TY - JOUR
AB - This paper provides an a priori error analysis of a localized orthogonal decomposition method for the numerical stochastic homogenization of a model random diffusion problem. If the uniformly elliptic and bounded random coefficient field of the model problem is stationary and satisfies a quantitative decorrelation assumption in the form of the spectral gap inequality, then the expected $L^2$ error of the method can be estimated, up to logarithmic factors, by $H+(\varepsilon/H)^{d/2}$, $\varepsilon$ being the small correlation length of the random coefficient and $H$ the width of the coarse finite element mesh that determines the spatial resolution. The proof bridges recent results of numerical homogenization and quantitative stochastic homogenization.
AU - Fischer, Julian L
AU - Gallistl, Dietmar
AU - Peterseim, Dietmar
ID - 9352
IS - 2
JF - SIAM Journal on Numerical Analysis
SN - 0036-1429
TI - A priori error analysis of a numerical stochastic homogenization method
VL - 59
ER -
TY - JOUR
AB - Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.
AU - Inglés Prieto, Álvaro
AU - Furthmann, Nikolas
AU - Crossman, Samuel H.
AU - Tichy, Alexandra Madelaine
AU - Hoyer, Nina
AU - Petersen, Meike
AU - Zheden, Vanessa
AU - Bicher, Julia
AU - Gschaider-Reichhart, Eva
AU - György, Attila
AU - Siekhaus, Daria E
AU - Soba, Peter
AU - Winklhofer, Konstanze F.
AU - Janovjak, Harald L
ID - 9363
IS - 4
JF - PLoS genetics
TI - Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease
VL - 17
ER -
TY - JOUR
AB - The multimeric matrix (M) protein of clinically relevant paramyxoviruses orchestrates assembly and budding activity of viral particles at the plasma membrane (PM). We identified within the canine distemper virus (CDV) M protein two microdomains, potentially assuming α-helix structures, which are essential for membrane budding activity. Remarkably, while two rationally designed microdomain M mutants (E89R, microdomain 1 and L239D, microdomain 2) preserved proper folding, dimerization, interaction with the nucleocapsid protein, localization at and deformation of the PM, the virus-like particle formation, as well as production of infectious virions (as monitored using a membrane budding-complementation system), were, in sharp contrast, strongly impaired. Of major importance, raster image correlation spectroscopy (RICS) revealed that both microdomains contributed to finely tune M protein mobility specifically at the PM. Collectively, our data highlighted the cornerstone membrane budding-priming activity of two spatially discrete M microdomains, potentially by coordinating the assembly of productive higher oligomers at the PM.
AU - Gast, Matthieu
AU - Kadzioch, Nicole P.
AU - Milius, Doreen
AU - Origgi, Francesco
AU - Plattet, Philippe
ID - 9361
IS - 2
JF - mSphere
TI - Oligomerization and cell egress controlled by two microdomains of canine distemper virus matrix protein
VL - 6
ER -
TY - JOUR
AB - A central goal in systems neuroscience is to understand the functions performed by neural circuits. Previous top-down models addressed this question by comparing the behaviour of an ideal model circuit, optimised to perform a given function, with neural recordings. However, this requires guessing in advance what function is being performed, which may not be possible for many neural systems. To address this, we propose an inverse reinforcement learning (RL) framework for inferring the function performed by a neural network from data. We assume that the responses of each neuron in a network are optimised so as to drive the network towards ‘rewarded’ states, that are desirable for performing a given function. We then show how one can use inverse RL to infer the reward function optimised by the network from observing its responses. This inferred reward function can be used to predict how the neural network should adapt its dynamics to perform the same function when the external environment or network structure changes. This could lead to theoretical predictions about how neural network dynamics adapt to deal with cell death and/or varying sensory stimulus statistics.
AU - Chalk, Matthew J
AU - Tkačik, Gašper
AU - Marre, Olivier
ID - 9362
IS - 4 April
JF - PLoS ONE
TI - Inferring the function performed by a recurrent neural network
VL - 16
ER -
TY - JOUR
AB - In this paper, we propose a new iterative method with alternated inertial step for solving split common null point problem in real Hilbert spaces. We obtain weak convergence of the proposed iterative algorithm. Furthermore, we introduce the notion of bounded linear regularity property for the split common null point problem and obtain the linear convergence property for the new algorithm under some mild assumptions. Finally, we provide some numerical examples to demonstrate the performance and efficiency of the proposed method.
AU - Ogbuisi, Ferdinard U.
AU - Shehu, Yekini
AU - Yao, Jen Chih
ID - 9365
JF - Optimization
SN - 02331934
TI - Convergence analysis of new inertial method for the split common null point problem
ER -
TY - JOUR
AB - We prove that the factorization homologies of a scheme with coefficients in truncated polynomial algebras compute the cohomologies of its generalized configuration spaces. Using Koszul duality between commutative algebras and Lie algebras, we obtain new expressions for the cohomologies of the latter. As a consequence, we obtain a uniform and conceptual approach for treating homological stability, homological densities, and arithmetic densities of generalized configuration spaces. Our results categorify, generalize, and in fact provide a conceptual understanding of the coincidences appearing in the work of Farb--Wolfson--Wood. Our computation of the stable homological densities also yields rational homotopy types, answering a question posed by Vakil--Wood. Our approach hinges on the study of homological stability of cohomological Chevalley complexes, which is of independent interest.
AU - Ho, Quoc P
ID - 9359
IS - 2
JF - Geometry & Topology
KW - Generalized configuration spaces
KW - homological stability
KW - homological densities
KW - chiral algebras
KW - chiral homology
KW - factorization algebras
KW - Koszul duality
KW - Ran space
SN - 1364-0380
TI - Homological stability and densities of generalized configuration spaces
VL - 25
ER -
TY - JOUR
AU - Bolger-Munro, Madison
AU - Choi, Kate
AU - Cheung, Faith
AU - Liu, Yi Tian
AU - Dang-Lawson, May
AU - Deretic, Nikola
AU - Keane, Connor
AU - Gold, Michael R.
