TY - JOUR AB - Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof. AU - Petrov, Tatjana AU - Igler, Claudia AU - Sezgin, Ali AU - Henzinger, Thomas A AU - Guet, Calin C ID - 9647 JF - Theoretical Computer Science SN - 0304-3975 TI - Long lived transients in gene regulation VL - 893 ER - TY - JOUR AB - The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs. AU - Muench, Nicole A. AU - Patel, Sonia AU - Maes, Margaret E AU - Donahue, Ryan J. AU - Ikeda, Akihiro AU - Nickells, Robert W. ID - 9761 IS - 7 JF - Cells TI - The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease VL - 10 ER - TY - JOUR AB - At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation. AU - Fredes, Felipe AU - Shigemoto, Ryuichi ID - 9641 JF - Neurobiology of Learning and Memory SN - 10747427 TI - The role of hippocampal mossy cells in novelty detection VL - 183 ER - TY - CONF AB - We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude. AU - Wang, Jinyi AU - Sun, Yican AU - Fu, Hongfei AU - Chatterjee, Krishnendu AU - Goharshady, Amir Kafshdar ID - 9646 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Quantitative analysis of assertion violations in probabilistic programs ER - TY - CONF AB - We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis. We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods. AU - Asadi, Ali AU - Chatterjee, Krishnendu AU - Fu, Hongfei AU - Goharshady, Amir Kafshdar AU - Mahdavi, Mohammad ID - 9645 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Polynomial reachability witnesses via Stellensätze ER - TY - JOUR AU - Bartlett, Michael John AU - Arslan, Feyza N AU - Bankston, Adriana AU - Sarabipour, Sarvenaz ID - 9759 IS - 7 JF - PLoS Computational Biology SN - 1553734X TI - Ten simple rules to improve academic work- life balance VL - 17 ER - TY - JOUR AB - Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science. AU - Zisis, Themistoklis AU - Schwarz, Jan AU - Balles, Miriam AU - Kretschmer, Maibritt AU - Nemethova, Maria AU - Chait, Remy P AU - Hauschild, Robert AU - Lange, Janina AU - Guet, Calin C AU - Sixt, Michael K AU - Zahler, Stefan ID - 9822 IS - 30 JF - ACS Applied Materials and Interfaces SN - 19448244 TI - Sequential and switchable patterning for studying cellular processes under spatiotemporal control VL - 13 ER - TY - JOUR AB - Photorealistic editing of head portraits is a challenging task as humans are very sensitive to inconsistencies in faces. We present an approach for high-quality intuitive editing of the camera viewpoint and scene illumination (parameterised with an environment map) in a portrait image. This requires our method to capture and control the full reflectance field of the person in the image. Most editing approaches rely on supervised learning using training data captured with setups such as light and camera stages. Such datasets are expensive to acquire, not readily available and do not capture all the rich variations of in-the-wild portrait images. In addition, most supervised approaches only focus on relighting, and do not allow camera viewpoint editing. Thus, they only capture and control a subset of the reflectance field. Recently, portrait editing has been demonstrated by operating in the generative model space of StyleGAN. While such approaches do not require direct supervision, there is a significant loss of quality when compared to the supervised approaches. In this paper, we present a method which learns from limited supervised training data. The training images only include people in a fixed neutral expression with eyes closed, without much hair or background variations. Each person is captured under 150 one-light-at-a-time conditions and under 8 camera poses. Instead of training directly in the image space, we design a supervised problem which learns transformations in the latent space of StyleGAN. This combines the best of supervised learning and generative adversarial modeling. We show that the StyleGAN prior allows for generalisation to different expressions, hairstyles and backgrounds. This produces high-quality photorealistic results for in-the-wild images and significantly outperforms existing methods. Our approach can edit the illumination and pose simultaneously, and runs at interactive rates. AU - Mallikarjun, B. R. AU - Tewari, Ayush AU - Dib, Abdallah AU - Weyrich, Tim AU - Bickel, Bernd AU - Seidel, Hans Peter AU - Pfister, Hanspeter AU - Matusik, Wojciech AU - Chevallier, Louis AU - Elgharib, Mohamed A. AU - Theobalt, Christian ID - 9819 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - PhotoApp: Photorealistic appearance editing of head portraits VL - 40 ER - TY - JOUR AB - Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test. AU - Hledik, Michal AU - Polechova, Jitka AU - Beiglböck, Mathias AU - Herdina, Anna Nele AU - Strassl, Robert AU - Posch, Martin ID - 9816 IS - 7 JF - PLoS ONE TI - Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program VL - 16 ER - TY - JOUR AB - Heart rate variability (hrv) is a physiological phenomenon of the variation in the length of the time interval between consecutive heartbeats. In many cases it could be an indicator of the development of pathological states. The classical approach to the analysis of hrv includes time domain methods and frequency domain methods. However, attempts are still being made to define new and more effective hrv assessment tools. Persistent homology is a novel data analysis tool developed in the recent decades that is rooted at algebraic topology. The Topological Data Analysis (TDA) approach focuses on examining the shape of the data in terms of connectedness and holes, and has recently proved to be very effective in various fields of research. In this paper we propose the use of persistent homology to the hrv analysis. We recall selected topological descriptors used in the literature and we introduce some new topological descriptors that reflect the specificity of hrv, and we discuss their relation to the standard hrv measures. In particular, we show that this novel approach provides a collection of indices that might be at least as