TY - JOUR AB - The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science. AU - Bluvstein, D. AU - Omran, A. AU - Levine, H. AU - Keesling, A. AU - Semeghini, G. AU - Ebadi, S. AU - Wang, T. T. AU - Michailidis, Alexios AU - Maskara, N. AU - Ho, W. W. AU - Choi, S. AU - Serbyn, Maksym AU - Greiner, M. AU - Vuletić, V. AU - Lukin, M. D. ID - 9618 IS - 6536 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - Controlling quantum many-body dynamics in driven Rydberg atom arrays VL - 371 ER - TY - JOUR AB - To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia. AU - Gao, Z AU - Chen, Z AU - Cui, Y AU - Ke, M AU - Xu, H AU - Xu, Q AU - Chen, J AU - Li, Y AU - Huang, L AU - Zhao, H AU - Huang, D AU - Mai, S AU - Xu, T AU - Liu, X AU - Li, S AU - Guan, Y AU - Yang, W AU - Friml, Jiří AU - Petrášek, J AU - Zhang, J AU - Chen, X ID - 9657 IS - 9 JF - Plant Cell SN - 1040-4651 TI - GmPIN-dependent polar auxin transport is involved in soybean nodule development VL - 33 ER - TY - JOUR AB - Selection and random drift determine the probability that novel mutations fixate in a population. Population structure is known to affect the dynamics of the evolutionary process. Amplifiers of selection are population structures that increase the fixation probability of beneficial mutants compared to well-mixed populations. Over the past 15 years, extensive research has produced remarkable structures called strong amplifiers which guarantee that every beneficial mutation fixates with high probability. But strong amplification has come at the cost of considerably delaying the fixation event, which can slow down the overall rate of evolution. However, the precise relationship between fixation probability and time has remained elusive. Here we characterize the slowdown effect of strong amplification. First, we prove that all strong amplifiers must delay the fixation event at least to some extent. Second, we construct strong amplifiers that delay the fixation event only marginally as compared to the well-mixed populations. Our results thus establish a tight relationship between fixation probability and time: Strong amplification always comes at a cost of a slowdown, but more than a marginal slowdown is not needed. AU - Tkadlec, Josef AU - Pavlogiannis, Andreas AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 9640 IS - 1 JF - Nature Communications TI - Fast and strong amplifiers of natural selection VL - 12 ER - TY - JOUR AB - Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underly differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, and a crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment. AU - Han, Huibin AU - Adamowski, Maciek AU - Qi, Linlin AU - Alotaibi, SS AU - Friml, Jiří ID - 9656 IS - 2 JF - New Phytologist SN - 0028-646x TI - PIN-mediated polar auxin transport regulations in plant tropic responses VL - 232 ER - TY - JOUR AB - The relative motion of three impenetrable particles on a ring, in our case two identical fermions and one impurity, is isomorphic to a triangular quantum billiard. Depending on the ratio κ of the impurity and fermion masses, the billiards can be integrable or non-integrable (also referred to in the main text as chaotic). To set the stage, we first investigate the energy level distributions of the billiards as a function of 1/κ ∈ [0, 1] and find no evidence of integrable cases beyond the limiting values 1/κ = 1 and 1/κ = 0. Then, we use machine learning tools to analyze properties of probability distributions of individual quantum states. We find that convolutional neural networks can correctly classify integrable and non-integrable states. The decisive features of the wave functions are the normalization and a large number of zero elements, corresponding to the existence of a nodal line. The network achieves typical accuracies of 97%, suggesting that machine learning tools can be used to analyze and classify the morphology of probability densities obtained in theory or experiment. AU - Huber, David AU - Marchukov, Oleksandr V. AU - Hammer, Hans Werner AU - Volosniev, Artem ID - 9679 IS - 6 JF - New Journal of Physics TI - Morphology of three-body quantum states from machine learning VL - 23 ER - TY - JOUR AB - Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis. AU - Yang, Qiutan AU - Xue, Shi-lei AU - Chan, Chii Jou AU - Rempfler, Markus AU - Vischi, Dario AU - Maurer-Gutierrez, Francisca AU - Hiiragi, Takashi AU - Hannezo, Edouard B AU - Liberali, Prisca ID - 9629 JF - Nature Cell Biology SN - 1465-7392 TI - Cell fate coordinates mechano-osmotic forces in intestinal crypt formation VL - 23 ER - TY - JOUR AB - SnSe, a wide-bandgap semiconductor, has attracted significant attention from the thermoelectric (TE) community due to its outstanding TE performance deriving from the ultralow thermal conductivity and advantageous electronic structures. Here, we promoted the TE performance of n-type SnSe polycrystals through bandgap engineering and vacancy compensation. We found that PbTe can significantly reduce the wide bandgap of SnSe to reduce the impurity transition energy, largely enhancing the carrier concentration. Also, PbTe-induced crystal symmetry promotion increases the carrier mobility, preserving large Seebeck coefficient. Consequently, a maximum ZT of ∼1.4 at 793 K is obtained in Br doped SnSe–13%PbTe. Furthermore, we found that extra Sn in n-type SnSe can compensate for the intrinsic Sn vacancies and form electron donor-like metallic Sn nanophases. The Sn nanophases near the grain boundary could also reduce the intergrain energy barrier which largely enhances the carrier mobility. As a result, a maximum ZT value of ∼1.7 at 793 K and an average ZT (ZTave) of ∼0.58 in 300–793 K are achieved in Br doped Sn1.08Se–13%PbTe. Our findings provide a novel strategy to promote the TE performance in wide-bandgap semiconductors. AU - Su, Lizhong AU - Hong, Tao AU - Wang, Dongyang AU - Wang, Sining AU - Qin, Bingchao AU - Zhang, Mengmeng AU - Gao, Xiang AU - Chang, Cheng AU - Zhao, Li Dong ID - 9626 JF - Materials Today Physics TI - Realizing high doping efficiency and thermoelectric performance in n-type SnSe polycrystals via bandgap engineering and vacancy compensation VL - 20 ER - TY - JOUR AB - The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses. AU - Vandael, David H AU - Okamoto, Yuji AU - Jonas, Peter M ID - 9778 IS - 1 JF - Nature Communications KW - general physics and astronomy KW - general biochemistry KW - genetics and molecular biology KW - general chemistry SN - 2041-1723 TI - Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses VL - 12 ER - TY - JOUR AB - Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof. AU - Petrov, Tatjana AU - Igler, Claudia AU - Sezgin, Ali AU - Henzinger, Thomas A AU - Guet, Calin C ID - 9647 JF - Theoretical Computer Science SN - 0304-3975 TI - Long lived transients in gene regulation VL - 893 ER - TY - JOUR AB - The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs. AU - Muench, Nicole A. AU - Patel, Sonia AU - Maes, Margaret E AU - Donahue, Ryan J. AU - Ikeda, Akihiro AU - Nickells, Robert W. ID - 9761 IS - 7 JF - Cells TI - The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease VL - 10 ER - TY - JOUR AB - At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation. AU - Fredes, Felipe AU - Shigemoto, Ryuichi ID - 9641 JF - Neurobiology of Learning and Memory SN - 10747427 TI - The role of hippocampal mossy cells in novelty detection VL - 183 ER - TY - CONF AB - We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude. AU - Wang, Jinyi AU - Sun, Yican AU - Fu, Hongfei AU - Chatterjee, Krishnendu AU - Goharshady, Amir Kafshdar ID - 9646 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Quantitative analysis of assertion violations in probabilistic programs ER - TY - CONF AB - We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis. We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods. AU - Asadi, Ali AU - Chatterjee, Krishnendu AU - Fu, Hongfei AU - Goharshady, Amir Kafshdar AU - Mahdavi, Mohammad ID - 9645 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Polynomial reachability witnesses via Stellensätze ER - TY - JOUR AU - Bartlett, Michael John AU - Arslan, Feyza N AU - Bankston, Adriana AU - Sarabipour, Sarvenaz ID - 9759 IS - 7 JF - PLoS Computational Biology SN - 1553734X TI - Ten simple rules to improve academic work- life balance VL - 17 ER - TY - JOUR AB - Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science. AU - Zisis, Themistoklis AU - Schwarz, Jan AU - Balles, Miriam AU - Kretschmer, Maibritt AU - Nemethova, Maria AU - Chait, Remy P AU - Hauschild, Robert AU - Lange, Janina AU - Guet, Calin C AU - Sixt, Michael K AU - Zahler, Stefan ID - 9822 IS - 30 JF - ACS Applied Materials and Interfaces SN - 19448244 TI - Sequential and switchable patterning for studying cellular processes under spatiotemporal control VL - 13 ER - TY - JOUR AB - Photorealistic editing of head portraits is a challenging task as humans are very sensitive to inconsistencies in faces. We present an approach for high-quality intuitive editing of the camera viewpoint and scene illumination (parameterised with an environment map) in a portrait image. This requires our method to capture and control the full reflectance field of the person in the image. Most editing approaches rely on supervised learning using training data captured with setups such as light and camera stages. Such datasets are expensive to acquire, not readily available and do not capture all the rich variations of in-the-wild portrait images. In addition, most supervised approaches only focus on relighting, and do not allow camera viewpoint editing. Thus, they only capture and control a subset of the reflectance field. Recently, portrait editing has been demonstrated by operating in the generative model space of StyleGAN. While such approaches do not require direct supervision, there is a significant loss of quality when compared to the supervised approaches. In this paper, we present a method which learns from limited supervised training data. The training images only include people in a fixed neutral expression with eyes closed, without much hair or background variations. Each person is captured under 150 one-light-at-a-time conditions and under 8 camera poses. Instead of training directly in the image space, we design a supervised problem which learns transformations in the latent space of StyleGAN. This combines the best of supervised learning and generative adversarial modeling. We show that the StyleGAN prior allows for generalisation to different expressions, hairstyles and backgrounds. This produces high-quality photorealistic results for in-the-wild images and significantly outperforms existing methods. Our approach can edit the illumination and pose simultaneously, and runs at interactive rates. AU - Mallikarjun, B. R. AU - Tewari, Ayush AU - Dib, Abdallah AU - Weyrich, Tim AU - Bickel, Bernd AU - Seidel, Hans Peter AU - Pfister, Hanspeter AU - Matusik, Wojciech AU - Chevallier, Louis AU - Elgharib, Mohamed A. AU - Theobalt, Christian ID - 9819 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - PhotoApp: Photorealistic appearance editing of head portraits VL - 40 ER - TY - JOUR AB - Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test. AU - Hledik, Michal AU - Polechova, Jitka AU - Beiglböck, Mathias AU - Herdina, Anna Nele AU - Strassl, Robert AU - Posch, Martin ID - 9816 IS - 7 JF - PLoS ONE TI - Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program VL - 16 ER - TY - JOUR AB - Heart rate variability (hrv) is a physiological phenomenon of the variation in the length of the time interval between consecutive heartbeats. In many cases it could be an indicator of the development of pathological states. The classical approach to the analysis of hrv includes time domain methods and frequency domain methods. However, attempts are still being made to define new and more effective hrv assessment tools. Persistent homology is a novel data analysis tool developed in the recent decades that is rooted at algebraic topology. The Topological Data Analysis (TDA) approach focuses on examining the shape of the data in terms of connectedness and holes, and has recently proved to be very effective in various fields of research. In this paper we propose the use of persistent homology to the hrv analysis. We recall selected topological descriptors used in the literature and we introduce some new topological descriptors that reflect the specificity of hrv, and we discuss their relation to the standard hrv measures. In particular, we show that this novel approach provides a collection of indices that might be at least as useful as the classical parameters in differentiating between series of beat-to-beat intervals (RR-intervals) in healthy subjects and patients suffering from a stroke episode. AU - Graff, Grzegorz AU - Graff, Beata AU - Pilarczyk, Pawel AU - Jablonski, Grzegorz AU - Gąsecki, Dariusz AU - Narkiewicz, Krzysztof ID - 9821 IS - 7 JF - PLoS ONE TI - Persistent homology as a new method of the assessment of heart rate variability VL - 16 ER - TY - JOUR AB - Material appearance hinges on material reflectance properties but also surface geometry and illumination. The unlimited number of potential combinations between these factors makes understanding and predicting material appearance a very challenging task. In this work, we collect a large-scale dataset of perceptual ratings of appearance attributes with more than 215,680 responses for 42,120 distinct combinations of material, shape, and illumination. The goal of this dataset is twofold. First, we analyze for the first time the effects of illumination and geometry in material perception across such a large collection of varied appearances. We connect our findings to those of the literature, discussing how previous knowledge generalizes across very diverse