ID - 9379
JF - Frontiers in Cell and Developmental Biology
KW - B cell
KW - actin
KW - immune synapse
KW - cell spreading
KW - cofilin
KW - WDR1 (AIP1)
KW - LIM domain kinase
KW - B cell receptor (BCR)
TI - The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced actin remodeling and signaling at the immune synapse
VL - 9
ER -
TY - CHAP
AB - Optimal decision making requires individuals to know their available options and to anticipate correctly what consequences these options have. In many social interactions, however, we refrain from gathering all relevant information, even if this information would help us make better decisions and is costless to obtain. This chapter examines several examples of “deliberate ignorance.” Two simple models are proposed to illustrate how ignorance can evolve among self-interested and payoff - maximizing individuals, and open problems are highlighted that lie ahead for future research to explore.
AU - Schmid, Laura
AU - Hilbe, Christian
ED - Hertwig, Ralph
ED - Engel, Christoph
ID - 9403
SN - 978-0-262-04559-9
T2 - Deliberate Ignorance: Choosing Not To Know
TI - The evolution of strategic ignorance in strategic interaction
VL - 29
ER -
TY - JOUR
AB - We extend our recent result [22] on the central limit theorem for the linear eigenvalue statistics of non-Hermitian matrices X with independent, identically distributed complex entries to the real symmetry class. We find that the expectation and variance substantially differ from their complex counterparts, reflecting (i) the special spectral symmetry of real matrices onto the real axis; and (ii) the fact that real i.i.d. matrices have many real eigenvalues. Our result generalizes the previously known special cases where either the test function is analytic [49] or the first four moments of the matrix elements match the real Gaussian [59, 44]. The key element of the proof is the analysis of several weakly dependent Dyson Brownian motions (DBMs). The conceptual novelty of the real case compared with [22] is that the correlation structure of the stochastic differentials in each individual DBM is non-trivial, potentially even jeopardising its well-posedness.
AU - Cipolloni, Giorgio
AU - Erdös, László
AU - Schröder, Dominik J
ID - 9412
JF - Electronic Journal of Probability
TI - Fluctuation around the circular law for random matrices with real entries
VL - 26
ER -
TY - JOUR
AB - The dynamics of a triangular magnetocapillary swimmer is studied using the lattice Boltzmann method. We extend on our previous work, which deals with the self-assembly and a specific type of the swimmer motion characterized by the swimmer’s maximum velocity centred around the particle’s inverse viscous time. Here, we identify additional regimes of motion. First, modifying the ratio of surface tension and magnetic forces allows to study the swimmer propagation in the regime of significantly lower frequencies mainly defined by the strength of the magnetocapillary potential. Second, introducing a constant magnetic contribution in each of the particles in addition to their magnetic moment induced by external fields leads to another regime characterized by strong in-plane swimmer reorientations that resemble experimental observations.
AU - Sukhov, Alexander
AU - Hubert, Maxime
AU - Grosjean, Galien M
AU - Trosman, Oleg
AU - Ziegler, Sebastian
AU - Collard, Ylona
AU - Vandewalle, Nicolas
AU - Smith, Ana Sunčana
AU - Harting, Jens
ID - 9411
IS - 4
JF - European Physical Journal E
SN - 12928941
TI - Regimes of motion of magnetocapillary swimmers
VL - 44
ER -
TY - JOUR
AB - We present a computational design system that assists users to model, optimize, and fabricate quad-robots with soft skins. Our system addresses the challenging task of predicting their physical behavior by fully integrating the multibody dynamics of the mechanical skeleton and the elastic behavior of the soft skin. The developed motion control strategy uses an alternating optimization scheme to avoid expensive full space time-optimization, interleaving space-time optimization for the skeleton, and frame-by-frame optimization for the full dynamics. The output are motor torques to drive the robot to achieve a user prescribed motion trajectory. We also provide a collection of convenient engineering tools and empirical manufacturing guidance to support the fabrication of the designed quad-robot. We validate the feasibility of designs generated with our system through physics simulations and with a physically-fabricated prototype.
AU - Feng, Xudong
AU - Liu, Jiafeng
AU - Wang, Huamin
AU - Yang, Yin
AU - Bao, Hujun
AU - Bickel, Bernd
AU - Xu, Weiwei
ID - 9408
IS - 6
JF - IEEE Transactions on Visualization and Computer Graphics
SN - 19410506
TI - Computational design of skinned Quad-Robots
VL - 27
ER -
TY - JOUR
AB - Antibiotic concentrations vary dramatically in the body and the environment. Hence, understanding the dynamics of resistance evolution along antibiotic concentration gradients is critical for predicting and slowing the emergence and spread of resistance. While it has been shown that increasing the concentration of an antibiotic slows resistance evolution, how adaptation to one antibiotic concentration correlates with fitness at other points along the gradient has not received much attention. Here, we selected populations of Escherichia coli at several points along a concentration gradient for three different antibiotics, asking how rapidly resistance evolved and whether populations became specialized to the antibiotic concentration they were selected on. Populations selected at higher concentrations evolved resistance more slowly but exhibited equal or higher fitness across the whole gradient. Populations selected at lower concentrations evolved resistance rapidly, but overall fitness in the presence of antibiotics was lower. However, these populations readily adapted to higher concentrations upon subsequent selection. Our results indicate that resistance management strategies must account not only for the rates of resistance evolution but also for the fitness of evolved strains.