useful as the classical parameters in differentiating between series of beat-to-beat intervals (RR-intervals) in healthy subjects and patients suffering from a stroke episode. AU - Graff, Grzegorz AU - Graff, Beata AU - Pilarczyk, Pawel AU - Jablonski, Grzegorz AU - Gąsecki, Dariusz AU - Narkiewicz, Krzysztof ID - 9821 IS - 7 JF - PLoS ONE TI - Persistent homology as a new method of the assessment of heart rate variability VL - 16 ER - TY - JOUR AB - Material appearance hinges on material reflectance properties but also surface geometry and illumination. The unlimited number of potential combinations between these factors makes understanding and predicting material appearance a very challenging task. In this work, we collect a large-scale dataset of perceptual ratings of appearance attributes with more than 215,680 responses for 42,120 distinct combinations of material, shape, and illumination. The goal of this dataset is twofold. First, we analyze for the first time the effects of illumination and geometry in material perception across such a large collection of varied appearances. We connect our findings to those of the literature, discussing how previous knowledge generalizes across very diverse materials, shapes, and illuminations. Second, we use the collected dataset to train a deep learning architecture for predicting perceptual attributes that correlate with human judgments. We demonstrate the consistent and robust behavior of our predictor in various challenging scenarios, which, for the first time, enables estimating perceived material attributes from general 2D images. Since our predictor relies on the final appearance in an image, it can compare appearance properties across different geometries and illumination conditions. Finally, we demonstrate several applications that use our predictor, including appearance reproduction using 3D printing, BRDF editing by integrating our predictor in a differentiable renderer, illumination design, or material recommendations for scene design. AU - Serrano, Ana AU - Chen, Bin AU - Wang, Chao AU - Piovarci, Michael AU - Seidel, Hans Peter AU - Didyk, Piotr AU - Myszkowski, Karol ID - 9820 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - The effect of shape and illumination on material perception: Model and applications VL - 40 ER - TY - JOUR AB - Triangle mesh-based simulations are able to produce satisfying animations of knitted and woven cloth; however, they lack the rich geometric detail of yarn-level simulations. Naive texturing approaches do not consider yarn-level physics, while full yarn-level simulations may become prohibitively expensive for large garments. We propose a method to animate yarn-level cloth geometry on top of an underlying deforming mesh in a mechanics-aware fashion. Using triangle strains to interpolate precomputed yarn geometry, we are able to reproduce effects such as knit loops tightening under stretching. In combination with precomputed mesh animation or real-time mesh simulation, our method is able to animate yarn-level cloth in real-time at large scales. AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9818 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - Mechanics-aware deformation of yarn pattern geometry VL - 40 ER - TY - JOUR AB - Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals. AU - Gabrielaitis, Mantas ID - 9828 JF - IEEE Transactions on Signal Processing SN - 1053-587X TI - Fast and accurate amplitude demodulation of wideband signals VL - 69 ER - TY - COMP AB - This archive contains the missing sweater mesh animations and displacement models for the code of "Mechanics-Aware Deformation of Yarn Pattern Geometry" Code Repository: https://git.ist.ac.at/gsperl/MADYPG AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9327 TI - Mechanics-Aware Deformation of Yarn Pattern Geometry (Additional Animation/Model Data) ER - TY - JOUR AB - We study an effective one-dimensional quantum model that includes friction and spin-orbit coupling (SOC), and show that the model exhibits spin polarization when both terms are finite. Most important, strong spin polarization can be observed even for moderate SOC, provided that the friction is strong. Our findings might help to explain the pronounced effect of chirality on spin distribution and transport in chiral molecules. In particular, our model implies static magnetic properties of a chiral molecule, which lead to Shiba-like states when a molecule is placed on a superconductor, in accordance with recent experimental data. AU - Volosniev, Artem AU - Alpern, Hen AU - Paltiel, Yossi AU - Millo, Oded AU - Lemeshko, Mikhail AU - Ghazaryan, Areg ID - 9770 IS - 2 JF - Physical Review B SN - 2469-9950 TI - Interplay between friction and spin-orbit coupling as a source of spin polarization VL - 104 ER - TY - JOUR AB - The Nearest neighbour search (NNS) is a fundamental problem in many application domains dealing with multidimensional data. In a concurrent setting, where dynamic modifications are allowed, a linearizable implementation of the NNS is highly desirable.This paper introduces the LockFree-kD-tree (LFkD-tree ): a lock-free concurrent kD-tree, which implements an abstract data type (ADT) that provides the operations Add, Remove, Contains, and NNS. Our implementation is linearizable. The operations in the LFkD-tree use single-word read and compare-and-swap (Image 1 ) atomic primitives, which are readily supported on available multi-core processors. We experimentally evaluate the LFkD-tree using several benchmarks comprising real-world and synthetic datasets. The experiments show that the presented design is scalable and achieves significant speed-up compared to the implementations of an existing sequential kD-tree and a recently proposed multidimensional indexing structure, PH-tree. AU - Chatterjee, Bapi AU - Walulya, Ivan AU - Tsigas, Philippas ID - 9827 JF - Theoretical Computer Science KW - Concurrent data structure KW - kD-tree KW - Nearest neighbor search KW - Similarity search KW - Lock-free KW - Linearizability SN - 0304-3975 TI - Concurrent linearizable