TY - JOUR AB - Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles. AU - Obr, Martin AU - Ricana, Clifton L. AU - Nikulin, Nadia AU - Feathers, Jon-Philip R. AU - Klanschnig, Marco AU - Thader, Andreas AU - Johnson, Marc C. AU - Vogt, Volker M. AU - Schur, Florian KM AU - Dick, Robert A. ID - 9431 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry TI - Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer VL - 12 ER - TY - JOUR AB - Turbulence in the flow of fluid through a pipe can be suppressed by buoyancy forces. As the suppression of turbulence leads to severe heat transfer deterioration, this is an important and undesirable phenomenon in both heating and cooling applications. Vertical flow is often considered, as the axial buoyancy force can help drive the flow. With heating measured by the buoyancy parameter 𝐶, our direct numerical simulations show that shear-driven turbulence may either be completely laminarised or it transitions to a relatively quiescent convection-driven state. Buoyancy forces cause a flattening of the base flow profile, which in isothermal pipe flow has recently been linked to complete suppression of turbulence (Kühnen et al., Nat. Phys., vol. 14, 2018, pp. 386–390), and the flattened laminar base profile has enhanced nonlinear stability (Marensi et al., J. Fluid Mech., vol. 863, 2019, pp. 50–875). In agreement with these findings, the nonlinear lower-branch travelling-wave solution analysed here, which is believed to mediate transition to turbulence in isothermal pipe flow, is shown to be suppressed by buoyancy. A linear instability of the laminar base flow is responsible for the appearance of the relatively quiescent convection driven state for 𝐶≳4 across the range of Reynolds numbers considered. In the suppression of turbulence, however, i.e. in the transition from turbulence, we find clearer association with the analysis of He et al. (J. Fluid Mech., vol. 809, 2016, pp. 31–71) than with the above dynamical systems approach, which describes better the transition to turbulence. The laminarisation criterion He et al. propose, based on an apparent Reynolds number of the flow as measured by its driving pressure gradient, is found to capture the critical 𝐶=𝐶𝑐𝑟(𝑅𝑒) above which the flow will be laminarised or switch to the convection-driven type. Our analysis suggests that it is the weakened rolls, rather than the streaks, which appear to be critical for laminarisation. AU - Marensi, Elena AU - He, Shuisheng AU - Willis, Ashley P. ID - 9467 JF - Journal of Fluid Mechanics SN - 00221120 TI - Suppression of turbulence and travelling waves in a vertical heated pipe VL - 919 ER - TY - JOUR AB - A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance. AU - Berdan, Emma L. AU - Blanckaert, Alexandre AU - Slotte, Tanja AU - Suh, Alexander AU - Westram, Anja M AU - Fragata, Inês ID - 9470 IS - 12 JF - Molecular Ecology SN - 09621083 TI - Unboxing mutations: Connecting mutation types with evolutionary consequences VL - 30 ER - TY - JOUR AB - Motivated by the successful application of geometry to proving the Harary--Hill conjecture for “pseudolinear” drawings of $K_n$, we introduce “pseudospherical” drawings of graphs. A spherical drawing of a graph $G$ is a drawing in the unit sphere $\mathbb{S}^2$ in which the vertices of $G$ are represented as points---no three on a great circle---and the edges of $G$ are shortest-arcs in $\mathbb{S}^2$ connecting pairs of vertices. Such a drawing has three properties: (1) every edge $e$ is contained in a simple closed curve $\gamma_e$ such that the only vertices in $\gamma_e$ are the ends of $e$; (2) if $e\ne f$, then $\gamma_e\cap\gamma_f$ has precisely two crossings; and (3) if $e\ne f$, then $e$ intersects $\gamma_f$ at most once, in either a crossing or an end of $e$. We use properties (1)--(3) to define a pseudospherical drawing of $G$. Our main result is that for the complete graph, properties (1)--(3) are equivalent to the same three properties but with “precisely two crossings” in (2) replaced by “at most two crossings.” The proof requires a result in the geometric transversal theory of arrangements of pseudocircles. This is proved using the surprising result that the absence of special arcs (coherent spirals) in an arrangement of simple closed curves characterizes the fact that any two curves in the arrangement have at most two crossings. Our studies provide the necessary ideas for exhibiting a drawing of $K_{10}$ that has no extension to an arrangement of pseudocircles and a drawing of $K_9$ that does extend to an arrangement of pseudocircles, but no such extension has all pairs of pseudocircles crossing twice. AU - Arroyo Guevara, Alan M AU - Richter, R. Bruce AU - Sunohara, Matthew ID - 9468 IS - 2 JF - SIAM Journal on Discrete Mathematics SN - 08954801 TI - Extending drawings of complete graphs into arrangements of pseudocircles VL - 35 ER - TY - JOUR AB - We consider a system of N trapped bosons with repulsive interactions in a combined semiclassical mean-field limit at positive temperature. We show that the free energy