materials, shapes, and illuminations. Second, we use the collected dataset to train a deep learning architecture for predicting perceptual attributes that correlate with human judgments. We demonstrate the consistent and robust behavior of our predictor in various challenging scenarios, which, for the first time, enables estimating perceived material attributes from general 2D images. Since our predictor relies on the final appearance in an image, it can compare appearance properties across different geometries and illumination conditions. Finally, we demonstrate several applications that use our predictor, including appearance reproduction using 3D printing, BRDF editing by integrating our predictor in a differentiable renderer, illumination design, or material recommendations for scene design. AU - Serrano, Ana AU - Chen, Bin AU - Wang, Chao AU - Piovarci, Michael AU - Seidel, Hans Peter AU - Didyk, Piotr AU - Myszkowski, Karol ID - 9820 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - The effect of shape and illumination on material perception: Model and applications VL - 40 ER - TY - JOUR AB - Triangle mesh-based simulations are able to produce satisfying animations of knitted and woven cloth; however, they lack the rich geometric detail of yarn-level simulations. Naive texturing approaches do not consider yarn-level physics, while full yarn-level simulations may become prohibitively expensive for large garments. We propose a method to animate yarn-level cloth geometry on top of an underlying deforming mesh in a mechanics-aware fashion. Using triangle strains to interpolate precomputed yarn geometry, we are able to reproduce effects such as knit loops tightening under stretching. In combination with precomputed mesh animation or real-time mesh simulation, our method is able to animate yarn-level cloth in real-time at large scales. AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9818 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - Mechanics-aware deformation of yarn pattern geometry VL - 40 ER - TY - JOUR AB - Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals. AU - Gabrielaitis, Mantas ID - 9828 JF - IEEE Transactions on Signal Processing SN - 1053-587X TI - Fast and accurate amplitude demodulation of wideband signals VL - 69 ER - TY - COMP AB - This archive contains the missing sweater mesh animations and displacement models for the code of "Mechanics-Aware Deformation of Yarn Pattern Geometry" Code Repository: https://git.ist.ac.at/gsperl/MADYPG AU - Sperl, Georg AU - Narain, Rahul AU - Wojtan, Christopher J ID - 9327 TI - Mechanics-Aware Deformation of Yarn Pattern Geometry (Additional Animation/Model Data) ER - TY - JOUR AB - We study an effective one-dimensional quantum model that includes friction and spin-orbit coupling (SOC), and show that the model exhibits spin polarization when both terms are finite. Most important, strong spin polarization can be observed even for moderate SOC, provided that the friction is strong. Our findings might help to explain the pronounced effect of chirality on spin distribution and transport in chiral molecules. In particular, our model implies static magnetic properties of a chiral molecule, which lead to Shiba-like states when a molecule is placed on a superconductor, in accordance with recent experimental data. AU - Volosniev, Artem AU - Alpern, Hen AU - Paltiel, Yossi AU - Millo, Oded AU - Lemeshko, Mikhail AU - Ghazaryan, Areg ID - 9770 IS - 2 JF - Physical Review B SN - 2469-9950 TI - Interplay between friction and spin-orbit coupling as a source of spin polarization VL - 104 ER - TY - JOUR AB - The Nearest neighbour search (NNS) is a fundamental problem in many application domains dealing with multidimensional data. In a concurrent setting, where dynamic modifications are allowed, a linearizable implementation of the NNS is highly desirable.This paper introduces the LockFree-kD-tree (LFkD-tree ): a lock-free concurrent kD-tree, which implements an abstract data type (ADT) that provides the operations Add, Remove, Contains, and NNS. Our implementation is linearizable. The operations in the LFkD-tree use single-word read and compare-and-swap (Image 1 ) atomic primitives, which are readily supported on available multi-core processors. We experimentally evaluate the LFkD-tree using several benchmarks comprising real-world and synthetic datasets. The experiments show that the presented design is scalable and achieves significant speed-up compared to the implementations of an existing sequential kD-tree and a recently proposed multidimensional indexing structure, PH-tree. AU - Chatterjee, Bapi AU - Walulya, Ivan AU - Tsigas, Philippas ID - 9827 JF - Theoretical Computer Science KW - Concurrent data structure KW - kD-tree KW - Nearest neighbor search KW - Similarity search KW - Lock-free KW - Linearizability SN - 0304-3975 TI - Concurrent linearizable nearest neighbour search in LockFree-kD-tree VL - 886 ER - TY - JOUR AB - Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution. AU - Rodrigues, Jessica A. AU - Hsieh, Ping-Hung AU - Ruan, Deling AU - Nishimura, Toshiro AU - Sharma, Manoj K. AU - Sharma, Rita AU - Ye, XinYi AU - Nguyen, Nicholas D. AU - Nijjar, Sukhranjan AU - Ronald, Pamela C. AU - Fischer, Robert L. AU - Zilberman, Daniel ID - 9877 IS - 29 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting VL - 118 ER - TY - JOUR AB - Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart. AU - Raso, Andrea AU - Dirkx, Ellen AU - Sampaio-Pinto, Vasco AU - el Azzouzi, Hamid AU - Cubero, Ryan J AU - Sorensen, Daniel W. AU - Ottaviani, Lara AU - Olieslagers, Servé AU - Huibers, Manon M. AU - de Weger, Roel AU - Siddiqi, Sailay AU - Moimas, Silvia AU - Torrini, Consuelo AU - Zentillin, Lorena AU - Braga, Luca AU - Nascimento, Diana S. AU - da Costa Martins, Paula A. AU - van Berlo, Jop H. AU - Zacchigna, Serena AU - Giacca, Mauro AU - De Windt, Leon J. ID - 9874 JF - Nature Communications TI - A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration VL - 12 ER - TY - JOUR AB - A few years ago, flow equations were introduced as a technique for calculating the ground-state energies of cold Bose gases with and without impurities. In this paper, we extend this approach to compute observables other than the energy. As an example, we calculate the densities, and phase fluctuations of one-dimensional Bose gases with one and two impurities. For a single mobile impurity, we use flow equations to validate the mean-field results obtained upon the Lee-Low-Pines transformation. We show that the mean-field approximation is accurate for all values of the boson-impurity interaction strength as long as the phase coherence length is much larger than the healing length of the condensate. For two static impurities, we calculate impurity-impurity interactions induced by the Bose gas. We find that leading order perturbation theory fails when boson-impurity interactions are stronger than boson-boson