nearest neighbour search in LockFree-kD-tree VL - 886 ER - TY - JOUR AB - Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution. AU - Rodrigues, Jessica A. AU - Hsieh, Ping-Hung AU - Ruan, Deling AU - Nishimura, Toshiro AU - Sharma, Manoj K. AU - Sharma, Rita AU - Ye, XinYi AU - Nguyen, Nicholas D. AU - Nijjar, Sukhranjan AU - Ronald, Pamela C. AU - Fischer, Robert L. AU - Zilberman, Daniel ID - 9877 IS - 29 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting VL - 118 ER - TY - JOUR AB - Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart. AU - Raso, Andrea AU - Dirkx, Ellen AU - Sampaio-Pinto, Vasco AU - el Azzouzi, Hamid AU - Cubero, Ryan J AU - Sorensen, Daniel W. AU - Ottaviani, Lara AU - Olieslagers, Servé AU - Huibers, Manon M. AU - de Weger, Roel AU - Siddiqi, Sailay AU - Moimas, Silvia AU - Torrini, Consuelo AU - Zentillin, Lorena AU - Braga, Luca AU - Nascimento, Diana S. AU - da Costa Martins, Paula A. AU - van Berlo, Jop H. AU - Zacchigna, Serena AU - Giacca, Mauro AU - De Windt, Leon J. ID - 9874 JF - Nature Communications TI - A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration VL - 12 ER - TY - JOUR AB - A few years ago, flow equations were introduced as a technique for calculating the ground-state energies of cold Bose gases with and without impurities. In this paper, we extend this approach to compute observables other than the energy. As an example, we calculate the densities, and phase fluctuations of one-dimensional Bose gases with one and two impurities. For a single mobile impurity, we use flow equations to validate the mean-field results obtained upon the Lee-Low-Pines transformation. We show that the mean-field approximation is accurate for all values of the boson-impurity interaction strength as long as the phase coherence length is much larger than the healing length of the condensate. For two static impurities, we calculate impurity-impurity interactions induced by the Bose gas. We find that leading order perturbation theory fails when boson-impurity interactions are stronger than boson-boson interactions. The mean-field approximation reproduces the flow equation results for all values of the boson-impurity interaction strength as long as boson-boson interactions are weak. AU - Brauneis, Fabian AU - Hammer, Hans-Werner AU - Lemeshko, Mikhail AU - Volosniev, Artem ID - 9769 IS - 1 JF - SciPost Physics TI - Impurities in a one-dimensional Bose gas: The flow equation approach VL - 11 ER - TY - JOUR AB - Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs. AU - Batra, Aditi AU - Römhild, Roderich AU - Rousseau, Emilie AU - Franzenburg, Sören AU - Niemann, Stefan AU - Schulenburg, Hinrich ID - 9746 JF - eLife TI - High potency of sequential therapy with only beta-lactam antibiotics VL - 10 ER - TY - JOUR AB - A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics. AU - Nelson, Glyn AU - Boehm, Ulrike AU - Bagley, Steve AU - Bajcsy, Peter AU - Bischof, Johanna AU - Brown, Claire M. AU - Dauphin, Aurélien AU - Dobbie, Ian M. AU - Eriksson, John E. AU - Faklaris, Orestis AU - Fernandez-Rodriguez, Julia AU - Ferrand, Alexia AU - Gelman, Laurent AU - Gheisari, Ali AU - Hartmann, Hella AU - Kukat, Christian AU - Laude, Alex AU - Mitkovski, Miso AU - Munck, Sebastian AU - North, Alison J. AU - Rasse, Tobias M. AU - Resch-Genger, Ute AU - Schuetz, Lucas C. AU - Seitz, Arne AU - Strambio-De-Castillia, Caterina AU - Swedlow, Jason R. AU - Alexopoulos, Ioannis AU - Aumayr, Karin AU - Avilov, Sergiy AU - Bakker, Gert Jan AU - Bammann, Rodrigo R. AU - Bassi, Andrea AU - Beckert, Hannes AU - Beer, Sebastian AU - Belyaev, Yury AU - Bierwagen, Jakob AU - Birngruber, Konstantin A. AU - Bosch, Manel AU - Breitlow, Juergen AU - Cameron, Lisa A. AU - Chalfoun, Joe AU - Chambers, James J. AU - Chen, Chieh Li AU - Conde-Sousa, Eduardo AU - Corbett, Alexander D. AU - Cordelieres, Fabrice P. AU - Nery, Elaine Del AU - Dietzel, Ralf AU - Eismann, Frank AU - Fazeli, Elnaz AU - Felscher, Andreas AU - Fried, Hans AU - Gaudreault, Nathalie AU - Goh, Wah Ing AU - Guilbert, Thomas AU - Hadleigh, Roland AU - Hemmerich, Peter AU - Holst, Gerhard A. AU - Itano, Michelle S. AU - Jaffe, Claudia B. AU - Jambor, Helena K. AU - Jarvis, Stuart C. AU - Keppler, Antje AU - Kirchenbuechler, David AU - Kirchner, Marcel AU - Kobayashi, Norio AU - Krens, Gabriel AU - Kunis, Susanne AU - Lacoste, Judith AU - Marcello, Marco AU - Martins, Gabriel G. AU - Metcalf, Daniel J. AU - Mitchell, Claire A. AU - Moore, Joshua AU - Mueller, Tobias AU - Nelson, Michael S. AU - Ogg, Stephen AU - Onami, Shuichi AU - Palmer, Alexandra L. AU - Paul-Gilloteaux, Perrine AU - Pimentel, Jaime A. AU - Plantard, Laure AU - Podder, Santosh AU - Rexhepaj, Elton AU - Royon, Arnaud AU - Saari, Markku A. AU - Schapman, Damien AU - Schoonderwoert, Vincent AU - Schroth-Diez, Britta AU - Schwartz, Stanley AU - Shaw, Michael AU - Spitaler, Martin AU - Stoeckl, Martin T. AU - Sudar, Damir AU - Teillon, Jeremie AU - Terjung, Stefan AU - Thuenauer, Roland AU - Wilms, Christian D. AU - Wright, Graham D. AU - Nitschke, Roland ID - 9911 IS - 1 JF - Journal of Microscopy SN - 0022-2720 TI - QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy VL - 284 ER - TY - JOUR AB - Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways. AU - Yotova, Iveta AU - Hudson, Quanah J. AU - Pauler, Florian AU - Proestling, Katharina AU - Haslinger, Isabella AU - Kuessel, Lorenz AU - Perricos, Alexandra AU - Husslein, Heinrich AU - Wenzl, René ID - 9906 IS - 16 JF - International Journal of Molecular Sciences SN - 16616596 TI - LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line VL - 22 ER - TY - JOUR AB - Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait. AU - Slavskii, Sergei A. AU - Kuznetsov, Ivan A. AU - Shashkova, Tatiana I. AU - Bazykin, Georgii A. AU - Axenovich, Tatiana I. AU - Kondrashov, Fyodor AU - Aulchenko, Yurii S. ID - 9910 IS - 7 JF - European Journal of Human Genetics SN - 10184813 TI - The limits of normal approximation for adult height VL - 29 ER - TY - JOUR AB - In the customary random matrix model for transport