TY - CONF AB - We evaluate the usefulness of persistent homology in the analysis of heart rate variability. In our approach we extract several topological descriptors characterising datasets of RR-intervals, which are later used in classical machine learning algorithms. By this method we are able to differentiate the group of patients with the history of transient ischemic attack and the group of hypertensive patients. AU - Graff, Grzegorz AU - Graff, Beata AU - Jablonski, Grzegorz AU - Narkiewicz, Krzysztof ID - 8580 SN - 9781728157511 T2 - 11th Conference of the European Study Group on Cardiovascular Oscillations: Computation and Modelling in Physiology: New Challenges and Opportunities, TI - The application of persistent homology in the analysis of heart rate variability ER - TY - JOUR AB - Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma. AU - Tian, Anhao AU - Kang, Bo AU - Li, Baizhou AU - Qiu, Biying AU - Jiang, Wenhong AU - Shao, Fangjie AU - Gao, Qingqing AU - Liu, Rui AU - Cai, Chengwei AU - Jing, Rui AU - Wang, Wei AU - Chen, Pengxiang AU - Liang, Qinghui AU - Bao, Lili AU - Man, Jianghong AU - Wang, Yan AU - Shi, Yu AU - Li, Jin AU - Yang, Minmin AU - Wang, Lisha AU - Zhang, Jianmin AU - Hippenmeyer, Simon AU - Zhu, Junming AU - Bian, Xiuwu AU - Wang, Ying‐Jie AU - Liu, Chong ID - 8592 IS - 21 JF - Advanced Science KW - General Engineering KW - General Physics and Astronomy KW - General Materials Science KW - Medicine (miscellaneous) KW - General Chemical Engineering KW - Biochemistry KW - Genetics and Molecular Biology (miscellaneous) SN - 2198-3844 TI - Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting VL - 7 ER - TY - JOUR AB - Aqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries. AU - Prehal, Christian AU - Fitzek, Harald AU - Kothleitner, Gerald AU - Presser, Volker AU - Gollas, Bernhard AU - Freunberger, Stefan Alexander AU - Abbas, Qamar ID - 8568 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Persistent and reversible solid iodine electrodeposition in nanoporous carbons VL - 11 ER - TY - JOUR AB - The parabigeminal nucleus (PBG) is the mammalian homologue to the isthmic complex of other vertebrates. Optogenetic stimulation of the PBG induces freezing and escape in mice, a result thought to be caused by a PBG projection to the central nucleus of the amygdala. However, the isthmic complex, including the PBG, has been classically considered satellite nuclei of the Superior Colliculus (SC), which upon stimulation of its medial part also triggers fear and avoidance reactions. As the PBG-SC connectivity is not well characterized, we investigated whether the topology of the PBG projection to the SC could be related to the behavioral consequences of PBG stimulation. To that end, we performed immunohistochemistry, in situ hybridization and neural tracer injections in the SC and PBG in a diurnal rodent, the Octodon degus. We found that all PBG neurons expressed both glutamatergic and cholinergic markers and were distributed in clearly defined anterior (aPBG) and posterior (pPBG) subdivisions. The pPBG is connected reciprocally and topographically to the ipsilateral SC, whereas the aPBG receives afferent axons from the ipsilateral SC and projected exclusively to the contralateral SC. This contralateral projection forms a dense field of terminals that is restricted to the medial SC, in correspondence with the SC representation of the aerial binocular field which, we also found, in O. degus prompted escape reactions upon looming stimulation. Therefore, this specialized topography allows binocular interactions in the SC region controlling responses to aerial predators, suggesting a link between the mechanisms by which the SC and PBG produce defensive behaviors. AU - Deichler, Alfonso AU - Carrasco, Denisse AU - Lopez-Jury, Luciana AU - Vega Zuniga, Tomas A AU - Marquez, Natalia AU - Mpodozis, Jorge AU - Marin, Gonzalo ID - 8643 JF - Scientific Reports TI - A specialized reciprocal connectivity suggests a link between the mechanisms by which the superior colliculus and parabigeminal nucleus produce defensive behaviors in rodents VL - 10 ER - TY - JOUR AB - Epistasis, the context-dependence of the contribution of an amino acid substitution to fitness, is common in evolution. To detect epistasis, fitness must be measured for at least four genotypes: the reference genotype, two different single mutants and a double mutant with both of the single mutations. For higher-order epistasis of the order n, fitness has to be measured for all 2n genotypes of an n-dimensional hypercube in genotype space forming a ‘combinatorially complete dataset’. So far, only a handful of such datasets have been produced by manual