AU - Lagator, Mato
AU - Uecker, Hildegard
AU - Neve, Paul
ID - 9410
IS - 5
JF - Biology letters
TI - Adaptation at different points along antibiotic concentration gradients
VL - 17
ER -
TY - JOUR
AB - This paper presents a method for designing planar multistable compliant structures. Given a sequence of desired stable states and the corresponding poses of the structure, we identify the topology and geometric realization of a mechanism—consisting of bars and joints—that is able to physically reproduce the desired multistable behavior. In order to solve this problem efficiently, we build on insights from minimally rigid graph theory to identify simple but effective topologies for the mechanism. We then optimize its geometric parameters, such as joint positions and bar lengths, to obtain correct transitions between the given poses. Simultaneously, we ensure adequate stability of each pose based on an effective approximate error metric related to the elastic energy Hessian of the bars in the mechanism. As demonstrated by our results, we obtain functional multistable mechanisms of manageable complexity that can be fabricated using 3D printing. Further, we evaluated the effectiveness of our method on a large number of examples in the simulation and fabricated several physical prototypes.
AU - Zhang, Ran
AU - Auzinger, Thomas
AU - Bickel, Bernd
ID - 9376
JF - ACM Transactions on Graphics
KW - multistability
KW - mechanism
KW - computational design
KW - rigidity
TI - Computational design of planar multistable compliant structures
ER -
TY - JOUR
AB - We derive rigorously the leading order of the correlation energy of a Fermi gas in a scaling regime of high density and weak interaction. The result verifies the prediction of the random-phase approximation. Our proof refines the method of collective bosonization in three dimensions. We approximately diagonalize an effective Hamiltonian describing approximately bosonic collective excitations around the Hartree–Fock state, while showing that gapless and non-collective excitations have only a negligible effect on the ground state energy.
AU - Benedikter, Niels P
AU - Nam, Phan Thành
AU - Porta, Marcello
AU - Schlein, Benjamin
AU - Seiringer, Robert
ID - 7901
JF - Inventiones Mathematicae
SN - 00209910
TI - Correlation energy of a weakly interacting Fermi gas
ER -
TY - GEN
AB - For any given positive integer l, we prove that every plane deformation of a circlewhich preserves the 1/2and 1/ (2l + 1) -rational caustics is trivial i.e. the deformationconsists only of similarities (rescalings and isometries).
AU - Kaloshin, Vadim
AU - Koudjinan, Edmond
ID - 9435
TI - Non co-preservation of the 1/2 and 1/(2l+1)-rational caustics along deformations of circles
ER -
TY - JOUR
AB - The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems.
AU - Goodrich, Carl Peter
AU - King, Ella M.
AU - Schoenholz, Samuel S.
AU - Cubuk, Ekin D.
AU - Brenner, Michael P.
ID - 9257
IS - 10
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Designing self-assembling kinetics with differentiable statistical physics models
VL - 118
ER -
TY - JOUR
AB - Lithium bis(trifluoromethylsulfonyl)imide (LiTFSI) based water-in-salt electrolytes (WiSEs) has recently emerged as a new promising class of electrolytes, primarily owing to their wide electrochemical stability windows (~3–4 V), that by far exceed the thermodynamic stability window of water (1.23 V). Upon increasing the salt concentration towards superconcentration the onset of the oxygen evolution reaction (OER) shifts more significantly than the hydrogen evolution reaction (HER) does. The OER shift has been explained by the accumulation of hydrophobic anions blocking water access to the electrode surface, hence by double layer theory. Here we demonstrate that the processes during oxidation are much more complex, involving OER, carbon and salt decomposition by OER intermediates, and salt precipitation upon local oversaturation. The positive shift in the onset potential of oxidation currents was elucidated by combining several advanced analysis techniques: rotating ring-disk electrode voltammetry, online electrochemical mass spectrometry, and X-ray photoelectron spectroscopy, using both dilute and superconcentrated electrolytes. The results demonstrate the importance of reactive OER intermediates and surface films for electrolyte and electrode stability and motivate further studies of the nature of the electrode.
AU - Maffre, Marion
AU - Bouchal, Roza
AU - Freunberger, Stefan Alexander
AU - Lindahl, Niklas
AU - Johansson, Patrik
AU - Favier, Frédéric
AU - Fontaine, Olivier
AU - Bélanger, Daniel
ID - 9447
IS - 5
JF - Journal of The Electrochemical Society
KW - Renewable Energy
KW - Sustainability and the Environment
KW - Electrochemistry
KW - Materials Chemistry
KW - Electronic
KW - Optical and Magnetic Materials
KW - Surfaces
KW - Coatings and Films
KW - Condensed Matter Physics
SN - 0013-4651
TI - Investigation of electrochemical and chemical processes occurring at positive potentials in “Water-in-Salt” electrolytes
VL - 168
ER -
TY - JOUR
AB - Given a locally finite set 𝑋⊆ℝ𝑑 and an integer 𝑘≥0, we consider the function 𝐰𝑘:Del𝑘(𝑋)→ℝ on the dual of the order-k Voronoi tessellation, whose sublevel sets generalize the notion of alpha shapes from order-1 to order-k (Edelsbrunner et al. in IEEE Trans Inf Theory IT-29:551–559, 1983; Krasnoshchekov and Polishchuk in Inf Process Lett 114:76–83, 2014). While this function is not necessarily generalized discrete Morse, in the sense of Forman (Adv Math 134:90–145, 1998) and Freij (Discrete Math 309:3821–3829, 2009), we prove that it satisfies similar properties so that its increments can be meaningfully classified into critical and non-critical steps. This result extends to the case of weighted points and sheds light on k-fold covers with balls in Euclidean space.
AU - Edelsbrunner, Herbert
AU - Nikitenko, Anton
AU - Osang, Georg F
ID - 9465
IS - 1
JF - Journal of Geometry
SN - 00472468
TI - A step in the Delaunay mosaic of order k
VL - 112
ER -
TY - CONF
AB - We firstly introduce the self-assembled growth of highly uniform Ge quantum wires with controllable position, distance and length on patterned Si (001) substrates. We then present the electrically tunable strong spin-orbit coupling, the first Ge hole spin qubit and ultrafast operation of hole spin qubit in the Ge/Si quantum wires.