in quantum dots with M internal degrees of freedom coupled to a chaotic environment via 𝑁≪𝑀 channels, the density 𝜌 of transmission eigenvalues is computed from a specific invariant ensemble for which explicit formula for the joint probability density of all eigenvalues is available. We revisit this problem in the large N regime allowing for (i) arbitrary ratio 𝜙:=𝑁/𝑀≤1; and (ii) general distributions for the matrix elements of the Hamiltonian of the quantum dot. In the limit 𝜙→0, we recover the formula for the density 𝜌 that Beenakker (Rev Mod Phys 69:731–808, 1997) has derived for a special matrix ensemble. We also prove that the inverse square root singularity of the density at zero and full transmission in Beenakker’s formula persists for any 𝜙<1 but in the borderline case 𝜙=1 an anomalous 𝜆−2/3 singularity arises at zero. To access this level of generality, we develop the theory of global and local laws on the spectral density of a large class of noncommutative rational expressions in large random matrices with i.i.d. entries. AU - Erdös, László AU - Krüger, Torben H AU - Nemish, Yuriy ID - 9912 JF - Annales Henri Poincaré SN - 1424-0637 TI - Scattering in quantum dots via noncommutative rational functions VL - 22 ER - TY - JOUR AB - Extending on ideas of Lewin, Lieb, and Seiringer [Phys. Rev. B 100, 035127 (2019)], we present a modified “floating crystal” trial state for jellium (also known as the classical homogeneous electron gas) with density equal to a characteristic function. This allows us to show that three definitions of the jellium energy coincide in dimensions d ≥ 2, thus extending the result of Cotar and Petrache [“Equality of the Jellium and uniform electron gas next-order asymptotic terms for Coulomb and Riesz potentials,” arXiv: 1707.07664 (2019)] and Lewin, Lieb, and Seiringer [Phys. Rev. B 100, 035127 (2019)] that the three definitions coincide in dimension d ≥ 3. We show that the jellium energy is also equivalent to a “renormalized energy” studied in a series of papers by Serfaty and others, and thus, by the work of Bétermin and Sandier [Constr. Approximation 47, 39–74 (2018)], we relate the jellium energy to the order n term in the logarithmic energy of n points on the unit 2-sphere. We improve upon known lower bounds for this renormalized energy. Additionally, we derive formulas for the jellium energy of periodic configurations. AU - Lauritsen, Asbjørn Bækgaard ID - 9891 IS - 8 JF - Journal of Mathematical Physics KW - Mathematical Physics KW - Statistical and Nonlinear Physics SN - 0022-2488 TI - Floating Wigner crystal and periodic jellium configurations VL - 62 ER - TY - JOUR AB - Roots are composed of different root types and, in the dicotyledonous Arabidopsis, typically consist of a primary root that branches into lateral roots. Adventitious roots emerge from non-root tissue and are formed upon wounding or other types of abiotic stress. Here, we investigated adventitious root (AR) formation in Arabidopsis hypocotyls under conditions of altered abscisic acid (ABA) signaling. Exogenously applied ABA suppressed AR formation at 0.25 µM or higher doses. AR formation was less sensitive to the synthetic ABA analog pyrabactin (PB). However, PB was a more potent inhibitor at concentrations above 1 µM, suggesting that it was more selective in triggering a root inhibition response. Analysis of a series of phosphonamide and phosphonate pyrabactin analogs suggested that adventitious root formation and lateral root branching are differentially regulated by ABA signaling. ABA biosynthesis and signaling mutants affirmed a general inhibitory role of ABA and point to PYL1 and PYL2 as candidate ABA receptors that regulate AR inhibition. AU - Zeng, Yinwei AU - Verstraeten, Inge AU - Trinh, Hoang Khai AU - Heugebaert, Thomas AU - Stevens, Christian V. AU - Garcia-Maquilon, Irene AU - Rodriguez, Pedro L. AU - Vanneste, Steffen AU - Geelen, Danny ID - 9909 IS - 8 JF - Genes TI - Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling VL - 12 ER - TY - JOUR AB - DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane. AU - Labajová, Naďa AU - Baranova, Natalia S. AU - Jurásek, Miroslav AU - Vácha, Robert AU - Loose, Martin AU - Barák, Imrich ID - 9907 IS - 15 JF - International Journal of Molecular Sciences SN - 16616596 TI - Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva VL - 22 ER - TY - JOUR AB - Vaccines are thought to be the best available solution for controlling the ongoing SARS-CoV-2 pandemic. However, the emergence of vaccine-resistant strains may come too rapidly for current vaccine developments to alleviate the health, economic and social consequences of the pandemic. To quantify and characterize the risk of such a scenario, we created a SIR-derived model with initial stochastic dynamics of the vaccine-resistant strain to study the probability of its emergence and establishment. Using parameters realistically resembling SARS-CoV-2 transmission, we model a wave-like pattern of the pandemic and consider the impact of the rate of vaccination and the strength of non-pharmaceutical intervention measures on the probability of emergence of a resistant strain. As expected, we found that a fast rate of vaccination decreases the probability of emergence of a resistant strain. Counterintuitively, when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased. Consequently, we show that a period of transmission reduction close to the end of the vaccination campaign can substantially reduce the probability of resistant strain establishment. Our results suggest that policymakers and individuals should consider maintaining non-pharmaceutical interventions and transmission-reducing behaviours throughout the entire vaccination period. AU - Rella, Simon AU - Kulikova, Yuliya A. AU - Dermitzakis, Emmanouil T. AU - Kondrashov, Fyodor ID - 9905 IS - 1 JF - Scientific Reports TI - Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains VL - 11 ER - TY - JOUR AB - Eigenstate thermalization in quantum many-body systems implies that eigenstates at high energy are similar to random