interactions. The mean-field approximation reproduces the flow equation results for all values of the boson-impurity interaction strength as long as boson-boson interactions are weak. AU - Brauneis, Fabian AU - Hammer, Hans-Werner AU - Lemeshko, Mikhail AU - Volosniev, Artem ID - 9769 IS - 1 JF - SciPost Physics TI - Impurities in a one-dimensional Bose gas: The flow equation approach VL - 11 ER - TY - JOUR AB - Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs. AU - Batra, Aditi AU - Römhild, Roderich AU - Rousseau, Emilie AU - Franzenburg, Sören AU - Niemann, Stefan AU - Schulenburg, Hinrich ID - 9746 JF - eLife TI - High potency of sequential therapy with only beta-lactam antibiotics VL - 10 ER - TY - JOUR AB - A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics. AU - Nelson, Glyn AU - Boehm, Ulrike AU - Bagley, Steve AU - Bajcsy, Peter AU - Bischof, Johanna AU - Brown, Claire M. AU - Dauphin, Aurélien AU - Dobbie, Ian M. AU - Eriksson, John E. AU - Faklaris, Orestis AU - Fernandez-Rodriguez, Julia AU - Ferrand, Alexia AU - Gelman, Laurent AU - Gheisari, Ali AU - Hartmann, Hella AU - Kukat, Christian AU - Laude, Alex AU - Mitkovski, Miso AU - Munck, Sebastian AU - North, Alison J. AU - Rasse, Tobias M. AU - Resch-Genger, Ute AU - Schuetz, Lucas C. AU - Seitz, Arne AU - Strambio-De-Castillia, Caterina AU - Swedlow, Jason R. AU - Alexopoulos, Ioannis AU - Aumayr, Karin AU - Avilov, Sergiy AU - Bakker, Gert Jan AU - Bammann, Rodrigo R. AU - Bassi, Andrea AU - Beckert, Hannes AU - Beer, Sebastian AU - Belyaev, Yury AU - Bierwagen, Jakob AU - Birngruber, Konstantin A. AU - Bosch, Manel AU - Breitlow, Juergen AU - Cameron, Lisa A. AU - Chalfoun, Joe AU - Chambers, James J. AU - Chen, Chieh Li AU - Conde-Sousa, Eduardo AU - Corbett, Alexander D. AU - Cordelieres, Fabrice P. AU - Nery, Elaine Del AU - Dietzel, Ralf AU - Eismann, Frank AU - Fazeli, Elnaz AU - Felscher, Andreas AU - Fried, Hans AU - Gaudreault, Nathalie AU - Goh, Wah Ing AU - Guilbert, Thomas AU - Hadleigh, Roland AU - Hemmerich, Peter AU - Holst, Gerhard A. AU - Itano, Michelle S. AU - Jaffe, Claudia B. AU - Jambor, Helena K. AU - Jarvis, Stuart C. AU - Keppler, Antje AU - Kirchenbuechler, David AU - Kirchner, Marcel AU - Kobayashi, Norio AU - Krens, Gabriel AU - Kunis, Susanne AU - Lacoste, Judith AU - Marcello, Marco AU - Martins, Gabriel G. AU - Metcalf, Daniel J. AU - Mitchell, Claire A. AU - Moore, Joshua AU - Mueller, Tobias AU - Nelson, Michael S. AU - Ogg, Stephen AU - Onami, Shuichi AU - Palmer, Alexandra L. AU - Paul-Gilloteaux, Perrine AU - Pimentel, Jaime A. AU - Plantard, Laure AU - Podder, Santosh AU - Rexhepaj, Elton AU - Royon, Arnaud AU - Saari, Markku A. AU - Schapman, Damien AU - Schoonderwoert, Vincent AU - Schroth-Diez, Britta AU - Schwartz, Stanley AU - Shaw, Michael AU - Spitaler, Martin AU - Stoeckl, Martin T. AU - Sudar, Damir AU - Teillon, Jeremie AU - Terjung, Stefan AU - Thuenauer, Roland AU - Wilms, Christian D. AU - Wright, Graham D. AU - Nitschke, Roland ID - 9911 IS - 1 JF - Journal of Microscopy SN - 0022-2720 TI - QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy VL - 284 ER - TY - JOUR AB - Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways. AU - Yotova, Iveta AU - Hudson, Quanah J. AU - Pauler, Florian AU - Proestling, Katharina AU - Haslinger, Isabella AU - Kuessel, Lorenz AU - Perricos, Alexandra AU - Husslein, Heinrich AU - Wenzl, René ID - 9906 IS - 16 JF - International Journal of Molecular Sciences SN - 16616596 TI - LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line VL - 22 ER - 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 - TY - JOUR AB - The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a [Formula: see text] level, among women in how blood count values change through pregnancy for mean corpuscular hemoglobin, mean corpuscular volume, mean platelet volume, platelet count and red cell distribution width. We find evidence that almost all complete blood count values show trimester-specific associations with PPH. For example, high platelet count (OR 1.20, 95% CI 1.01-1.53), high mean platelet volume (OR 1.58, 95% CI 1.04-2.08), and high erythrocyte levels (OR 1.36, 95% CI 1.01-1.57) in trimester 1 increased PPH, but high values in trimester 3 decreased PPH risk (OR 0.85, 0.79, 0.67 respectively). We show that differences among women in the course of blood cell counts throughout pregnancy have an important role in shaping pregnancy outcome and tracking blood count value changes through pregnancy improves identification of women at increased risk of postpartum hemorrhage. This study provides greater understanding of the complex changes in blood count values that occur through pregnancy and provides indicators to guide the stratification of patients into risk groups. AU - Robinson, Matthew Richard AU - Patxot, Marion AU - Stojanov, Miloš AU - Blum, Sabine AU - Baud, David ID - 10069 JF - Scientific Reports TI - Postpartum hemorrhage risk is driven by changes in blood composition through pregnancy VL - 11 ER - TY - JOUR AB - Ferromagnetism is most common in transition metal compounds but may also arise in low-density two-dimensional electron systems, with signatures observed in silicon, III-V semiconductor systems, and graphene moiré heterostructures. Here we show that gate-tuned van Hove singularities in rhombohedral trilayer graphene drive the spontaneous ferromagnetic polarization of the electron system into one or more spin- and valley flavors. Using capacitance measurements on graphite-gated van der Waals heterostructures, we find a cascade of density- and electronic displacement field tuned phase transitions marked by negative electronic compressibility. The transitions define the boundaries between phases where quantum oscillations have either four-fold, two-fold, or one-fold degeneracy, associated with a spin and valley degenerate normal metal, spin-polarized `half-metal', and spin and valley polarized `quarter metal', respectively. For electron doping, the salient features are well captured by a phenomenological Stoner model with a valley-anisotropic Hund's coupling, likely arising from interactions at the lattice scale. For hole filling, we observe a richer phase diagram featuring a delicate interplay of broken symmetries and transitions in the Fermi surface topology. Finally, by rotational alignment of a hexagonal boron nitride substrate to induce a moiré superlattice, we find that the superlattice perturbs the preexisting isospin order only weakly, leaving the basic phase diagram intact while catalyzing the formation of topologically nontrivial gapped states whenever itinerant half- or quarter metal states occur at half- or quarter superlattice band filling. Our results show that rhombohedral trilayer graphene is an ideal platform for well-controlled tests of many-body theory and reveal magnetism in moiré materials to be fundamentally itinerant in nature. AU - Zhou, Haoxin AU - Xie, Tian