TY - JOUR
AB - Large oligomeric enzymes control a myriad of cellular processes, from protein synthesis and degradation to metabolism. The 0.5 MDa large TET2 aminopeptidase, a prototypical protease important for cellular homeostasis, degrades peptides within a ca. 60 Å wide tetrahedral chamber with four lateral openings. The mechanisms of substrate trafficking and processing remain debated. Here, we integrate magic-angle spinning (MAS) NMR, mutagenesis, co-evolution analysis and molecular dynamics simulations and reveal that a loop in the catalytic chamber is a key element for enzymatic function. The loop is able to stabilize ligands in the active site and may additionally have a direct role in activating the catalytic water molecule whereby a conserved histidine plays a key role. Our data provide a strong case for the functional importance of highly dynamic - and often overlooked - parts of an enzyme, and the potential of MAS NMR to investigate their dynamics at atomic resolution.
AU - Gauto, Diego F.
AU - Macek, Pavel
AU - Malinverni, Duccio
AU - Fraga, Hugo
AU - Paloni, Matteo
AU - Sučec, Iva
AU - Hessel, Audrey
AU - Bustamante, Juan Pablo
AU - Barducci, Alessandro
AU - Schanda, Paul
ID - 11179
JF - Nature Communications
TI - Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR
VL - 13
ER -
TY - JOUR
AB - Rotational dynamics of D2 molecules inside helium nanodroplets is induced by a moderately intense femtosecond pump pulse and measured as a function of time by recording the yield of HeD+ ions, created through strong-field dissociative ionization with a delayed femtosecond probe pulse. The yield oscillates with a period of 185 fs, reflecting field-free rotational wave packet dynamics, and the oscillation persists for more than 500 periods. Within the experimental uncertainty, the rotational constant BHe of the in-droplet D2 molecule, determined by Fourier analysis, is the same as Bgas for an isolated D2 molecule. Our observations show that the D2 molecules inside helium nanodroplets essentially rotate as free D2 molecules.
AU - Qiang, Junjie
AU - Zhou, Lianrong
AU - Lu, Peifen
AU - Lin, Kang
AU - Ma, Yongzhe
AU - Pan, Shengzhe
AU - Lu, Chenxu
AU - Jiang, Wenyu
AU - Sun, Fenghao
AU - Zhang, Wenbin
AU - Li, Hui
AU - Gong, Xiaochun
AU - Averbukh, Ilya Sh
AU - Prior, Yehiam
AU - Schouder, Constant A.
AU - Stapelfeldt, Henrik
AU - Cherepanov, Igor
AU - Lemeshko, Mikhail
AU - Jäger, Wolfgang
AU - Wu, Jian
ID - 11552
IS - 24
JF - Physical Review Letters
SN - 00319007
TI - Femtosecond rotational dynamics of D2 molecules in superfluid helium nanodroplets
VL - 128
ER -
TY - JOUR
AB - We revisit two basic Direct Simulation Monte Carlo Methods to model aggregation kinetics and extend them for aggregation processes with collisional fragmentation (shattering). We test the performance and accuracy of the extended methods and compare their performance with efficient deterministic finite-difference method applied to the same model. We validate the stochastic methods on the test problems and apply them to verify the existence of oscillating regimes in the aggregation-fragmentation kinetics recently detected in deterministic simulations. We confirm the emergence of steady oscillations of densities in such systems and prove the stability of the
oscillations with respect to fluctuations and noise.
AU - Kalinov, Aleksei
AU - Osinskiy, A.I.
AU - Matveev, S.A.
AU - Otieno, W.
AU - Brilliantov, N.V.
ID - 11556
JF - Journal of Computational Physics
KW - Computer Science Applications
KW - Physics and Astronomy (miscellaneous)
KW - Applied Mathematics
KW - Computational Mathematics
KW - Modeling and Simulation
KW - Numerical Analysis
SN - 0021-9991
TI - Direct simulation Monte Carlo for new regimes in aggregation-fragmentation kinetics
VL - 467
ER -
TY - JOUR
AB - Visualizing cell behavior and effector function on a single cell level has been crucial for understanding key aspects of mammalian biology. Due to their small size, large number and rapid recruitment into thrombi, there is a lack of data on fate and behavior of individual platelets in thrombosis and hemostasis. Here we report the use of platelet lineage restricted multi-color reporter mouse strains to delineate platelet function on a single cell level. We show that genetic labeling allows for single platelet and megakaryocyte (MK) tracking and morphological analysis in vivo and in vitro, while not affecting lineage functions. Using Cre-driven Confetti expression, we provide insights into temporal gene expression patterns as well as spatial clustering of MK in the bone marrow. In the vasculature, shape analysis of activated platelets recruited to thrombi identifies ubiquitous filopodia formation with no evidence of lamellipodia formation. Single cell tracking in complex thrombi reveals prominent myosin-dependent motility of platelets and highlights thrombus formation as a highly dynamic process amenable to modification and intervention of the acto-myosin cytoskeleton. Platelet function assays combining flow cytrometry, as well as in vivo, ex vivo and in vitro imaging show unaltered platelet functions of multicolor reporter mice compared to wild-type controls. In conclusion, platelet lineage multicolor reporter mice prove useful in furthering our understanding of platelet and MK biology on a single cell level.
AU - Nicolai, Leo
AU - Kaiser, Rainer
AU - Escaig, Raphael
AU - Hoffknecht, Marie Louise
AU - Anjum, Afra
AU - Leunig, Alexander
AU - Pircher, Joachim
AU - Ehrlich, Andreas
AU - Lorenz, Michael
AU - Ishikawa-Ankerhold, Hellen
AU - Aird, William C.
AU - Massberg, Steffen
AU - Gärtner, Florian R
ID - 11588
IS - 7
JF - Haematologica
SN - 0390-6078
TI - Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo
VL - 107
ER -
TY - JOUR
AB - We investigate the ground-state properties of weakly repulsive one-dimensional bosons in the presence of an attractive zero-range impurity potential. First, we derive mean-field solutions to the problem on a finite ring for the two asymptotic cases: (i) all bosons are bound to the impurity and (ii) all bosons are in a scattering state. Moreover, we derive the critical line that separates these regimes in the parameter space. In the thermodynamic limit, this critical line determines the maximum number of bosons that can be bound by the impurity potential, forming an artificial atom. Second, we validate the mean-field results using the flow equation approach and the multi-layer multi-configuration time-dependent Hartree method for atomic mixtures. While beyond-mean-field effects destroy long-range order in the Bose gas, the critical boson number is unaffected. Our findings are important for understanding such artificial atoms in low-density Bose gases with static and mobile impurities.
AU - Brauneis, Fabian
AU - Backert, Timothy G.
AU - Mistakidis, Simeon I.
AU - Lemeshko, Mikhail
AU - Hammer, Hans Werner
AU - Volosniev, Artem
ID - 11590
IS - 6
JF - New Journal of Physics
SN - 1367-2630
TI - Artificial atoms from cold bosons in one dimension
VL - 24
ER -
TY - JOUR
AB - We investigate the deterministic generation and distribution of entanglement in large quantum networks by driving distant qubits with the output fields of a nondegenerate parametric amplifier. In this setting, the amplifier produces a continuous Gaussian two-mode squeezed state, which acts as a quantum-correlated reservoir for the qubits and relaxes them into a highly entangled steady state. Here we are interested in the maximal amount of entanglement and the optimal entanglement generation rates that can be achieved with this scheme under realistic conditions taking, in particular, the finite amplifier bandwidth, waveguide losses, and propagation delays into account. By combining exact numerical simulations of the full network with approximate analytic results, we predict the optimal working point for the amplifier and the corresponding qubit-qubit entanglement under various conditions. Our findings show that this passive conversion of Gaussian into discrete-variable entanglement offers a robust and experimentally very attractive approach for operating large optical, microwave, or hybrid quantum networks, for which efficient parametric amplifiers are currently developed.
AU - Agustí, J.
AU - Minoguchi, Y.
AU - Fink, Johannes M
AU - Rabl, P.
ID - 11591
IS - 6
JF - Physical Review A
SN - 2469-9926
TI - Long-distance distribution of qubit-qubit entanglement using Gaussian-correlated photonic beams
VL - 105
ER -
TY - JOUR
AB - We compare recent experimental results [Science 375, 528 (2022)] of the superfluid unitary Fermi gas near the critical temperature with a thermodynamic model based on the elementary excitations of the system. We find good agreement between experimental data and our theory for several quantities such as first sound, second sound, and superfluid fraction. We also show that mode mixing between first and second sound occurs. Finally, we characterize the response amplitude to a density perturbation: Close to the critical temperature both first and second sound can be excited through a density perturbation, whereas at lower temperatures only the first sound mode exhibits a significant response.
AU - Bighin, Giacomo
AU - Cappellaro, Alberto
AU - Salasnich, L.
ID - 11592
IS - 6
JF - Physical Review A
SN - 2469-9926
TI - Unitary Fermi superfluid near the critical temperature: Thermodynamics and sound modes from elementary excitations
VL - 105
ER -
TY - JOUR
AB - Background: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.
Results: We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts—twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage.
Conclusions: AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species.
AU - Zhang, Runxuan
AU - Kuo, Richard
AU - Coulter, Max
AU - Calixto, Cristiane P.G.
AU - Entizne, Juan Carlos
AU - Guo, Wenbin
AU - Marquez, Yamile
AU - Milne, Linda
AU - Riegler, Stefan
AU - Matsui, Akihiro
AU - Tanaka, Maho
AU - Harvey, Sarah
AU - Gao, Yubang
AU - Wießner-Kroh, Theresa
AU - Paniagua, Alejandro
AU - Crespi, Martin
AU - Denby, Katherine
AU - Hur, Asa Ben
AU - Huq, Enamul
AU - Jantsch, Michael
AU - Jarmolowski, Artur
AU - Koester, Tino
AU - Laubinger, Sascha
AU - Li, Qingshun Quinn
AU - Gu, Lianfeng
AU - Seki, Motoaki
AU - Staiger, Dorothee
AU - Sunkar, Ramanjulu
AU - Szweykowska-Kulinska, Zofia
AU - Tu, Shih Long
AU - Wachter, Andreas
AU - Waugh, Robbie
AU - Xiong, Liming
AU - Zhang, Xiao Ning
AU - Conesa, Ana
AU - Reddy, Anireddy S.N.
AU - Barta, Andrea
AU - Kalyna, Maria
AU - Brown, John W.S.
ID - 11587
JF - Genome Biology
TI - A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis
VL - 23
ER -
TY - JOUR
AB - Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.
AU - Saona Urmeneta, Raimundo J
AU - Kondrashov, Fyodor
AU - Khudiakova, Kseniia
ID - 11447
IS - 8
JF - Bulletin of Mathematical Biology
KW - Computational Theory and Mathematics
KW - General Agricultural and Biological Sciences
KW - Pharmacology
KW - General Environmental Science
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Mathematics
KW - Immunology
KW - General Neuroscience
SN - 0092-8240
TI - Relation between the number of peaks and the number of reciprocal sign epistatic interactions
VL - 84
ER -
TY - JOUR
AB - In this article we study the noncommutative transport distance introduced by Carlen and Maas and its entropic regularization defined by Becker and Li. We prove a duality formula that can be understood as a quantum version of the dual Benamou–Brenier formulation of the Wasserstein distance in terms of subsolutions of a Hamilton–Jacobi–Bellmann equation.
AU - Wirth, Melchior
ID - 11330
IS - 2
JF - Journal of Statistical Physics
SN - 00224715
TI - A dual formula for the noncommutative transport distance
VL - 187
ER -
TY - JOUR
AB - Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.
AU - Assen, Frank P
AU - Abe, Jun
AU - Hons, Miroslav
AU - Hauschild, Robert
AU - Shamipour, Shayan
AU - Kaufmann, Walter
AU - Costanzo, Tommaso
AU - Krens, Gabriel
AU - Brown, Markus
AU - Ludewig, Burkhard
AU - Hippenmeyer, Simon
AU - Heisenberg, Carl-Philipp J
AU - Weninger, Wolfgang
AU - Hannezo, Edouard B
AU - Luther, Sanjiv A.
AU - Stein, Jens V.
AU - Sixt, Michael K
ID - 9794
JF - Nature Immunology
SN - 1529-2908
TI - Multitier mechanics control stromal adaptations in swelling lymph nodes
ER -
TY - JOUR
AB - The ability to detect and respond to acute oxygen (O2) shortages is indispensable to aerobic life. The molecular mechanisms and circuits underlying this capacity are poorly understood. Here, we characterize the behavioral responses of feeding Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. While the behavioral responses to 1% O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome function inhibits escape from 1% O2 due to increased cGMP signaling. A primary source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP) receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+ decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial complex I (MCIII), which lead to persistently high reactive oxygen species (ROS), abrogate acute hypoxia responses. In particular, repressing the expression of isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1% O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia responses. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute responses to hypoxia by C. elegans.
AU - Zhao, Lina
AU - Fenk, Lorenz A.
AU - Nilsson, Lars
AU - Amin-Wetzel, Niko Paresh
AU - Ramirez, Nelson
AU - De Bono, Mario
AU - Chen, Changchun
ID - 11637
IS - 6
JF - PLoS Biology
TI - ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans
VL - 20
ER -
TY - JOUR
AB - Statistical inference is central to many scientific endeavors, yet how it works remains unresolved. Answering this requires a quantitative understanding of the intrinsic interplay between statistical models, inference methods, and the structure in the data. To this end, we characterize the efficacy of direct coupling analysis (DCA)—a highly successful method for analyzing amino acid sequence data—in inferring pairwise interactions from samples of ferromagnetic Ising models on random graphs. Our approach allows for physically motivated exploration of qualitatively distinct data regimes separated by phase transitions. We show that inference quality depends strongly on the nature of data-generating distributions: optimal accuracy occurs at an intermediate temperature where the detrimental effects from macroscopic order and thermal noise are minimal. Importantly our results indicate that DCA does not always outperform its local-statistics-based predecessors; while DCA excels at low temperatures, it becomes inferior to simple correlation thresholding at virtually all temperatures when data are limited. Our findings offer insights into the regime in which DCA operates so successfully, and more broadly, how inference interacts with the structure in the data.