vectors. Identifying systems where at least some eigenstates are nonthermal is an outstanding question. In this Letter we show that interacting quantum models that have a nullspace—a degenerate subspace of eigenstates at zero energy (zero modes), which corresponds to infinite temperature, provide a route to nonthermal eigenstates. We analytically show the existence of a zero mode which can be represented as a matrix product state for a certain class of local Hamiltonians. In the more general case we use a subspace disentangling algorithm to generate an orthogonal basis of zero modes characterized by increasing entanglement entropy. We show evidence for an area-law entanglement scaling of the least-entangled zero mode in the broad parameter regime, leading to a conjecture that all local Hamiltonians with the nullspace feature zero modes with area-law entanglement scaling and, as such, break the strong thermalization hypothesis. Finally, we find zero modes in constrained models and propose a setup for observing their experimental signatures. AU - Karle, Volker AU - Serbyn, Maksym AU - Michailidis, Alexios ID - 9903 IS - 6 JF - Physical Review Letters SN - 0031-9007 TI - Area-law entangled eigenstates from nullspaces of local Hamiltonians VL - 127 ER - TY - JOUR AB - Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry. AU - Chaigne, Agathe AU - Smith, Matthew B. AU - Cavestany, R. L. AU - Hannezo, Edouard B AU - Chalut, Kevin J. AU - Paluch, Ewa K. ID - 9952 IS - 14 JF - Journal of Cell Science SN - 00219533 TI - Three-dimensional geometry controls division symmetry in stem cell colonies VL - 134 ER - TY - JOUR AB - About eight million animal species are estimated to live on Earth, and all except those belonging to one subphylum are invertebrates. Invertebrates are incredibly diverse in their morphologies, life histories, and in the range of the ecological niches that they occupy. A great variety of modes of reproduction and sex determination systems is also observed among them, and their mosaic-distribution across the phylogeny shows that transitions between them occur frequently and rapidly. Genetic conflict in its various forms is a long-standing theory to explain what drives those evolutionary transitions. Here, we review (1) the different modes of reproduction among invertebrate species, highlighting sexual reproduction as the probable ancestral state; (2) the paradoxical diversity of sex determination systems; (3) the different types of genetic conflicts that could drive the evolution of such different systems. AU - Picard, Marion A L AU - Vicoso, Beatriz AU - Bertrand, Stéphanie AU - Escriva, Hector ID - 9908 IS - 8 JF - Genes TI - Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict VL - 12 ER - TY - JOUR AB - In 2020, many in-person scientific events were canceled due to the COVID-19 pandemic, creating a vacuum in networking and knowledge exchange between scientists. To fill this void in scientific communication, a group of early career nanocrystal enthusiasts launched the virtual seminar series, News in Nanocrystals, in the summer of 2020. By the end of the year, the series had attracted over 850 participants from 46 countries. In this Nano Focus, we describe the process of organizing the News in Nanocrystals seminar series; discuss its growth, emphasizing what the organizers have learned in terms of diversity and accessibility; and provide an outlook for the next steps and future opportunities. This summary and analysis of experiences and learned lessons are intended to inform the broader scientific community, especially those who are looking for avenues to continue fostering discussion and scientific engagement virtually, both during the pandemic and after. AU - Baranov, Dmitry AU - Šverko, Tara AU - Moot, Taylor AU - Keller, Helena R. AU - Klein, Megan D. AU - Vishnu, E. K. AU - Balazs, Daniel AU - Shulenberger, Katherine E. ID - 9829 IS - 7 JF - ACS Nano SN - 19360851 TI - News in Nanocrystals seminar: Self-assembly of early career researchers toward globally accessible nanoscience VL - 15 ER - TY - GEN AB - This dataset comprises all data shown in the figures of the submitted article "Geometric superinductance qubits: Controlling phase delocalization across a single Josephson junction". Additional raw data are available from the corresponding author on reasonable request. AU - Peruzzo, Matilda AU - Hassani, Farid AU - Szep, Grisha AU - Trioni, Andrea AU - Redchenko, Elena AU - Zemlicka, Martin AU - Fink, Johannes M ID - 13057 TI - Geometric superinductance qubits: Controlling phase delocalization across a single Josephson junction ER - TY - JOUR AB - AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity. AU - Watson, Jake AU - Pinggera, Alexandra AU - Ho, Hinze AU - Greger, Ingo H. ID - 9985 IS - 1 JF - Nature Communications TI - AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions VL - 12 ER - TY - JOUR AB - The numerical simulation of dynamical phenomena in interacting quantum systems is a notoriously hard problem. Although a number of promising numerical methods exist, they often have limited applicability due to the growth of entanglement or the presence of the so-called sign problem. In this work, we develop an importance sampling scheme for the simulation of quantum spin dynamics, building on a recent approach mapping quantum spin systems to classical stochastic processes. The importance sampling scheme is based on identifying the classical trajectory that yields the largest contribution to a given quantum observable. An exact transformation is then carried out to preferentially sample trajectories that are close to the dominant one. We demonstrate that this approach is capable of reducing the temporal growth of fluctuations in the stochastic quantities, thus extending the range of accessible times and system sizes compared to direct sampling. We discuss advantages and limitations of the proposed approach, outlining directions for further developments. AU - De Nicola, Stefano ID - 9981 IS - 3 JF - SciPost Physics KW - General Physics and Astronomy SN - 2542-4653 TI - Importance sampling scheme for the stochastic simulation of quantum spin dynamics VL - 11 ER - TY - CONF AB - There has recently been a surge of interest in the computational and complexity properties of the population model, which assumes n anonymous, computationally-bounded nodes, interacting at random, with the goal of jointly computing global predicates. Significant work has gone towards investigating majority or consensus dynamics in this model: that is, assuming that every node is initially in one of two states X or Y, determine which state had higher initial count. In this paper, we consider a natural generalization of majority/consensus, which we call comparison : in its simplest formulation, we are given two baseline states, X and Y, present in any initial configuration in fixed, but possibly small counts. One of these states has higher count than the other: we will assume |X_0| > C |Y_0| for some constant C > 1. The challenge is to design a protocol by which nodes can quickly and reliably decide on which of the baseline states X_0 and Y_0 has higher initial count. We begin by analyzing a simple and general dynamics solving the above comparison problem, which uses O( log n ) states per node, and converges in O(log n) (parallel) time, with high probability, to a state where the whole population votes on opinions X or Y at rates proportional to the initial concentrations of |X_0| vs. |Y_0|. We then describe how this procedure can be bootstrapped to solve comparison, i.e. have every node in the population reach the "correct'' decision, with probability 1 - o(1), at the cost of O (log log n) additional states. Further, we prove that this dynamics is self-stabilizing, in the sense that it converges to the correct decision from arbitrary initial states, and leak-robust, in the sense that it can withstand spurious faulty reactions, which are known to occur in practical implementations of population protocols. Our analysis is based on a new martingale concentration result relating the discrete-time evolution of a population protocol to its expected (steady-state) analysis, which should be a useful tool when analyzing opinion dynamics and epidemic dissemination in the population model. AU - Alistarh, Dan-Adrian AU - Töpfer, Martin AU - Uznański, Przemysław ID - 9951 SN - 9781450385480 T2 - Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing TI - Comparison dynamics in population protocols ER - TY - JOUR AB - The control of many-body quantum dynamics in complex systems is a key challenge in the quest to reliably produce and manipulate large-scale quantum entangled states. Recently, quench experiments in Rydberg atom arrays [Bluvstein et al. Science 371, 1355 (2021)] demonstrated that coherent revivals associated with quantum many-body scars can be stabilized by periodic driving, generating stable subharmonic responses over a wide parameter regime. We analyze a simple, related model where these phenomena originate from spatiotemporal ordering in an effective Floquet unitary, corresponding to discrete time-crystalline behavior in a prethermal regime. Unlike conventional discrete time crystals, the subharmonic response exists only for Néel-like initial states, associated with quantum scars. We predict robustness to perturbations and identify emergent timescales that could be observed in future experiments. Our results suggest a route to controlling entanglement in interacting quantum systems by combining periodic driving with many-body scars. AU - Maskara, N. AU - Michailidis, Alexios AU - Ho, W. W. AU - Bluvstein, D. AU - Choi, S. AU - Lukin, M. D. AU - Serbyn, Maksym ID - 9960 IS - 9 JF - Physical Review Letters SN - 0031-9007 TI - Discrete time-crystalline order enabled by quantum many-body scars: Entanglement steering via periodic driving VL - 127 ER - TY - JOUR AB - The notion of Thouless energy plays a central role in the theory of Anderson localization. We investigate and compare the scaling of Thouless energy across the many-body localization (MBL) transition in a Floquet model. We use a combination of methods that are reliable on the ergodic side of the transition (e.g., spectral form factor) and methods that work on the MBL side (e.g., typical matrix elements of local operators) to obtain a complete picture of the Thouless energy behavior across the transition. On the ergodic side, Thouless energy decreases slowly with the system size, while at the transition it becomes comparable to the level spacing. Different probes yield consistent estimates of Thouless energy in their overlapping regime of applicability, giving the location of the transition point nearly free of finite-size drift. This work establishes a connection between different definitions of Thouless energy in a many-body setting and yields insights into the MBL transition in Floquet systems. AU - Sonner, Michael AU - Serbyn, Maksym AU - Papić, Zlatko AU - Abanin, Dmitry A. ID - 9961 IS - 8 JF - Physical Review B SN - 2469-9950 TI - Thouless energy across the many-body localization transition in Floquet systems VL - 104 ER - TY - CONF AB - The reflectance field of a face describes the reflectance properties responsible for complex lighting effects including diffuse, specular, inter-reflection and self shadowing. Most existing methods for estimating the face reflectance from a monocular image assume faces to be diffuse with very few approaches adding a specular component. This still leaves out important perceptual aspects of reflectance as higher-order global illumination effects and self-shadowing are not modeled. We present a new neural representation for face reflectance where we can estimate all components of the reflectance responsible for the final appearance from a single monocular image. Instead of modeling each component of the reflectance separately using parametric models, our neural representation allows us to generate a basis set of faces in a geometric deformation-invariant space, parameterized by the input light direction, viewpoint and face geometry. We learn to reconstruct this reflectance field of a face just