AU - Gao, Fei
AU - Zhang, Jie Yin
AU - Wang, Jian Huan
AU - Ming, Ming
AU - Wang, Tina
AU - Zhang, Jian Jun
AU - Watzinger, Hannes
AU - Kukucka, Josip
AU - Vukušić, Lada
AU - Katsaros, Georgios
AU - Wang, Ke
AU - Xu, Gang
AU - Li, Hai Ou
AU - Guo, Guo Ping
ID - 9464
SN - 9781728181769
T2 - 2021 5th IEEE Electron Devices Technology and Manufacturing Conference, EDTM 2021
TI - Ge/Si quantum wires for quantum computing
ER -
TY - JOUR
AB - A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance.
AU - Berdan, Emma L.
AU - Blanckaert, Alexandre
AU - Slotte, Tanja
AU - Suh, Alexander
AU - Westram, Anja M
AU - Fragata, Inês
ID - 9470
IS - 12
JF - Molecular Ecology
SN - 09621083
TI - Unboxing mutations: Connecting mutation types with evolutionary consequences
VL - 30
ER -
TY - JOUR
AB - Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.
AU - Zhang, Tingting
AU - Liu, Tengyuan
AU - Mora, Natalia
AU - Guegan, Justine
AU - Bertrand, Mathilde
AU - Contreras, Ximena
AU - Hansen, Andi H
AU - Streicher, Carmen
AU - Anderle, Marica
AU - Danda, Natasha
AU - Tiberi, Luca
AU - Hippenmeyer, Simon
AU - Hassan, Bassem A.
ID - 8546
IS - 10
JF - Cell Reports
TI - Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum
VL - 35
ER -
TY - JOUR
AB - We prove that the energy of any eigenvector of a sum of several independent large Wigner matrices is equally distributed among these matrices with very high precision. This shows a particularly strong microcanonical form of the equipartition principle for quantum systems whose components are modelled by Wigner matrices.
AU - Bao, Zhigang
AU - Erdös, László
AU - Schnelli, Kevin
ID - 9550
JF - Forum of Mathematics, Sigma
TI - Equipartition principle for Wigner matrices
VL - 9
ER -
TY - JOUR
AB - De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.
AU - Morandell, Jasmin
AU - Schwarz, Lena A
AU - Basilico, Bernadette
AU - Tasciyan, Saren
AU - Dimchev, Georgi A
AU - Nicolas, Armel
AU - Sommer, Christoph M
AU - Kreuzinger, Caroline
AU - Dotter, Christoph
AU - Knaus, Lisa
AU - Dobler, Zoe
AU - Cacci, Emanuele
AU - Schur, Florian KM
AU - Danzl, Johann G
AU - Novarino, Gaia
ID - 9429
IS - 1
JF - Nature Communications
KW - General Biochemistry
KW - Genetics and Molecular Biology
TI - Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development
VL - 12
ER -
TY - JOUR
AB - The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.
AU - Prattes, Michael
AU - Grishkovskaya, Irina
AU - Hodirnau, Victor-Valentin
AU - Rössler, Ingrid
AU - Klein, Isabella
AU - Hetzmannseder, Christina
AU - Zisser, Gertrude
AU - Gruber, Christian C.
AU - Gruber, Karl
AU - Haselbach, David
AU - Bergler, Helmut
ID - 9540
IS - 1
JF - Nature Communications
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Physics and Astronomy
KW - General Chemistry
TI - Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine
VL - 12
ER -
TY - JOUR
AB - The Massively Parallel Computation (MPC) model is an emerging model that distills core aspects of distributed and parallel computation, developed as a tool to solve combinatorial (typically graph) problems in systems of many machines with limited space. Recent work has focused on the regime in which machines have sublinear (in n, the number of nodes in the input graph) space, with randomized algorithms presented for the fundamental problems of Maximal Matching and Maximal Independent Set. However, there have been no prior corresponding deterministic algorithms. A major challenge underlying the sublinear space setting is that the local space of each machine might be too small to store all edges incident to a single node. This poses a considerable obstacle compared to classical models in which each node is assumed to know and have easy access to its incident edges. To overcome this barrier, we introduce a new graph sparsification technique that deterministically computes a low-degree subgraph, with the additional property that solving the problem on this subgraph provides significant progress towards solving the problem for the original input graph. Using this framework to derandomize the well-known algorithm of Luby [SICOMP’86], we obtain O(log Δ + log log n)-round deterministic MPC algorithms for solving the problems of Maximal Matching and Maximal Independent Set with O(nɛ) space on each machine for any constant ɛ > 0. These algorithms also run in O(log Δ) rounds in the closely related model of CONGESTED CLIQUE, improving upon the state-of-the-art bound of O(log 2Δ) rounds by Censor-Hillel et al. [DISC’17].
AU - Czumaj, Artur
AU - Davies, Peter
AU - Parter, Merav
ID - 9541
IS - 2
JF - ACM Transactions on Algorithms
SN - 1549-6325
TI - Graph sparsification for derandomizing massively parallel computation with low space
VL - 17
ER -
TY - JOUR
AB - While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.
AU - Bespalov, Anton
AU - Bernard, René
AU - Gilis, Anja
AU - Gerlach, Björn
AU - Guillén, Javier
AU - Castagné, Vincent
AU - Lefevre, Isabel A.
AU - Ducrey, Fiona
AU - Monk, Lee
AU - Bongiovanni, Sandrine
AU - Altevogt, Bruce
AU - Arroyo-Araujo, María
AU - Bikovski, Lior
AU - De Bruin, Natasja
AU - Castaños-Vélez, Esmeralda
AU - Dityatev, Alexander
AU - Emmerich, Christoph H.