AU - Ngampruetikorn, Vudtiwat
AU - Sachdeva, Vedant
AU - Torrence, Johanna
AU - Humplik, Jan
AU - Schwab, David J.
AU - Palmer, Stephanie E.
ID - 11638
IS - 2
JF - Physical Review Research
SN - 2643-1564
TI - Inferring couplings in networks across order-disorder phase transitions
VL - 4
ER -
TY - JOUR
AB - Many studies have quantified the distribution of heterozygosity and relatedness in natural populations, but few have examined the demographic processes driving these patterns. In this study, we take a novel approach by studying how population structure affects both pairwise identity and the distribution of heterozygosity in a natural population of the self-incompatible plant Antirrhinum majus. Excess variance in heterozygosity between individuals is due to identity disequilibrium, which reflects the variance in inbreeding between individuals; it is measured by the statistic g2. We calculated g2 together with FST and pairwise relatedness (Fij) using 91 SNPs in 22,353 individuals collected over 11 years. We find that pairwise Fij declines rapidly over short spatial scales, and the excess variance in heterozygosity between individuals reflects significant variation in inbreeding. Additionally, we detect an excess of individuals with around half the average heterozygosity, indicating either selfing or matings between close relatives. We use 2 types of simulation to ask whether variation in heterozygosity is consistent with fine-scale spatial population structure. First, by simulating offspring using parents drawn from a range of spatial scales, we show that the known pollen dispersal kernel explains g2. Second, we simulate a 1,000-generation pedigree using the known dispersal and spatial distribution and find that the resulting g2 is consistent with that observed from the field data. In contrast, a simulated population with uniform density underestimates g2, indicating that heterogeneous density promotes identity disequilibrium. Our study shows that heterogeneous density and leptokurtic dispersal can together explain the distribution of heterozygosity.
AU - Surendranadh, Parvathy
AU - Arathoon, Louise S
AU - Baskett, Carina
AU - Field, David
AU - Pickup, Melinda
AU - Barton, Nicholas H
ID - 11411
IS - 3
JF - Genetics
TI - Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study of Antirrhinum majus
VL - 221
ER -
TY - DATA
AB - Here are the research data underlying the publication "Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study of Antirrhinum majus" Further information are summed up in the README document.
AU - Surendranadh, Parvathy
AU - Arathoon, Louise S
AU - Baskett, Carina
AU - Field, David
AU - Pickup, Melinda
AU - Barton, Nicholas H
ID - 11321
TI - Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study of Antirrhinum majus
ER -
TY - JOUR
AB - The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.
AU - Hansen, Andi H
AU - Pauler, Florian
AU - Riedl, Michael
AU - Streicher, Carmen
AU - Heger, Anna-Magdalena
AU - Laukoter, Susanne
AU - Sommer, Christoph M
AU - Nicolas, Armel
AU - Hof, Björn
AU - Tsai, Li Huei
AU - Rülicke, Thomas
AU - Hippenmeyer, Simon
ID - 10791
IS - 1
JF - Oxford Open Neuroscience
TI - Tissue-wide effects override cell-intrinsic gene function in radial neuron migration
VL - 1
ER -
TY - JOUR
AB - The depth of a cell in an arrangement of n (non-vertical) great-spheres in Sd is the number of great-spheres that pass above the cell. We prove Euler-type relations, which imply extensions of the classic Dehn–Sommerville relations for convex polytopes to sublevel sets of the depth function, and we use the relations to extend the expressions for the number of faces of neighborly polytopes to the number of cells of levels in neighborly arrangements.
AU - Biswas, Ranita
AU - Cultrera di Montesano, Sebastiano
AU - Edelsbrunner, Herbert
AU - Saghafian, Morteza
ID - 11658
JF - Leibniz International Proceedings on Mathematics
TI - Depth in arrangements: Dehn–Sommerville–Euler relations with applications
ER -
TY - JOUR
AB - We characterize critical points of 1-dimensional maps paired in persistent homology geometrically and this way get elementary proofs of theorems about the symmetry of persistence diagrams and the variation of such maps. In particular, we identify branching points and endpoints of networks as the sole source of asymmetry and relate the cycle basis in persistent homology with a version of the stable marriage problem. Our analysis provides the foundations of fast algorithms for maintaining collections of interrelated sorted lists together with their persistence diagrams.
AU - Biswas, Ranita
AU - Cultrera di Montesano, Sebastiano
AU - Edelsbrunner, Herbert
AU - Saghafian, Morteza
ID - 11660
JF - LIPIcs
TI - A window to the persistence of 1D maps. I: Geometric characterization of critical point pairs
ER -
TY - JOUR
AB - We compute the deterministic approximation of products of Sobolev functions of large Wigner matrices W and provide an optimal error bound on their fluctuation with very high probability. This generalizes Voiculescu's seminal theorem from polynomials to general Sobolev functions, as well as from tracial quantities to individual matrix elements. Applying the result to eitW for large t, we obtain a precise decay rate for the overlaps of several deterministic matrices with temporally well separated Heisenberg time evolutions; thus we demonstrate the thermalisation effect of the unitary group generated by Wigner matrices.
AU - Cipolloni, Giorgio
AU - Erdös, László
AU - Schröder, Dominik J
ID - 10732
IS - 8
JF - Journal of Functional Analysis
SN - 0022-1236
TI - Thermalisation for Wigner matrices
VL - 282
ER -
TY - JOUR
AB - Mathematical models often aim to describe a complicated mechanism in a cohesive and simple manner. However, reaching perfect balance between being simple enough or overly simplistic is a challenging task. Frequently, game-theoretic models have an underlying assumption that players, whenever they choose to execute a specific action, do so perfectly. In fact, it is rare that action execution perfectly coincides with intentions of individuals, giving rise to behavioural mistakes. The concept of incompetence of players was suggested to address this issue in game-theoretic settings. Under the assumption of incompetence, players have non-zero probabilities of executing a different strategy from the one they chose, leading to stochastic outcomes of the interactions. In this article, we survey results related to the concept of incompetence in classic as well as evolutionary game theory and provide several new results. We also suggest future extensions of the model and argue why it is important to take into account behavioural mistakes when analysing interactions among players in both economic and biological settings.
AU - Graham, Thomas
AU - Kleshnina, Maria
AU - Filar, Jerzy A.
ID - 10770
JF - Dynamic Games and Applications
SN - 2153-0785
TI - Where do mistakes lead? A survey of games with incompetent players
ER -
TY - JOUR
AB - We introduce tropical corals, balanced trees in a half-space, and show that they correspond to holomorphic polygons capturing the product rule in Lagrangian Floer theory for the elliptic curve. We then prove a correspondence theorem equating counts of tropical corals to punctured log Gromov–Witten invariants of the Tate curve. This implies that the homogeneous coordinate ring of the mirror to the Tate curve is isomorphic to the degree-zero part of symplectic cohomology, confirming a prediction of homological mirror symmetry.
AU - Arguez, Nuroemuer Huelya
ID - 10772
IS - 1
JF - Journal of the London Mathematical Society
SN - 0024-6107
TI - Mirror symmetry for the Tate curve via tropical and log corals
VL - 105
ER -
TY - GEN
AB - Background
Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology .
Methods
Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild type cells concomitantly in vivo using immunofluorescent techniques.
Results
We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients.
Conclusions
Our genetic approach revealed several cell autonomous requirements of Wdfy3 in neuronal development that could underly the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for Wdfy3 in regulating neuronal function and interconnectivity in postnatal life.
AU - Schaaf, Zachary
AU - Tat, Lyvin
AU - Cannizzaro, Noemi
AU - Green, Ralph
AU - Rülicke, Thomas
AU - Hippenmeyer, Simon
AU - Zarbalis, K
ID - 10792
TI - WDFY3 cell autonomously controls neuronal migration
ER -
TY - JOUR
AB - We establish the Hardy-Littlewood property (à la Borovoi-Rudnick) for Zariski open subsets in affine quadrics of the form q(x1,...,xn)=m, where q is a non-degenerate integral quadratic form in n>3 variables and m is a non-zero integer. This gives asymptotic formulas for the density of integral points taking coprime polynomial values, which is a quantitative version of the arithmetic purity of strong approximation property off infinity for affine quadrics.
AU - Cao, Yang
AU - Huang, Zhizhong
ID - 10765
IS - 3
JF - Advances in Mathematics
SN - 0001-8708
TI - Arithmetic purity of the Hardy-Littlewood property and geometric sieve for affine quadrics
VL - 398
ER -
TY - JOUR
AB - Enabling additive manufacturing to employ a wide range of novel, functional materials can be a major boost to this technology. However, making such materials printable requires painstaking trial-and-error by an expert operator,
as they typically tend to exhibit peculiar rheological or hysteresis properties. Even in the case of successfully finding the process parameters, there is no guarantee of print-to-print consistency due to material differences between batches. These challenges make closed-loop feedback an attractive option where the process parameters are adjusted on-the-fly. There are several challenges for designing an efficient controller: the deposition parameters are complex and highly coupled, artifacts occur after long time horizons, simulating the deposition is computationally costly, and learning on hardware is intractable. In this work, we demonstrate the feasibility of learning a closed-loop control policy for additive manufacturing using reinforcement learning. We show that approximate, but efficient, numerical simulation is
sufficient as long as it allows learning the behavioral patterns of deposition that translate to real-world experiences. In combination with reinforcement learning, our model can be used to discover control policies that outperform
baseline controllers. Furthermore, the recovered policies have a minimal sim-to-real gap. We showcase this by applying our control policy in-vivo on a single-layer, direct ink writing printer.
AU - Piovarci, Michael
AU - Foshey, Michael
AU - Xu, Jie
AU - Erps, Timothy
AU - Babaei, Vahid
AU - Didyk, Piotr
AU - Rusinkiewicz, Szymon
AU - Matusik, Wojciech
AU - Bickel, Bernd
ID - 11442
IS - 4
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - Closed-loop control of direct ink writing via reinforcement learning
VL - 41
ER -
TY - JOUR
AB - Cell dispersion from a confined area is fundamental in a number of biological processes,
including cancer metastasis. To date, a quantitative understanding of the interplay of single
cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role
of E- and N-Cadherin junctions, central components of intercellular contacts, is still
controversial. Combining theoretical modeling with in vitro observations, we investigate the
collective spreading behavior of colonies of human cancer cells (T24). The spreading of these
colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts.
We find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average
spreading velocities, without affecting the strength of correlations in spreading velocities of
neighboring cells. Based on a biophysical simulation model for cell migration, we show that the
behavioral changes upon disruption of these junctions can be explained by reduced repulsive
excluded volume interactions between cells. This suggests that in cancer cell migration,
cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than
cohesive interactions between cells, thereby promoting efficient cell spreading during collective
migration.
AU - Zisis, Themistoklis
AU - Brückner, David
AU - Brandstätter, Tom
AU - Siow, Wei Xiong
AU - d’Alessandro, Joseph
AU - Vollmar, Angelika M.
AU - Broedersz, Chase P.
AU - Zahler, Stefan
ID - 10530
IS - 1
JF - Biophysical Journal
KW - Biophysics
SN - 0006-3495
TI - Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration
VL - 121
ER -
TY - JOUR
AB - This paper characterizes the latency of the simplified successive-cancellation (SSC) decoding scheme for polar codes under hardware resource constraints. In particular, when the number of processing elements P that can perform SSC decoding operations in parallel is limited, as is the case in practice, the latency of SSC decoding is O(N1-1/μ + N/P log2 log2 N/P), where N is the block length of the code and μ is the scaling exponent of the channel. Three direct consequences of this bound are presented. First, in a fully-parallel implementation where P = N/2, the latency of SSC decoding is O(N1-1/μ), which is sublinear in the block length. This recovers a result from our earlier work. Second, in a fully-serial implementation where P = 1, the latency of SSC decoding scales as O(N log2 log2 N). The multiplicative constant is also calculated: we show that the latency of SSC decoding when P = 1 is given by (2 + o(1))N log2 log2 N. Third, in a semi-parallel implementation, the smallest P that gives the same latency as that of the fully-parallel implementation is P = N1/μ. The tightness of our bound on SSC decoding latency and the applicability of the foregoing results is validated through extensive simulations.
AU - Hashemi, Seyyed Ali
AU - Mondelli, Marco
AU - Fazeli, Arman
AU - Vardy, Alexander
AU - Cioffi, John
AU - Goldsmith, Andrea
ID - 10364
IS - 6
JF - IEEE Transactions on Wireless Communications
SN - 1536-1276
TI - Parallelism versus latency in simplified successive-cancellation decoding of polar codes
VL - 21
ER -
TY - JOUR
AB - Sometimes, it is possible to represent a complicated polytope as a projection of a much simpler polytope. To quantify this phenomenon, the extension complexity of a polytope P is defined to be the minimum number of facets of a (possibly higher-dimensional) polytope from which P can be obtained as a (linear) projection. This notion is motivated by its relevance to combinatorial optimisation, and has been studied intensively for various specific polytopes associated with important optimisation problems. In this paper we study extension complexity as a parameter of general polytopes, more specifically considering various families of low-dimensional polytopes. First, we prove that for a fixed dimension d, the extension complexity of a random d-dimensional polytope (obtained as the convex hull of random points in a ball or on a sphere) is typically on the order of the square root of its number of vertices. Second, we prove that any cyclic n-vertex polygon (whose vertices lie on a circle) has extension complexity at most 24√n. This bound is tight up to the constant factor 24. Finally, we show that there exists an no(1)-dimensional polytope with at most n vertices and extension complexity n1−o(1). Our theorems are proved with a range of different techniques, which we hope will be of further interest.
