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 - TY - CONF AB - Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity. AU - Avarikioti, Zeta AU - Kokoris Kogias, Eleftherios AU - Wattenhofer, Roger AU - Zindros, Dionysis ID - 10324 SN - 0302-9743 T2 - 25th International Conference on Financial Cryptography and Data Security TI - Brick: Asynchronous incentive-compatible payment channels VL - 12675 ER - TY - JOUR AB - Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia. AU - Lee, Jungmin AU - Vernet, Andyna AU - Gruber, Nathalie AU - Kready, Kasia M. AU - Burrill, Devin R. AU - Way, Jeffrey C. AU - Silver, Pamela A. ID - 10363 JF - Protein Engineering, Design and Selection SN - 1741-0126 TI - Rational engineering of an erythropoietin fusion protein to treat hypoxia VL - 34 ER - TY - JOUR AU - Heisenberg, Carl-Philipp J AU - Lennon, Ana Maria AU - Mayor, Roberto AU - Salbreux, Guillaume ID - 10366 IS - 12 JF - Cells and Development SN - 2667-2901 TI - Special rebranding issue: “Quantitative cell and developmental biology” VL - 168 ER - TY - JOUR AB - Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales. AU - Ucar, Mehmet C AU - Kamenev, Dmitrii AU - Sunadome, Kazunori AU - Fachet, Dominik C AU - Lallemend, Francois AU - Adameyko, Igor AU - Hadjab, Saida AU - Hannezo, Edouard B ID - 10402 JF - Nature Communications TI - Theory of branching morphogenesis by local interactions and global guidance VL - 12 ER - TY - CONF AB - Digital hardware Trojans are integrated circuits whose implementation differ from the specification in an arbitrary and malicious way. For example, the circuit can differ from its specified input/output behavior after some fixed number of queries (known as “time bombs”) or on some particular input (known as “cheat codes”). To detect such Trojans, countermeasures using multiparty computation (MPC) or verifiable computation (VC) have been proposed. On a high level, to realize a circuit with specification F one has more sophisticated circuits F⋄ manufactured (where F⋄ specifies a MPC or VC of F ), and then embeds these F⋄ ’s into a master circuit which must be trusted but is relatively simple compared to F . Those solutions impose a significant overhead as F⋄ is much more complex than F , also the master circuits are not exactly trivial. In this work, we show that in restricted settings, where F has no evolving state and is queried on independent inputs, we can achieve a relaxed security notion using very simple constructions. In particular, we do not change the specification of the circuit at all (i.e., F=F⋄ ). Moreover the master circuit basically just queries a subset of its manufactured circuits and checks if they’re all the same. The security we achieve guarantees that, if the manufactured circuits are initially tested on up to T inputs, the master circuit will catch Trojans that try to deviate on significantly more than a 1/T fraction of the inputs. This bound is optimal for the type of construction considered, and we provably achieve it using a construction where 12 instantiations of F need to be embedded into the master. We also discuss an extremely simple construction with just 2 instantiations for which we conjecture that it already achieves the optimal bound. AU - Chakraborty, Suvradip AU - Dziembowski, Stefan AU - Gałązka, Małgorzata AU - Lizurej, Tomasz AU - Pietrzak, Krzysztof Z AU - Yeo, Michelle X ID - 10407 SN - 0302-9743 TI - Trojan-resilience without cryptography VL - 13043 ER - TY - JOUR AB - Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits. AU - Biane, Celia AU - Rückerl, Florian AU - Abrahamsson, Therese AU - Saint-Cloment, Cécile AU - Mariani, Jean AU - Shigemoto, Ryuichi AU - Digregorio, David A. AU - Sherrard, Rachel M. AU - Cathala, Laurence ID - 10403 JF - eLife TI - Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons VL - 10 ER - TY - JOUR AB - Theoretical and experimental studies of the interaction between spins and temperature are vital for the development of spin caloritronics, as they dictate the design of future devices. In this work, we propose a two-terminal cold-atom simulator to study that interaction. The proposed quantum simulator consists of strongly interacting atoms that occupy two temperature reservoirs connected by a one-dimensional link. First, we argue that the dynamics in the link can be described using an inhomogeneous Heisenberg spin chain whose couplings are defined by the local temperature. Second, we show the existence of a spin current in a system with a temperature difference by studying the dynamics that follows the spin-flip of an atom in the link. A temperature gradient accelerates the impurity in one direction more than in the other, leading to an overall spin current similar to the spin Seebeck effect. AU - Barfknecht, Rafael E. AU - Foerster, Angela AU - Zinner, Nikolaj T. AU - Volosniev, Artem ID - 10401 IS - 1 JF - Communications Physics TI - Generation of spin currents by a temperature gradient in a two-terminal device VL - 4 ER - TY - JOUR AB - While convolutional