg, Eva and Friml, Jirí}, journal = {Current Biology}, number = {23}, pages = {2786 -- 2791}, publisher = {Cell Press}, title = {{Directional auxin transport mechanisms in early diverging land plants}}, doi = {10.1016/j.cub.2014.09.056}, volume = {24}, year = {2014}, } @article{1995, abstract = {Optical transport represents a natural route towards fast communications, and it is currently used in large scale data transfer. The progressive miniaturization of devices for information processing calls for the microscopic tailoring of light transport and confinement at length scales appropriate for upcoming technologies. With this goal in mind, we present a theoretical analysis of a one-dimensional Fabry-Perot interferometer built with two highly saturable nonlinear mirrors: a pair of two-level systems. Our approach captures nonlinear and nonreciprocal effects of light transport that were not reported previously. Remarkably, we show that such an elementary device can operate as a microscopic integrated optical rectifier.}, author = {Fratini, Filippo and Mascarenhas, Eduardo and Safari, Laleh and Poizat, Jean and Valente, Daniel and Auffèves, Alexia and Gerace, Dario and Santos, Marcelo}, journal = {Physical Review Letters}, number = {24}, publisher = {American Physical Society}, title = {{Fabry-Perot interferometer with quantum mirrors: Nonlinear light transport and rectification}}, doi = {10.1103/PhysRevLett.113.243601}, volume = {113}, year = {2014}, } @article{1996, abstract = {Auxin polar transport, local maxima, and gradients have become an importantmodel system for studying self-organization. Auxin distribution is regulated by auxin-dependent positive feedback loops that are not well-understood at the molecular level. Previously, we showed the involvement of the RHO of Plants (ROP) effector INTERACTOR of CONSTITUTIVELY active ROP 1 (ICR1) in regulation of auxin transport and that ICR1 levels are posttranscriptionally repressed at the site of maximum auxin accumulation at the root tip. Here, we show that bimodal regulation of ICR1 levels by auxin is essential for regulating formation of auxin local maxima and gradients. ICR1 levels increase concomitant with increase in auxin response in lateral root primordia, cotyledon tips, and provascular tissues. However, in the embryo hypophysis and root meristem, when auxin exceeds critical levels, ICR1 is rapidly destabilized by an SCF(TIR1/AFB) [SKP, Cullin, F-box (transport inhibitor response 1/auxin signaling F-box protein)]-dependent auxin signaling mechanism. Furthermore, ectopic expression of ICR1 in the embryo hypophysis resulted in reduction of auxin accumulation and concomitant root growth arrest. ICR1 disappeared during root regeneration and lateral root initiation concomitantly with the formation of a local auxin maximum in response to external auxin treatments and transiently after gravitropic stimulation. Destabilization of ICR1 was impaired after inhibition of auxin transport and signaling, proteasome function, and protein synthesis. A mathematical model based on these findings shows that an in vivo-like auxin distribution, rootward auxin flux, and shootward reflux can be simulated without assuming preexisting tissue polarity. Our experimental results and mathematical modeling indicate that regulation of auxin distribution is tightly associated with auxin-dependent ICR1 levels.}, author = {Hazak, Ora and Obolski, Uri and Prat, Tomas and Friml, Jiří and Hadany, Lilach and Yalovsky, Shaul}, journal = {PNAS}, number = {50}, pages = {E5471 -- E5479}, publisher = {National Academy of Sciences}, title = {{Bimodal regulation of ICR1 levels generates self-organizing auxin distribution}}, doi = {10.1073/pnas.1413918111}, volume = {111}, year = {2014}, } @article{1998, abstract = {Immune systems are able to protect the body against secondary infection with the same parasite. In insect colonies, this protection is not restricted to the level of the individual organism, but also occurs at the societal level. Here, we review recent evidence for and insights into the mechanisms underlying individual and social immunisation in insects. We disentangle general immune-protective effects from specific immune memory (priming), and examine immunisation in the context of the lifetime of an individual and that of a colony, and of transgenerational immunisation that benefits offspring. When appropriate, we discuss parallels with disease defence strategies in human societies. We propose that recurrent parasitic threats have shaped the evolution of both the individual immune systems and colony-level social immunity in insects.