AU - Kwan, Matthew Alan
AU - Sauermann, Lisa
AU - Zhao, Yufei
ID - 11443
IS - 6
JF - Transactions of the American Mathematical Society
SN - 0002-9947
TI - Extension complexity of low-dimensional polytopes
VL - 375
ER -
TY - JOUR
AB - Polyploidization may precipitate dramatic changes to the genome, including chromosome rearrangements, gene loss, and changes in gene expression. In dioecious plants, the sex-determining mechanism may also be disrupted by polyploidization, with the potential evolution of hermaphroditism. However, while dioecy appears to have persisted through a ploidy transition in some species, it is unknown whether the newly formed polyploid maintained its sex-determining system uninterrupted, or whether dioecy re-evolved after a period of hermaphroditism. Here, we develop a bioinformatic pipeline using RNA-sequencing data from natural populations to demonstrate that the allopolyploid plant Mercurialis canariensis directly inherited its sex-determining region from one of its diploid progenitor species, M. annua, and likely remained dioecious through the transition. The sex-determining region of M. canariensis is smaller than that of its diploid progenitor, suggesting that the non-recombining region of M. annua expanded subsequent to the polyploid origin of M. canariensis. Homeologous pairs show partial sexual subfunctionalization. We discuss the possibility that gene duplicates created by polyploidization might contribute to resolving sexual antagonism.
AU - Toups, Melissa A
AU - Vicoso, Beatriz
AU - Pannell, John R.
ID - 11703
IS - 7
JF - PLoS Genetics
TI - Dioecy and chromosomal sex determination are maintained through allopolyploid speciation in the plant genus Mercurialis
VL - 18
ER -
TY - CONF
AB - In this work we introduce the graph-theoretic notion of mendability: for each locally checkable graph problem we can define its mending radius, which captures the idea of how far one needs to modify a partial solution in order to “patch a hole.” We explore how mendability is connected to the existence of efficient algorithms, especially in distributed, parallel, and fault-tolerant settings. It is easy to see that O(1)-mendable problems are also solvable in O(log∗n) rounds in the LOCAL model of distributed computing. One of the surprises is that in paths and cycles, a converse also holds in the following sense: if a problem Π can be solved in O(log∗n), there is always a restriction Π′⊆Π that is still efficiently solvable but that is also O(1)-mendable. We also explore the structure of the landscape of mendability. For example, we show that in trees, the mending radius of any locally checkable problem is O(1), Θ(logn), or Θ(n), while in general graphs the structure is much more diverse.
AU - Balliu, Alkida
AU - Hirvonen, Juho
AU - Melnyk, Darya
AU - Olivetti, Dennis
AU - Rybicki, Joel
AU - Suomela, Jukka
ED - Parter, Merav
ID - 11707
SN - 0302-9743
T2 - International Colloquium on Structural Information and Communication Complexity
TI - Local mending
VL - 13298
ER -
TY - JOUR
AB - We say that (Formula presented.) if, in every edge coloring (Formula presented.), we can find either a 1-colored copy of (Formula presented.) or a 2-colored copy of (Formula presented.). The well-known states that the threshold for the property (Formula presented.) is equal to (Formula presented.), where (Formula presented.) is given by (Formula presented.) for any pair of graphs (Formula presented.) and (Formula presented.) with (Formula presented.). In this article, we show the 0-statement of the Kohayakawa–Kreuter conjecture for every pair of cycles and cliques.
AU - Liebenau, Anita
AU - Mattos, Letícia
AU - Mendonca Dos Santos, Walner
AU - Skokan, Jozef
ID - 11706
JF - Random Structures and Algorithms
SN - 1042-9832
TI - Asymmetric Ramsey properties of random graphs involving cliques and cycles
ER -
TY - JOUR
AB - Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA).
Results: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes.
AU - Nikolic, Nela
AU - Sauert, Martina
AU - Albanese, Tanino G.
AU - Moll, Isabella
ID - 11713
JF - BMC Research Notes
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Medicine
SN - 1756-0500
TI - Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli
VL - 15
ER -
TY - JOUR
AB - In this paper we develop a new approach to nonlinear stochastic partial differential equations with Gaussian noise. Our aim is to provide an abstract framework which is applicable to a large class of SPDEs and includes many important cases of nonlinear parabolic problems which are of quasi- or semilinear type. This first part is on local existence and well-posedness. A second part in preparation is on blow-up criteria and regularization. Our theory is formulated in an Lp-setting, and because of this we can deal with nonlinearities in a very efficient way. Applications to several concrete problems and their quasilinear variants are given. This includes Burgers' equation, the Allen–Cahn equation, the Cahn–Hilliard equation, reaction–diffusion equations, and the porous media equation. The interplay of the nonlinearities and the critical spaces of initial data leads to new results and insights for these SPDEs. The proofs are based on recent developments in maximal regularity theory for the linearized problem for deterministic and stochastic evolution equations. In particular, our theory can be seen as a stochastic version of the theory of critical spaces due to Prüss–Simonett–Wilke (2018). Sharp weighted time-regularity allow us to deal with rough initial values and obtain instantaneous regularization results. The abstract well-posedness results are obtained by a combination of several sophisticated splitting and truncation arguments.
AU - Agresti, Antonio
AU - Veraar, Mark
ID - 11701
IS - 8
JF - Nonlinearity
SN - 0951-7715
TI - Nonlinear parabolic stochastic evolution equations in critical spaces Part I. Stochastic maximal regularity and local existence
VL - 35
ER -
TY - JOUR
AB - When Mendel’s work was rediscovered in 1900, and extended to establish classical genetics, it was initially seen in opposition to Darwin’s theory of evolution by natural selection on continuous variation, as represented by the biometric research program that was the foundation of quantitative genetics. As Fisher, Haldane, and Wright established a century ago, Mendelian inheritance is exactly what is needed for natural selection to work efficiently. Yet, the synthesis remains unfinished. We do not understand why sexual reproduction and a fair meiosis predominate in eukaryotes, or how far these are responsible for their diversity and complexity. Moreover, although quantitative geneticists have long known that adaptive variation is highly polygenic, and that this is essential for efficient selection, this is only now becoming appreciated by molecular biologists—and we still do not have a good framework for understanding polygenic variation or diffuse function.
AU - Barton, Nicholas H
ID - 11702
IS - 30
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
TI - The "New Synthesis"
VL - 119
ER -
TY - JOUR
AB - This paper contains two contributions in the study of optimal transport on metric graphs. Firstly, we prove a Benamou–Brenier formula for the Wasserstein distance, which establishes the equivalence of static and dynamical optimal transport. Secondly, in the spirit of Jordan–Kinderlehrer–Otto, we show that McKean–Vlasov equations can be formulated as gradient flow of the free energy in the Wasserstein space of probability measures. The proofs of these results are based on careful regularisation arguments to circumvent some of the difficulties arising in metric graphs, namely, branching of geodesics and the failure of semi-convexity of entropy functionals in the Wasserstein space.
AU - Erbar, Matthias
AU - Forkert, Dominik L
AU - Maas, Jan
AU - Mugnolo, Delio
ID - 11700
IS - 5
JF - Networks and Heterogeneous Media
SN - 1556-1801
TI - Gradient flow formulation of diffusion equations in the Wasserstein space over a metric graph
VL - 17
ER -
TY - JOUR
AB - A species distributed across diverse environments may adapt to local conditions. We ask how quickly such a species changes its range in response to changed conditions. Szép et al. (Szép E, Sachdeva H, Barton NH. 2021 Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model. Evolution75, 1030–1045 (doi:10.1111/evo.14210)) used the infinite island model to find the stationary distribution of allele frequencies and deme sizes. We extend this to find how a metapopulation responds to changes in carrying capacity, selection strength, or migration rate when deme sizes are fixed. We further develop a ‘fixed-state’ approximation. Under this approximation, polymorphism is only possible for a narrow range of habitat proportions when selection is weak compared to drift, but for a much wider range otherwise. When rates of selection or migration relative to drift change in a single deme of the metapopulation, the population takes a time of order m−1 to reach the new equilibrium. However, even with many loci, there can be substantial fluctuations in net adaptation, because at each locus, alleles randomly get lost or fixed. Thus, in a finite metapopulation, variation may gradually be lost by chance, even if it would persist in an infinite metapopulation. When conditions change across the whole metapopulation, there can be rapid change, which is predicted well by the fixed-state approximation. This work helps towards an understanding of how metapopulations extend their range across diverse environments.
This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
AU - Barton, Nicholas H
AU - Olusanya, Oluwafunmilola O
ID - 10787
IS - 1848
JF - Philosophical Transactions of the Royal Society B: Biological Sciences
KW - General Agricultural and Biological Sciences
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 0962-8436
TI - The response of a metapopulation to a changing environment
VL - 377
ER -
TY - JOUR
AB - The Voronoi tessellation in Rd is defined by locally minimizing the power distance to given weighted points. Symmetrically, the Delaunay mosaic can be defined by locally maximizing the negative power distance to other such points. We prove that the average of the two piecewise quadratic functions is piecewise linear, and that all three functions have the same critical points and values. Discretizing the two piecewise quadratic functions, we get the alpha shapes as sublevel sets of the discrete function on the Delaunay mosaic, and analogous shapes as superlevel sets of the discrete function on the Voronoi tessellation. For the same non-critical value, the corresponding shapes are disjoint, separated by a narrow channel that contains no critical points but the entire level set of the piecewise linear function.
AU - Biswas, Ranita
AU - Cultrera Di Montesano, Sebastiano
AU - Edelsbrunner, Herbert
AU - Saghafian, Morteza
ID - 10773
JF - Discrete and Computational Geometry
SN - 0179-5376
TI - Continuous and discrete radius functions on Voronoi tessellations and Delaunay mosaics
VL - 67
ER -
TY - CONF
AB - List-decodability of Reed-Solomon codes has re-ceived a lot of attention, but the best-possible dependence between the parameters is still not well-understood. In this work, we focus on the case where the list-decoding radius is of the form r=1−ε for ε tending to zero. Our main result states that there exist Reed-Solomon codes with rate Ω(ε) which are (1−ε,O(1/ε) -list-decodable, meaning that any Hamming ball of radius 1−ε contains at most O(1/ε) codewords. This trade-off between rate and list-decoding radius is best-possible for any code with list size less than exponential in the block length. By achieving this trade-off between rate and list-decoding radius we improve a recent result of Guo, Li, Shangguan, Tamo, and Wootters, and resolve the main motivating question of their work. Moreover, while their result requires the field to be exponentially large in the block length, we only need the field size to be polynomially large (and in fact, almost-linear suffices). We deduce our main result from a more general theorem, in which we prove good list-decodability properties of random puncturings of any given code with very large distance.
AU - Ferber, Asaf
AU - Kwan, Matthew Alan
AU - Sauermann, Lisa
ID - 11145
SN - 0272-5428
T2 - 62nd Annual IEEE Symposium on Foundations of Computer Science
TI - List-decodability with large radius for Reed-Solomon codes
VL - 2022
ER -
TY - JOUR
AB - A critical overview of the theory of the chirality-induced spin selectivity (CISS) effect, that is, phenomena in which the chirality of molecular species imparts significant spin selectivity to various electron processes, is provided. Based on discussions in a recently held workshop, and further work published since, the status of CISS effects—in electron transmission, electron transport, and chemical reactions—is reviewed. For each, a detailed discussion of the state-of-the-art in theoretical understanding is provided and remaining challenges and research opportunities are identified.
AU - Evers, Ferdinand
AU - Aharony, Amnon
AU - Bar-Gill, Nir
AU - Entin-Wohlman, Ora
AU - Hedegård, Per
AU - Hod, Oded
AU - Jelinek, Pavel
AU - Kamieniarz, Grzegorz
AU - Lemeshko, Mikhail
AU - Michaeli, Karen
AU - Mujica, Vladimiro
AU - Naaman, Ron
AU - Paltiel, Yossi
AU - Refaely-Abramson, Sivan
AU - Tal, Oren
AU - Thijssen, Jos
AU - Thoss, Michael
AU - Van Ruitenbeek, Jan M.
AU - Venkataraman, Latha
AU - Waldeck, David H.
AU - Yan, Binghai
AU - Kronik, Leeor
ID - 10771
IS - 13
JF - Advanced Materials
SN - 09359648
TI - Theory of chirality induced spin selectivity: Progress and challenges
VL - 34
ER -
TY - JOUR
AB - List-decodability of Reed–Solomon codes has received a lot of attention, but the best-possible dependence between the parameters is still not well-understood. In this work, we focus on the case where the list-decoding radius is of the form r = 1-ε for ε tending to zero. Our main result states that there exist Reed–Solomon codes with rate Ω(ε) which are (1 - ε, O(1/ε))-list-decodable, meaning that any Hamming ball of radius 1-ε contains at most O(1/ε) codewords. This trade-off between rate and list-decoding radius is best-possible for any code with list size less than exponential in the block length. By achieving this trade-off between rate and list-decoding radius we improve a recent result of Guo, Li, Shangguan, Tamo, and Wootters, and resolve the main motivating question of their work. Moreover, while their result requires the field to be exponentially large in the block length, we only need the field size to be polynomially large (and in fact, almost-linear suffices). We deduce our main result from a more general theorem, in which we prove good list-decodability properties of random puncturings of any given code with very large distance.
AU - Ferber, Asaf
AU - Kwan, Matthew Alan
AU - Sauermann, Lisa
ID - 10775
IS - 6
JF - IEEE Transactions on Information Theory
SN - 0018-9448
TI - List-decodability with large radius for Reed-Solomon codes
VL - 68
ER -
TY - JOUR
AB - Let K be a convex body in Rn (i.e., a compact convex set with nonempty interior). Given a point p in the interior of K, a hyperplane h passing through p is called barycentric if p is the barycenter of K∩h. In 1961, Grünbaum raised the question whether, for every K, there exists an interior point p through which there are at least n+1 distinct barycentric hyperplanes. Two years later, this was seemingly resolved affirmatively by showing that this is the case if p=p0 is the point of maximal depth in K. However, while working on a related question, we noticed that one of the auxiliary claims in the proof is incorrect. Here, we provide a counterexample; this re-opens Grünbaum’s question. It follows from known results that for n≥2, there are always at least three distinct barycentric cuts through the point p0∈K of maximal depth. Using tools related to Morse theory we are able to improve this bound: four distinct barycentric cuts through p0 are guaranteed if n≥3.