is well approximated by the minimum of the Hartree free energy functional – a natural extension of the Hartree energy functional to positive temperatures. The Hartree free energy functional converges in the same limit to a semiclassical free energy functional, and we show that the system displays Bose–Einstein condensation if and only if it occurs in the semiclassical free energy functional. This allows us to show that for weak coupling the critical temperature decreases due to the repulsive interactions. AU - Deuchert, Andreas AU - Seiringer, Robert ID - 9462 IS - 6 JF - Journal of Functional Analysis SN - 0022-1236 TI - Semiclassical approximation and critical temperature shift for weakly interacting trapped bosons VL - 281 ER - TY - JOUR AB - In this paper, we consider reflected three-operator splitting methods for monotone inclusion problems in real Hilbert spaces. To do this, we first obtain weak convergence analysis and nonasymptotic O(1/n) convergence rate of the reflected Krasnosel'skiĭ-Mann iteration for finding a fixed point of nonexpansive mapping in real Hilbert spaces under some seemingly easy to implement conditions on the iterative parameters. We then apply our results to three-operator splitting for the monotone inclusion problem and consequently obtain the corresponding convergence analysis. Furthermore, we derive reflected primal-dual algorithms for highly structured monotone inclusion problems. Some numerical implementations are drawn from splitting methods to support the theoretical analysis. AU - Iyiola, Olaniyi S. AU - Enyi, Cyril D. AU - Shehu, Yekini ID - 9469 JF - Optimization Methods and Software SN - 1055-6788 TI - Reflected three-operator splitting method for monotone inclusion problem ER - TY - JOUR AB - The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases. AU - Prattes, Michael AU - Grishkovskaya, Irina AU - Hodirnau, Victor-Valentin AU - Rössler, Ingrid AU - Klein, Isabella AU - Hetzmannseder, Christina AU - Zisser, Gertrude AU - Gruber, Christian C. AU - Gruber, Karl AU - Haselbach, David AU - Bergler, Helmut ID - 9540 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry TI - Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine VL - 12 ER - TY - JOUR AB - AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. AU - Zhang, Danyang AU - Watson, Jake AU - Matthews, Peter M. AU - Cais, Ondrej AU - Greger, Ingo H. ID - 9549 JF - Nature SN - 0028-0836 TI - Gating and modulation of a hetero-octameric AMPA glutamate receptor VL - 594 ER - TY - JOUR AB - We prove that the energy of any eigenvector of a sum of several independent large Wigner matrices is equally distributed among these matrices with very high precision. This shows a particularly strong microcanonical form of the equipartition principle for quantum systems whose components are modelled by Wigner matrices. AU - Bao, Zhigang AU - Erdös, László AU - Schnelli, Kevin ID - 9550 JF - Forum of Mathematics, Sigma TI - Equipartition principle for Wigner matrices VL - 9 ER - TY - JOUR AB - We present conductance-matrix measurements in long, three-terminal hybrid superconductor-semiconductor nanowires, and compare with theoretical predictions of a magnetic-field-driven, topological quantum phase transition. By examining the nonlocal conductance, we identify the closure of the excitation gap in the bulk of the semiconductor before the emergence of zero-bias peaks, ruling out spurious gap-closure signatures from localized states. We observe that after the gap closes, nonlocal signals and zero-bias peaks fluctuate strongly at both ends, inconsistent with a simple picture of clean topological superconductivity. AU - Puglia, Denise AU - Martinez, E. A. AU - Ménard, G. C. AU - Pöschl, A. AU - Gronin, S. AU - Gardner, G. C. AU - Kallaher, R. AU - Manfra, M. J. AU - Marcus, C. M. AU - Higginbotham, Andrew P AU - Casparis, L. ID - 9570 IS - 23 JF - Physical Review B SN - 24699950 TI - Closing of the induced gap in a hybrid superconductor-semiconductor nanowire VL - 103 ER - TY - JOUR AB - We extend the notion of the minimal volume ellipsoid containing a convex body in Rd to the setting of logarithmically concave functions. We consider a vast class of logarithmically concave functions whose superlevel sets are concentric ellipsoids. For a fixed function from this class, we consider the set of all its “affine” positions. For any log-concave function f on Rd, we consider functions belonging to this set of “affine” positions, and find the one with the minimal integral under the condition that it is pointwise greater than or equal to f. We study the properties of existence and uniqueness of the solution to this problem. For any s∈[0,+∞), we consider the construction dual to the recently defined John s-function (Ivanov and Naszódi in Functional John ellipsoids. arXiv preprint: arXiv:2006.09934, 2020). We prove that such a construction determines a unique function and call it the Löwner s-function of f. We study the Löwner s-functions as s tends to zero and to infinity. Finally, extending the notion of the outer volume ratio, we