}, author = {El Masri, Leila and Cremer, Sylvia}, journal = {Trends in Immunology}, number = {10}, pages = {471 -- 482}, publisher = {Elsevier}, title = {{Individual and social immunisation in insects}}, doi = {10.1016/j.it.2014.08.005}, volume = {35}, year = {2014}, } @inbook{19994, abstract = {Firing patterns of hippocampal principal cells are thought to participate in the formation of mnemonic representations of place, which ultimately can be used to guide the behavior of animals in space. Past studies have suggested that place-selective activity in the hippocampus can emphasize the representation of discrete locations associated with a strong behavioral salience. In the first part of this book chapter, we review work that has described how that hippocampal neuronal activity patterns reorganize during spatial learning. These studies revealed that new hippocampal maps emerge during spatial learning to represent the location of goal locations and demonstrated that, during recall, the reinstatement of these maps predicts successful memory performance. In the second part of this chapter, we discuss the role of sleep in memory consolidation in the context of goal-oriented spatial learning. We summarize work that has demonstrated the replay of goal-oriented neuronal assembly patterns that predict subsequent memory recall. Moreover, we argue that the initial strengthening of new maps may in fact take place during learning, triggered by waking sharp-wave/ripple patterns occurring at goal locations. These reviewed studies highlight that the reorganization and replay of place cell firing patterns might constitute a circuit signature for the expression of newly acquired hippocampal engrams.}, author = {Dupret, David and Csicsvari, Jozsef L}, booktitle = {Analysis and Modeling of Coordinated Multi-neuronal Activity}, isbn = {9781493919680}, issn = {2197-1919}, publisher = {Springer Nature}, title = {{Reorganization of Hippocampal Place-Selective Patterns During Goal-Directed Learning and Their Reactivation During Sleep}}, doi = {10.1007/978-1-4939-1969-7_6}, volume = {12}, year = {2014}, } @article{2002, abstract = {Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outsideout patch recordings from CA1 pyramidal neuron axons revealed a high density of a-dendrotoxin (α-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA1 pyramidal neurons and O-LM interneurons. CA1 pyramidal neuron-O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by α-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA1 pyramidal neuron axons substantially enhances the efficacy of principal neuron-interneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits.}, author = {Kim, Sooyun}, journal = {PLoS One}, number = {11}, publisher = {Public Library of Science}, title = {{Action potential modulation in CA1 pyramidal neuron axons facilitates OLM interneuron activation in recurrent inhibitory microcircuits of rat hippocampus}}, doi = {10.1371/journal.pone.0113124}, volume = {9}, year = {2014}, } @article{2003, abstract = {Learning can be facilitated by previous knowledge when it is organized into relational representations forming schemas. In this issue of Neuron, McKenzie et al. (2014) demonstrate that the hippocampus rapidly forms interrelated, hierarchical memory representations to support schema-based learning.}, author = {O'Neill, Joseph and Csicsvari, Jozsef L}, journal = {Neuron}, number = {1}, pages = {8 -- 10}, publisher = {Elsevier}, title = {{Learning by example in the hippocampus}}, doi = {10.1016/j.neuron.2014.06.013}, volume = {83}, year = {2014}, } @article{2004, abstract = {We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.}, author = {Lovrics, Anna and Gao, Yu and Juhász, Bianka and Bock, István and Byrne, Helen and Dinnyés, András and Kovács, Krisztián}, journal = {PLoS One}, number = {11}, publisher = {Public Library of Science}, title = {{Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord}}, doi = {10.1371/journal.pone.0111430}, volume = {9}, year = {2014}, } @article{2005, abstract = {By eliciting a natural exploratory behavior in rats, head scanning, a study reveals that hippocampal place cells form new, stable firing fields in those locations where the behavior has just occurred.