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 10776
JF - Discrete and Computational Geometry
SN - 0179-5376
TI - Barycentric cuts through a convex body
ER -
TY - JOUR
AB - We introduce a new way of representing logarithmically concave functions on Rd. It allows us to extend the notion of the largest volume ellipsoid contained in a convex body to the setting of logarithmically concave functions as follows. For every s>0, we define a class of non-negative functions on Rd derived from ellipsoids in Rd+1. For any log-concave function f on Rd , and any fixed s>0, we consider functions belonging to this class, and find the one with the largest integral under the condition that it is pointwise less than or equal to f, and we call it the John s-function of f. After establishing existence and uniqueness, we give a characterization of this function similar to the one given by John in his fundamental theorem. We find that John s-functions converge to characteristic functions of ellipsoids as s tends to zero and to Gaussian densities as s tends to infinity.
As an application, we prove a quantitative Helly type result: the integral of the pointwise minimum of any family of log-concave functions is at least a constant cd multiple of the integral of the pointwise minimum of a properly chosen subfamily of size 3d+2, where cd depends only on d.
AU - Ivanov, Grigory
AU - Naszódi, Márton
ID - 10887
IS - 11
JF - Journal of Functional Analysis
SN - 0022-1236
TI - Functional John ellipsoids
VL - 282
ER -
TY - JOUR
AB - Redox mediators could catalyse otherwise slow and energy-inefficient cycling of Li–S and Li–O2 batteries by shuttling electrons or holes between the electrode and the solid insulating storage materials. For mediators to work efficiently they need to oxidize the solid with fast kinetics but with the lowest possible overpotential. However, the dependence of kinetics and overpotential is unclear, which hinders informed improvement. Here, we find that when the redox potentials of mediators are tuned via, for example, Li+ concentration in the electrolyte, they exhibit distinct threshold potentials, where the kinetics accelerate several-fold within a range as small as 10 mV. This phenomenon is independent of types of mediator and electrolyte. The acceleration originates from the overpotentials required to activate fast Li+/e− extraction and the following chemical step at specific abundant surface facets. Efficient redox catalysis at insulating solids therefore requires careful consideration of the surface conditions of the storage materials and electrolyte-dependent redox potentials, which may be tuned by salt concentrations or solvents.
AU - Cao, Deqing
AU - Shen, Xiaoxiao
AU - Wang, Aiping
AU - Yu, Fengjiao
AU - Wu, Yuping
AU - Shi, Siqi
AU - Freunberger, Stefan Alexander
AU - Chen, Yuhui
ID - 10813
JF - Nature Catalysis
KW - Process Chemistry and Technology
KW - Biochemistry
KW - Bioengineering
KW - Catalysis
SN - 2520-1158
TI - Threshold potentials for fast kinetics during mediated redox catalysis of insulators in Li–O2 and Li–S batteries
VL - 5
ER -
TY - JOUR
AB - Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.
AU - Emtenani, Shamsi
AU - Martin, Elliot T
AU - György, Attila
AU - Bicher, Julia
AU - Genger, Jakob-Wendelin
AU - Köcher, Thomas
AU - Akhmanova, Maria
AU - Pereira Guarda, Mariana
AU - Roblek, Marko
AU - Bergthaler, Andreas
AU - Hurd, Thomas R
AU - Rangan, Prashanth
AU - Siekhaus, Daria E
ID - 10918
JF - The Embo Journal
TI - Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila
VL - 41
ER -
TY - JOUR
AB - The potential of energy filtering and direct electron detection for cryo-electron microscopy (cryo-EM) has been well documented. Here, we assess the performance of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram averaging (STA), an increasingly popular structural determination method for complex 3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs) on two contemporary cryo-EM systems equipped with different energy filters and direct electron detectors (DED), specifically a Krios G4, equipped with a cold field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter, and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG), a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based STA on equally sized datasets acquired on the respective systems. The resulting EIAV CA hexamer reconstructions show that both systems perform comparably in the 4–6 Å resolution range based on Fourier-Shell correlation (FSC). In addition, by employing a recently introduced multiparticle refinement approach, we obtained a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the potential of the new generation of energy filters and DEDs for STA, and the effects of using different processing pipelines on their STA outcomes.
AU - Obr, Martin
AU - Hagen, Wim J.H.
AU - Dick, Robert A.
AU - Yu, Lingbo
AU - Kotecha, Abhay
AU - Schur, Florian KM
ID - 11155
IS - 2
JF - Journal of Structural Biology
KW - Structural Biology
SN - 1047-8477
TI - Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs
VL - 214
ER -
TY - JOUR
AB - Direct numerical simulations (DNS) of turbulent channel flows up to Reτ≈1000 are conducted to investigate the three-dimensional (consisting of streamwise wavenumber, spanwise wavenumber and frequency) spectrum of wall pressure fluctuations. To develop a predictive model of the wavenumber–frequency spectrum from the wavenumber spectrum, the time decorrelation mechanisms of wall pressure fluctuations are investigated. It is discovered that the energy-containing part of the wavenumber–frequency spectrum of wall pressure fluctuations can be well predicted using a similar random sweeping model for streamwise velocity fluctuations. To refine the investigation, we further decompose the spectrum of the total wall pressure fluctuations into the autospectra of rapid and slow pressure fluctuations, and the cross-spectrum between them. We focus on evaluating the assumption applied in many predictive models, that is, the magnitude of the cross-spectrum is negligibly small. The present DNS shows that neglecting the cross-spectrum causes a maximum error up to 4.7 dB in the subconvective region for all Reynolds numbers under test. Our analyses indicate that the approximation of neglecting the cross-spectrum needs to be applied carefully in the investigations of acoustics at low Mach numbers, in which the subconvective components of wall pressure fluctuations make important contributions to the radiated acoustic power.
AU - Yang, Bowen
AU - Yang, Zixuan
ID - 10925
JF - Journal of Fluid Mechanics
SN - 0022-1120
TI - On the wavenumber-frequency spectrum of the wall pressure fluctuations in turbulent channel flow
VL - 937
ER -
TY - JOUR
AB - Intragenic regions that are removed during maturation of the RNA transcript—introns—are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein genes that differ primarily in their introns2,3. Although studies have shed light on the role of ribosomal protein introns under stress and starvation4,5,6, understanding the contribution of introns to ribosome regulation remains challenging. Here, by combining isogrowth profiling7 with single-cell protein measurements8, we show that introns can mediate inducible phenotypic heterogeneity that confers a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low levels of Rps22B protein result in prolonged survival under sustained starvation, whereas high levels of Rps22B enable cells to grow faster after transient starvation. Furthermore, yeasts growing at high concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression of Rps22B when approaching the stationary phase. Differential intron-mediated regulation of ribosomal protein genes thus provides a way to diversify the population when starvation threatens in natural environments. Our findings reveal a role for introns in inducing phenotypic heterogeneity in changing environments, and suggest that duplicated ribosomal protein genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness9.
AU - Lukacisin, Martin
AU - Espinosa-Cantú, Adriana
AU - Bollenbach, Mark Tobias
ID - 11341
JF - Nature
SN - 0028-0836
TI - Intron-mediated induction of phenotypic heterogeneity
VL - 605
ER -
TY - JOUR
AB - Hybridization is a common evolutionary process with multiple possible outcomes. In vertebrates, interspecific hybridization has repeatedly generated parthenogenetic hybrid species. However, it is unknown whether the generation of parthenogenetic hybrids is a rare outcome of frequent hybridization between sexual species within a genus or the typical outcome of rare hybridization events. Darevskia is a genus of rock lizards with both hybrid parthenogenetic and sexual species. Using capture sequencing, we estimate phylogenetic relationships and gene flow among the sexual species, to determine how introgressive hybridization relates to the origins of parthenogenetic hybrids. We find evidence for widespread hybridization with gene flow, both between recently diverged species and deep branches. Surprisingly, we find no signal of gene flow between parental species of the parthenogenetic hybrids, suggesting that the parental pairs were either reproductively or geographically isolated early in their divergence. The generation of parthenogenetic hybrids in Darevskia is, then, a rare outcome of the total occurrence of hybridization within the genus, but the typical outcome when specific species pairs hybridize. Our results question the conventional view that parthenogenetic lineages are generated by hybridization in a window of divergence. Instead, they suggest that some lineages possess specific properties that underpin successful parthenogenetic reproduction.
AU - Freitas, Susana
AU - Westram, Anja M
AU - Schwander, Tanja
AU - Arakelyan, Marine
AU - Ilgaz, Çetin
AU - Kumlutas, Yusuf
AU - Harris, David James
AU - Carretero, Miguel A.
AU - Butlin, Roger K.
ID - 11334
IS - 5
JF - Evolution
SN - 0014-3820
TI - Parthenogenesis in Darevskia lizards: A rare outcome of common hybridization, not a common outcome of rare hybridization
VL - 76
ER -
TY - JOUR
AB - We show that the fluctuations of the largest eigenvalue of a real symmetric or complex Hermitian Wigner matrix of size N converge to the Tracy–Widom laws at a rate O(N^{-1/3+\omega }), as N tends to infinity. For Wigner matrices this improves the previous rate O(N^{-2/9+\omega }) obtained by Bourgade (J Eur Math Soc, 2021) for generalized Wigner matrices. Our result follows from a Green function comparison theorem, originally introduced by Erdős et al. (Adv Math 229(3):1435–1515, 2012) to prove edge universality, on a finer spectral parameter scale with improved error estimates. The proof relies on the continuous Green function flow induced by a matrix-valued Ornstein–Uhlenbeck process. Precise estimates on leading contributions from the third and fourth order moments of the matrix entries are obtained using iterative cumulant expansions and recursive comparisons for correlation functions, along with uniform convergence estimates for correlation kernels of the Gaussian invariant ensembles.
AU - Schnelli, Kevin
AU - Xu, Yuanyuan
ID - 11332
JF - Communications in Mathematical Physics
SN - 0010-3616
TI - Convergence rate to the Tracy–Widom laws for the largest Eigenvalue of Wigner matrices
VL - 393
ER -
TY - JOUR
AB - Multistable systems are characterized by exhibiting domain coexistence, where each domain accounts for the different equilibrium states. In case these systems are described by vectorial fields, domains can be connected through topological defects. Vortices are one of the most frequent and studied topological defect points. Optical vortices are equally relevant for their fundamental features as beams with topological features and their applications in image processing, telecommunications, optical tweezers, and quantum information. A natural source of optical vortices is the interaction of light beams with matter vortices in liquid crystal cells. The rhythms that govern the emergence of matter vortices due to fluctuations are not established. Here, we investigate the nucleation mechanisms of the matter vortices in liquid crystal cells and establish statistical laws that govern them. Based on a stochastic amplitude equation, the law for the number of nucleated vortices as a function of anisotropy, voltage, and noise level intensity is set. Experimental observations in a nematic liquid crystal cell with homeotropic anchoring and a negative anisotropic dielectric constant under the influence of a transversal electric field show a qualitative agreement with the theoretical findings.
AU - Aguilera, Esteban
AU - Clerc, Marcel G.
AU - Zambra, Valeska
ID - 11343
JF - Nonlinear Dynamics
KW - Electrical and Electronic Engineering
KW - Applied Mathematics
KW - Mechanical Engineering
KW - Ocean Engineering
KW - Aerospace Engineering
KW - Control and Systems Engineering
SN - 0924-090X
TI - Vortices nucleation by inherent fluctuations in nematic liquid crystal cells
VL - 108
ER -
TY - JOUR
AB - Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I.
AU - Kampjut, Domen
AU - Sazanov, Leonid A
ID - 11167
JF - Current Opinion in Structural Biology
KW - Molecular Biology
KW - Structural Biology
SN - 0959-440X
TI - Structure of respiratory complex I – An emerging blueprint for the mechanism
VL - 74
ER -
TY - JOUR
AB - One hallmark of plant cells is their cell wall. They protect cells against the environment and high turgor and mediate morphogenesis through the dynamics of their mechanical and chemical properties. The walls are a complex polysaccharidic structure. Although their biochemical composition is well known, how the different components organize in the volume of the cell wall and interact with each other is not well understood and yet is key to the wall’s mechanical properties. To investigate the ultrastructure of the plant cell wall, we imaged the walls of onion (Allium cepa) bulbs in a near-native state via cryo-focused ion beam milling (cryo-FIB milling) and cryo-electron tomography (cryo-ET). This allowed the high-resolution visualization of cellulose fibers in situ. We reveal the coexistence of dense fiber fields bathed in a reticulated matrix we termed “meshing,” which is more abundant at the inner surface of the cell wall. The fibers adopted a regular bimodal angular distribution at all depths in the cell wall and bundled according to their orientation, creating layers within the cell wall. Concomitantly, employing homogalacturonan (HG)-specific enzymatic digestion, we observed changes in the meshing, suggesting that it is—at least in part—composed of HG pectins. We propose the following model for the construction of the abaxial epidermal primary cell wall: the cell deposits successive layers of cellulose fibers at −45° and +45° relative to the cell’s long axis and secretes the surrounding HG-rich meshing proximal to the plasma membrane, which then migrates to more distal regions of the cell wall.
AU - Nicolas, William J.