define the outer integral ratio of a log-concave function and give an asymptotically tight bound on it. AU - Ivanov, Grigory AU - Tsiutsiurupa, Igor ID - 9548 JF - Journal of Geometric Analysis SN - 1050-6926 TI - Functional Löwner ellipsoids VL - 31 ER - TY - GEN AB - Data for the manuscript 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire' ([2006.01275] Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire (arxiv.org)) We upload a pdf with extended data sets, and the raw data for these extended datasets as well. AU - Puglia, Denise AU - Martinez, Esteban AU - Menard, Gerbold AU - Pöschl, Andreas AU - Gronin, Sergei AU - Gardner, Geoffrey AU - Kallaher, Ray AU - Manfra, Michael AU - Marcus, Charles AU - Higginbotham, Andrew P AU - Casparis, Lucas ID - 13080 TI - Data for 'Closing of the Induced Gap in a Hybrid Superconductor-Semiconductor Nanowire ER - TY - JOUR AB - We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values. AU - Dar, M. S. AU - Akram, Khush Bakhat AU - Sohail, Ayesha AU - Arif, Fatima AU - Zabihi, Fatemeh AU - Yang, Shengyuan AU - Munir, Shamsa AU - Zhu, Meifang AU - Abid, M. AU - Nauman, Muhammad ID - 9569 IS - 35 JF - RSC Advances TI - Heat induction in two-dimensional graphene–Fe3O4 nanohybrids for magnetic hyperthermia applications with artificial neural network modeling VL - 11 ER - TY - JOUR AB - We show that turbulent dynamics that arise in simulations of the three-dimensional Navier--Stokes equations in a triply-periodic domain under sinusoidal forcing can be described as transient visits to the neighborhoods of unstable time-periodic solutions. Based on this description, we reduce the original system with more than 10^5 degrees of freedom to a 17-node Markov chain where each node corresponds to the neighborhood of a periodic orbit. The model accurately reproduces long-term averages of the system's observables as weighted sums over the periodic orbits. AU - Yalniz, Gökhan AU - Hof, Björn AU - Budanur, Nazmi B ID - 9558 IS - 24 JF - Physical Review Letters SN - 0031-9007 TI - Coarse graining the state space of a turbulent flow using periodic orbits VL - 126 ER - TY - JOUR AB - While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use. AU - Bespalov, Anton AU - Bernard, René AU - Gilis, Anja AU - Gerlach, Björn AU - Guillén, Javier AU - Castagné, Vincent AU - Lefevre, Isabel A. AU - Ducrey, Fiona AU - Monk, Lee AU - Bongiovanni, Sandrine AU - Altevogt, Bruce AU - Arroyo-Araujo, María AU - Bikovski, Lior AU - De Bruin, Natasja AU - Castaños-Vélez, Esmeralda AU - Dityatev, Alexander AU - Emmerich, Christoph H. AU - Fares, Raafat AU - Ferland-Beckham, Chantelle AU - Froger-Colléaux, Christelle AU - Gailus-Durner, Valerie AU - Hölter, Sabine M. AU - Hofmann, Martine Cj AU - Kabitzke, Patricia AU - Kas, Martien Jh AU - Kurreck, Claudia AU - Moser, Paul AU - Pietraszek, Malgorzata AU - Popik, Piotr AU - Potschka, Heidrun AU - Prado Montes De Oca, Ernesto AU - Restivo, Leonardo AU - Riedel, Gernot AU - Ritskes-Hoitinga, Merel AU - Samardzic, Janko AU - Schunn, Michael AU - Stöger, Claudia AU - Voikar, Vootele AU - Vollert, Jan AU - Wever, Kimberley E. AU - Wuyts, Kathleen AU - Macleod, Malcolm R. AU - Dirnagl, Ulrich AU - Steckler, Thomas ID - 9607 JF - eLife TI - Introduction to the EQIPD quality system VL - 10 ER - TY - JOUR AB - In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation. AU - Santini, Laura AU - Halbritter, Florian AU - Titz-Teixeira, Fabian AU - Suzuki, Toru AU - Asami, Maki AU - Ma, Xiaoyan AU - Ramesmayer, Julia AU - Lackner, Andreas AU - Warr, Nick AU - Pauler, Florian AU - Hippenmeyer, Simon AU - Laue, Ernest AU - Farlik, Matthias AU - Bock, Christoph AU - Beyer, Andreas AU - Perry, Anthony C.F. AU - Leeb, Martin ID - 9601 IS - 1 JF - Nature Communications TI - Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3 VL - 12 ER - TY - JOUR AB - An ordered graph is a graph with a linear ordering on its vertex set. We prove that for every positive integer k, there exists a constant ck > 0 such that any ordered graph G on n vertices with the property that neither G nor its complement contains an induced monotone path of size k, has either a clique or an independent set of size at least n^ck . This strengthens a result of Bousquet, Lagoutte, and Thomassé, who proved the analogous result for unordered graphs. A key idea of the above paper was to show that any unordered graph on n vertices that does not contain an induced path of size k, and whose maximum degree is at most c(k)n for some small c(k) > 0, contains two disjoint linear size subsets with no edge between them. This approach fails for ordered graphs, because the analogous statement is false for k ≥ 3, by a construction of Fox. We provide some further examples showing that this statement also fails for ordered graphs avoiding other ordered trees. AU - Pach, János AU - Tomon, István ID - 9602 JF - Journal of Combinatorial Theory. Series B SN - 0095-8956 TI - Erdős-Hajnal-type results for monotone paths VL - 151 ER - TY - JOUR AB - Sound propagation is a macroscopic manifestation of