AU - Fares, Raafat
AU - Ferland-Beckham, Chantelle
AU - Froger-Colléaux, Christelle
AU - Gailus-Durner, Valerie
AU - Hölter, Sabine M.
AU - Hofmann, Martine Cj
AU - Kabitzke, Patricia
AU - Kas, Martien Jh
AU - Kurreck, Claudia
AU - Moser, Paul
AU - Pietraszek, Malgorzata
AU - Popik, Piotr
AU - Potschka, Heidrun
AU - Prado Montes De Oca, Ernesto
AU - Restivo, Leonardo
AU - Riedel, Gernot
AU - Ritskes-Hoitinga, Merel
AU - Samardzic, Janko
AU - Schunn, Michael
AU - Stöger, Claudia
AU - Voikar, Vootele
AU - Vollert, Jan
AU - Wever, Kimberley E.
AU - Wuyts, Kathleen
AU - Macleod, Malcolm R.
AU - Dirnagl, Ulrich
AU - Steckler, Thomas
ID - 9607
JF - eLife
TI - Introduction to the EQIPD quality system
VL - 10
ER -
TY - JOUR
AB - We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values.
AU - Dar, M. S.
AU - Akram, Khush Bakhat
AU - Sohail, Ayesha
AU - Arif, Fatima
AU - Zabihi, Fatemeh
AU - Yang, Shengyuan
AU - Munir, Shamsa
AU - Zhu, Meifang
AU - Abid, M.
AU - Nauman, Muhammad
ID - 9569
IS - 35
JF - RSC Advances
TI - Heat induction in two-dimensional graphene–Fe3O4 nanohybrids for magnetic hyperthermia applications with artificial neural network modeling
VL - 11
ER -
TY - CONF
AB - Generalizing Lee’s inductive argument for counting the cells of higher order Voronoi tessellations in ℝ² to ℝ³, we get precise relations in terms of Morse theoretic quantities for piecewise constant functions on planar arrangements. Specifically, we prove that for a generic set of n ≥ 5 points in ℝ³, the number of regions in the order-k Voronoi tessellation is N_{k-1} - binom(k,2)n + n, for 1 ≤ k ≤ n-1, in which N_{k-1} is the sum of Euler characteristics of these function’s first k-1 sublevel sets. We get similar expressions for the vertices, edges, and polygons of the order-k Voronoi tessellation.
AU - Biswas, Ranita
AU - Cultrera di Montesano, Sebastiano
AU - Edelsbrunner, Herbert
AU - Saghafian, Morteza
ID - 9604
SN - 18688969
T2 - Leibniz International Proceedings in Informatics
TI - Counting cells of order-k voronoi tessellations in ℝ^{3} with morse theory
VL - 189
ER -
TY - CONF
AB - In runtime verification, a monitor watches a trace of a system and, if possible, decides after observing each finite prefix whether or not the unknown infinite trace satisfies a given specification. We generalize the theory of runtime verification to monitors that attempt to estimate numerical values of quantitative trace properties (instead of attempting to conclude boolean values of trace specifications), such as maximal or average response time along a trace. Quantitative monitors are approximate: with every finite prefix, they can improve their estimate of the infinite trace's unknown property value. Consequently, quantitative monitors can be compared with regard to a precision-cost trade-off: better approximations of the property value require more monitor resources, such as states (in the case of finite-state monitors) or registers, and additional resources yield better approximations. We introduce a formal framework for quantitative and approximate monitoring, show how it conservatively generalizes the classical boolean setting for monitoring, and give several precision-cost trade-offs for monitors. For example, we prove that there are quantitative properties for which every additional register improves monitoring precision.
AU - Henzinger, Thomas A
AU - Sarac, Naci E
ID - 9356
T2 - Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Quantitative and approximate monitoring
ER -
TY - JOUR
AB - We investigate how the critical driving amplitude at the Floquet many-body localized (MBL) to ergodic phase transition differs between smooth and nonsmooth drives. To this end, we numerically study a disordered spin-1/2 chain which is periodically driven by a sine or square-wave drive over a wide range of driving frequencies. In both cases the critical driving amplitude increases monotonically with the frequency, and at large frequencies it is identical for the two drives. However, at low and intermediate frequencies the critical amplitude of the square-wave drive depends strongly on the frequency, while that of the sinusoidal drive is almost constant over a wide frequency range. By analyzing the density of drive-induced resonances we conclude that this difference is due to resonances induced by the higher harmonics which are present (absent) in the Fourier spectrum of the square-wave (sine) drive. Furthermore, we suggest a numerically efficient method for estimating the frequency dependence of the critical driving amplitudes for different drives which is based on calculating the density of drive-induced resonances. We conclude that delocalization occurs once the density of drive-induced resonances reaches a critical value determined only by the static system.
AU - Diringer, Asaf A.
AU - Gulden, Tobias
ID - 8198
IS - 21
JF - Physical Review B
SN - 24699950
TI - Impact of drive harmonics on the stability of Floquet many-body localization
VL - 103
ER -
TY - JOUR
AB - When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special “basic” holes guarantee foldability.
AU - Aichholzer, Oswin
AU - Akitaya, Hugo A.
AU - Cheung, Kenneth C.
AU - Demaine, Erik D.
AU - Demaine, Martin L.
AU - Fekete, Sándor P.