AU - Fäßler, Florian
AU - Dutka, Przemysław
AU - Schur, Florian KM
AU - Jensen, Grant
AU - Meyerowitz, Elliot
ID - 11351
IS - 11
JF - Current Biology
KW - General Agricultural and Biological Sciences
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 0960-9822
TI - Cryo-electron tomography of the onion cell wall shows bimodally oriented cellulose fibers and reticulated homogalacturonan networks
VL - 32
ER -
TY - JOUR
AB - We establish global-in-time existence results for thermodynamically consistent reaction-(cross-)diffusion systems coupled to an equation describing heat transfer. Our main interest is to model species-dependent diffusivities,
while at the same time ensuring thermodynamic consistency. A key difficulty of the non-isothermal case lies in the intrinsic presence of cross-diffusion type phenomena like the Soret and the Dufour effect: due to the temperature/energy dependence of the thermodynamic equilibria, a nonvanishing temperature gradient may drive a concentration flux even in a situation with constant concentrations; likewise, a nonvanishing concentration gradient may drive a heat flux even in a case of spatially constant temperature. We use time discretisation and regularisation techniques and derive a priori estimates based on a suitable entropy and the associated entropy production. Renormalised solutions are used in cases where non-integrable diffusion fluxes or reaction terms appear.
AU - Fischer, Julian L
AU - Hopf, Katharina
AU - Kniely, Michael
AU - Mielke, Alexander
ID - 10547
IS - 1
JF - SIAM Journal on Mathematical Analysis
KW - Energy-Reaction-Diffusion Systems
KW - Cross Diffusion
KW - Global-In-Time Existence of Weak/Renormalised Solutions
KW - Entropy Method
KW - Onsager System
KW - Soret/Dufour Effect
SN - 0036-1410
TI - Global existence analysis of energy-reaction-diffusion systems
VL - 54
ER -
TY - JOUR
AB - The synthetic strigolactone (SL) analog, rac-GR24, has been instrumental in studying the role of SLs as well as karrikins because it activates the receptors DWARF14 (D14) and KARRIKIN INSENSITIVE 2 (KAI2) of their signaling pathways, respectively. Treatment with rac-GR24 modifies the root architecture at different levels, such as decreasing the lateral root density (LRD), while promoting root hair elongation or flavonol accumulation. Previously, we have shown that the flavonol biosynthesis is transcriptionally activated in the root by rac-GR24 treatment, but, thus far, the molecular players involved in that response have remained unknown. To get an in-depth insight into the changes that occur after the compound is perceived by the roots, we compared the root transcriptomes of the wild type and the more axillary growth2 (max2) mutant, affected in both SL and karrikin signaling pathways, with and without rac-GR24 treatment. Quantitative reverse transcription (qRT)-PCR, reporter line analysis and mutant phenotyping indicated that the flavonol response and the root hair elongation are controlled by the ELONGATED HYPOCOTYL 5 (HY5) and MYB12 transcription factors, but HY5, in contrast to MYB12, affects the LRD as well. Furthermore, we identified the transcription factors TARGET OF MONOPTEROS 5 (TMO5) and TMO5 LIKE1 as negative and the Mediator complex as positive regulators of the rac-GR24 effect on LRD. Altogether, hereby, we get closer toward understanding the molecular mechanisms that underlay the rac-GR24 responses in the root.
AU - Struk, Sylwia
AU - Braem, Lukas
AU - Matthys, Cedrick
AU - Walton, Alan
AU - Vangheluwe, Nick
AU - Van Praet, Stan
AU - Jiang, Lingxiang
AU - Baster, Pawel
AU - De Cuyper, Carolien
AU - Boyer, Francois-Didier
AU - Stes, Elisabeth
AU - Beeckman, Tom
AU - Friml, Jiří
AU - Gevaert, Kris
AU - Goormachtig, Sofie
ID - 10583
IS - 1
JF - Plant & Cell Physiology
KW - flavonols
KW - MAX2
KW - rac-Gr24
KW - RNA-seq
KW - root development
KW - transcriptional regulation
SN - 0032-0781
TI - Transcriptional analysis in the Arabidopsis roots reveals new regulators that link rac-GR24 treatment with changes in flavonol accumulation, root hair elongation and lateral root density
VL - 63
ER -
TY - CONF
AB - We study the problem of specifying sequential information-flow properties of systems. Information-flow properties are hyperproperties, as they compare different traces of a system. Sequential information-flow properties can express changes, over time, in the information-flow constraints. For example, information-flow constraints during an initialization phase of a system may be different from information-flow constraints that are required during the operation phase. We formalize several variants of interpreting sequential information-flow constraints, which arise from different assumptions about what can be observed of the system. For this purpose, we introduce a first-order logic, called Hypertrace Logic, with both trace and time quantifiers for specifying linear-time hyperproperties. We prove that HyperLTL, which corresponds to a fragment of Hypertrace Logic with restricted quantifier prefixes, cannot specify the majority of the studied variants of sequential information flow, including all variants in which the transition between sequential phases (such as initialization and operation) happens asynchronously. Our results rely on new equivalences between sets of traces that cannot be distinguished by certain classes of formulas from Hypertrace Logic. This presents a new approach to proving inexpressiveness results for HyperLTL.
AU - Bartocci, Ezio
AU - Ferrere, Thomas
AU - Henzinger, Thomas A
AU - Nickovic, Dejan
AU - Da Costa, Ana Oliveira
ID - 10774
SN - 03029743
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Flavors of sequential information flow
VL - 13182
ER -
TY - JOUR
AB - Directed percolation (DP) has recently emerged as a possible solution to the century old puzzle surrounding the transition to turbulence. Multiple model studies reported DP exponents, however, experimental evidence is limited since the largest possible observation times are orders of magnitude shorter than the flows’ characteristic timescales. An exception is cylindrical Couette flow where the limit is not temporal, but rather the realizable system size. We present experiments in a Couette setup of unprecedented azimuthal and axial aspect ratios. Approaching the critical point to within less than 0.1% we determine five critical exponents, all of which are in excellent agreement with the 2+1D DP universality class. The complex dynamics encountered at
the onset of turbulence can hence be fully rationalized within the framework of statistical mechanics.
AU - Klotz, Lukasz
AU - Lemoult, Grégoire M
AU - Avila, Kerstin
AU - Hof, Björn
ID - 10654
IS - 1
JF - Physical Review Letters
SN - 0031-9007
TI - Phase transition to turbulence in spatially extended shear flows
VL - 128
ER -
TY - CONF
AB - To maximize the performance of concurrent data structures, researchers have often turned to highly complex fine-grained techniques, resulting in efficient and elegant algorithms, which can however be often difficult to understand and prove correct. While simpler techniques exist, such as transactional memory, they can have limited performance or portability relative to their fine-grained counterparts. Approaches at both ends of this complexity-performance spectrum have been extensively explored, but relatively less is known about the middle ground: approaches that are willing to sacrifice some performance for simplicity, while remaining competitive with state-of-the-art handcrafted designs. In this paper, we explore this middle ground, and present PathCAS, a primitive that combines ideas from multi-word CAS (KCAS) and transactional memory approaches, while carefully avoiding overhead. We show how PathCAS can be used to implement efficient search data structures relatively simply, using an internal binary search tree as an example, then extending this to an AVL tree. Our best implementations outperform many handcrafted search trees: in search-heavy workloads, it rivals the BCCO tree [5], the fastest known concurrent binary tree in terms of search performance [3]. Our results suggest that PathCAS can yield concurrent data structures that are relatively easy to build and prove correct, while offering surprisingly high performance.
AU - Brown, Trevor A
AU - Sigouin, William
AU - Alistarh, Dan-Adrian
ID - 11181
SN - 9781450392044
T2 - Proceedings of the 27th ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming
TI - PathCAS: An efficient middle ground for concurrent search data structures
ER -
TY - JOUR
AB - Conflict over reproduction between females and males exists because of anisogamy and promiscuity. Together they generate differences in fitness optima between the sexes and result in antagonistic coevolution of female and male reproductive traits. Mounting duration is likely to be a compromise between male and female interests whose outcome depends on the intensity of sexual selection. The timing of sperm transfer during mounting is critical. For example, mountings may be interrupted before sperm is transferred as a consequence of female or male choice, or they may be prolonged to function as mate guarding. In the highly promiscuous intertidal snail Littorina saxatilis, mountings vary substantially in duration, from less than a minute to more than an hour, and it has been assumed that mountings of a few minutes do not result in any sperm being transferred. Here, we examined the timing of sperm transfer, a reproductive trait that is likely affected by sexual conflict. We performed time-controlled mounting trials using L. saxatilis males and virgin females, aiming to examine indirectly when the transfer of sperm starts. We observed the relationship between mounting duration and the proportion of developing embryos out of all eggs and embryos in the brood pouch. Developing embryos were observed in similar proportions in all treatments (i.e. 1, 5 and 10 or more minutes at which mountings were artificially interrupted), suggesting that sperm transfer begins rapidly (within 1 min) in L. saxatilis and very short matings do not result in sperm shortage in the females. We discuss how the observed pattern can be influenced by predation risk, population density, and female status and receptivity.
AU - Perini, Samuel
AU - Butlin, Rogerk
AU - Westram, Anja M
AU - Johannesson, Kerstin
ID - 10926
IS - 1
JF - Journal of Molluscan Studies
SN - 0260-1230
TI - Very short mountings are enough for sperm transfer in Littorina saxatilis
VL - 88
ER -
TY - JOUR
AB - We consider a generalised model of a random simplicial complex, which arises from a random hypergraph. Our model is generated by taking the downward-closure of a non-uniform binomial random hypergraph, in which for each k, each set of k+1 vertices forms an edge with some probability pk independently. As a special case, this contains an extensively studied model of a (uniform) random simplicial complex, introduced by Meshulam and Wallach [Random Structures & Algorithms 34 (2009), no. 3, pp. 408–417].
We consider a higher-dimensional notion of connectedness on this new model according to the vanishing of cohomology groups over an arbitrary abelian group R. We prove that this notion of connectedness displays a phase transition and determine the threshold. We also prove a hitting time result for a natural process interpretation, in which simplices and their downward-closure are added one by one. In addition, we determine the asymptotic behaviour of cohomology groups inside the critical window around the time of the phase transition.
AU - Cooley, Oliver
AU - Del Giudice, Nicola
AU - Kang, Mihyun
AU - Sprüssel, Philipp
ID - 11740
IS - 3
JF - Electronic Journal of Combinatorics
TI - Phase transition in cohomology groups of non-uniform random simplicial complexes
VL - 29
ER -
TY - JOUR
AB - Spin-orbit coupling in thin HgTe quantum wells results in a relativistic-like electron band structure, making it a versatile solid state platform to observe and control nontrivial electrodynamic phenomena. Here we report an observation of universal terahertz (THz) transparency determined by fine-structure constant α≈1/137 in 6.5-nm-thick HgTe layer, close to the critical thickness separating phases with topologically different electronic band structure. Using THz spectroscopy in a magnetic field we obtain direct evidence of asymmetric spin splitting of the Dirac cone. This particle-hole asymmetry facilitates optical control of edge spin currents in the quantum wells.
AU - Dziom, Uladzislau
AU - Shuvaev, A.
AU - Gospodarič, J.
AU - Novik, E. G.
AU - Dobretsova, A. A.
AU - Mikhailov, N. N.
AU - Kvon, Z. D.
AU - Alpichshev, Zhanybek
AU - Pimenov, A.
ID - 11737
IS - 4
JF - Physical Review B
SN - 2469-9950
TI - Universal transparency and asymmetric spin splitting near the Dirac point in HgTe quantum wells
VL - 106
ER -
TY - JOUR
AB - We consider finite-volume approximations of Fokker--Planck equations on bounded convex domains in $\mathbb{R}^d$ and study the corresponding gradient flow structures. We reprove the convergence of the discrete to continuous Fokker--Planck equation via the method of evolutionary $\Gamma$-convergence, i.e., we pass to the limit at the level of the gradient flow structures, generalizing the one-dimensional result obtained by Disser and Liero. The proof is of variational nature and relies on a Mosco convergence result for functionals in the discrete-to-continuum limit that is of independent interest. Our results apply to arbitrary regular meshes, even though the associated discrete transport distances may fail to converge to the Wasserstein distance in this generality.
AU - Forkert, Dominik L
AU - Maas, Jan
AU - Portinale, Lorenzo
ID - 11739
IS - 4
JF - SIAM Journal on Mathematical Analysis
KW - Fokker--Planck equation
KW - gradient flow
KW - evolutionary $\Gamma$-convergence
SN - 0036-1410
TI - Evolutionary $\Gamma$-convergence of entropic gradient flow structures for Fokker-Planck equations in multiple dimensions
VL - 54
ER -
TY - JOUR
AB - Mineral nutrition is one of the key environmental factors determining plant development and growth. Nitrate is the major form of macronutrient nitrogen that plants take up from the soil. Fluctuating availability or deficiency of this element severely limits plant growth and negatively affects crop production in the agricultural system. To cope with the heterogeneity of nitrate distribution in soil, plants evolved a complex regulatory mechanism that allows rapid adjustment of physiological and developmental processes to the status of this nutrient. The root, as a major exploitation organ that controls the uptake of nitrate to the plant body, acts as a regulatory hub that, according to nitrate availability, coordinates the growth and development of other plant organs. Here, we identified a regulatory framework, where cytokinin response factors (CRFs) play a central role as a molecular readout of the nitrate status in roots to guide shoot adaptive developmental response. We show that nitrate-driven activation of NLP7, a master regulator of nitrate response in plants, fine tunes biosynthesis of cytokinin in roots and its translocation to shoots where it enhances expression of CRFs. CRFs, through direct transcriptional regulation of PIN auxin transporters, promote the flow of auxin and thereby stimulate the development of shoot organs.