neural networks (CNNs) have found wide adoption as state-of-the-art models for image-related tasks, their predictions are often highly sensitive to small input perturbations, which the human vision is robust against. This paper presents Perturber, a web-based application that allows users to instantaneously explore how CNN activations and predictions evolve when a 3D input scene is interactively perturbed. Perturber offers a large variety of scene modifications, such as camera controls, lighting and shading effects, background modifications, object morphing, as well as adversarial attacks, to facilitate the discovery of potential vulnerabilities. Fine-tuned model versions can be directly compared for qualitative evaluation of their robustness. Case studies with machine learning experts have shown that Perturber helps users to quickly generate hypotheses about model vulnerabilities and to qualitatively compare model behavior. Using quantitative analyses, we could replicate users’ insights with other CNN architectures and input images, yielding new insights about the vulnerability of adversarially trained models. AU - Sietzen, Stefan AU - Lechner, Mathias AU - Borowski, Judy AU - Hasani, Ramin AU - Waldner, Manuela ID - 10404 IS - 7 JF - Computer Graphics Forum SN - 0167-7055 TI - Interactive analysis of CNN robustness VL - 40 ER - TY - JOUR AB - Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future. AU - Mishra, Nikhil AU - Heisenberg, Carl-Philipp J ID - 10406 JF - Annual Review of Genetics KW - morphogenesis KW - forward genetics KW - high-resolution microscopy KW - biophysics KW - biochemistry KW - patterning SN - 0066-4197 TI - Dissecting organismal morphogenesis by bridging genetics and biophysics VL - 55 ER - TY - GEN AB - The zip file includes source data used in the main text of the manuscript "Theory of branching morphogenesis by local interactions and global guidance", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt. AU - Ucar, Mehmet C ID - 13058 TI - Source data for the manuscript "Theory of branching morphogenesis by local interactions and global guidance" ER - TY - CONF AB - Key trees are often the best solution in terms of transmission cost and storage requirements for managing keys in a setting where a group needs to share a secret key, while being able to efficiently rotate the key material of users (in order to recover from a potential compromise, or to add or remove users). Applications include multicast encryption protocols like LKH (Logical Key Hierarchies) or group messaging like the current IETF proposal TreeKEM. A key tree is a (typically balanced) binary tree, where each node is identified with a key: leaf nodes hold users’ secret keys while the root is the shared group key. For a group of size N, each user just holds log(N) keys (the keys on the path from its leaf to the root) and its entire key material can be rotated by broadcasting 2log(N) ciphertexts (encrypting each fresh key on the path under the keys of its parents). In this work we consider the natural setting where we have many groups with partially overlapping sets of users, and ask if we can find solutions where the cost of rotating a key is better than in the trivial one where we have a separate key tree for each group. We show that in an asymptotic setting (where the number m of groups is fixed while the number N of users grows) there exist more general key graphs whose cost converges to the cost of a single group, thus saving a factor linear in the number of groups over the trivial solution. As our asymptotic “solution” converges very slowly and performs poorly on concrete examples, we propose an algorithm that uses a natural heuristic to compute a key graph for any given group structure. Our algorithm combines two greedy algorithms, and is thus very efficient: it first converts the group structure into a “lattice graph”, which is then turned into a key graph by repeatedly applying the algorithm for constructing a Huffman code. To better understand how far our proposal is from an optimal solution, we prove lower bounds on the update cost of continuous group-key agreement and multicast encryption in a symbolic model admitting (asymmetric) encryption, pseudorandom generators, and secret sharing as building blocks. AU - Alwen, Joel F AU - Auerbach, Benedikt AU - Baig, Mirza Ahad AU - Cueto Noval, Miguel AU - Klein, Karen AU - Pascual Perez, Guillermo AU - Pietrzak, Krzysztof Z AU - Walter, Michael ID - 10408 SN - 0302-9743 T2 - 19th International Conference TI - Grafting key trees: Efficient key management for overlapping groups VL - 13044 ER - TY - JOUR AB - We show that in a two-dimensional electron gas with an annular Fermi surface, long-range Coulomb interactions can lead to unconventional superconductivity by the Kohn-Luttinger mechanism. Superconductivity is strongly enhanced when the inner and outer Fermi surfaces are close to each other. The most prevalent state has chiral p-wave symmetry, but d-wave and extended s-wave pairing are also possible. We discuss