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 -