the interplay between the equilibrium thermodynamics and the dynamical transport properties of fluids. Here, for a two-dimensional system of ultracold fermions, we calculate the first and second sound velocities across the whole BCS-BEC crossover, and we analyze the system response to an external perturbation. In the low-temperature regime we reproduce the recent measurements [Phys. Rev. Lett. 124, 240403 (2020)] of the first sound velocity, which, due to the decoupling of density and entropy fluctuations, is the sole mode excited by a density probe. Conversely, a heat perturbation excites only the second sound, which, being sensitive to the superfluid depletion, vanishes in the deep BCS regime and jumps discontinuously to zero at the Berezinskii-Kosterlitz-Thouless superfluid transition. A mixing between the modes occurs only in the finite-temperature BEC regime, where our theory converges to the purely bosonic results. AU - Tononi, A. AU - Cappellaro, Alberto AU - Bighin, Giacomo AU - Salasnich, L. ID - 9606 IS - 6 JF - Physical Review A SN - 24699926 TI - Propagation of first and second sound in a two-dimensional Fermi superfluid VL - 103 ER - TY - JOUR AB - Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain. AU - Venturino, Alessandro AU - Schulz, Rouven AU - De Jesús-Cortés, Héctor AU - Maes, Margaret E AU - Nagy, Balint AU - Reilly-Andújar, Francis AU - Colombo, Gloria AU - Cubero, Ryan J AU - Schoot Uiterkamp, Florianne E AU - Bear, Mark F. AU - Siegert, Sandra ID - 9642 IS - 1 JF - Cell Reports TI - Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain VL - 36 ER - TY - JOUR AB - Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division. AU - Contreras, Ximena AU - Amberg, Nicole AU - Davaatseren, Amarbayasgalan AU - Hansen, Andi H AU - Sonntag, Johanna AU - Andersen, Lill AU - Bernthaler, Tina AU - Streicher, Carmen AU - Heger, Anna-Magdalena AU - Johnson, Randy L. AU - Schwarz, Lindsay A. AU - Luo, Liqun AU - Rülicke, Thomas AU - Hippenmeyer, Simon ID - 9603 IS - 12 JF - Cell Reports TI - A genome-wide library of MADM mice for single-cell genetic mosaic analysis VL - 35 ER - TY - JOUR AB - The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science. AU - Bluvstein, D. AU - Omran, A. AU - Levine, H. AU - Keesling, A. AU - Semeghini, G. AU - Ebadi, S. AU - Wang, T. T. AU - Michailidis, Alexios AU - Maskara, N. AU - Ho, W. W. AU - Choi, S. AU - Serbyn, Maksym AU - Greiner, M. AU - Vuletić, V. AU - Lukin, M. D. ID - 9618 IS - 6536 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - Controlling quantum many-body dynamics in driven Rydberg atom arrays VL - 371 ER - TY - JOUR AB - To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia. AU - Gao, Z AU - Chen, Z AU - Cui, Y AU - Ke, M AU - Xu, H AU - Xu, Q AU - Chen, J AU - Li, Y AU - Huang, L AU - Zhao, H AU - Huang, D AU - Mai, S AU - Xu, T AU - Liu, X AU - Li, S AU - Guan, Y AU - Yang, W AU - Friml, Jiří AU - Petrášek, J AU - Zhang, J AU - Chen, X ID - 9657 IS - 9 JF - Plant Cell SN - 1040-4651 TI - GmPIN-dependent polar auxin transport is involved in soybean nodule development VL - 33 ER - TY - JOUR AB - Selection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed. AU - Tkadlec, Josef AU - Pavlogiannis, Andreas AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 9640 IS - 1 JF - Nature Communications TI - Fast and strong amplifiers of natural selection VL - 12 ER - TY - JOUR AB - Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underly differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, and a crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment. AU - Han, Huibin AU - Adamowski, Maciek AU - Qi, Linlin AU - Alotaibi, SS AU - Friml, Jiří ID - 9656 IS - 2 JF - New Phytologist SN - 0028-646x TI - PIN-mediated polar auxin transport regulations in plant tropic responses VL - 232 ER - TY - JOUR AB - The relative motion of three impenetrable particles on a ring, in our case two identical fermions and one impurity, is isomorphic to a triangular quantum billiard. Depending on the ratio κ of the impurity and fermion masses, the billiards can be integrable or non-integrable (also referred to in the main text as chaotic). To set the stage, we first investigate the energy level distributions of the billiards as a function of 1/κ ∈ [0, 1] and find no evidence of integrable cases beyond the limiting values 1/κ = 1 and 1/κ = 0. Then, we use machine learning tools to analyze properties of probability distributions of individual quantum states. We find that convolutional neural networks can correctly classify integrable and non-integrable states. The decisive features of the wave functions are the normalization and a large number of zero elements, corresponding to the existence of a nodal line. The network achieves typical accuracies of 97%, suggesting that machine learning tools can be used to analyze and classify the morphology of probability densities obtained in theory or experiment. AU - Huber, David AU - Marchukov, Oleksandr V. AU - Hammer, Hans Werner AU - Volosniev, Artem ID - 9679 IS - 6 JF - New Journal of