these results in the context of rhombohedral trilayer graphene, where superconductivity was recently discovered in regimes where the normal state has an annular Fermi surface. Using realistic parameters, our mechanism can account for the order of magnitude of Tc, as well as its trends as a function of electron density and perpendicular displacement field. Moreover, it naturally explains some of the outstanding puzzles in this material, that include the weak temperature dependence of the resistivity above Tc, and the proximity of spin singlet superconductivity to the ferromagnetic phase. AU - Ghazaryan, Areg AU - Holder, Tobias AU - Serbyn, Maksym AU - Berg, Erez ID - 10527 IS - 24 JF - Physical Review Letters KW - general physics and astronomy SN - 0031-9007 TI - Unconventional superconductivity in systems with annular Fermi surfaces: Application to rhombohedral trilayer graphene VL - 127 ER - TY - JOUR AB - For many years, fullerene derivatives have been the main n-type material of organic electronics and optoelectronics. Recently, fullerene derivatives functionalized with ethylene glycol (EG) side chains have been showing important properties such as enhanced dielectric constants, facile doping and enhanced self-assembly capabilities. Here, we have prepared field-effect transistors using a series of these fullerene derivatives equipped with EG side chains of different lengths. Transport data show the beneficial effect of increasing the EG side chain. In order to understand the material properties, full structural determination of these fullerene derivatives has been achieved by coupling the X-ray data with molecular dynamics (MD) simulations. The increase in transport properties is paired with the formation of extended layered structures, efficient molecular packing and an increase in the crystallite alignment. The layer-like structure is composed of conducting layers, containing of closely packed C60 balls approaching the inter-distance of 1 nm, that are separated by well-defined EG layers, where the EG chains are rather splayed with the chain direction almost perpendicular to the layer normal. Such a layered structure appears highly ordered and highly aligned with the C60 planes oriented parallel to the substrate in the thin film configuration. The order inside the thin film increases with the EG chain length, allowing the systems to achieve mobilities as high as 0.053 cm2 V−1 s−1. Our work elucidates the structure of these interesting semiconducting organic molecules and shows that the synergistic use of X-ray structural analysis and MD simulations is a powerful tool to identify the structure of thin organic films for optoelectronic applications. AU - Dong, Jingjin AU - Sami, Selim AU - Balazs, Daniel AU - Alessandri, Riccardo AU - Jahani, Fatimeh AU - Qiu, Li AU - Marrink, Siewert J. AU - Havenith, Remco W.A. AU - Hummelen, Jan C. AU - Loi, Maria A. AU - Portale, Giuseppe ID - 10534 IS - 45 JF - Journal of Materials Chemistry C SN - 2050-7534 TI - Fullerene derivatives with oligoethylene-glycol side chains: An investigation on the origin of their outstanding transport properties VL - 9 ER - TY - JOUR AB - Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin. AU - Choi, Jaemyung AU - Lyons, David B AU - Zilberman, Daniel ID - 10533 JF - eLife KW - genetics and molecular biology SN - 2050-084X TI - Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin VL - 10 ER - TY - JOUR AB - TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner. AU - Stefanescu, Cristina AU - Van Gogh, Merel AU - Roblek, Marko AU - Heikenwalder, Mathias AU - Borsig, Lubor ID - 10536 JF - Frontiers in Oncology TI - TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms VL - 11 ER - TY - JOUR AB - We consider the quantum many-body evolution of a homogeneous Fermi gas in three dimensions in the coupled semiclassical and mean-field scaling regime. We study a class of initial data describing collective particle–hole pair excitations on the Fermi ball. Using a rigorous version of approximate bosonization, we prove that the many-body evolution can be approximated in Fock space norm by a quasi-free bosonic evolution of the collective particle–hole excitations. AU - Benedikter, Niels P AU - Nam, Phan Thành AU - Porta, Marcello AU - Schlein, Benjamin AU - Seiringer, Robert ID - 10537 JF - Annales Henri Poincaré SN - 1424-0637 TI - Bosonization of fermionic many-body dynamics ER - TY - JOUR AB - We derive optimal-order homogenization rates for random nonlinear elliptic PDEs with monotone nonlinearity in the uniformly elliptic case. More precisely, for a random monotone operator on \mathbb {R}^d with stationary law (that is spatially homogeneous statistics) and fast decay of correlations on scales larger than the microscale \varepsilon >0, we establish homogenization error estimates of the order \varepsilon in case d\geqq 3, and of the order \varepsilon |\log \varepsilon |^{1/2} in case d=2. Previous results in nonlinear stochastic homogenization have been limited to a small algebraic rate