AU - Kleist, Linda
AU - Kostitsyna, Irina
AU - Löffler, Maarten
AU - Masárová, Zuzana
AU - Mundilova, Klara
AU - Schmidt, Christiane
ID - 8317
JF - Computational Geometry: Theory and Applications
SN - 09257721
TI - Folding polyominoes with holes into a cube
VL - 93
ER -
TY - JOUR
AB - Resting-state brain activity is characterized by the presence of neuronal avalanches showing absence of characteristic size. Such evidence has been interpreted in the context of criticality and associated with the normal functioning of the brain. A distinctive attribute of systems at criticality is the presence of long-range correlations. Thus, to verify the hypothesis that the brain operates close to a critical point and consequently assess deviations from criticality for diagnostic purposes, it is of primary importance to robustly and reliably characterize correlations in resting-state brain activity. Recent works focused on the analysis of narrow-band electroencephalography (EEG) and magnetoencephalography (MEG) signal amplitude envelope, showing evidence of long-range temporal correlations (LRTC) in neural oscillations. However, brain activity is a broadband phenomenon, and a significant piece of information useful to precisely discriminate between normal (critical) and pathological behavior (non-critical), may be encoded in the broadband spatio-temporal cortical dynamics. Here we propose to characterize the temporal correlations in the broadband brain activity through the lens of neuronal avalanches. To this end, we consider resting-state EEG and long-term MEG recordings, extract the corresponding neuronal avalanche sequences, and study their temporal correlations. We demonstrate that the broadband resting-state brain activity consistently exhibits long-range power-law correlations in both EEG and MEG recordings, with similar values of the scaling exponents. Importantly, although we observe that the avalanche size distribution depends on scale parameters, scaling exponents characterizing long-range correlations are quite robust. In particular, they are independent of the temporal binning (scale of analysis), indicating that our analysis captures intrinsic characteristics of the underlying dynamics. Because neuronal avalanches constitute a fundamental feature of neural systems with universal characteristics, the proposed approach may serve as a general, systems- and experiment-independent procedure to infer the existence of underlying long-range correlations in extended neural systems, and identify pathological behaviors in the complex spatio-temporal interplay of cortical rhythms.
AU - Lombardi, Fabrizio
AU - Shriki, Oren
AU - Herrmann, Hans J
AU - de Arcangelis, Lucilla
ID - 7463
JF - Neurocomputing
SN - 09252312
TI - Long-range temporal correlations in the broadband resting state activity of the human brain revealed by neuronal avalanches
ER -
TY - JOUR
AB - SnSe, a wide-bandgap semiconductor, has attracted significant attention from the thermoelectric (TE) community due to its outstanding TE performance deriving from the ultralow thermal conductivity and advantageous electronic structures. Here, we promoted the TE performance of n-type SnSe polycrystals through bandgap engineering and vacancy compensation. We found that PbTe can significantly reduce the wide bandgap of SnSe to reduce the impurity transition energy, largely enhancing the carrier concentration. Also, PbTe-induced crystal symmetry promotion increases the carrier mobility, preserving large Seebeck coefficient. Consequently, a maximum ZT of ∼1.4 at 793 K is obtained in Br doped SnSe–13%PbTe. Furthermore, we found that extra Sn in n-type SnSe can compensate for the intrinsic Sn vacancies and form electron donor-like metallic Sn nanophases. The Sn nanophases near the grain boundary could also reduce the intergrain energy barrier which largely enhances the carrier mobility. As a result, a maximum ZT value of ∼1.7 at 793 K and an average ZT (ZTave) of ∼0.58 in 300–793 K are achieved in Br doped Sn1.08Se–13%PbTe. Our findings provide a novel strategy to promote the TE performance in wide-bandgap semiconductors.
AU - Su, Lizhong
AU - Hong, Tao
AU - Wang, Dongyang
AU - Wang, Sining
AU - Qin, Bingchao
AU - Zhang, Mengmeng
AU - Gao, Xiang
AU - Chang, Cheng
AU - Zhao, Li Dong
ID - 9626
JF - Materials Today Physics
TI - Realizing high doping efficiency and thermoelectric performance in n-type SnSe polycrystals via bandgap engineering and vacancy compensation
VL - 20
ER -
TY - JOUR
AB - Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.
AU - Vandael, David H
AU - Okamoto, Yuji
AU - Borges Merjane, Carolina
AU - Vargas Barroso, Victor M
AU - Suter, Benjamin
AU - Jonas, Peter M
ID - 9438
IS - 6
JF - Nature Protocols
SN - 17542189
TI - Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses
VL - 16
ER -
TY - JOUR
AB - As the size and complexity of models and datasets grow, so does the need for communication-efficient variants of stochastic gradient descent that can be deployed to perform parallel model training. One popular communication-compression method for data-parallel SGD is QSGD (Alistarh et al., 2017), which quantizes and encodes gradients to reduce communication costs. The baseline variant of QSGD provides strong theoretical guarantees, however, for practical purposes, the authors proposed a heuristic variant which we call QSGDinf, which demonstrated impressive empirical gains for distributed training of large neural networks. In this paper, we build on this work to propose a new gradient quantization scheme, and show that it has both stronger theoretical guarantees than QSGD, and matches and exceeds the empirical performance of the QSGDinf heuristic and of other compression methods.
AU - Ramezani-Kebrya, Ali
AU - Faghri, Fartash
AU - Markov, Ilya
AU - Aksenov, Vitalii
AU - Alistarh, Dan-Adrian
AU - Roy, Daniel M.
ID - 9571
IS - 114
JF - Journal of Machine Learning Research
SN - 15324435
TI - NUQSGD: Provably communication-efficient data-parallel SGD via nonuniform quantization
VL - 22
ER -
TY - JOUR
AB - Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.
AU - Yang, Qiutan
AU - Xue, Shi-lei
AU - Chan, Chii Jou
AU - Rempfler, Markus
AU - Vischi, Dario
AU - Maurer-Gutierrez, Francisca
AU - Hiiragi, Takashi
AU - Hannezo, Edouard B
AU - Liberali, Prisca
ID - 9629
JF - Nature Cell Biology
SN - 14657392
TI - Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
ER -
TY - JOUR
AB - At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.