}, author = {Dupret, David and Csicsvari, Jozsef L}, journal = {Nature Neuroscience}, number = {5}, pages = {643 -- 644}, publisher = {Nature Publishing Group}, title = {{Turning heads to remember places}}, doi = {10.1038/nn.3700}, volume = {17}, year = {2014}, } @misc{2007, abstract = {Maximum likelihood estimation under relational models, with or without the overall effect. For more information see the reference manual}, author = {Klimova, Anna and Rudas, Tamás}, publisher = {The Comprehensive R Archive Network}, title = {{gIPFrm: Generalized iterative proportional fitting for relational models}}, year = {2014}, } @article{2011, abstract = {The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of “an attack” on GWAS data by Homer et al. (2008). Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. (2013) proposed new methods to release aggregate GWAS data without compromising an individual’s privacy. We extend the methods developed in Uhler et al. (2013) for releasing differentially-private χ2χ2-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls’ data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov (2013).}, author = {Yu, Fei and Fienberg, Stephen and Slaković, Alexandra and Uhler, Caroline}, journal = {Journal of Biomedical Informatics}, pages = {133 -- 141}, publisher = {Elsevier}, title = {{Scalable privacy-preserving data sharing methodology for genome-wide association studies}}, doi = {10.1016/j.jbi.2014.01.008}, volume = {50}, year = {2014}, } @inproceedings{2012, abstract = {The classical sphere packing problem asks for the best (infinite) arrangement of non-overlapping unit balls which cover as much space as possible. We define a generalized version of the problem, where we allow each ball a limited amount of overlap with other balls. We study two natural choices of overlap measures and obtain the optimal lattice packings in a parameterized family of lattices which contains the FCC, BCC, and integer lattice.}, author = {Iglesias Ham, Mabel and Kerber, Michael and Uhler, Caroline}, booktitle = {26th Canadian Conference on Computational Geometry}, location = {Halifax, Canada}, pages = {155--161}, publisher = {Canadian Conference on Computational Geometry}, title = {{Sphere packing with limited overlap}}, year = {2014}, } @article{2013, abstract = {An asymptotic theory is developed for computing volumes of regions in the parameter space of a directed Gaussian graphical model that are obtained by bounding partial correlations. We study these volumes using the method of real log canonical thresholds from algebraic geometry. Our analysis involves the computation of the singular loci of correlation hypersurfaces. Statistical applications include the strong-faithfulness assumption for the PC algorithm and the quantification of confounder bias in causal inference. A detailed analysis is presented for trees, bow ties, tripartite graphs, and complete graphs. }, author = {Lin, Shaowei and Uhler, Caroline and Sturmfels, Bernd and Bühlmann, Peter}, journal = {Foundations of Computational Mathematics}, number = {5}, pages = {1079 -- 1116}, publisher = {Springer}, title = {{Hypersurfaces and their singularities in partial correlation testing}}, doi = {10.1007/s10208-014-9205-0}, volume = {14}, year = {2014}, } @unpublished{2017, abstract = { Gaussian graphical models have received considerable attention during the past four decades from the statistical and machine learning communities. In Bayesian treatments of this model, the G-Wishart distribution serves as the conjugate prior for inverse covariance matrices satisfying graphical constraints. While it is straightforward to posit the unnormalized densities, the normalizing constants of these distributions have been known only for graphs that are chordal, or decomposable. Up until now, it was unknown whether the normalizing constant for a general graph could be represented explicitly, and a considerable body of computational literature emerged that attempted to avoid this apparent intractability. We close this question by providing an explicit representation of the G-Wishart normalizing constant for general graphs.}, author = {Uhler, Caroline and Lenkoski, Alex and Richards, Donald}, booktitle = {ArXiv}, title = {{ Exact formulas for the normalizing constants of Wishart distributions for graphical models}}, doi = {10.48550/arXiv.1406.4901}, year = {2014}, }