of convergence \varepsilon ^\delta . We also establish error estimates for the approximation of the homogenized operator by the method of representative volumes of the order (L/\varepsilon )^{-d/2} for a representative volume of size L. Our results also hold in the case of systems for which a (small-scale) C^{1,\alpha } regularity theory is available. AU - Fischer, Julian L AU - Neukamm, Stefan ID - 10549 IS - 1 JF - Archive for Rational Mechanics and Analysis KW - Mechanical Engineering KW - Mathematics (miscellaneous) KW - Analysis SN - 0003-9527 TI - Optimal homogenization rates in stochastic homogenization of nonlinear uniformly elliptic equations and systems VL - 242 ER - TY - CONF AB - We show that Yao’s garbling scheme is adaptively indistinguishable for the class of Boolean circuits of size S and treewidth w with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z ID - 10409 SN - 0302-9743 T2 - 19th International Conference TI - On treewidth, separators and Yao’s garbling VL - 13043 ER - TY - JOUR AB - Classical models with complex energy landscapes represent a perspective avenue for the near-term application of quantum simulators. Until now, many theoretical works studied the performance of quantum algorithms for models with a unique ground state. However, when the classical problem is in a so-called clustering phase, the ground state manifold is highly degenerate. As an example, we consider a 3-XORSAT model defined on simple hypergraphs. The degeneracy of classical ground state manifold translates into the emergence of an extensive number of Z2 symmetries, which remain intact even in the presence of a quantum transverse magnetic field. We establish a general duality approach that restricts the quantum problem to a given sector of conserved Z2 charges and use it to study how the outcome of the quantum adiabatic algorithm depends on the hypergraph geometry. We show that the tree hypergraph which corresponds to a classically solvable instance of the 3-XORSAT problem features a constant gap, whereas the closed hypergraph encounters a second-order phase transition with a gap vanishing as a power-law in the problem size. The duality developed in this work provides a practical tool for studies of quantum models with classically degenerate energy manifold and reveals potential connections between glasses and gauge theories. AU - Medina Ramos, Raimel A AU - Serbyn, Maksym ID - 10545 IS - 6 JF - Physical Review A SN - 2469-9926 TI - Duality approach to quantum annealing of the 3-variable exclusive-or satisfiability problem (3-XORSAT) VL - 104 ER - TY - CONF AB - We present DAG-Rider, the first asynchronous Byzantine Atomic Broadcast protocol that achieves optimal resilience, optimal amortized communication complexity, and optimal time complexity. DAG-Rider is post-quantum safe and ensures that all values proposed by correct processes eventually get delivered. We construct DAG-Rider in two layers: In the first layer, processes reliably broadcast their proposals and build a structured Directed Acyclic Graph (DAG) of the communication among them. In the second layer, processes locally observe their DAGs and totally order all proposals with no extra communication. AU - Keidar, Idit AU - Kokoris Kogias, Eleftherios AU - Naor, Oded AU - Spiegelman, Alexander ID - 10554 SN - 978-1-4503-8548-0 T2 - Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing TI - All You Need is DAG ER - TY - JOUR AB - Genetic adaptation and phenotypic plasticity facilitate the migration into new habitats and enable organisms to cope with a rapidly changing environment. In contrast to genetic adaptation that spans multiple generations as an evolutionary process, phenotypic plasticity allows acclimation within the life-time of an organism. Genetic adaptation and phenotypic plasticity are usually studied in isolation, however, only by including their interactive impact, we can understand acclimation and adaptation in nature. We aimed to explore the contribution of adaptation and plasticity in coping with an abiotic (salinity) and a biotic (Vibrio bacteria) stressor using six different populations of the broad-nosed pipefish Syngnathus typhle that originated from either high [14–17 Practical Salinity Unit (PSU)] or low (7–11 PSU) saline environments along the German coastline of the Baltic Sea. We exposed wild caught animals, to either high (15 PSU) or low (7 PSU) salinity, representing native and novel salinity conditions and allowed animals to mate. After male pregnancy, offspring was split and each half was exposed to one of the two salinities and infected with Vibrio alginolyticus bacteria that were evolved at either of the two salinities in a fully reciprocal design. We investigated life-history traits of fathers and expression of 47 target genes in mothers and offspring. Pregnant males originating from high salinity exposed to low salinity were highly susceptible to opportunistic fungi infections resulting in decreased offspring size and number. In contrast, no signs of fungal infection