AU - Fredes, Felipe
AU - Shigemoto, Ryuichi
ID - 9641
JF - Neurobiology of Learning and Memory
SN - 10747427
TI - The role of hippocampal mossy cells in novelty detection
VL - 183
ER -
TY - JOUR
AB - The relative motion of three impenetrable particles on a ring, in our case two identical fermions and one impurity, is isomorphic to a triangular quantum billiard. Depending on the ratio κ of the impurity and fermion masses, the billiards can be integrable or non-integrable (also referred to in the main text as chaotic). To set the stage, we first investigate the energy level distributions of the billiards as a function of 1/κ ∈ [0, 1] and find no evidence of integrable cases beyond the limiting values 1/κ = 1 and 1/κ = 0. Then, we use machine learning tools to analyze properties of probability distributions of individual quantum states. We find that convolutional neural networks can correctly classify integrable and non-integrable states. The decisive features of the wave functions are the normalization and a large number of zero elements, corresponding to the existence of a nodal line. The network achieves typical accuracies of 97%, suggesting that machine learning tools can be used to analyze and classify the morphology of probability densities obtained in theory or experiment.
AU - Huber, David
AU - Marchukov, Oleksandr V.
AU - Hammer, Hans Werner
AU - Volosniev, Artem
ID - 9679
IS - 6
JF - New Journal of Physics
TI - Morphology of three-body quantum states from machine learning
VL - 23
ER -
TY - JOUR
AB - We compute the deficiency spaces of operators of the form 𝐻𝐴⊗̂ 𝐼+𝐼⊗̂ 𝐻𝐵, for symmetric 𝐻𝐴 and self-adjoint 𝐻𝐵. This enables us to construct self-adjoint extensions (if they exist) by means of von Neumann's theory. The structure of the deficiency spaces for this case was asserted already in Ibort et al. [Boundary dynamics driven entanglement, J. Phys. A: Math. Theor. 47(38) (2014) 385301], but only proven under the restriction of 𝐻𝐵 having discrete, non-degenerate spectrum.
AU - Lenz, Daniel
AU - Weinmann, Timon
AU - Wirth, Melchior
ID - 9627
JF - Proceedings of the Edinburgh Mathematical Society
SN - 00130915
TI - Self-adjoint extensions of bipartite Hamiltonians
ER -
TY - JOUR
AB - Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.
AU - Petrov, Tatjana
AU - Igler, Claudia
AU - Sezgin, Ali
AU - Henzinger, Thomas A
AU - Guet, Calin C
ID - 9647
JF - Theoretical Computer Science
SN - 03043975
TI - Long lived transients in gene regulation
ER -
TY - CONF
AB - We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude.
AU - Wang, Jinyi
AU - Sun, Yican
AU - Fu, Hongfei
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir Kafshdar
ID - 9646
SN - 9781450383912
T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation
TI - Quantitative analysis of assertion violations in probabilistic programs
ER -
TY - CONF
AB - We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis.
We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods.
AU - Asadi, Ali
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Goharshady, Amir Kafshdar
AU - Mahdavi, Mohammad
ID - 9645
SN - 9781450383912
T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation
TI - Polynomial reachability witnesses via Stellensätze
ER -
TY - CONF
AB - We present a new approach to proving non-termination of non-deterministic integer programs. Our technique is rather simple but efficient. It relies on a purely syntactic reversal of the program's transition system followed by a constraint-based invariant synthesis with constraints coming from both the original and the reversed transition system. The latter task is performed by a simple call to an off-the-shelf SMT-solver, which allows us to leverage the latest advances in SMT-solving. Moreover, our method offers a combination of features not present (as a whole) in previous approaches: it handles programs with non-determinism, provides relative completeness guarantees and supports programs with polynomial arithmetic. The experiments performed with our prototype tool RevTerm show that our approach, despite its simplicity and stronger theoretical guarantees, is at least on par with the state-of-the-art tools, often achieving a non-trivial improvement under a proper configuration of its parameters.
AU - Chatterjee, Krishnendu
AU - Goharshady, Ehsan Kafshdar
AU - Novotný, Petr
AU - Zikelic, Dorde
ID - 9644
SN - 9781450383912
T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation
TI - Proving non-termination by program reversal
ER -
TY - JOUR
AB - Isomanifolds are the generalization of isosurfaces to arbitrary dimension and codimension, i.e. manifolds defined as the zero set of some multivariate vector-valued smooth function f : Rd → Rd−n. A natural (and efficient) way to approximate an isomanifold is to consider its Piecewise-Linear (PL) approximation based on a triangulation T of the ambient space Rd. In this paper, we give conditions under which the PL-approximation of an isomanifold is topologically equivalent to the isomanifold. The conditions are easy to satisfy in the sense that they can always be met by taking a sufficiently
fine triangulation T . This contrasts with previous results on the triangulation of manifolds where, in arbitrary dimensions, delicate perturbations are needed to guarantee topological correctness, which leads to strong limitations in practice. We further give a bound on the Fréchet distance between the original isomanifold and its PL-approximation. Finally we show analogous results for the PL-approximation of an isomanifold with boundary.
AU - Boissonnat, Jean-Daniel
AU - Wintraecken, Mathijs
ID - 9649
JF - Foundations of Computational Mathematics
TI - The topological correctness of PL approximations of isomanifolds
ER -
TY - CONF
AB - We introduce a new graph problem, the token dropping game, and we show how to solve it efficiently in a distributed setting. We use the token dropping game as a tool to design an efficient distributed algorithm for stable orientations and more generally for locally optimal semi-matchings. The prior work by Czygrinow et al. (DISC 2012) finds a stable orientation in O(Δ^5) rounds in graphs of maximum degree Δ, while we improve it to O(Δ^4) and also prove a lower bound of Ω(Δ). For the more general problem of locally optimal semi-matchings, the prior upper bound is O(S^5) and our new algorithm runs in O(C · S^4) rounds, which is an improvement for C = o(S); here C and S are the maximum degrees of customers and servers, respectively.