from a monocular image, which can be used to render the face from any viewpoint in any light condition. Our method is trained on a light-stage training dataset, which captures 300 people illuminated with 150 light conditions from 8 viewpoints. We show that our method outperforms existing monocular reflectance reconstruction methods, in terms of photorealism due to better capturing of physical premitives, such as sub-surface scattering, specularities, self-shadows and other higher-order effects. AU - B R, Mallikarjun AU - Tewari, Ayush AU - Oh, Tae-Hyun AU - Weyrich, Tim AU - Bickel, Bernd AU - Seidel, Hans-Peter AU - Pfister, Hanspeter AU - Matusik, Wojciech AU - Elgharib, Mohamed AU - Theobalt, Christian ID - 9957 SN - 1063-6919 T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition TI - Monocular reconstruction of neural face reflectance fields ER - TY - JOUR AB - In this article we introduce a complete gradient estimate for symmetric quantum Markov semigroups on von Neumann algebras equipped with a normal faithful tracial state, which implies semi-convexity of the entropy with respect to the recently introduced noncommutative 2-Wasserstein distance. We show that this complete gradient estimate is stable under tensor products and free products and establish its validity for a number of examples. As an application we prove a complete modified logarithmic Sobolev inequality with optimal constant for Poisson-type semigroups on free group factors. AU - Wirth, Melchior AU - Zhang, Haonan ID - 9973 JF - Communications in Mathematical Physics KW - Mathematical Physics KW - Statistical and Nonlinear Physics SN - 0010-3616 TI - Complete gradient estimates of quantum Markov semigroups VL - 387 ER - TY - JOUR AB - Inhibition or targeted deletion of histone deacetylase 3 (HDAC3) is neuroprotective in a variety neurodegenerative conditions, including retinal ganglion cells (RGCs) after acute optic nerve damage. Consistent with this, induced HDAC3 expression in cultured cells shows selective toxicity to neurons. Despite an established role for HDAC3 in neuronal pathology, little is known regarding the mechanism of this pathology. AU - Schmitt, Heather M. AU - Fehrman, Rachel L. AU - Maes, Margaret E AU - Yang, Huan AU - Guo, Lian Wang AU - Schlamp, Cassandra L. AU - Pelzel, Heather R. AU - Nickells, Robert W. ID - 10000 IS - 10 JF - Investigative Ophthalmology and Visual Science SN - 0146-0404 TI - Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression VL - 62 ER - TY - JOUR AB - We define quantum equivariant K-theory of Nakajima quiver varieties. We discuss type A in detail as well as its connections with quantum XXZ spin chains and trigonometric Ruijsenaars-Schneider models. Finally we study a limit which produces a K-theoretic version of results of Givental and Kim, connecting quantum geometry of flag varieties and Toda lattice. AU - Koroteev, Peter AU - Pushkar, Petr AU - Smirnov, Andrey V. AU - Zeitlin, Anton M. ID - 9998 IS - 5 JF - Selecta Mathematica SN - 1022-1824 TI - Quantum K-theory of quiver varieties and many-body systems VL - 27 ER - TY - JOUR AB - The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development. Impact Statement: Incomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site. AU - Pulgar, Eduardo AU - Schwayer, Cornelia AU - Guerrero, Néstor AU - López, Loreto AU - Márquez, Susana AU - Härtel, Steffen AU - Soto, Rodrigo AU - Heisenberg, Carl Philipp AU - Concha, Miguel L. ID - 9999 JF - eLife KW - cell delamination KW - apical constriction KW - dragging KW - mechanical forces KW - collective 18 locomotion KW - dorsal forerunner cells KW - zebrafish TI - Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism VL - 10 ER - TY - CONF AB - We present a faster symbolic algorithm for the following central problem in probabilistic verification: Compute the maximal end-component (MEC) decomposition of Markov decision processes (MDPs). This problem generalizes the SCC decomposition problem of graphs and closed recurrent sets of Markov chains. The model of symbolic algorithms is widely used in formal verification and model-checking, where access to the input model is restricted to only symbolic operations (e.g., basic set operations and computation of one-step neighborhood). For an input MDP with n vertices and m edges, the classical symbolic algorithm from the 1990s for the MEC decomposition requires O(n2) symbolic operations and O(1) symbolic space. The only other symbolic algorithm for the MEC decomposition requires O(nm−−√) symbolic operations and O(m−−√) symbolic space. A main open question is whether the worst-case O(n2) bound for symbolic operations can be beaten. We present a symbolic algorithm that requires O˜(n1.5) symbolic operations and O˜(n−−√) symbolic space. Moreover, the parametrization of our algorithm provides a trade-off between symbolic operations and symbolic space: for all 0<ϵ≤1/2 the symbolic algorithm requires O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space ( O˜ hides poly-logarithmic factors). Using our techniques we present faster algorithms for computing the almost-sure winning regions of ω -regular objectives for MDPs. We consider the canonical parity objectives for ω -regular objectives, and for parity objectives with d -priorities we present an algorithm that computes the almost-sure winning region with O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space, for all 0<ϵ≤1/2 . AU - Chatterjee, Krishnendu AU - Dvorak, Wolfgang AU - Henzinger, Monika H AU - Svozil, Alexander ID - 10002 KW - Computer science KW - Computational modeling KW - Markov processes KW - Probabilistic logic KW - Formal verification KW - Game Theory SN - 1043-6871 T2 - Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science TI - Symbolic time and space tradeoffs for probabilistic verification ER - TY - JOUR AB - In this paper, we introduce a random environment for the exclusion process in obtained by assigning a maximal occupancy to each site. This maximal occupancy is allowed to randomly vary among sites, and partial exclusion occurs. Under the