AU - Abualia, Rashed
AU - Ötvös, Krisztina
AU - Novák, Ondřej
AU - Bouguyon, Eleonore
AU - Domanegg, Kevin
AU - Krapp, Anne
AU - Nacry, Philip
AU - Gojon, Alain
AU - Lacombe, Benoit
AU - Benková, Eva
ID - 11734
IS - 31
JF - Proceedings of the National Academy of Sciences of the United States of America
TI - Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses
VL - 119
ER -
TY - JOUR
AB - Genetically informed, deep-phenotyped biobanks are an important research resource and it is imperative that the most powerful, versatile, and efficient analysis approaches are used. Here, we apply our recently developed Bayesian grouped mixture of regressions model (GMRM) in the UK and Estonian Biobanks and obtain the highest genomic prediction accuracy reported to date across 21 heritable traits. When compared to other approaches, GMRM accuracy was greater than annotation prediction models run in the LDAK or LDPred-funct software by 15% (SE 7%) and 14% (SE 2%), respectively, and was 18% (SE 3%) greater than a baseline BayesR model without single-nucleotide polymorphism (SNP) markers grouped into minor allele frequency–linkage disequilibrium (MAF-LD) annotation categories. For height, the prediction accuracy R2 was 47% in a UK Biobank holdout sample, which was 76% of the estimated h2SNP. We then extend our GMRM prediction model to provide mixed-linear model association (MLMA) SNP marker estimates for genome-wide association (GWAS) discovery, which increased the independent loci detected to 16,162 in unrelated UK Biobank individuals, compared to 10,550 from BoltLMM and 10,095 from Regenie, a 62 and 65% increase, respectively. The average χ2 value of the leading markers increased by 15.24 (SE 0.41) for every 1% increase in prediction accuracy gained over a baseline BayesR model across the traits. Thus, we show that modeling genetic associations accounting for MAF and LD differences among SNP markers, and incorporating prior knowledge of genomic function, is important for both genomic prediction and discovery in large-scale individual-level studies.
AU - Orliac, Etienne J.
AU - Trejo Banos, Daniel
AU - Ojavee, Sven E.
AU - Läll, Kristi
AU - Mägi, Reedik
AU - Visscher, Peter M.
AU - Robinson, Matthew Richard
ID - 11733
IS - 31
JF - Proceedings of the National Academy of Sciences of the United States of America
TI - Improving GWAS discovery and genomic prediction accuracy in biobank data
VL - 119
ER -
TY - JOUR
AB - We study two interacting quantum particles forming a bound state in d-dimensional free
space, and constrain the particles in k directions to (0, ∞)k ×Rd−k, with Neumann boundary
conditions. First, we prove that the ground state energy strictly decreases upon going from k
to k+1. This shows that the particles stick to the corner where all boundary planes intersect.
Second, we show that for all k the resulting Hamiltonian, after removing the free part of the
kinetic energy, has only finitely many eigenvalues below the essential spectrum. This paper
generalizes the work of Egger, Kerner and Pankrashkin (J. Spectr. Theory 10(4):1413–1444,
2020) to dimensions d > 1.
AU - Roos, Barbara
AU - Seiringer, Robert
ID - 10850
IS - 12
JF - Journal of Functional Analysis
KW - Analysis
SN - 0022-1236
TI - Two-particle bound states at interfaces and corners
VL - 282
ER -
TY - JOUR
AB - We provide a definition of the effective mass for the classical polaron described by the Landau–Pekar (LP) equations. It is based on a novel variational principle, minimizing the energy functional over states with given (initial) velocity. The resulting formula for the polaron's effective mass agrees with the prediction by LP (1948 J. Exp. Theor. Phys. 18 419–423).
AU - Feliciangeli, Dario
AU - Rademacher, Simone Anna Elvira
AU - Seiringer, Robert
ID - 10755
IS - 1
JF - Journal of Physics A: Mathematical and Theoretical
SN - 1751-8113
TI - The effective mass problem for the Landau-Pekar equations
VL - 55
ER -
TY - JOUR
AB - We consider a gas of N bosons with interactions in the mean-field scaling regime. We review the proof of an asymptotic expansion of its low-energy spectrum, eigenstates, and dynamics, which provides corrections to Bogoliubov theory to all orders in 1/ N. This is based on joint works with Petrat, Pickl, Seiringer, and Soffer. In addition, we derive a full asymptotic expansion of the ground state one-body reduced density matrix.
AU - Bossmann, Lea
ID - 11783
IS - 6
JF - Journal of Mathematical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0022-2488
TI - Low-energy spectrum and dynamics of the weakly interacting Bose gas
VL - 63
ER -
TY - JOUR
AB - We study the BCS energy gap Ξ in the high–density limit and derive an asymptotic formula, which strongly depends on the strength of the interaction potential V on the Fermi surface. In combination with the recent result by one of us (Math. Phys. Anal. Geom. 25, 3, 2022) on the critical temperature Tc at high densities, we prove the universality of the ratio of the energy gap and the critical temperature.
AU - Henheik, Sven Joscha
AU - Lauritsen, Asbjørn Bækgaard
ID - 11732
JF - Journal of Statistical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0022-4715
TI - The BCS energy gap at high density
VL - 189
ER -
TY - JOUR
AB - We consider the flow of two viscous and incompressible fluids within a bounded domain modeled by means of a two-phase Navier–Stokes system. The two fluids are assumed to be immiscible, meaning that they are separated by an interface. With respect to the motion of the interface, we consider pure transport by the fluid flow. Along the boundary of the domain, a complete slip boundary condition for the fluid velocities and a constant ninety degree contact angle condition for the interface are assumed. In the present work, we devise for the resulting evolution problem a suitable weak solution concept based on the framework of varifolds and establish as the main result a weak-strong uniqueness principle in 2D. The proof is based on a relative entropy argument and requires a non-trivial further development of ideas from the recent work of Fischer and the first author (Arch. Ration. Mech. Anal. 236, 2020) to incorporate the contact angle condition. To focus on the effects of the necessarily singular geometry of the evolving fluid domains, we work for simplicity in the regime of same viscosities for the two fluids.
AU - Hensel, Sebastian
AU - Marveggio, Alice
ID - 11842
IS - 3
JF - Journal of Mathematical Fluid Mechanics
SN - 1422-6928
TI - Weak-strong uniqueness for the Navier–Stokes equation for two fluids with ninety degree contact angle and same viscosities
VL - 24
ER -
TY - CONF
AB - The medial axis of a set consists of the points in the ambient space without a unique closest point on the original set. Since its introduction, the medial axis has been used extensively in many applications as a method of computing a topologically equivalent skeleton. Unfortunately, one limiting factor in the use of the medial axis of a smooth manifold is that it is not necessarily topologically stable under small perturbations of the manifold. To counter these instabilities various prunings of the medial axis have been proposed. Here, we examine one type of pruning, called burning. Because of the good experimental results, it was hoped that the burning method of simplifying the medial axis would be stable. In this work we show a simple example that dashes such hopes based on Bing’s house with two rooms, demonstrating an isotopy of a shape where the medial axis goes from collapsible to non-collapsible.
AU - Chambers, Erin
AU - Fillmore, Christopher D
AU - Stephenson, Elizabeth R
AU - Wintraecken, Mathijs
ED - Goaoc, Xavier
ED - Kerber, Michael
ID - 11428
SN - 1868-8969
T2 - 38th International Symposium on Computational Geometry
TI - A cautionary tale: Burning the medial axis is unstable
VL - 224
ER -
TY - JOUR
AB - A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.
AU - Tomasek, Kathrin
AU - Leithner, Alexander F
AU - Glatzová, Ivana
AU - Lukesch, Michael S.
AU - Guet, Calin C
AU - Sixt, Michael K
ID - 11843
JF - eLife
TI - Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
VL - 11
ER -
TY - JOUR
AB - This paper is a continuation of Part I of this project, where we developed a new local well-posedness theory for nonlinear stochastic PDEs with Gaussian noise. In the current Part II we consider blow-up criteria and regularization phenomena. As in Part I we can allow nonlinearities with polynomial growth and rough initial values from critical spaces. In the first main result we obtain several new blow-up criteria for quasi- and semilinear stochastic evolution equations. In particular, for semilinear equations we obtain a Serrin type blow-up criterium, which extends a recent result of Prüss–Simonett–Wilke (J Differ Equ 264(3):2028–2074, 2018) to the stochastic setting. Blow-up criteria can be used to prove global well-posedness for SPDEs. As in Part I, maximal regularity techniques and weights in time play a central role in the proofs. Our second contribution is a new method to bootstrap Sobolev and Hölder regularity in time and space, which does not require smoothness of the initial data. The blow-up criteria are at the basis of these new methods. Moreover, in applications the bootstrap results can be combined with our blow-up criteria, to obtain efficient ways to prove global existence. This gives new results even in classical 𝐿2-settings, which we illustrate for a concrete SPDE. In future works in preparation we apply the results of the current paper to obtain global well-posedness results and regularity for several concrete SPDEs. These include stochastic Navier–Stokes equations, reaction– diffusion equations and the Allen–Cahn equation. Our setting allows to put these SPDEs into a more flexible framework, where less restrictions on the nonlinearities are needed, and we are able to treat rough initial values from critical spaces. Moreover, we will obtain higher-order regularity results.
AU - Agresti, Antonio
AU - Veraar, Mark
ID - 11858
IS - 2
JF - Journal of Evolution Equations
KW - Mathematics (miscellaneous)
SN - 1424-3199
TI - Nonlinear parabolic stochastic evolution equations in critical spaces part II
VL - 22
ER -
TY - CONF
AB - In the stochastic population protocol model, we are given a connected graph with n nodes, and in every time step, a scheduler samples an edge of the graph uniformly at random and the nodes connected by this edge interact. A fundamental task in this model is stable leader election, in which all nodes start in an identical state and the aim is to reach a configuration in which (1) exactly one node is elected as leader and (2) this node remains as the unique leader no matter what sequence of interactions follows. On cliques, the complexity of this problem has recently been settled: time-optimal protocols stabilize in Θ(n log n) expected steps using Θ(log log n) states, whereas protocols that use O(1) states require Θ(n2) expected steps.
In this work, we investigate the complexity of stable leader election on general graphs. We provide the first non-trivial time lower bounds for leader election on general graphs, showing that, when moving beyond cliques, the complexity landscape of leader election becomes very diverse: the time required to elect a leader can range from O(1) to Θ(n3) expected steps. On the upper bound side, we first observe that there exists a protocol that is time-optimal on many graph families, but uses polynomially-many states. In contrast, we give a near-time-optimal protocol that uses only O(log2n) states that is at most a factor log n slower. Finally, we show that the constant-state protocol of Beauquier et al. [OPODIS 2013] is at most a factor n log n slower than the fast polynomial-state protocol. Moreover, among constant-state protocols, this protocol has near-optimal average case complexity on dense random graphs.
AU - Alistarh, Dan-Adrian
AU - Rybicki, Joel
AU - Voitovych, Sasha
ID - 11844
SN - 9781450392624
T2 - Proceedings of the Annual ACM Symposium on Principles of Distributed Computing
TI - Near-optimal leader election in population protocols on graphs
ER -
TY - JOUR
AB - We study the many-body dynamics of an initially factorized bosonic wave function in the mean-field regime. We prove large deviation estimates for the fluctuations around the condensate. We derive an upper bound extending a recent result to more general interactions. Furthermore, we derive a new lower bound which agrees with the upper bound in leading order.
AU - Rademacher, Simone Anna Elvira
AU - Seiringer, Robert
ID - 11917
JF - Journal of Statistical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0022-4715
TI - Large deviation estimates for weakly interacting bosons
VL - 188
ER -
TY - JOUR
AB - The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.
AU - Belyaeva, Vera
AU - Wachner, Stephanie
AU - György, Attila
AU - Emtenani, Shamsi
AU - Gridchyn, Igor
AU - Akhmanova, Maria
AU - Linder, M
AU - Roblek, Marko
AU - Sibilia, M
AU - Siekhaus, Daria E
ID - 10614
IS - 1
JF - PLoS Biology
SN - 1544-9173
TI - Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila
VL - 20
ER -
TY - JOUR
AB - Squall lines are known to be the consequence of the interaction of low-level shear with cold pools associated with convective downdrafts. Also, as the magnitude of the shear increases beyond a critical shear, squall lines tend to orient themselves. The existing literature suggests that this orientation reduces incoming wind shear to the squall line, and maintains equilibrium between wind shear and cold pool spreading. Although this theory is widely accepted, very few quantitative studies have been conducted on supercritical regime especially. Here, we test this hypothesis with tropical squall lines obtained by imposing a vertical wind shear in cloud resolving simulations in radiative convective equilibrium. In the sub-critical regime, squall lines are perpendicular to the shear. In the super-critical regime, their orientation maintain the equilibrium, supporting existing theories. We also find that as shear increases, cold pools become more intense. However, this intensification has little impact on squall line orientation.
AU - Abramian, Sophie
AU - Muller, Caroline J
AU - Risi, Camille
ID - 10653
IS - 1
JF - Geophysical Research Letters
SN - 0094-8276
TI - Shear-convection interactions and orientation of tropical squall lines
VL - 49
ER -
TY - THES
AB - In this dissertation we study coboundary expansion of simplicial complex with a view of giving geometric applications.
Our main novel tool is an equivariant version of Gromov's celebrated Topological Overlap Theorem. The equivariant topological overlap theorem leads to various geometric applications including a quantitative non-embeddability result for sufficiently thick buildings (which partially resolves a conjecture of Tancer and Vorwerk) and an improved lower bound on the pair-crossing number of (bounded degree) expander graphs. Additionally, we will give new proofs for several known lower bounds for geometric problems such as the number of Tverberg partitions or the crossing number of complete bipartite graphs.
For the aforementioned applications one is naturally lead to study expansion properties of joins of simplicial complexes. In the presence of a special certificate for expansion (as it is the case, e.g., for spherical buildings), the join of two expanders is an expander. On the flip-side, we report quite some evidence that coboundary expansion exhibits very non-product-like behaviour under taking joins. For instance, we exhibit infinite families of graphs $(G_n)_{n\in \mathbb{N}}$ and $(H_n)_{n\in\mathbb{N}}$ whose join $G_n*H_n$ has expansion of lower order than the product of the expansion constant of the graphs. Moreover, we show an upper bound of $(d+1)/2^d$ on the normalized coboundary expansion constants for the complete multipartite complex $[n]^{*(d+1)}$ (under a mild divisibility condition on $n$).