curation. Concurrently, random mutagenesis experiments have produced measurements of fitness and other phenotypes in a high-throughput manner, potentially containing a number of combinatorially complete datasets. We present an effective recursive algorithm for finding all hypercube structures in random mutagenesis experimental data. To test the algorithm, we applied it to the data from a recent HIS3 protein dataset and found all 199 847 053 unique combinatorially complete genotype combinations of dimensionality ranging from 2 to 12. The algorithm may be useful for researchers looking for higher-order epistasis in their high-throughput experimental data. AU - Esteban, Laura A AU - Lonishin, Lyubov R AU - Bobrovskiy, Daniil M AU - Leleytner, Gregory AU - Bogatyreva, Natalya S AU - Kondrashov, Fyodor AU - Ivankov, Dmitry N ID - 8645 IS - 6 JF - Bioinformatics SN - 1367-4803 TI - HypercubeME: Two hundred million combinatorially complete datasets from a single experiment VL - 36 ER - TY - JOUR AB - Error analysis and data visualization of positive COVID-19 cases in 27 countries have been performed up to August 8, 2020. This survey generally observes a progression from early exponential growth transitioning to an intermediate power-law growth phase, as recently suggested by Ziff and Ziff. The occurrence of logistic growth after the power-law phase with lockdowns or social distancing may be described as an effect of avoidance. A visualization of the power-law growth exponent over short time windows is qualitatively similar to the Bhatia visualization for pandemic progression. Visualizations like these can indicate the onset of second waves and may influence social policy. AU - Merrin, Jack ID - 8597 IS - 6 JF - Physical Biology TI - Differences in power law growth over time and indicators of COVID-19 pandemic progression worldwide VL - 17 ER - TY - JOUR AB - Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections. AU - Henneberger, Christian AU - Bard, Lucie AU - Panatier, Aude AU - Reynolds, James P. AU - Kopach, Olga AU - Medvedev, Nikolay I. AU - Minge, Daniel AU - Herde, Michel K. AU - Anders, Stefanie AU - Kraev, Igor AU - Heller, Janosch P. AU - Rama, Sylvain AU - Zheng, Kaiyu AU - Jensen, Thomas P. AU - Sanchez-Romero, Inmaculada AU - Jackson, Colin J. AU - Janovjak, Harald L AU - Ottersen, Ole Petter AU - Nagelhus, Erlend Arnulf AU - Oliet, Stephane H.R. AU - Stewart, Michael G. AU - Nägerl, U. VAlentin AU - Rusakov, Dmitri A. ID - 8674 IS - 5 JF - Neuron SN - 08966273 TI - LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia VL - 108 ER - TY - JOUR AB - Nature creates electrons with two values of the spin projection quantum number. In certain applications, it is important to filter electrons with one spin projection from the rest. Such filtering is not trivial, since spin-dependent interactions are often weak, and cannot lead to any substantial effect. Here we propose an efficient spin filter based upon scattering from a two-dimensional crystal, which is made of aligned point magnets. The polarization of the outgoing electron flux is controlled by the crystal, and reaches maximum at specific values of the parameters. In our scheme, polarization increase is accompanied by higher reflectivity of the crystal. High transmission is feasible in scattering from a quantum cavity made of two crystals. Our findings can be used for studies of low-energy spin-dependent scattering from two-dimensional ordered structures made of magnetic atoms or aligned chiral molecules. AU - Ghazaryan, Areg AU - Lemeshko, Mikhail AU - Volosniev, Artem ID - 8652 JF - Communications Physics SN - 2399-3650 TI - Filtering spins by scattering from a lattice of point magnets VL - 3 ER - TY - JOUR AB - Pancreatic islets play an essential role in regulating blood glucose level. Although the molecular pathways underlying islet cell differentiation are beginning to be resolved, the cellular basis of islet morphogenesis and fate allocation remain unclear. By combining unbiased and targeted lineage tracing, we address the events leading to islet formation in the mouse. From the statistical analysis of clones induced at multiple embryonic timepoints, here we show that, during the secondary transition, islet formation involves the aggregation of multiple equipotent endocrine progenitors that transition from a phase of stochastic amplification by cell division into a phase of sublineage restriction and limited islet fission. Together, these results explain quantitatively the heterogeneous size distribution and degree of polyclonality of maturing islets, as well as dispersion of progenitors within and between islets. Further, our results show that, during the secondary transition, α- and