AU - Ghazaryan, Areg AU - Holder, Tobias AU - Ehrets, James R. AU - Spanton, Eric M. AU - Taniguchi, Takashi AU - Watanabe, Kenji AU - Berg, Erez AU - Serbyn, Maksym AU - Young, Andrea F. ID - 10025 JF - Nature KW - condensed matter - mesoscale and nanoscale physics KW - condensed matter - strongly correlated electrons KW - multidisciplinary SN - 0028-0836 TI - Half and quarter metals in rhombohedral trilayer graphene ER - TY - CONF AB - We present a novel approach for blockchain asset owners to reclaim their funds in case of accidental private-key loss or transfer to a mistyped address. Our solution can be deployed upon failure or absence of proactively implemented backup mechanisms, such as secret sharing and cold storage. The main advantages against previous proposals is it does not require any prior action from users and works with both single-key and multi-sig accounts. We achieve this by a 3-phase Commit()→Reveal()→Claim()−or−Challenge() smart contract that enables accessing funds of addresses for which the spending key is not available. We provide an analysis of the threat and incentive models and formalize the concept of reactive KEy-Loss Protection (KELP). AU - Blackshear, Sam AU - Chalkias, Konstantinos AU - Chatzigiannis, Panagiotis AU - Faizullabhoy, Riyaz AU - Khaburzaniya, Irakliy AU - Kokoris Kogias, Eleftherios AU - Lind, Joshua AU - Wong, David AU - Zakian, Tim ID - 10076 SN - 0302-9743 T2 - FC 2021 Workshops TI - Reactive key-loss protection in blockchains VL - 12676 ER - TY - JOUR AB - We extensively discuss the Rademacher and Sobolev-to-Lipschitz properties for generalized intrinsic distances on strongly local Dirichlet spaces possibly without square field operator. We present many non-smooth and infinite-dimensional examples. As an application, we prove the integral Varadhan short-time asymptotic with respect to a given distance function for a large class of strongly local Dirichlet forms. AU - Dello Schiavo, Lorenzo AU - Suzuki, Kohei ID - 10070 IS - 11 JF - Journal of Functional Analysis SN - 0022-1236 TI - Rademacher-type theorems and Sobolev-to-Lipschitz properties for strongly local Dirichlet spaces VL - 281 ER - TY - JOUR AB - Solution synthesis of particles emerged as an alternative to prepare thermoelectric materials with less demanding processing conditions than conventional solid-state synthetic methods. However, solution synthesis generally involves the presence of additional molecules or ions belonging to the precursors or added to enable solubility and/or regulate nucleation and growth. These molecules or ions can end up in the particles as surface adsorbates and interfere in the material properties. This work demonstrates that ionic adsorbates, in particular Na⁺ ions, are electrostatically adsorbed in SnSe particles synthesized in water and play a crucial role not only in directing the material nano/microstructure but also in determining the transport properties of the consolidated material. In dense pellets prepared by sintering SnSe particles, Na remains within the crystal lattice as dopant, in dislocations, precipitates, and forming grain boundary complexions. These results highlight the importance of considering all the possible unintentional impurities to establish proper structure-property relationships and control material properties in solution-processed thermoelectric materials. AU - Liu, Yu AU - Calcabrini, Mariano AU - Yu, Yuan AU - Genç, Aziz AU - Chang, Cheng AU - Costanzo, Tommaso AU - Kleinhanns, Tobias AU - Lee, Seungho AU - Llorca, Jordi AU - Cojocaru‐Mirédin, Oana AU - Ibáñez, Maria ID - 10123 IS - 52 JF - Advanced Materials KW - mechanical engineering KW - mechanics of materials KW - general materials science SN - 0935-9648 TI - The importance of surface adsorbates in solution‐processed thermoelectric materials: The case of SnSe VL - 33 ER - TY - JOUR AB - Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism. AU - Artan, Murat AU - Barratt, Stephen AU - Flynn, Sean M. AU - Begum, Farida AU - Skehel, Mark AU - Nicolas, Armel AU - De Bono, Mario ID - 10117 IS - 3 JF - Journal of Biological Chemistry SN - 0021-9258 TI - Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling VL - 297 ER - TY - CONF AB - We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs. AU - Mühlböck, Fabian AU - Henzinger, Thomas A ID - 10108 KW - run-time verification KW - software engineering KW - implicit specification SN - 0302-9743 T2 - International Conference on Runtime Verification TI - Differential monitoring VL - 12974 ER - TY - JOUR AB - The ubiquitous Ca2+ sensor calmodulin (CaM) binds and regulates many proteins, including ion channels, CaM kinases, and calcineurin, according to Ca2+-CaM levels. What regulates neuronal CaM levels, is, however, unclear. CaM-binding transcription activators (CAMTAs) are ancient proteins expressed broadly in nervous systems and whose loss confers pleiotropic behavioral defects in flies, mice, and humans. Using Caenorhabditis elegans and Drosophila, we show that CAMTAs control neuronal CaM levels. The behavioral and neuronal Ca2+ signaling defects in mutants lacking camt-1, the sole C. elegans CAMTA, can be rescued by supplementing neuronal CaM. CAMT-1 binds multiple sites in the CaM promoter and deleting these sites phenocopies camt-1. Our data suggest CAMTAs mediate a conserved and general mechanism that controls neuronal CaM levels, thereby regulating Ca2+ signaling, physiology, and behavior. AU - Vuong-Brender, Thanh AU - Flynn, Sean AU - Vallis, Yvonne AU - De Bono, Mario ID - 10116 JF - eLife TI - Neuronal calmodulin levels are controlled by CAMTA transcription factors VL - 10 ER - TY - JOUR AB - The small cellular molecule inositol hexakisphosphate (IP6) has been known for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like particles. However, the molecular details underlying this effect have been determined only recently, with the identification of the IP6 binding site in the immature Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice via a second IP6 binding site, and enhances core stability, creating a favorable environment for reverse transcription. IP6 also enhances assembly of other retroviruses, from both the Lentivirus and the Alpharetrovirus genera. These findings suggest that IP6 may have a conserved function throughout the family Retroviridae. Here, we discuss the different steps in the viral life cycle that are influenced by IP6, and describe in detail how IP6 interacts with the immature and mature lattices of different retroviruses. AU - Obr, Martin AU - Schur, Florian KM AU - Dick, Robert A. ID - 10103 IS - 9 JF - Viruses KW - virology KW - infectious diseases SN - 1999-4915 TI - A structural perspective of the role of IP6 in immature and mature retroviral assembly VL - 13 ER - TY - JOUR AB - The search for novel entangled phases of matter has lead to the recent discovery of a new class of “entanglement transitions,” exemplified by random tensor