Via the probabilistic method the latter result extends to an upper bound of $(d+1)/2^d+\varepsilon$ on the coboundary expansion constant of the spherical building associated with $\mathrm{PGL}_{d+2}(\mathbb{F}_q)$ for any $\varepsilon>0$ and sufficiently large $q=q(\varepsilon)$. This disproves a conjecture of Lubotzky, Meshulam and Mozes -- in a rather strong sense.
By improving on existing lower bounds we make further progress towards closing the gap between the known lower and upper bounds on the coboundary expansion constants of $[n]^{*(d+1)}$. The best improvements we achieve using computer-aided proofs and flag algebras. The exact value even for the complete $3$-partite $2$-dimensional complex $[n]^{*3}$ remains unknown but we are happy to conjecture a precise value for every $n$. %Moreover, we show that a previously shown lower bound on the expansion constant of the spherical building associated with $\mathrm{PGL}_{2}(\mathbb{F}_q)$ is not tight.
In a loosely structured, last chapter of this thesis we collect further smaller observations related to expansion. We point out a link between discrete Morse theory and a technique for showing coboundary expansion, elaborate a bit on the hardness of computing coboundary expansion constants, propose a new criterion for coboundary expansion (in a very dense setting) and give one way of making the folklore result that expansion of links is a necessary condition for a simplicial complex to be an expander precise.
AU - Wild, Pascal
ID - 11777
SN - 2663-337X
TI - High-dimensional expansion and crossing numbers of simplicial complexes
ER -
TY - JOUR
AB - A matching is compatible to two or more labeled point sets of size n with labels {1, . . . , n} if its straight-line drawing on each of these point sets is crossing-free. We study the maximum number of edges in a matching compatible to two or more labeled point sets in general position in the plane. We show that for any two labeled sets of n points in convex position there exists a compatible matching with ⌊√2n + 1 − 1⌋ edges. More generally, for any ℓ labeled point sets we construct compatible matchings of size Ω(n1/ℓ). As a corresponding upper bound, we use probabilistic arguments to show that for any ℓ given sets of n points there exists a labeling of each set such that the largest compatible matching has O(n2/(ℓ+1)) edges. Finally, we show that Θ(log n) copies of any set of n points are necessary and sufficient for the existence of labelings of these point sets such that any compatible matching consists only of a single edge.
AU - Aichholzer, Oswin
AU - Arroyo Guevara, Alan M
AU - Masárová, Zuzana
AU - Parada, Irene
AU - Perz, Daniel
AU - Pilz, Alexander
AU - Tkadlec, Josef
AU - Vogtenhuber, Birgit
ID - 11938
IS - 2
JF - Journal of Graph Algorithms and Applications
SN - 1526-1719
TI - On compatible matchings
VL - 26
ER -
TY - JOUR
AB - Most experimentally known high-pressure ice phases have a body-centred cubic (bcc) oxygen lattice. Our large-scale molecular-dynamics simulations with a machine-learning potential indicate that, amongst these bcc ice phases, ices VII, VII′ and X are the same thermodynamic phase under different conditions, whereas superionic ice VII″ has a first-order phase boundary with ice VII′. Moreover, at about 300 GPa, the transformation between ice X and the Pbcm phase has a sharp structural change but no apparent activation barrier, whilst at higher pressures the barrier gradually increases. Our study thus clarifies the phase behaviour of the high-pressure ices and reveals peculiar solid–solid transition mechanisms not known in other systems.
AU - Reinhardt, Aleks
AU - Bethkenhagen, Mandy
AU - Coppari, Federica
AU - Millot, Marius
AU - Hamel, Sebastien
AU - Cheng, Bingqing
ID - 11937
JF - Nature Communications
TI - Thermodynamics of high-pressure ice phases explored with atomistic simulations
VL - 13
ER -
TY - GEN
AB - We determine an asymptotic formula for the number of integral points of
bounded height on a certain toric variety, which is incompatible with part of a
preprint by Chambert-Loir and Tschinkel. We provide an alternative
interpretation of the asymptotic formula we get. To do so, we construct an
analogue of Peyre's constant $\alpha$ and describe its relation to a new
obstruction to the Zariski density of integral points in certain regions of
varieties.
AU - Wilsch, Florian Alexander
ID - 10788
KW - Integral point
KW - toric variety
KW - Manin's conjecture
T2 - arXiv
TI - Integral points of bounded height on a certain toric variety
ER -
TY - THES
AB - Deep learning has enabled breakthroughs in challenging computing problems and has emerged as the standard problem-solving tool for computer vision and natural language processing tasks.
One exception to this trend is safety-critical tasks where robustness and resilience requirements contradict the black-box nature of neural networks.
To deploy deep learning methods for these tasks, it is vital to provide guarantees on neural network agents' safety and robustness criteria.
This can be achieved by developing formal verification methods to verify the safety and robustness properties of neural networks.
Our goal is to design, develop and assess safety verification methods for neural networks to improve their reliability and trustworthiness in real-world applications.
This thesis establishes techniques for the verification of compressed and adversarially trained models as well as the design of novel neural networks for verifiably safe decision-making.
First, we establish the problem of verifying quantized neural networks. Quantization is a technique that trades numerical precision for the computational efficiency of running a neural network and is widely adopted in industry.
We show that neglecting the reduced precision when verifying a neural network can lead to wrong conclusions about the robustness and safety of the network, highlighting that novel techniques for quantized network verification are necessary. We introduce several bit-exact verification methods explicitly designed for quantized neural networks and experimentally confirm on realistic networks that the network's robustness and other formal properties are affected by the quantization.
Furthermore, we perform a case study providing evidence that adversarial training, a standard technique for making neural networks more robust, has detrimental effects on the network's performance. This robustness-accuracy tradeoff has been studied before regarding the accuracy obtained on classification datasets where each data point is independent of all other data points. On the other hand, we investigate the tradeoff empirically in robot learning settings where a both, a high accuracy and a high robustness, are desirable.
Our results suggest that the negative side-effects of adversarial training outweigh its robustness benefits in practice.
Finally, we consider the problem of verifying safety when running a Bayesian neural network policy in a feedback loop with systems over the infinite time horizon. Bayesian neural networks are probabilistic models for learning uncertainties in the data and are therefore often used on robotic and healthcare applications where data is inherently stochastic.
We introduce a method for recalibrating Bayesian neural networks so that they yield probability distributions over safe decisions only.
Our method learns a safety certificate that guarantees safety over the infinite time horizon to determine which decisions are safe in every possible state of the system.
We demonstrate the effectiveness of our approach on a series of reinforcement learning benchmarks.
AU - Lechner, Mathias
ID - 11362
KW - neural networks
KW - verification
KW - machine learning
SN - 978-3-99078-017-6
TI - Learning verifiable representations
ER -
TY - GEN
AB - Adversarial training (i.e., training on adversarially perturbed input data) is a well-studied method for making neural networks robust to potential adversarial attacks during inference. However, the improved robustness does not
come for free but rather is accompanied by a decrease in overall model accuracy and performance. Recent work has shown that, in practical robot learning applications, the effects of adversarial training do not pose a fair trade-off
but inflict a net loss when measured in holistic robot performance. This work revisits the robustness-accuracy trade-off in robot learning by systematically analyzing if recent advances in robust training methods and theory in
conjunction with adversarial robot learning can make adversarial training suitable for real-world robot applications. We evaluate a wide variety of robot learning tasks ranging from autonomous driving in a high-fidelity environment
amenable to sim-to-real deployment, to mobile robot gesture recognition. Our results demonstrate that, while these techniques make incremental improvements on the trade-off on a relative scale, the negative side-effects caused by
adversarial training still outweigh the improvements by an order of magnitude. We conclude that more substantial advances in robust learning methods are necessary before they can benefit robot learning tasks in practice.
AU - Lechner, Mathias
AU - Amini, Alexander
AU - Rus, Daniela
AU - Henzinger, Thomas A
ID - 11366
T2 - arXiv
TI - Revisiting the adversarial robustness-accuracy tradeoff in robot learning
ER -
TY - CONF
AB - Contract-based design is a promising methodology for taming the complexity of developing sophisticated systems. A formal contract distinguishes between assumptions, which are constraints that the designer of a component puts on the environments in which the component can be used safely, and guarantees, which are promises that the designer asks from the team that implements the component. A theory of formal contracts can be formalized as an interface theory, which supports the composition and refinement of both assumptions and guarantees.
Although there is a rich landscape of contract-based design methods that address functional and extra-functional properties, we present the first interface theory that is designed for ensuring system-wide security properties. Our framework provides a refinement relation and a composition operation that support both incremental design and independent implementability. We develop our theory for both stateless and stateful interfaces. We illustrate the applicability of our framework with an example inspired from the automotive domain.
AU - Bartocci, Ezio
AU - Ferrere, Thomas
AU - Henzinger, Thomas A
AU - Nickovic, Dejan
AU - Da Costa, Ana Oliveira
ID - 11355
SN - 0302-9743
T2 - Fundamental Approaches to Software Engineering
TI - Information-flow interfaces
VL - 13241
ER -
TY - JOUR
AB - The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.
AU - Ben Simon, Yoav
AU - Käfer, Karola
AU - Velicky, Philipp
AU - Csicsvari, Jozsef L
AU - Danzl, Johann G
AU - Jonas, Peter M
ID - 11951
JF - Nature Communications
KW - General Physics and Astronomy
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Chemistry
KW - Multidisciplinary
SN - 2041-1723
TI - A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory
VL - 13
ER -
TY - JOUR
AB - Maternally inherited Wolbachia transinfections are being introduced into natural mosquito populations to reduce the transmission of dengue, Zika, and other arboviruses. Wolbachia-induced cytoplasmic incompatibility provides a frequency-dependent reproductive advantage to infected females that can spread transinfections within and among populations. However, because transinfections generally reduce host fitness, they tend to spread within populations only after their frequency exceeds a critical threshold. This produces bistability with stable equilibrium frequencies at both 0 and 1, analogous to the bistability produced by underdominance between alleles or karyotypes and by population dynamics under Allee effects. Here, we analyze how stochastic frequency variation produced by finite population size can facilitate the local spread of variants with bistable dynamics into areas where invasion is unexpected from deterministic models. Our exemplar is the establishment of wMel Wolbachia in the Aedes aegypti population of Pyramid Estates (PE), a small community in far north Queensland, Australia. In 2011, wMel was stably introduced into Gordonvale, separated from PE by barriers to A. aegypti dispersal. After nearly 6 years during which wMel was observed only at low frequencies in PE, corresponding to an apparent equilibrium between immigration and selection, wMel rose to fixation by 2018. Using analytic approximations and statistical analyses, we demonstrate that the observed fixation of wMel at PE is consistent with both stochastic transition past an unstable threshold frequency and deterministic transformation produced by steady immigration at a rate just above the threshold required for deterministic invasion. The indeterminacy results from a delicate balance of parameters needed to produce the delayed transition observed. Our analyses suggest that once Wolbachia transinfections are established locally through systematic introductions, stochastic “threshold crossing” is likely to only minimally enhance spatial spread, providing a local ratchet that slightly—but systematically—aids area-wide transformation of disease-vector populations in heterogeneous landscapes.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 10604
IS - 1
JF - Evolution Letters
KW - genetics
KW - ecology
KW - evolution
KW - behavior and systematics
TI - Why did the Wolbachia transinfection cross the road? Drift, deterministic dynamics, and disease control
VL - 6
ER -
TY - JOUR
AB - The precursor conversion chemistry and surface chemistry of Cu3N and Cu3PdN nanocrystals are unknown or contested. Here, we first obtain phase-pure, colloidally stable nanocubes. Second, we elucidate the pathway by which copper(II) nitrate and oleylamine form Cu3N. We find that oleylamine is both a reductant and a nitrogen source. Oleylamine is oxidized by nitrate to a primary aldimine, which reacts further with excess oleylamine to a secondary aldimine, eliminating ammonia. Ammonia reacts with CuI to form Cu3N. Third, we investigated the surface chemistry and find a mixed ligand shell of aliphatic amines and carboxylates (formed in situ). While the carboxylates appear tightly bound, the amines are easily desorbed from the surface. Finally, we show that doping with palladium decreases the band gap and the material becomes semi-metallic. These results bring insight into the chemistry of metal nitrides and might help the development of other metal nitride nanocrystals.
AU - Parvizian, Mahsa
AU - Duràn Balsa, Alejandra
AU - Pokratath, Rohan
AU - Kalha, Curran
AU - Lee, Seungho
AU - Van Den Eynden, Dietger
AU - Ibáñez, Maria
AU - Regoutz, Anna
AU - De Roo, Jonathan
ID - 11451
IS - 31
JF - Angewandte Chemie - International Edition
SN - 1433-7851
TI - The chemistry of Cu₃N and Cu₃PdN nanocrystals
VL - 61
ER -
TY - JOUR
AB - A novel multivariable system, combining a transistor with fiber optic-based surface plasmon resonance spectroscopy with the gate electrode simultaneously acting as the fiber optic sensor surface, is reported. The dual-mode sensor allows for discrimination of mass and charge contributions for binding assays on the same sensor surface. Furthermore, we optimize the sensor geometry by investigating the influence of the fiber area to transistor channel area ratio and distance. We show that larger fiber optic tip diameters are favorable for electronic and optical signals and demonstrate the reversibility of plasmon resonance wavelength shifts after electric field application. As a proof of principle, a layer-by-layer assembly of polyelectrolytes is performed to benchmark the system against multivariable sensing platforms with planar surface plasmon resonance configurations. Furthermore, the biosensing performance is assessed using a thrombin binding assay with surface-immobilized aptamers as receptors, allowing for the detection of medically relevant thrombin concentrations.