were identified in fathers originating from low saline conditions suggesting that genetic adaptation has the potential to overcome the challenges encountered at low salinity. Offspring from parents with low saline origin survived better at low salinity suggesting genetic adaptation to low salinity. In addition, gene expression analyses of juveniles indicated patterns of local adaptation, trans-generational plasticity and developmental plasticity. In conclusion, our study suggests that pipefish are locally adapted to the low salinity in their environment, however, they are retaining phenotypic plasticity, which allows them to also cope with ancestral salinity levels and prevailing pathogens. AU - Goehlich, Henry AU - Sartoris, Linda AU - Wagner, Kim-Sara AU - Wendling, Carolin C. AU - Roth, Olivia ID - 10568 JF - Frontiers in Ecology and Evolution KW - ecology KW - evolution KW - behavior and systematics KW - trans-generational plasticity KW - genetic adaptation KW - local adaptation KW - phenotypic plasticity KW - Baltic Sea KW - climate change KW - salinity KW - syngnathids SN - 2296-701X TI - Pipefish locally adapted to low salinity in the Baltic Sea retain phenotypic plasticity to cope with ancestral salinity levels VL - 9 ER - TY - JOUR AB - A facile approach for developing an interfacial solar evaporator by heat localization of solar-thermal energy conversion at water-air liquid composed by in-situ polymerization of Fe2O3 nanoparticles (Fe2O3@PPy) deposited over a facial sponge is proposed. The demonstrated system consists of a floating solar receiver having a vertically cross-linked microchannel for wicking up saline water. The in situ polymerized Fe2O3@PPy interfacial layer promotes diffuse reflection and its rough black surface allows Omni-directional solar absorption (94%) and facilitates efficient thermal localization at the water/air interface and offers a defect-rich surface to promote heat localization (41.9 °C) and excellent thermal management due to cellulosic content. The self-floating composite foam reveals continuous vapors generation at a rate of 1.52 kg m−2 h−1 under one 1 kW m−2 and profound evaporating efficiency (95%) without heat losses that dissipates in its surroundings. Indeed, long-term evaporation experiments reveal the negligible disparity in continuous evaporation rate (33.84 kg m−2/8.3 h) receiving two sun solar intensity, and ensures the stability of the device under intense seawater conditions synchronized with excellent salt rejection potential. More importantly, Raman spectroscopy investigation validates the orange dye rejection via Fe2O3@PPy solar evaporator. The combined advantages of high efficiency, self-floating capability, multimedia rejection, low cost, and this configuration are promising for producing large-scale solar steam generating systems appropriate for commercial clean water yield due to their scalable fabrication. AU - Lu, Yuzheng AU - Arshad, Naila AU - Irshad, Muhammad Sultan AU - Ahmed, Iftikhar AU - Ahmad, Shafiq AU - Alshahrani, Lina Abdullah AU - Yousaf, Muhammad AU - Sayed, Abdelaty Edrees AU - Nauman, Muhammad ID - 10586 IS - 12 JF - Crystals TI - Fe2O3 nanoparticles deposited over self-floating facial sponge for facile interfacial seawater solar desalination VL - 11 ER - TY - JOUR AB - For animals to survive until reproduction, it is crucial that juveniles successfully detect potential predators and respond with appropriate behavior. The recognition of cues originating from predators can be innate or learned. Cues of various modalities might be used alone or in multi-modal combinations to detect and distinguish predators but studies investigating multi-modal integration in predator avoidance are scarce. Here, we used wild, naive tadpoles of the Neotropical poison frog Allobates femoralis ( Boulenger, 1884) to test their reaction to cues with two modalities from two different sympatrically occurring potential predators: heterospecific predatory Dendrobates tinctorius tadpoles and dragonfly larvae. We presented A. femoralis tadpoles with olfactory or visual cues, or a combination of the two, and compared their reaction to a water control in a between-individual design. In our trials, A. femoralis tadpoles reacted to multi-modal stimuli (a combination of visual and chemical information) originating from dragonfly larvae with avoidance but showed no reaction to uni-modal cues or cues from heterospecific tadpoles. In addition, visual cues from conspecifics increased swimming activity while cues from predators had no effect on tadpole activity. Our results show that A. femoralis tadpoles can innately recognize some predators and probably need both visual and chemical information to effectively avoid them. This is the first study looking at anti-predator behavior in poison frog tadpoles. We discuss how parental care might influence the expression of predator avoidance responses in tadpoles. AU - Szabo, B AU - Mangione, R AU - Rath, M AU - Pašukonis, A AU - Reber, SA AU - Oh, Jinook AU - Ringler, M AU - Ringler, E