networks and monitored quantum circuits. Most known examples can be understood as some classical ordering transitions in an underlying statistical mechanics model, where entanglement maps onto the free-energy cost of inserting a domain wall. In this paper we study the possibility of entanglement transitions driven by physics beyond such statistical mechanics mappings. Motivated by recent applications of neural-network-inspired variational Ansätze, we investigate under what conditions on the variational parameters these Ansätze can capture an entanglement transition. We study the entanglement scaling of short-range restricted Boltzmann machine (RBM) quantum states with random phases. For uncorrelated random phases, we analytically demonstrate the absence of an entanglement transition and reveal subtle finite-size effects in finite-size numerical simulations. Introducing phases with correlations decaying as 1/r^α in real space, we observe three regions with a different scaling of entanglement entropy depending on the exponent α. We study the nature of the transition between these regions, finding numerical evidence for critical behavior. Our work establishes the presence of long-range correlated phases in RBM-based wave functions as a required ingredient for entanglement transitions. AU - Medina Ramos, Raimel A AU - Vasseur, Romain AU - Serbyn, Maksym ID - 10067 IS - 10 JF - Physical Review B SN - 2469-9950 TI - Entanglement transitions from restricted Boltzmann machines VL - 104 ER - TY - GEN AB - We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs. AU - Mühlböck, Fabian AU - Henzinger, Thomas A ID - 9946 KW - run-time verification KW - software engineering KW - implicit specification SN - 2664-1690 TI - Differential monitoring ER - TY - JOUR AB - Thermoelectric materials enable the direct conversion between heat and electricity. SnTe is a promising candidate due to its high charge transport performance. Here, we prepared SnTe nanocomposites by employing an aqueous method to synthetize SnTe nanoparticles (NP), followed by a unique surface treatment prior NP consolidation. This synthetic approach allowed optimizing the charge and phonon transport synergistically. The novelty of this strategy was the use of a soluble PbS molecular complex prepared using a thiol-amine solvent mixture that upon blending is adsorbed on the SnTe NP surface. Upon consolidation with spark plasma sintering, SnTe-PbS nanocomposite is formed. The presence of PbS complexes significantly compensates for the Sn vacancy and increases the average grain size of the nanocomposite, thus improving the carrier mobility. Moreover, lattice thermal conductivity is also reduced by the Pb and S-induced mass and strain fluctuation. As a result, an enhanced ZT of ca. 0.8 is reached at 873 K. Our finding provides a novel strategy to conduct rational surface treatment on NP-based thermoelectrics. AU - Chang, Cheng AU - Ibáñez, Maria ID - 10073 IS - 18 JF - Materials TI - Enhanced thermoelectric performance by surface engineering in SnTe-PbS nanocomposites VL - 14 ER - TY - JOUR AB - Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group. AU - Elkrewi, Marwan N AU - Moldovan, Mikhail A. AU - Picard, Marion A L AU - Vicoso, Beatriz ID - 10167 JF - Molecular Biology and Evolution KW - sex chromosomes KW - evolutionary strata KW - W-linked gene KW - sex determining gene KW - schistosome parasites SN - 0737-4038 TI - Schistosome W-Linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination ER - TY - JOUR AB - The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay. AU - Appel, Lisa-Marie AU - Franke, Vedran AU - Bruno, Melania AU - Grishkovskaya, Irina AU - Kasiliauskaite, Aiste AU - Kaufmann, Tanja AU - Schoeberl, Ursula E. AU - Puchinger, Martin G. AU - Kostrhon, Sebastian AU - Ebenwaldner, Carmen AU - Sebesta, Marek AU - Beltzung, Etienne AU - Mechtler, Karl AU - Lin, Gen AU - Vlasova, Anna AU - Leeb, Martin AU - Pavri, Rushad AU - Stark, Alexander AU - Akalin, Altuna AU - Stefl, Richard AU - Bernecky, Carrie A AU - Djinovic-Carugo, Kristina AU - Slade, Dea ID - 10163 IS - 1 JF - Nature Communications KW - general physics and astronomy KW - general biochemistry KW - genetics and molecular biology KW - general chemistry TI - PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC VL - 12 ER - TY - JOUR AB - With the wider availability of full-color 3D printers, color-accurate 3D-print preparation has received increased attention. A key challenge lies in the inherent translucency of commonly used print materials that blurs out details of the color texture. Previous work tries to compensate for these scattering effects through strategic assignment of colored primary materials to printer voxels. To date, the highest-quality approach uses iterative optimization that relies on computationally expensive Monte Carlo light transport simulation to predict the surface appearance from subsurface scattering within a given print material distribution; that optimization, however, takes in the order of days on a single machine. In our work, we dramatically speed up the process by replacing the light transport simulation with a data-driven approach. Leveraging a deep neural network to predict the scattering within a highly heterogeneous medium, our method performs around two orders of magnitude faster than Monte Carlo rendering while yielding optimization results of similar quality level. The network is based on an established method from atmospheric cloud rendering, adapted to our domain and extended by a physically motivated weight sharing scheme that substantially reduces the network size. We analyze its performance in an end-to-end print preparation pipeline and compare quality and runtime to alternative approaches, and demonstrate its generalization to unseen geometry and material values. This for the first time enables full heterogenous material optimization for 3D-print preparation within time frames in the order of the actual printing time. AU - Rittig, Tobias AU - Sumin, Denis AU - Babaei, Vahid AU - Didyk, Piotr AU - Voloboy, Alexey AU - Wilkie, Alexander AU - Bickel, Bernd AU - Myszkowski, Karol AU - Weyrich, Tim AU - Křivánek, Jaroslav ID - 9547 IS - 2 JF - Computer Graphics Forum SN - 0167-7055 TI - Neural acceleration of scattering-aware color 3D printing VL - 40 ER - TY - JOUR AB - Phonon polaritons (PhPs)—light coupled to lattice vibrations—with in-plane hyperbolic dispersion exhibit ray-like propagation with large wave vectors and enhanced density of optical states along certain directions on a surface. As such, they have raised a surge of interest, promising unprecedented manipulation of infrared light at the nanoscale in a planar circuitry. Here, we demonstrate focusing of in-plane hyperbolic PhPs propagating along thin slabs of α-MoO3. To that end, we developed metallic nanoantennas of convex geometries for both efficient launching and focusing of the polaritons. The foci