assumption of ergodicity under translation and uniform ellipticity of the environment, we derive a quenched hydrodynamic limit in path space by strengthening the mild solution approach initiated in Nagy (2002) and Faggionato (2007). To this purpose, we prove, employing the technology developed for the random conductance model, a homogenization result in the form of an arbitrary starting point quenched invariance principle for a single particle in the same environment, which is a result of independent interest. The self-duality property of the partial exclusion process allows us to transfer this homogenization result to the particle system and, then, apply the tightness criterion in Redig et al. (2020). AU - Floreani, Simone AU - Redig, Frank AU - Sau, Federico ID - 10024 JF - Stochastic Processes and their Applications KW - hydrodynamic limit KW - random environment KW - random conductance model KW - arbitrary starting point quenched invariance principle KW - duality KW - mild solution SN - 0304-4149 TI - Hydrodynamics for the partial exclusion process in random environment VL - 142 ER - TY - CONF AB - Markov chains are the de facto finite-state model for stochastic dynamical systems, and Markov decision processes (MDPs) extend Markov chains by incorporating non-deterministic behaviors. Given an MDP and rewards on states, a classical optimization criterion is the maximal expected total reward where the MDP stops after T steps, which can be computed by a simple dynamic programming algorithm. We consider a natural generalization of the problem where the stopping times can be chosen according to a probability distribution, such that the expected stopping time is T, to optimize the expected total reward. Quite surprisingly we establish inter-reducibility of the expected stopping-time problem for Markov chains with the Positivity problem (which is related to the well-known Skolem problem), for which establishing either decidability or undecidability would be a major breakthrough. Given the hardness of the exact problem, we consider the approximate version of the problem: we show that it can be solved in exponential time for Markov chains and in exponential space for MDPs. AU - Chatterjee, Krishnendu AU - Doyen, Laurent ID - 10004 KW - Computer science KW - Heuristic algorithms KW - Memory management KW - Automata KW - Markov processes KW - Probability distribution KW - Complexity theory SN - 1043-6871 T2 - Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science TI - Stochastic processes with expected stopping time ER - TY - CONF 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+NPlog2log2NP), where N is the block length of the code and μ is the scaling exponent of polar codes for the channel. Three direct consequences of this bound are presented. First, in a fully-parallel implementation where P=N2 , the latency of SSC decoding is O(N1−1/μ) , which is sublinear in the block length. This recovers a result from an earlier work. Second, in a fully-serial implementation where P=1 , the latency of SSC decoding scales as O(Nlog2log2N) . The multiplicative constant is also calculated: we show that the latency of SSC decoding when P=1 is given by (2+o(1))Nlog2log2N . 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 - 10053 SN - 2157-8095 T2 - 2021 IEEE International Symposium on Information Theory TI - Parallelism versus latency in simplified successive-cancellation decoding of polar codes ER - TY - JOUR AB - The ⊗*-monoidal structure on the category of sheaves on the Ran space is not pro-nilpotent in the sense of [3]. However, under some connectivity assumptions, we prove that Koszul duality induces an equivalence of categories and that this equivalence behaves nicely with respect to Verdier duality on the Ran space and integrating along the Ran space, i.e. taking factorization homology. Based on ideas sketched in [4], we show that these results also offer a simpler alternative to one of the two main steps in the proof of the Atiyah-Bott formula given in [7] and [5]. AU - Ho, Quoc P ID - 10033 JF - Advances in Mathematics KW - Chiral algebras KW - Chiral homology KW - Factorization algebras KW - Koszul duality KW - Ran space SN - 0001-8708 TI - The Atiyah-Bott formula and connectivity in chiral Koszul duality VL - 392 ER - TY - JOUR AB - Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization. AU - Butola, Tanvi AU - Alvanos, Theocharis AU - Hintze, Anika AU - Koppensteiner, Peter AU - Kleindienst, David AU - Shigemoto, Ryuichi AU - Wichmann, Carolin AU - Moser, Tobias ID - 10051 IS - 37 JF - Journal of Neuroscience SN - 0270-6474 TI - RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse VL - 41 ER - TY - CONF AB - Repeated idempotent elements are commonly used to characterise iterable behaviours in abstract models of computation. Therefore, given a monoid M, it is natural to ask how long a sequence of elements of M needs to be to ensure the presence of consecutive idempotent factors. This question is formalised through the notion of the Ramsey function R_M associated to M, obtained by mapping every k ∈ ℕ to the minimal integer R_M(k) such that every word u ∈ M^* of length R_M(k) contains k consecutive non-empty factors that correspond to the same idempotent element of M. In this work, we study the behaviour of the Ramsey function R_M by investigating the regular 𝒟-length of M, defined as the largest size L(M) of a submonoid of M isomorphic to the set of natural numbers {1,2, …, L(M)} equipped with the max operation. We show that the regular 𝒟-length of M determines the degree of R_M, by proving that k^L(M) ≤ R_M(k) ≤ (k|M|⁴)^L(M). To allow applications of this result, we provide the value of the regular 𝒟-length of diverse monoids. In particular, we prove that the full monoid of n × n Boolean matrices, which is used to express transition monoids of non-deterministic automata, has a regular 𝒟-length of (n²+n+2)/2. AU - Jecker, Ismael R ID - 10055 SN - 1868-8969 T2 - 38th International Symposium on Theoretical Aspects of Computer Science TI - A Ramsey theorem for finite monoids VL - 187 ER -