ID - 10569 IS - 24 JF - Journal of Experimental Biology SN - 0022-0949 TI - Naïve poison frog tadpoles use bi-modal cues to avoid insect predators but not heterospecific predatory tadpoles VL - 224 ER - TY - JOUR AB - The choice of the boundary conditions in mechanical problems has to reflect the interaction of the considered material with the surface. Still the assumption of the no-slip condition is preferred in order to avoid boundary terms in the analysis and slipping effects are usually overlooked. Besides the “static slip models”, there are phenomena that are not accurately described by them, e.g. at the moment when the slip changes rapidly, the wall shear stress and the slip can exhibit a sudden overshoot and subsequent relaxation. When these effects become significant, the so-called dynamic slip phenomenon occurs. We develop a mathematical analysis of Navier–Stokes-like problems with a dynamic slip boundary condition, which requires a proper generalization of the Gelfand triplet and the corresponding function space setting. AU - Abbatiello, Anna AU - Bulíček, Miroslav AU - Maringová, Erika ID - 10575 IS - 11 JF - Mathematical Models and Methods in Applied Sciences SN - 0218-2025 TI - On the dynamic slip boundary condition for Navier-Stokes-like problems VL - 31 ER - TY - JOUR AB - The understanding of material appearance perception is a complex problem due to interactions between material reflectance, surface geometry, and illumination. Recently, Serrano et al. collected the largest dataset to date with subjective ratings of material appearance attributes, including glossiness, metallicness, sharpness and contrast of reflections. In this work, we make use of their dataset to investigate for the first time the impact of the interactions between illumination, geometry, and eight different material categories in perceived appearance attributes. After an initial analysis, we select for further analysis the four material categories that cover the largest range for all perceptual attributes: fabric, plastic, ceramic, and metal. Using a cumulative link mixed model (CLMM) for robust regression, we discover interactions between these material categories and four representative illuminations and object geometries. We believe that our findings contribute to expanding the knowledge on material appearance perception and can be useful for many applications, such as scene design, where any particular material in a given shape can be aligned with dominant classes of illumination, so that a desired strength of appearance attributes can be achieved. AU - Chen, Bin AU - Wang, Chao AU - Piovarci, Michael AU - Seidel, Hans Peter AU - Didyk, Piotr AU - Myszkowski, Karol AU - Serrano, Ana ID - 10574 IS - 12 JF - Visual Computer SN - 0178-2789 TI - The effect of geometry and illumination on appearance perception of different material categories VL - 37 ER - TY - JOUR AB - How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering. AU - Munjal, Akankshi AU - Hannezo, Edouard B AU - Tsai, Tony Y.C. AU - Mitchison, Timothy J. AU - Megason, Sean G. ID - 10573 IS - 26 JF - Cell SN - 0092-8674 TI - Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis VL - 184 ER - TY - JOUR AB - In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets. AU - Aghajohari, Milad AU - Avni, Guy AU - Henzinger, Thomas A ID - 10674 IS - 1 JF - Logical Methods in Computer Science KW - computer science KW - computer science and game theory KW - logic in computer science TI - Determinacy in discrete-bidding infinite-duration games VL - 17 ER - TY - CONF AB - We study Multi-party computation (MPC) in the setting of subversion, where the adversary tampers with the machines of honest parties. Our goal is to construct actively secure MPC protocols where parties are corrupted adaptively by an adversary (as in the standard adaptive security setting), and in addition, honest parties’ machines are compromised. The idea of reverse firewalls (RF) was introduced at EUROCRYPT’15 by Mironov and Stephens-Davidowitz as an approach to protecting protocols against corruption of honest parties’ devices. Intuitively, an RF for a party P is an external entity that sits between P and the outside world and whose scope is to sanitize P ’s incoming and outgoing messages in the face of subversion of their computer. Mironov and Stephens-Davidowitz constructed a protocol for passively-secure two-party computation. At CRYPTO’20, Chakraborty, Dziembowski and Nielsen constructed a protocol for secure computation with firewalls that improved on this result, both by extending it to multi-party computation protocol, and considering active security in the presence of static corruptions. In this paper, we initiate the study of RF for MPC in the adaptive setting. We put forward a definition for adaptively secure MPC in the reverse firewall setting, explore relationships among the security notions, and then construct reverse firewalls for MPC in this stronger setting of adaptive security. We also resolve the open question of