β-cells are generated in a contemporary manner. Together, these findings provide insight into the cellular basis of islet development. AU - Sznurkowska, Magdalena K. AU - Hannezo, Edouard B AU - Azzarelli, Roberta AU - Chatzeli, Lemonia AU - Ikeda, Tatsuro AU - Yoshida, Shosei AU - Philpott, Anna AU - Simons, Benjamin D ID - 8669 JF - Nature Communications TI - Tracing the cellular basis of islet specification in mouse pancreas VL - 11 ER - TY - JOUR AB - Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions. AU - Chaigne, Agathe AU - Labouesse, Céline AU - White, Ian J. AU - Agnew, Meghan AU - Hannezo, Edouard B AU - Chalut, Kevin J. AU - Paluch, Ewa K. ID - 8672 IS - 2 JF - Developmental Cell SN - 15345807 TI - Abscission couples cell division to embryonic stem cell fate VL - 55 ER - TY - JOUR AB - In the computation of the material properties of random alloys, the method of 'special quasirandom structures' attempts to approximate the properties of the alloy on a finite volume with higher accuracy by replicating certain statistics of the random atomic lattice in the finite volume as accurately as possible. In the present work, we provide a rigorous justification for a variant of this method in the framework of the Thomas–Fermi–von Weizsäcker (TFW) model. Our approach is based on a recent analysis of a related variance reduction method in stochastic homogenization of linear elliptic PDEs and the locality properties of the TFW model. Concerning the latter, we extend an exponential locality result by Nazar and Ortner to include point charges, a result that may be of independent interest. AU - Fischer, Julian L AU - Kniely, Michael ID - 8697 IS - 11 JF - Nonlinearity SN - 09517715 TI - Variance reduction for effective energies of random lattices in the Thomas-Fermi-von Weizsäcker model VL - 33 ER - TY - JOUR AB - Animal development entails the organization of specific cell types in space and time, and spatial patterns must form in a robust manner. In the zebrafish spinal cord, neural progenitors form stereotypic patterns despite noisy morphogen signaling and large-scale cellular rearrangements during morphogenesis and growth. By directly measuring adhesion forces and preferences for three types of endogenous neural progenitors, we provide evidence for the differential adhesion model in which differences in intercellular adhesion mediate cell sorting. Cell type–specific combinatorial expression of different classes of cadherins (N-cadherin, cadherin 11, and protocadherin 19) results in homotypic preference ex vivo and patterning robustness in vivo. Furthermore, the differential adhesion code is regulated by the sonic hedgehog morphogen gradient. We propose that robust patterning during tissue morphogenesis results from interplay between adhesion-based self-organization and morphogen-directed patterning. AU - Tsai, Tony Y.-C. AU - Sikora, Mateusz K AU - Xia, Peng AU - Colak-Champollion, Tugba AU - Knaut, Holger AU - Heisenberg, Carl-Philipp J AU - Megason, Sean G. ID - 8680 IS - 6512 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - An adhesion code ensures robust pattern formation during tissue morphogenesis VL - 370 ER - TY - JOUR AB - Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data. AU - Galan, Silvia AU - Machnik, Nick N AU - Kruse, Kai AU - Díaz, Noelia AU - Marti-Renom, Marc A AU - Vaquerizas, Juan M ID - 8707 JF - Nature Genetics SN - 10614036 TI - CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction VL - 52 ER - TY - JOUR AB - A central goal of artificial intelligence in high-stakes decision-making applications is to design a single algorithm that simultaneously expresses generalizability by learning coherent representations of their world and interpretable explanations of its dynamics. Here, we combine brain-inspired neural computation principles and scalable deep learning architectures to design compact neural controllers for task-specific compartments of a full-stack autonomous vehicle control system. We discover that a single algorithm with 19 control neurons, connecting 32 encapsulated input features to outputs by 253 synapses, learns to map high-dimensional inputs into steering commands. This system shows superior generalizability, interpretability and robustness compared with orders-of-magnitude larger black-box learning systems. The obtained neural agents enable high-fidelity autonomy for task-specific parts of a complex autonomous system. AU - Lechner, Mathias AU - Hasani, Ramin AU - Amini, Alexander AU - Henzinger, Thomas A AU - Rus, Daniela AU - Grosu, Radu ID - 8679 JF - Nature Machine Intelligence TI - Neural circuit policies enabling auditable autonomy VL - 2 ER - TY - JOUR AB - The α–z Rényi relative