Physics TI - Morphology of three-body quantum states from machine learning VL - 23 ER - TY - JOUR AB - Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis. AU - Yang, Qiutan AU - Xue, Shi-lei AU - Chan, Chii Jou AU - Rempfler, Markus AU - Vischi, Dario AU - Maurer-Gutierrez, Francisca AU - Hiiragi, Takashi AU - Hannezo, Edouard B AU - Liberali, Prisca ID - 9629 JF - Nature Cell Biology SN - 1465-7392 TI - Cell fate coordinates mechano-osmotic forces in intestinal crypt formation VL - 23 ER - TY - JOUR AB - SnSe, a wide-bandgap semiconductor, has attracted significant attention from the thermoelectric (TE) community due to its outstanding TE performance deriving from the ultralow thermal conductivity and advantageous electronic structures. Here, we promoted the TE performance of n-type SnSe polycrystals through bandgap engineering and vacancy compensation. We found that PbTe can significantly reduce the wide bandgap of SnSe to reduce the impurity transition energy, largely enhancing the carrier concentration. Also, PbTe-induced crystal symmetry promotion increases the carrier mobility, preserving large Seebeck coefficient. Consequently, a maximum ZT of ∼1.4 at 793 K is obtained in Br doped SnSe–13%PbTe. Furthermore, we found that extra Sn in n-type SnSe can compensate for the intrinsic Sn vacancies and form electron donor-like metallic Sn nanophases. The Sn nanophases near the grain boundary could also reduce the intergrain energy barrier which largely enhances the carrier mobility. As a result, a maximum ZT value of ∼1.7 at 793 K and an average ZT (ZTave) of ∼0.58 in 300–793 K are achieved in Br doped Sn1.08Se–13%PbTe. Our findings provide a novel strategy to promote the TE performance in wide-bandgap semiconductors. AU - Su, Lizhong AU - Hong, Tao AU - Wang, Dongyang AU - Wang, Sining AU - Qin, Bingchao AU - Zhang, Mengmeng AU - Gao, Xiang AU - Chang, Cheng AU - Zhao, Li Dong ID - 9626 JF - Materials Today Physics TI - Realizing high doping efficiency and thermoelectric performance in n-type SnSe polycrystals via bandgap engineering and vacancy compensation VL - 20 ER - TY - JOUR AB - The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses. AU - Vandael, David H AU - Okamoto, Yuji AU - Jonas, Peter M ID - 9778 IS - 1 JF - Nature Communications KW - general physics and astronomy KW - general biochemistry KW - genetics and molecular biology KW - general chemistry SN - 2041-1723 TI - Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses VL - 12 ER - TY - JOUR AB - Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof. AU - Petrov, Tatjana AU - Igler, Claudia AU - Sezgin, Ali AU - Henzinger, Thomas A AU - Guet, Calin C ID - 9647 JF - Theoretical Computer Science SN - 0304-3975 TI - Long lived transients in gene regulation VL - 893 ER - TY - JOUR AB - The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs. AU - Muench, Nicole A. AU - Patel, Sonia AU - Maes, Margaret E AU - Donahue, Ryan J. AU - Ikeda, Akihiro AU - Nickells, Robert W. ID - 9761 IS - 7 JF - Cells TI - The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease VL - 10 ER - TY - JOUR AB - At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation. AU - Fredes, Felipe AU - Shigemoto, Ryuichi ID - 9641 JF - Neurobiology of Learning and Memory SN - 10747427 TI - The role of hippocampal mossy cells in novelty detection VL - 183 ER - TY - CONF AB - We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude. AU - Wang, Jinyi AU - Sun, Yican AU - Fu, Hongfei AU - Chatterjee, Krishnendu AU - Goharshady, Amir Kafshdar ID - 9646 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Quantitative analysis of assertion violations in probabilistic programs ER - TY - CONF AB - We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis. We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods. AU - Asadi, Ali AU - Chatterjee, Krishnendu AU - Fu, Hongfei AU - Goharshady, Amir Kafshdar AU - Mahdavi, Mohammad ID - 9645 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Polynomial reachability witnesses via Stellensätze ER - TY - JOUR AU - Bartlett, Michael John AU - Arslan, Feyza N AU - Bankston, Adriana AU - Sarabipour, Sarvenaz ID - 9759 IS - 7 JF - PLoS Computational Biology SN - 1553734X TI - Ten simple rules to improve academic work- life balance VL - 17 ER - TY - JOUR AB - Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science. AU - Zisis, Themistoklis AU - Schwarz, Jan AU - Balles, Miriam AU - Kretschmer, Maibritt AU - Nemethova, Maria AU - Chait, Remy P AU - Hauschild, Robert AU - Lange, Janina AU - Guet, Calin C AU - Sixt, Michael K AU - Zahler, Stefan ID - 9822 IS - 30 JF - ACS Applied Materials and Interfaces SN - 19448244 TI - Sequential and switchable patterning for studying cellular processes under spatiotemporal control VL - 13 ER - TY - JOUR AB - Photorealistic editing of head portraits is a challenging task as humans are very sensitive to inconsistencies in faces. We present an approach for high-quality intuitive editing of the camera viewpoint and scene illumination (parameterised with an environment map) in a portrait