Chakraborty, Dziembowski and Nielsen by removing the need for a trusted setup in constructing RF for MPC. Towards this end, we construct reverse firewalls for adaptively secure augmented coin tossing and adaptively secure zero-knowledge protocols and obtain a constant round adaptively secure MPC protocol in the reverse firewall setting without setup. Along the way, we propose a new multi-party adaptively secure coin tossing protocol in the plain model, that is of independent interest. AU - Chakraborty, Suvradip AU - Ganesh, Chaya AU - Pancholi, Mahak AU - Sarkar, Pratik ID - 10609 SN - 0302-9743 T2 - 27th International Conference on the Theory and Application of Cryptology and Information Security TI - Reverse firewalls for adaptively secure MPC without setup VL - 13091 ER - TY - JOUR AB - Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s). AU - Godard, Benoit G AU - Dumollard, Remi AU - Heisenberg, Carl-Philipp J AU - Mcdougall, Alex ID - 10606 JF - eLife TI - Combined effect of cell geometry and polarity domains determines the orientation of unequal division VL - 10 ER - TY - JOUR AB - The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders. AU - Venezia, Serena AU - Kaufmann, Walter AU - Wenning, Gregor K. AU - Stefanova, Nadia ID - 10607 JF - Parkinsonism & Related Disorders SN - 1353-8020 TI - Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease VL - 91 ER - TY - JOUR AB - The surface states of 3D topological insulators in general have negligible quantum oscillations (QOs) when the chemical potential is tuned to the Dirac points. In contrast, we find that topological Kondo insulators (TKIs) can support surface states with an arbitrarily large Fermi surface (FS) when the chemical potential is pinned to the Dirac point. We illustrate that these FSs give rise to finite-frequency QOs, which can become comparable to the extremal area of the unhybridized bulk bands. We show that this occurs when the crystal symmetry is lowered from cubic to tetragonal in a minimal two-orbital model. We label such surface modes as 'shadow surface states'. Moreover, we show that the sufficient next-nearest neighbor out-of-plane hybridization leading to shadow surface states can be self-consistently stabilized for tetragonal TKIs. Consequently, shadow surface states provide an important example of high-frequency QOs beyond the context of cubic TKIs. AU - Ghazaryan, Areg AU - Nica, Emilian M. AU - Erten, Onur AU - Ghaemi, Pouyan ID - 10628 IS - 12 JF - New Journal of Physics SN - 1367-2630 TI - Shadow surface states in topological Kondo insulators VL - 23 ER - TY - JOUR AB - We combine experimental and theoretical approaches to explore excited rotational states of molecules embedded in helium nanodroplets using CS2 and I2 as examples. Laser-induced nonadiabatic molecular alignment is employed to measure spectral lines for rotational states extending beyond those initially populated at the 0.37 K droplet temperature. We construct a simple quantum-mechanical model, based on a linear rotor coupled to a single-mode bosonic bath, to determine the rotational energy structure in its entirety. The calculated and measured spectral lines are in good agreement. We show that the effect of the surrounding superfluid on molecular rotation can be rationalized by a single quantity, the angular momentum, transferred from the molecule to the droplet. AU - Cherepanov, Igor AU - Bighin, Giacomo AU - Schouder, Constant A. AU - Chatterley, Adam S. AU - Albrechtsen, Simon H. AU - Muñoz, Alberto Viñas AU - Christiansen, Lars AU - Stapelfeldt, Henrik AU - Lemeshko, Mikhail ID - 10631 IS - 6 JF - Physical Review A SN - 2469-9926 TI - Excited rotational states of molecules in a superfluid VL - 104 ER - TY - CONF AB - We thank Emmanuel Abbe and Min Ye for providing us the implementation of RPA decoding. D. Fathollahi and M. Mondelli are partially supported by the 2019 Lopez-Loreta Prize. N. Farsad is supported by Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Canada Foundation for Innovation (CFI), John R. Evans Leader Fund. S. A. Hashemi is supported by a Postdoctoral Fellowship from NSERC. AU - Fathollahi, Dorsa AU - Farsad, Nariman AU - Hashemi, Seyyed Ali AU - Mondelli, Marco ID - 10597 SN - 978-1-5386-8210-4 T2 - 2021 IEEE International Symposium on Information Theory TI - Sparse multi-decoder recursive projection aggregation for Reed-Muller codes ER - TY - CONF AB - Adversarial training is an effective method to train deep learning models that are resilient to norm-bounded perturbations, with the cost of nominal performance drop. While adversarial training appears to enhance the robustness and safety of a deep model deployed in open-world decision-critical applications, counterintuitively, it induces undesired behaviors in robot learning settings. In this paper, we show theoretically and experimentally that neural controllers obtained via adversarial training are subjected to three types of defects, namely transient, systematic, and conditional errors. We first generalize adversarial training to a