obtained exhibit enhanced near-field confinement and absorption compared to foci produced by in-plane isotropic PhPs. Foci sizes as small as λp/4.5 = λ0/50 were achieved (λp is the polariton wavelength and λ0 is the photon wavelength). Focusing of in-plane hyperbolic polaritons introduces a first and most basic building block developing planar polariton optics using in-plane anisotropic van der Waals materials. AU - Martín-Sánchez, Javier AU - Duan, Jiahua AU - Taboada-Gutiérrez, Javier AU - Álvarez-Pérez, Gonzalo AU - Voronin, Kirill V. AU - Prieto Gonzalez, Ivan AU - Ma, Weiliang AU - Bao, Qiaoliang AU - Volkov, Valentyn S. AU - Hillenbrand, Rainer AU - Nikitin, Alexey Y. AU - Alonso-González, Pablo ID - 10177 IS - 41 JF - Science Advances TI - Focusing of in-plane hyperbolic polaritons in van der Waals crystals with tailored infrared nanoantennas VL - 7 ER - TY - JOUR AB - The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain. AU - Vercellino, Irene AU - Sazanov, Leonid A ID - 10146 IS - 7880 JF - Nature SN - 0028-0836 TI - Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV VL - 598 ER - TY - JOUR AB - We give a combinatorial model for r-spin surfaces with parameterized boundary based on Novak (“Lattice topological field theories in two dimensions,” Ph.D. thesis, Universität Hamburg, 2015). The r-spin structure is encoded in terms of ℤ𝑟-valued indices assigned to the edges of a polygonal decomposition. This combinatorial model is designed for our state-sum construction of two-dimensional topological field theories on r-spin surfaces. We show that an example of such a topological field theory computes the Arf-invariant of an r-spin surface as introduced by Randal-Williams [J. Topol. 7, 155 (2014)] and Geiges et al. [Osaka J. Math. 49, 449 (2012)]. This implies, in particular, that the r-spin Arf-invariant is constant on orbits of the mapping class group, providing an alternative proof of that fact. AU - Runkel, Ingo AU - Szegedy, Lorant ID - 10176 IS - 10 JF - Journal of Mathematical Physics SN - 00222488 TI - Topological field theory on r-spin surfaces and the Arf-invariant VL - 62 ER - TY - JOUR AB - Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling. AU - Bajaj, Sunanjay AU - Bagley, Joshua A. AU - Sommer, Christoph M AU - Vertesy, Abel AU - Nagumo Wong, Sakurako AU - Krenn, Veronica AU - Lévi-Strauss, Julie AU - Knoblich, Juergen A. ID - 10179 IS - 23 JF - EMBO Journal SN - 0261-4189 TI - Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration VL - 40 ER - TY - JOUR AB - Single photon emitters in atomically-thin semiconductors can be deterministically positioned using strain induced by underlying nano-structures. Here, we couple monolayer WSe2 to high-refractive-index gallium phosphide dielectric nano-antennas providing both optical enhancement and monolayer deformation. For single photon emitters formed on such nano-antennas, we find very low (femto-Joule) saturation pulse energies and up to 104 times brighter photoluminescence than in WSe2 placed on low-refractive-index SiO2 pillars. We show that the key to these observations is the increase on average by a factor of 5 of the quantum efficiency of the emitters coupled to the nano-antennas. This further allows us to gain new insights into their photoluminescence dynamics, revealing the roles of the dark exciton reservoir and Auger processes. We also find that the coherence time of such emitters is limited by intrinsic dephasing processes. Our work establishes dielectric nano-antennas as a platform for high-efficiency quantum light generation in monolayer semiconductors. AU - Sortino, Luca AU - Zotev, Panaiot G. AU - Phillips, Catherine L. AU - Brash, Alistair J. AU - Cambiasso, Javier AU - Marensi, Elena AU - Fox, A. Mark AU - Maier, Stefan A. AU - Sapienza, Riccardo AU - Tartakovskii, Alexander I. ID - 10203 JF - Nature Communications TI - Bright single photon emitters with enhanced quantum efficiency in a two-dimensional semiconductor coupled with dielectric nano-antennas VL - 12 ER - TY - JOUR AB - In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features. AU - Sahu, Preeti AU - Schwarz, J. M. AU - Manning, M. Lisa ID - 10178 IS - 9 JF - New Journal of Physics TI - Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue VL - 23 ER - TY - JOUR AB - In this article we study some geometric properties of proximally smooth sets. First, we introduce a modification of the metric projection and prove its existence. Then we provide an algorithm for constructing a rectifiable curve between two sufficiently close points of a proximally smooth set in a uniformly convex and uniformly smooth Banach space, with the moduli of smoothness and convexity of power type. Our algorithm returns a reasonably short curve between two sufficiently close points of a proximally smooth set, is iterative and uses our modification of the metric projection. We estimate the length of the constructed curve and its deviation from the segment with the same endpoints. These estimates coincide up to a constant factor with those for the geodesics in a proximally smooth set in a Hilbert space. AU - Ivanov, Grigory AU - Lopushanski, Mariana S. ID - 10181 JF - Set-Valued and Variational Analysis SN - 0927-6947 TI - Rectifiable curves in proximally smooth sets ER - TY - JOUR AB - Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant. AU - Pradhan, Saurabh J. AU - Reddy, Puli Chandramouli AU - Smutny, Michael AU - Sharma, Ankita AU - Sako, Keisuke AU - Oak, Meghana S. AU - Shah, Rini AU - Pal, Mrinmoy AU - Deshpande, Ojas AU - Dsilva, Greg AU - Tang, Yin AU - Mishra, Rakesh AU - Deshpande, Girish AU - Giraldez, Antonio J. AU - Sonawane, Mahendra AU - Heisenberg, Carl-Philipp J AU - Galande, Sanjeev ID - 10202 IS - 1 JF - Nature Communications TI - Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis VL - 12 ER - TY - JOUR AB - Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions. AU - Qi, Qin AU - Angermayr, S. Andreas AU - Bollenbach, Mark Tobias ID - 10271 JF - Frontiers in Microbiology KW - microbiology TI - Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli VL - 12 ER - TY - JOUR AB - We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020). AU - Cipolloni, Giorgio AU - Erdös, László AU - Schröder, Dominik J ID - 10221 IS - 2 JF - Communications in Mathematical Physics SN - 0010-3616 TI - Eigenstate thermalization hypothesis for Wigner matrices VL - 388 ER - TY - JOUR AB - We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging. AU - Feliciangeli, Dario AU - Seiringer, Robert ID - 10224 IS - 3 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics VL - 242 ER - TY - JOUR AB - Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems AU - Vasic, Verica AU - Jones, Mattson S.O. AU - Haslinger, Denise AU - Knaus, Lisa AU - Schmeisser, Michael J. AU - Novarino, Gaia AU - Chiocchetti, Andreas G. ID - 10281 IS - 11 JF - Genes TI - Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment VL - 12 