image. This requires our method to capture and control the full reflectance field of the person in the image. Most editing approaches rely on supervised learning using training data captured with setups such as light and camera stages. Such datasets are expensive to acquire, not readily available and do not capture all the rich variations of in-the-wild portrait images. In addition, most supervised approaches only focus on relighting, and do not allow camera viewpoint editing. Thus, they only capture and control a subset of the reflectance field. Recently, portrait editing has been demonstrated by operating in the generative model space of StyleGAN. While such approaches do not require direct supervision, there is a significant loss of quality when compared to the supervised approaches. In this paper, we present a method which learns from limited supervised training data. The training images only include people in a fixed neutral expression with eyes closed, without much hair or background variations. Each person is captured under 150 one-light-at-a-time conditions and under 8 camera poses. Instead of training directly in the image space, we design a supervised problem which learns transformations in the latent space of StyleGAN. This combines the best of supervised learning and generative adversarial modeling. We show that the StyleGAN prior allows for generalisation to different expressions, hairstyles and backgrounds. This produces high-quality photorealistic results for in-the-wild images and significantly outperforms existing methods. Our approach can edit the illumination and pose simultaneously, and runs at interactive rates. AU - Mallikarjun, B. R. AU - Tewari, Ayush AU - Dib, Abdallah AU - Weyrich, Tim AU - Bickel, Bernd AU - Seidel, Hans Peter AU - Pfister, Hanspeter AU - Matusik, Wojciech AU - Chevallier, Louis AU - Elgharib, Mohamed A. AU - Theobalt, Christian ID - 9819 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - PhotoApp: Photorealistic appearance editing of head portraits VL - 40 ER - TY - JOUR AB - Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test. AU - Hledik, Michal AU - Polechova, Jitka AU - Beiglböck, Mathias AU - Herdina, Anna Nele AU - Strassl, Robert AU - Posch, Martin ID - 9816 IS - 7 JF - PLoS ONE TI - Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program VL - 16 ER - TY - JOUR AB - Heart rate variability (hrv) is a physiological phenomenon of the variation in the length of the time interval between consecutive heartbeats. In many cases it could be an indicator of the development of pathological states. The classical approach to the analysis of hrv includes time domain methods and frequency domain methods. However, attempts are still being made to define new and more effective hrv assessment tools. Persistent homology is a novel data analysis tool developed in the recent decades that is rooted at algebraic topology. The Topological Data Analysis (TDA) approach focuses on examining the shape of the data in terms of connectedness and holes, and has recently proved to be very effective in various fields of research. In this paper we propose the use of persistent homology to the hrv analysis. We recall selected topological descriptors used in the literature and we introduce some new topological descriptors that reflect the specificity of hrv, and we discuss their relation to the standard hrv measures. In particular, we show that this novel approach provides a collection of indices that might be at least as useful as the classical parameters in differentiating between series of beat-to-beat intervals (RR-intervals) in healthy subjects and patients suffering from a stroke episode. AU - Graff, Grzegorz AU - Graff, Beata AU - Pilarczyk, Pawel AU - Jablonski, Grzegorz AU - Gąsecki, Dariusz AU - Narkiewicz, Krzysztof ID - 9821 IS - 7 JF - PLoS ONE TI - Persistent homology as a new method of the assessment of heart rate variability VL - 16 ER - TY - JOUR AB - Material appearance hinges on material reflectance properties but also surface geometry and illumination. The unlimited number of potential combinations between these factors makes understanding and predicting material appearance a very challenging task. In this work, we collect a large-scale dataset of perceptual ratings of appearance attributes with more than 215,680 responses for 42,120 distinct combinations of material, shape, and illumination. The goal of this dataset is twofold. First, we analyze for the first time the effects of illumination and geometry in material perception across such a large collection of varied appearances. We connect our findings to those of the literature, discussing how previous knowledge generalizes across very diverse materials, shapes, and illuminations. Second, we use the collected dataset to train a deep learning architecture for predicting perceptual attributes that correlate with human judgments. We demonstrate the consistent and robust behavior of our predictor in various challenging scenarios, which, for the first time, enables estimating perceived material attributes