safety-domain optimization scheme allowing for more generic specifications. We then prove that such a learning process tends to cause certain error profiles. We support our theoretical results by a thorough experimental safety analysis in a robot-learning task. Our results suggest that adversarial training is not yet ready for robot learning. AU - Lechner, Mathias AU - Hasani, Ramin AU - Grosu, Radu AU - Rus, Daniela AU - Henzinger, Thomas A ID - 10666 SN - 1050-4729 T2 - 2021 IEEE International Conference on Robotics and Automation TI - Adversarial training is not ready for robot learning ER - TY - JOUR AB - In this paper, we investigate the distribution of the maximum of partial sums of families of m -periodic complex-valued functions satisfying certain conditions. We obtain precise uniform estimates for the distribution function of this maximum in a near-optimal range. Our results apply to partial sums of Kloosterman sums and other families of ℓ -adic trace functions, and are as strong as those obtained by Bober, Goldmakher, Granville and Koukoulopoulos for character sums. In particular, we improve on the recent work of the third author for Birch sums. However, unlike character sums, we are able to construct families of m -periodic complex-valued functions which satisfy our conditions, but for which the Pólya–Vinogradov inequality is sharp. AU - Autissier, Pascal AU - Bonolis, Dante AU - Lamzouri, Youness ID - 10711 IS - 7 JF - Compositio Mathematica KW - Algebra and Number Theory SN - 0010-437X TI - The distribution of the maximum of partial sums of Kloosterman sums and other trace functions VL - 157 ER - TY - JOUR AB - Thermoelectric materials are engines that convert heat into an electrical current. Intuitively, the efficiency of this process depends on how many electrons (charge carriers) can move and how easily they do so, how much energy those moving electrons transport, and how easily the temperature gradient is maintained. In terms of material properties, an excellent thermoelectric material requires a high electrical conductivity σ, a high Seebeck coefficient S (a measure of the induced thermoelectric voltage as a function of temperature gradient), and a low thermal conductivity κ. The challenge is that these three properties are strongly interrelated in a conflicting manner (1). On page 722 of this issue, Roychowdhury et al. (2) have found a way to partially break these ties in silver antimony telluride (AgSbTe2) with the addition of cadmium (Cd) cations, which increase the ordering in this inherently disordered thermoelectric material. AU - Liu, Yu AU - Ibáñez, Maria ID - 10809 IS - 6530 JF - Science KW - multidisciplinary SN - 0036-8075 TI - Tidying up the mess VL - 371 ER - TY - JOUR AB - The cost-effective conversion of low-grade heat into electricity using thermoelectric devices requires developing alternative materials and material processing technologies able to reduce the currently high device manufacturing costs. In this direction, thermoelectric materials that do not rely on rare or toxic elements such as tellurium or lead need to be produced using high-throughput technologies not involving high temperatures and long processes. Bi2Se3 is an obvious possible Te-free alternative to Bi2Te3 for ambient temperature thermoelectric applications, but its performance is still low for practical applications, and additional efforts toward finding proper dopants are required. Here, we report a scalable method to produce Bi2Se3 nanosheets at low synthesis temperatures. We studied the influence of different dopants on the thermoelectric properties of this material. Among the elements tested, we demonstrated that Sn doping resulted in the best performance. Sn incorporation resulted in a significant improvement to the Bi2Se3 Seebeck coefficient and a reduction in the thermal conductivity in the direction of the hot-press axis, resulting in an overall 60% improvement in the thermoelectric figure of merit of Bi2Se3. AU - Li, Mengyao AU - Zhang, Yu AU - Zhang, Ting AU - Zuo, Yong AU - Xiao, Ke AU - Arbiol, Jordi AU - Llorca, Jordi AU - Liu, Yu AU - Cabot, Andreu ID - 10858 IS - 7 JF - Nanomaterials KW - General Materials Science KW - General Chemical Engineering SN - 2079-4991 TI - Enhanced thermoelectric performance of n-type Bi2Se3 nanosheets through Sn doping VL - 11 ER - TY - JOUR AB - Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis. AU - Stahnke, Stephanie AU - Döring, Hermann AU - Kusch, Charly AU - de Gorter, David J.J. AU - Dütting, Sebastian AU - Guledani, Aleks AU - Pleines, Irina AU - Schnoor, Michael AU - Sixt, Michael K AU - Geffers, Robert AU - Rohde, Manfred AU - Müsken, Mathias AU - Kage, Frieda AU - Steffen, Anika AU - Faix, Jan AU - Nieswandt, Bernhard AU - Rottner, Klemens AU - Stradal, Theresia E.B. ID - 10834 IS - 10 JF - Current Biology KW - General Agricultural and Biological Sciences KW - General Biochemistry KW - Genetics and Molecular Biology SN - 0960-9822 TI - Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion VL - 31 ER -