AU - Hasler, Roger
AU - Reiner-Rozman, Ciril
AU - Fossati, Stefan
AU - Aspermair, Patrik
AU - Dostalek, Jakub
AU - Lee, Seungho
AU - Ibáñez, Maria
AU - Bintinger, Johannes
AU - Knoll, Wolfgang
ID - 10829
IS - 2
JF - ACS Sensors
TI - Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device
VL - 7
ER -
TY - JOUR
AB - In Fall 2020, several European countries reported rapid increases in COVID-19 cases along with growing estimates of the effective reproduction rates. Such an acceleration in epidemic spread is usually attributed to time-dependent effects, e.g. human travel, seasonal behavioral changes, mutations of the pathogen etc. In this case however the acceleration occurred when counter measures such as testing and contact tracing exceeded their capacity limit. Considering Austria as an example, here we show that this dynamics can be captured by a time-independent, i.e. autonomous, compartmental model that incorporates these capacity limits. In this model, the epidemic acceleration coincides with the exhaustion of mitigation efforts, resulting in an increasing fraction of undetected cases that drive the effective reproduction rate progressively higher. We demonstrate that standard models which does not include this effect necessarily result in a systematic underestimation of the effective reproduction rate.
AU - Budanur, Nazmi B
AU - Hof, Björn
ID - 11704
IS - 7
JF - PLoS ONE
TI - An autonomous compartmental model for accelerating epidemics
VL - 17
ER -
TY - GEN
AB - Maternally inherited Wolbachia transinfections are being introduced into natural mosquito populations to reduce the transmission of dengue, Zika and other arboviruses. Wolbachia-induced cytoplasmic incompatibility provides a frequency-dependent reproductive advantage to infected females that can spread transinfections within and among populations. However, because transinfections generally reduce host fitness, they tend to spread within populations only after their frequency exceeds a critical threshold. This produces bistability with stable equilibrium frequencies at both 0 and 1, analogous to the bistability produced by underdominance between alleles or karyotypes and by population dynamics under Allee effects. Here, we analyze how stochastic frequency variation produced by finite population size can facilitate the local spread of variants with bistable dynamics into areas where invasion is unexpected from deterministic models. Our exemplar is the establishment of wMel Wolbachia in the Aedes aegypti population of Pyramid Estates (PE), a small community in far north Queensland, Australia. In 2011, wMel was stably introduced into Gordonvale, separated from PE by barriers to Ae. aegypti dispersal. After nearly six years during which wMel was observed only at low frequencies in PE, corresponding to an apparent equilibrium between immigration and selection, wMel rose to fixation by 2018. Using analytic approximations and statistical analyses, we demonstrate that the observed fixation of wMel at PE is consistent with both stochastic transition past an unstable threshold frequency and deterministic transformation produced by steady immigration at a rate just above the threshold required for deterministic invasion. The indeterminacy results from a delicate balance of parameters needed to produce the delayed transition observed. Our analyses suggest that once Wolbachia transinfections are established locally through systematic introductions, stochastic “threshold crossing” is likely to only minimally enhance spatial spread, providing a local ratchet that slightly – but systematically – aids area-wide transformation of disease-vector populations in heterogeneous landscapes.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 11686
KW - Biological sciences
TI - Wolbachia frequency data from: Why did the Wolbachia transinfection cross the road? Drift, deterministic dynamics and disease control
ER -
TY - GEN
AB - Detailed information about the data set see "dataset description.txt" file.
AU - Hasler, Roger
AU - Reiner-Rozman, Ciril
AU - Fossati, Stefan
AU - Aspermair, Patrik
AU - Dostalek, Jakub
AU - Lee, Seungho
AU - Ibáñez, Maria
AU - Bintinger, Johannes
AU - Knoll, Wolfgang
ID - 10833
TI - Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device
ER -
TY - GEN
AB - Data underlying the figures in the publication "The chemistry of Cu3N and Cu3PdN nanocrystals"
AU - Parvizian, Mahsa
AU - Duran Balsa, Alejandra
AU - Pokratath, Rohan
AU - Kalha, Curran
AU - Lee, Seungho
AU - Van den Eynden, Dietger
AU - Ibáñez, Maria
AU - Regoutz, Anna
AU - De Roo, Jonathan
ID - 11695
TI - Data for "The chemistry of Cu3N and Cu3PdN nanocrystals"
ER -
TY - GEN
AB - Codes and data for reproducing the results of N. B. Budanur and B. Hof "An autonomous compartmental model for accelerating epidemics"
AU - Budanur, Nazmi B
ID - 11711
TI - burakbudanur/autoacc-public
ER -
TY - CONF
AB - We consider the quantitative problem of obtaining lower-bounds on the probability of termination of a given non-deterministic probabilistic program. Specifically, given a non-termination threshold p∈[0,1], we aim for certificates proving that the program terminates with probability at least 1−p. The basic idea of our approach is to find a terminating stochastic invariant, i.e. a subset SI of program states such that (i) the probability of the program ever leaving SI is no more than p, and (ii) almost-surely, the program either leaves SI or terminates.
While stochastic invariants are already well-known, we provide the first proof that the idea above is not only sound, but also complete for quantitative termination analysis. We then introduce a novel sound and complete characterization of stochastic invariants that enables template-based approaches for easy synthesis of quantitative termination certificates, especially in affine or polynomial forms. Finally, by combining this idea with the existing martingale-based methods that are relatively complete for qualitative termination analysis, we obtain the first automated, sound, and relatively complete algorithm for quantitative termination analysis. Notably, our completeness guarantees for quantitative termination analysis are as strong as the best-known methods for the qualitative variant.
Our prototype implementation demonstrates the effectiveness of our approach on various probabilistic programs. We also demonstrate that our algorithm certifies lower bounds on termination probability for probabilistic programs that are beyond the reach of previous methods.
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir Kafshdar
AU - Meggendorfer, Tobias
AU - Zikelic, Dorde
ID - 12000
SN - 0302-9743
T2 - Proceedings of the 34th International Conference on Computer Aided Verification
TI - Sound and complete certificates for auantitative termination analysis of probabilistic programs
VL - 13371
ER -
TY - JOUR
AB - Recently it became possible to study highly excited rotational states of molecules in superfluid helium through nonadiabatic alignment experiments (Cherepanov et al 2021 Phys. Rev. A 104 L061303). This calls for theoretical approaches that go beyond explaining renormalized values of molecular spectroscopic constants, which suffices when only the lowest few rotational states are involved. As the first step in this direction, here we present a basic quantum mechanical model describing highly excited rotational states of molecules in superfluid helium nanodroplets. We show that a linear molecule immersed in a superfluid can be seen as an effective symmetric top, similar to the rotational structure of radicals, such as OH or NO, but with the angular momentum of the superfluid playing the role of the electronic angular momentum in free molecules. The simple theory sheds light onto what happens when the rotational angular momentum of the molecule increases beyond the lowest excited states accessible by infrared spectroscopy. In addition, the model allows to estimate the effective rotational and centrifugal distortion constants for a broad range of species and to explain the crossover between light and heavy molecules in superfluid 4He in terms of the many-body wavefunction structure. Some of the above mentioned insights can be acquired by analyzing a simple 2 × 2 matrix.
AU - Cherepanov, Igor
AU - Bighin, Giacomo
AU - Schouder, Constant A.
AU - Chatterley, Adam S.
AU - Stapelfeldt, Henrik
AU - Lemeshko, Mikhail
ID - 11998
IS - 7
JF - New Journal of Physics
SN - 1367-2630
TI - A simple model for high rotational excitations of molecules in a superfluid
VL - 24
ER -
TY - JOUR
AB - Sexual antagonism is a common hypothesis for driving the evolution of sex chromosomes, whereby recombination suppression is favored between sexually antagonistic loci and the sex-determining locus to maintain beneficial combinations of alleles. This results in the formation of a sex-determining region. Chromosomal inversions may contribute to recombination suppression but their precise role in sex chromosome evolution remains unclear. Because local adaptation is frequently facilitated through the suppression of recombination between adaptive loci by chromosomal inversions, there is potential for inversions that cover sex-determining regions to be involved in local adaptation as well, particularly if habitat variation creates environment-dependent sexual antagonism. With these processes in mind, we investigated sex determination in a well-studied example of local adaptation within a species: the intertidal snail, Littorina saxatilis. Using SNP data from a Swedish hybrid zone, we find novel evidence for a female-heterogametic sex determination system that is restricted to one ecotype. Our results suggest that four putative chromosomal inversions, two previously described and two newly discovered, span the putative sex chromosome pair. We determine their differing associations with sex, which suggest distinct strata of differing ages. The same inversions are found in the second ecotype but do not show any sex association. The striking disparity in inversion-sex associations between ecotypes that are connected by gene flow across a habitat transition that is just a few meters wide indicates a difference in selective regime that has produced a distinct barrier to the spread of the newly discovered sex-determining region between ecotypes. Such sex chromosome-environment interactions have not previously been uncovered in L. saxatilis and are known in few other organisms. A combination of both sex-specific selection and divergent natural selection is required to explain these highly unusual patterns.
AU - Hearn, Katherine E.
AU - Koch, Eva L.
AU - Stankowski, Sean
AU - Butlin, Roger K.
AU - Faria, Rui
AU - Johannesson, Kerstin
AU - Westram, Anja M
ID - 12001
JF - Evolution Letters
TI - Differing associations between sex determination and sex-linked inversions in two ecotypes of Littorina saxatilis
ER -
TY - JOUR
AB - A simple drawing D(G) of a graph G is one where each pair of edges share at most one point: either a common endpoint or a proper crossing. An edge e in the complement of G can be inserted into D(G) if there exists a simple drawing of G+e extending D(G). As a result of Levi’s Enlargement Lemma, if a drawing is rectilinear (pseudolinear), that is, the edges can be extended into an arrangement of lines (pseudolines), then any edge in the complement of G can be inserted. In contrast, we show that it is NP-complete to decide whether one edge can be inserted into a simple drawing. This remains true even if we assume that the drawing is pseudocircular, that is, the edges can be extended to an arrangement of pseudocircles. On the positive side, we show that, given an arrangement of pseudocircles A and a pseudosegment σ, it can be decided in polynomial time whether there exists a pseudocircle Φσ extending σ for which A∪{Φσ} is again an arrangement of pseudocircles.
AU - Arroyo Guevara, Alan M
AU - Klute, Fabian
AU - Parada, Irene
AU - Vogtenhuber, Birgit
AU - Seidel, Raimund
AU - Wiedera, Tilo
ID - 11999
JF - Discrete and Computational Geometry
SN - 0179-5376
TI - Inserting one edge into a simples drawing is hard
ER -
TY - JOUR
AB - G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.
AU - Schulz, Rouven
AU - Korkut, Medina
AU - Venturino, Alessandro
AU - Colombo, Gloria
AU - Siegert, Sandra
ID - 11995
JF - Nature Communications
TI - Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
VL - 13
ER -
TY - THES
AB - G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.
We validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.
Our DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level.
AU - Schulz, Rouven
ID - 11945
SN - 2663-337X
TI - Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function
ER -
TY - DATA
AU - Schulz, Rouven
ID - 11542
TI - Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses)
ER -
TY - JOUR
AB - Interlocking puzzles are intriguing geometric games where the puzzle pieces are held together based on their geometric arrangement, preventing the puzzle from falling apart. High-level-of-difficulty, or simply high-level, interlocking puzzles are a subclass of interlocking puzzles that require multiple moves to take out the first subassembly from the puzzle. Solving a high-level interlocking puzzle is a challenging task since one has to explore many different configurations of the puzzle pieces until reaching a configuration where the first subassembly can be taken out. Designing a high-level interlocking puzzle with a user-specified level of difficulty is even harder since the puzzle pieces have to be interlocking in all the configurations before the first subassembly is taken out.
In this paper, we present a computational approach to design high-level interlocking puzzles. The core idea is to represent all possible configurations of an interlocking puzzle as well as transitions among these configurations using a rooted, undirected graph called a disassembly graph and leverage this graph to find a disassembly plan that requires a minimal number of moves to take out the first subassembly from the puzzle. At the design stage, our algorithm iteratively constructs the geometry of each puzzle piece to expand the disassembly graph incrementally, aiming to achieve a user-specified level of difficulty. We show that our approach allows efficient generation of high-level interlocking puzzles of various shape complexities, including new solutions not attainable by state-of-the-art approaches.
AU - Chen, Rulin
AU - Wang, Ziqi
AU - Song, Peng
AU - Bickel, Bernd
ID - 11735
IS - 4
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - Computational design of high-level interlocking puzzles
VL - 41
ER -
TY - JOUR
AB - Moulding refers to a set of manufacturing techniques in which a mould, usually a cavity or a solid frame, is used to shape a liquid or pliable material into an object of the desired shape. The popularity of moulding comes from its effectiveness, scalability and versatility in terms of employed materials. Its relevance as a fabrication process is demonstrated by the extensive literature covering different aspects related to mould design, from material flow simulation to the automation of mould geometry design. In this state-of-the-art report, we provide an extensive review of the automatic methods for the design of moulds, focusing on contributions from a geometric perspective. We classify existing mould design methods based on their computational approach and the nature of their target moulding process. We summarize the relationships between computational approaches and moulding techniques, highlighting their strengths and limitations. Finally, we discuss potential future research directions.
AU - Alderighi, Thomas
AU - Malomo, Luigi
AU - Auzinger, Thomas
AU - Bickel, Bernd
AU - Cignoni, Paulo
AU - Pietroni, Nico
ID - 11993
JF - Computer Graphics Forum
KW - Computer Graphics and Computer-Aided Design
SN - 0167-7055
TI - State of the art in computational mould design
ER -
TY - JOUR
AB - We study the fate of an impurity in an ultracold heteronuclear Bose mixture, focusing on the experimentally relevant case of a ⁴¹K - ⁸⁷Rb mixture, with the impurity in a ⁴¹K hyperfine state. Our paper provides a comprehensive description of an impurity in a BEC mixture with contact interactions across its phase diagram. We present results for the miscible and immiscible regimes, as well as for the impurity in a self-bound quantum droplet. Here, varying the interactions, we find exotic states where the impurity localizes either at the center or
at the surface of the droplet.
AU - Bighin, Giacomo
AU - Burchianti, A.
AU - Minardi, F.
AU - Macrì, T.
ID - 11997
IS - 2
JF - Physical Review A
SN - 2469-9926
TI - Impurity in a heteronuclear two-component Bose mixture
VL - 106
ER -