from general 2D images. Since our predictor relies on the final appearance in an image, it can compare appearance properties across different geometries and illumination conditions. Finally, we demonstrate several applications that use our predictor, including appearance reproduction using 3D printing, BRDF editing by integrating our predictor in a differentiable renderer, illumination design, or material recommendations for scene design. AU - Serrano, Ana AU - Chen, Bin AU - Wang, Chao AU - Piovarci, Michael AU - Seidel, Hans Peter AU - Didyk, Piotr AU - Myszkowski, Karol ID - 9820 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - The effect of shape and illumination on material perception: Model and applications VL - 40 ER - TY - JOUR AB - Triangle mesh-based simulations are able to produce satisfying animations of knitted and woven cloth; however, they lack the rich geometric detail of yarn-level simulations. Naive texturing approaches do not consider yarn-level physics, while full yarn-level simulations may become prohibitively expensive for large garments. We propose a method to animate yarn-level cloth geometry on top of an underlying deforming mesh in a mechanics-aware fashion. Using triangle strains to interpolate precomputed yarn geometry, we are able to reproduce effects such as knit loops tightening under stretching. In combination with precomputed mesh animation or real-time mesh simulation, our method is able to animate yarn-level cloth in real-time at large scales. AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9818 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - Mechanics-aware deformation of yarn pattern geometry VL - 40 ER - TY - JOUR AB - Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals. AU - Gabrielaitis, Mantas ID - 9828 JF - IEEE Transactions on Signal Processing SN - 1053-587X TI - Fast and accurate amplitude demodulation of wideband signals VL - 69 ER - TY - COMP AB - This archive contains the missing sweater mesh animations and displacement models for the code of "Mechanics-Aware Deformation of Yarn Pattern Geometry" Code Repository: https://git.ist.ac.at/gsperl/MADYPG AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9327 TI - Mechanics-Aware Deformation of Yarn Pattern Geometry (Additional Animation/Model Data) ER - TY - JOUR AB - We study an effective one-dimensional quantum model that includes friction and spin-orbit coupling (SOC), and show that the model exhibits spin polarization when both terms are finite. Most important, strong spin polarization can be observed even for moderate SOC, provided that the friction is strong. Our findings might help to explain the pronounced effect of chirality on spin distribution and transport in chiral molecules. In particular, our model implies static magnetic properties of a chiral molecule, which lead to Shiba-like states when a molecule is placed on a superconductor, in accordance with recent experimental data. AU - Volosniev, Artem AU - Alpern, Hen AU - Paltiel, Yossi AU - Millo, Oded AU - Lemeshko, Mikhail AU - Ghazaryan, Areg ID - 9770 IS - 2 JF - Physical Review B SN - 2469-9950 TI - Interplay between friction and spin-orbit coupling as a source of spin polarization VL - 104 ER - TY - JOUR AB - The Nearest neighbour search (NNS) is a fundamental problem in many application domains dealing with multidimensional data. In a concurrent setting, where dynamic modifications are allowed, a linearizable implementation of the NNS is highly desirable.This paper introduces the LockFree-kD-tree (LFkD-tree ): a lock-free concurrent kD-tree, which implements an abstract data type (ADT) that provides the operations Add, Remove, Contains, and NNS. Our implementation is linearizable. The operations in the LFkD-tree use single-word read and compare-and-swap (Image 1 ) atomic primitives, which are readily supported on available multi-core processors. We experimentally evaluate the LFkD-tree using several benchmarks comprising real-world and synthetic datasets. The experiments show that the presented design is scalable and achieves significant speed-up compared to the implementations of an existing sequential kD-tree and a recently proposed multidimensional indexing structure, PH-tree. AU - Chatterjee, Bapi AU - Walulya, Ivan AU - Tsigas, Philippas ID - 9827 JF - Theoretical Computer Science KW - Concurrent data structure KW - kD-tree KW - Nearest neighbor search KW - Similarity search KW - Lock-free KW - Linearizability SN - 0304-3975 TI - Concurrent linearizable nearest neighbour search in LockFree-kD-tree VL - 886 ER - TY - JOUR AB - Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution. AU - Rodrigues, Jessica A. AU - Hsieh, Ping-Hung AU - Ruan, Deling AU - Nishimura, Toshiro AU - Sharma, Manoj K. AU - Sharma, Rita AU - Ye, XinYi AU - Nguyen, Nicholas D. AU - Nijjar, Sukhranjan AU - Ronald, Pamela C. AU - Fischer, Robert L. AU - Zilberman, Daniel ID - 9877 IS - 29 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting VL - 118 ER - TY - JOUR AB - Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart. AU - Raso, Andrea AU - Dirkx, Ellen AU - Sampaio-Pinto, Vasco AU - el Azzouzi, Hamid AU - Cubero, Ryan J AU - Sorensen, Daniel W. AU - Ottaviani, Lara AU - Olieslagers, Servé AU - Huibers, Manon M. AU - de Weger, Roel AU - Siddiqi, Sailay AU - Moimas, Silvia AU - Torrini, Consuelo AU - Zentillin, Lorena AU - Braga, Luca AU - Nascimento, Diana S. AU - da Costa Martins, Paula A. AU - van Berlo, Jop H. AU - Zacchigna, Serena AU - Giacca, Mauro AU - De Windt, Leon J. ID - 9874 JF - Nature Communications TI - A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration VL - 12 ER - TY - JOUR AB - A few years ago, flow equations were introduced as a technique for calculating the ground-state energies of cold Bose gases with and without impurities. In this paper, we extend this approach to compute observables other than the energy. As an example, we calculate the densities, and phase fluctuations of one-dimensional Bose gases with one and two impurities. For a single mobile impurity, we use flow equations to validate the mean-field results obtained upon the Lee-Low-Pines transformation. We show that the mean-field approximation is accurate for all values of the boson-impurity interaction strength as long as the phase coherence length is much larger than the healing length of the condensate. For two static impurities, we calculate impurity-impurity interactions induced by the Bose gas. We find that leading order perturbation theory fails when boson-impurity interactions are stronger than boson-boson interactions. The mean-field approximation reproduces the flow equation results for all values of the boson-impurity interaction strength as long as boson-boson interactions are weak. AU - Brauneis, Fabian AU - Hammer, Hans-Werner AU - Lemeshko, Mikhail AU - Volosniev, Artem ID - 9769 IS - 1 JF - SciPost Physics TI - Impurities in a one-dimensional Bose gas: The flow equation approach VL - 11 ER - TY - JOUR AB - Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs. AU - Batra, Aditi AU - Römhild, Roderich AU - Rousseau, Emilie AU - Franzenburg, Sören AU - Niemann, Stefan AU - Schulenburg, Hinrich ID - 9746 JF - eLife TI - High potency of sequential therapy with only beta-lactam antibiotics VL - 10 ER - TY - JOUR AB - A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics. AU - Nelson, Glyn AU - Boehm, Ulrike AU - Bagley, Steve AU - Bajcsy, Peter AU - Bischof, Johanna AU - Brown, Claire M. AU - Dauphin, Aurélien AU - Dobbie, Ian M. AU - Eriksson, John E. AU - Faklaris, Orestis AU - Fernandez-Rodriguez, Julia AU - Ferrand, Alexia AU - Gelman, Laurent AU - Gheisari, Ali AU - Hartmann, Hella AU - Kukat, Christian AU - Laude, Alex AU - Mitkovski, Miso AU - Munck, Sebastian AU - North, Alison J. AU - Rasse, Tobias M. AU - Resch-Genger, Ute AU - Schuetz, Lucas C. AU - Seitz, Arne AU - Strambio-De-Castillia, Caterina AU - Swedlow, Jason R. AU - Alexopoulos, Ioannis AU - Aumayr, Karin AU - Avilov, Sergiy AU - Bakker, Gert Jan AU - Bammann, Rodrigo R. AU - Bassi, Andrea AU - Beckert, Hannes AU - Beer, Sebastian AU - Belyaev, Yury AU - Bierwagen, Jakob AU - Birngruber, Konstantin A. AU - Bosch, Manel AU - Breitlow, Juergen AU - Cameron, Lisa A. AU - Chalfoun, Joe AU - Chambers, James J. AU - Chen, Chieh Li AU - Conde-Sousa, Eduardo AU - Corbett, Alexander D. AU - Cordelieres, Fabrice P. AU - Nery, Elaine Del AU - Dietzel, Ralf AU - Eismann, Frank AU - Fazeli, Elnaz AU - Felscher, Andreas AU - Fried, Hans AU - Gaudreault, Nathalie AU - Goh, Wah Ing AU - Guilbert, Thomas AU - Hadleigh, Roland AU - Hemmerich, Peter AU - Holst, Gerhard A. AU - Itano, Michelle S. AU - Jaffe, Claudia B. AU - Jambor, Helena K. AU - Jarvis, Stuart C. AU - Keppler, Antje AU - Kirchenbuechler, David AU - Kirchner, Marcel AU - Kobayashi, Norio AU - Krens, Gabriel AU - Kunis, Susanne AU - Lacoste, Judith AU - Marcello, Marco AU - Martins, Gabriel G. AU - Metcalf, Daniel J. AU - Mitchell, Claire A. AU - Moore, Joshua AU - Mueller, Tobias AU - Nelson, Michael S. AU - Ogg, Stephen AU - Onami, Shuichi AU - Palmer, Alexandra L. AU - Paul-Gilloteaux, Perrine AU - Pimentel, Jaime A. AU - Plantard, Laure AU - Podder, Santosh AU - Rexhepaj, Elton AU - Royon, Arnaud AU - Saari, Markku A. AU - Schapman, Damien AU - Schoonderwoert, Vincent AU - Schroth-Diez, Britta AU - Schwartz, Stanley AU - Shaw, Michael AU - Spitaler, Martin AU - Stoeckl, Martin T. AU - Sudar, Damir AU - Teillon, Jeremie AU - Terjung, Stefan AU - Thuenauer, Roland AU - Wilms, Christian D. AU - Wright, Graham D. AU - Nitschke, Roland ID - 9911 IS - 1 JF - Journal of Microscopy SN - 0022-2720 TI - QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy VL - 284 ER - TY - JOUR AB - Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways. AU - Yotova, Iveta AU - Hudson, Quanah J. AU - Pauler, Florian AU - Proestling, Katharina AU - Haslinger, Isabella AU - Kuessel, Lorenz AU - Perricos, Alexandra AU - Husslein, Heinrich AU - Wenzl, René ID - 9906 IS - 16 JF - International Journal of Molecular Sciences SN - 16616596 TI - LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line VL - 22 ER -