ER - TY - JOUR AB - Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development. AU - Kashkan, Ivan AU - Hrtyan, Mónika AU - Retzer, Katarzyna AU - Humpolíčková, Jana AU - Jayasree, Aswathy AU - Filepová, Roberta AU - Vondráková, Zuzana AU - Simon, Sibu AU - Rombaut, Debbie AU - Jacobs, Thomas B. AU - Frilander, Mikko J. AU - Hejátko, Jan AU - Friml, Jiří AU - Petrášek, Jan AU - Růžička, Kamil ID - 10282 JF - New Phytologist SN - 0028-646X TI - Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana VL - 233 ER - TY - JOUR AB - We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample. AU - Avvakumov, Sergey AU - Mabillard, Isaac AU - Skopenkov, Arkadiy B. AU - Wagner, Uli ID - 10220 JF - Israel Journal of Mathematics SN - 0021-2172 TI - Eliminating higher-multiplicity intersections. III. Codimension 2 VL - 245 ER - TY - GEN AB - Infections early in life can have enduring effects on an organism’s development and immunity. In this study, we show that this equally applies to developing “superorganisms” – incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen’s immune system to suppress pathogen proliferation. Early-life queen pathogen-exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen’s pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism. AU - Casillas Perez, Barbara E AU - Pull, Christopher AU - Naiser, Filip AU - Naderlinger, Elisabeth AU - Matas, Jiri AU - Cremer, Sylvia ID - 13061 TI - Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies ER - TY - JOUR AB - De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement. AU - Conde-Dusman, María J AU - Dey, Partha N AU - Elía-Zudaire, Óscar AU - Garcia Rabaneda, Luis E AU - García-Lira, Carmen AU - Grand, Teddy AU - Briz, Victor AU - Velasco, Eric R AU - Andero Galí, Raül AU - Niñerola, Sergio AU - Barco, Angel AU - Paoletti, Pierre AU - Wesseling, John F AU - Gardoni, Fabrizio AU - Tavalin, Steven J AU - Perez-Otaño, Isabel ID - 10301 JF - eLife KW - general immunology and microbiology KW - general biochemistry KW - genetics and molecular biology KW - general medicine KW - general neuroscience SN - 2050-084X TI - Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly VL - 10 ER - TY - JOUR AB - During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research. AU - Restivo, Leonardo AU - Gerlach, Björn AU - Tsoory, Michael AU - Bikovski, Lior AU - Badurek, Sylvia AU - Pitzer, Claudia AU - Kos-Braun, Isabelle C. AU - Mausset-Bonnefont, Anne Laure Mj AU - Ward, Jonathan AU - Schunn, Michael AU - Noldus, Lucas P.J.J. AU - Bespalov, Anton AU - Voikar, Vootele ID - 10283 JF - EMBO Reports SN - 1469-221X TI - Towards best practices in research: Role of academic core facilities VL - 22 ER - TY - JOUR AB - A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700. AU - Çoruh, Mehmet Orkun AU - Frank, Anna AU - Tanaka, Hideaki AU - Kawamoto, Akihiro AU - El-Mohsnawy, Eithar AU - Kato, Takayuki AU - Namba, Keiichi AU - Gerle, Christoph AU - Nowaczyk, Marc M. AU - Kurisu, Genji ID - 10310 IS - 1 JF - Communications Biology KW - general agricultural and biological Sciences KW - general biochemistry KW - genetics and molecular biology KW - medicine (miscellaneous) SN - 2399-3642 TI - Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster VL - 4 ER - TY - JOUR AB - Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development. AU - Marconi, Marco AU - Gallemi, Marçal AU - Benková, Eva AU - Wabnik, Krzysztof ID - 10270 JF - eLife SN - 2050-084X TI - A coupled mechano-biochemical model for cell polarity guided anisotropic root growth VL - 10 ER - TY - JOUR AB - Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number. AU - Choueiri, George H AU - Lopez Alonso, Jose M AU - Varshney, Atul AU - Sankar, Sarath AU - Hof, Björn ID - 10299 IS - 45 JF - Proceedings of the National Academy of Sciences KW - multidisciplinary KW - elastoinertial turbulence KW - viscoelastic flows KW - elastic instability KW - drag reduction SN - 0027-8424 TI - Experimental observation of the origin and structure of elastoinertial turbulence VL - 118 ER - TY - JOUR AB - Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials. AU - Aubret, Antoine AU - Martinet, Quentin AU - Palacci, Jérémie A ID - 10280 IS - 1 JF - Nature Communications TI - Metamachines of pluripotent colloids VL - 12 ER - TY - JOUR AB - To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - De Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 10322 IS - 11 JF - PLoS Biology SN - 1544-9173 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans VL - 19 ER - TY - JOUR AB - Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density. AU - Akopyan, Arseniy AU - Edelsbrunner, Herbert AU - Nikitenko, Anton ID - 10222 JF - Experimental Mathematics SN - 1058-6458 TI - The beauty of random polytopes inscribed in the 2-sphere ER - TY - JOUR AB - Molecular chaperones are central to cellular protein homeostasis. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. We focus hereby on chaperone-client interactions that are independent of ATP. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity. AU - Sučec, Iva AU - Bersch, Beate AU - Schanda, Paul ID - 10323 JF - Frontiers in Molecular Biosciences TI - How do chaperones bind (partly) unfolded client proteins? VL - 8 ER - TY - JOUR AB - Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants. AU - Xu, Enjun AU - Chai, Liang AU - Zhang, Shiqi AU - Yu, Ruixue AU - Zhang, Xixi AU - Xu, Chongyi AU - Hu, Yuxin ID - 10326 JF - Nature Plants TI - Catabolism of strigolactones by a carboxylesterase VL - 7 ER - TY - GEN AB - To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell-autonomous. We have discovered that, in Caenorhabditis elegans, neuronal Heat shock Factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR)- causes extensive fat remodelling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine, and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodelling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least six TAX-2/TAX-4 cGMP gated channel expressing sensory neurons and TGF-β/BMP are required for signalling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodelling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell non-autonomously coordinate membrane saturation and composition across tissues in a multicellular animal. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry-Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - de Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 13069 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans ER - TY - CONF AB - Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains. AU - Zamyatin, Alexei AU - Al-Bassam, Mustafa AU - Zindros, Dionysis AU - Kokoris Kogias, Eleftherios AU - Moreno-Sanchez, Pedro AU - Kiayias, Aggelos AU - Knottenbelt, William J. ID - 10325 SN - 0302-9743 T2 - 25th International Conference on Financial Cryptography and Data Security TI - SoK: Communication across distributed ledgers VL - 12675 ER -