AU - Brandt, Sebastian
AU - Keller, Barbara
AU - Rybicki, Joel
AU - Suomela, Jukka
AU - Uitto, Jara
ID - 9678
SN - 9781450380706
T2 - Annual ACM Symposium on Parallelism in Algorithms and Architectures
TI - Efficient load-balancing through distributed token dropping
ER -
TY - CONF
AB - Isomanifolds are the generalization of isosurfaces to arbitrary dimension and codimension, i.e. submanifolds of ℝ^d defined as the zero set of some multivariate multivalued smooth function f: ℝ^d → ℝ^{d-n}, where n is the intrinsic dimension of the manifold. A natural way to approximate a smooth isomanifold M is to consider its Piecewise-Linear (PL) approximation M̂ based on a triangulation 𝒯 of the ambient space ℝ^d. In this paper, we describe a simple algorithm to trace isomanifolds from a given starting point. The algorithm works for arbitrary dimensions n and d, and any precision D. Our main result is that, when f (or M) has bounded complexity, the complexity of the algorithm is polynomial in d and δ = 1/D (and unavoidably exponential in n). Since it is known that for δ = Ω (d^{2.5}), M̂ is O(D²)-close and isotopic to M, our algorithm produces a faithful PL-approximation of isomanifolds of bounded complexity in time polynomial in d. Combining this algorithm with dimensionality reduction techniques, the dependency on d in the size of M̂ can be completely removed with high probability. We also show that the algorithm can handle isomanifolds with boundary and, more generally, isostratifolds. The algorithm for isomanifolds with boundary has been implemented and experimental results are reported, showing that it is practical and can handle cases that are far ahead of the state-of-the-art.
AU - Boissonnat, Jean-Daniel
AU - Kachanovich, Siargey
AU - Wintraecken, Mathijs
ID - 9441
SN - 1868-8969
T2 - 37th International Symposium on Computational Geometry (SoCG 2021)
TI - Tracing isomanifolds in Rd in time polynomial in d using Coxeter-Freudenthal-Kuhn triangulations
VL - 189
ER -
TY - CONF
AB - In this note, we introduce a distributed twist on the classic coupon collector problem: a set of m collectors wish to each obtain a set of n coupons; for this, they can each sample coupons uniformly at random, but can also meet in pairwise interactions, during which they can exchange coupons. By doing so, they hope to reduce the number of coupons that must be sampled by each collector in order to obtain a full set. This extension is natural when considering real-world manifestations of the coupon collector phenomenon, and has been remarked upon and studied empirically (Hayes and Hannigan 2006, Ahmad et al. 2014, Delmarcelle 2019).
We provide the first theoretical analysis for such a scenario. We find that “coupon collecting with friends” can indeed significantly reduce the number of coupons each collector must sample, and raises interesting connections to the more traditional variants of the problem. While our analysis is in most cases asymptotically tight, there are several open questions raised, regarding finer-grained analysis of both “coupon collecting with friends,” and of a long-studied variant of the original problem in which a collector requires multiple full sets of coupons.
AU - Alistarh, Dan-Adrian
AU - Davies, Peter
ID - 9620
SN - 0302-9743
T2 - Structural Information and Communication Complexity
TI - Collecting coupons is faster with friends
VL - 12810
ER -
TY - CONF
AB - Formal design of embedded and cyber-physical systems relies on mathematical modeling. In this paper, we consider the model class of hybrid automata whose dynamics are defined by affine differential equations. Given a set of time-series data, we present an algorithmic approach to synthesize a hybrid automaton exhibiting behavior that is close to the data, up to a specified precision, and changes in synchrony with the data. A fundamental problem in our synthesis algorithm is to check membership of a time series in a hybrid automaton. Our solution integrates reachability and optimization techniques for affine dynamical systems to obtain both a sufficient and a necessary condition for membership, combined in a refinement framework. The algorithm processes one time series at a time and hence can be interrupted, provide an intermediate result, and be resumed. We report experimental results demonstrating the applicability of our synthesis approach.
AU - Garcia Soto, Miriam
AU - Henzinger, Thomas A
AU - Schilling, Christian
ID - 9200
KW - hybrid automaton
KW - membership
KW - system identification
SN - 9781450383394
T2 - HSCC '21: Proceedings of the 24th International Conference on Hybrid Systems: Computation and Control
TI - Synthesis of hybrid automata with affine dynamics from time-series data
ER -
TY - CONF
AB - Modeling a crystal as a periodic point set, we present a fingerprint consisting of density functionsthat facilitates the efficient search for new materials and material properties. We prove invarianceunder isometries, continuity, and completeness in the generic case, which are necessary featuresfor the reliable comparison of crystals. The proof of continuity integrates methods from discretegeometry and lattice theory, while the proof of generic completeness combines techniques fromgeometry with analysis. The fingerprint has a fast algorithm based on Brillouin zones and relatedinclusion-exclusion formulae. We have implemented the algorithm and describe its application tocrystal structure prediction.
AU - Edelsbrunner, Herbert
AU - Heiss, Teresa
AU - Kurlin , Vitaliy
AU - Smith, Philip
AU - Wintraecken, Mathijs
ID - 9345
SN - 1868-8969
T2 - 37th International Symposium on Computational Geometry (SoCG 2021)
TI - The density fingerprint of a periodic point set
VL - 189
ER -
TY - CONF
AB - 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 convex sets of n points there exists a compatible matching with ⌊2n−−√⌋ 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(logn) copies of any set of n points are necessary and sufficient for the existence of a labeling 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 - 9296
SN - 03029743
T2 - 15th International Conference on Algorithms and Computation
TI - On compatible matchings
VL - 12635
ER -