entropies are a two-parameter family of Rényi relative entropies that are quantum generalizations of the classical α-Rényi relative entropies. In the work [Adv. Math. 365, 107053 (2020)], we decided the full range of (α, z) for which the data processing inequality (DPI) is valid. In this paper, we give algebraic conditions for the equality in DPI. For the full range of parameters (α, z), we give necessary conditions and sufficient conditions. For most parameters, we give equivalent conditions. This generalizes and strengthens the results of Leditzky et al. [Lett. Math. Phys. 107, 61–80 (2017)]. AU - Zhang, Haonan ID - 8670 IS - 10 JF - Journal of Mathematical Physics SN - 00222488 TI - Equality conditions of data processing inequality for α-z Rényi relative entropies VL - 61 ER - TY - JOUR AB - The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural responses and deep learning, current approaches either do not scale to large neural populations or cannot be implemented using biologically realistic mechanisms. Inspired by the sparse and random connectivity of real neuronal circuits, we present a model for neural codes that accurately estimates the likelihood of individual spiking patterns and has a straightforward, scalable, efficient, learnable, and realistic neural implementation. This model’s performance on simultaneously recorded spiking activity of >100 neurons in the monkey visual and prefrontal cortices is comparable with or better than that of state-of-the-art models. Importantly, the model can be learned using a small number of samples and using a local learning rule that utilizes noise intrinsic to neural circuits. Slower, structural changes in random connectivity, consistent with rewiring and pruning processes, further improve the efficiency and sparseness of the resulting neural representations. Our results merge insights from neuroanatomy, machine learning, and theoretical neuroscience to suggest random sparse connectivity as a key design principle for neuronal computation. AU - Maoz, Ori AU - Tkačik, Gašper AU - Esteki, Mohamad Saleh AU - Kiani, Roozbeh AU - Schneidman, Elad ID - 8698 IS - 40 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Learning probabilistic neural representations with randomly connected circuits VL - 117 ER - TY - CONF AB - Traditional robotic control suits require profound task-specific knowledge for designing, building and testing control software. The rise of Deep Learning has enabled end-to-end solutions to be learned entirely from data, requiring minimal knowledge about the application area. We design a learning scheme to train end-to-end linear dynamical systems (LDS)s by gradient descent in imitation learning robotic domains. We introduce a new regularization loss component together with a learning algorithm that improves the stability of the learned autonomous system, by forcing the eigenvalues of the internal state updates of an LDS to be negative reals. We evaluate our approach on a series of real-life and simulated robotic experiments, in comparison to linear and nonlinear Recurrent Neural Network (RNN) architectures. Our results show that our stabilizing method significantly improves test performance of LDS, enabling such linear models to match the performance of contemporary nonlinear RNN architectures. A video of the obstacle avoidance performance of our method on a mobile robot, in unseen environments, compared to other methods can be viewed at https://youtu.be/mhEsCoNao5E. AU - Lechner, Mathias AU - Hasani, Ramin AU - Rus, Daniela AU - Grosu, Radu ID - 8704 SN - 10504729 T2 - Proceedings - IEEE International Conference on Robotics and Automation TI - Gershgorin loss stabilizes the recurrent neural network compartment of an end-to-end robot learning scheme ER - TY - JOUR AB - Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency. AU - Sokolova, E. E. AU - Vlasov, Petr AU - Egorova, T. V. AU - Shuvalov, A. V. AU - Alkalaeva, E. Z. ID - 8700 IS - 5 JF - Molecular Biology SN - 00268933 TI - The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes VL - 54 ER - TY - JOUR AB - Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency. AU - Sokolova, E. E. AU - Vlasov, Petr AU - Egorova, T. V. AU - Shuvalov, A. V. AU - Alkalaeva, E. Z. ID - 8701 IS - 5 JF - Molekuliarnaia biologiia SN - 00268984 TI - The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes VL - 54 ER - TY - GEN AB - A binary neutron star merger has been observed in a multi-messenger detection of gravitational wave (GW) and electromagnetic (EM) radiation. Binary neutron stars that merge within a Hubble time, as well as many other compact binaries, are expected to form via common envelope evolution. Yet five decades of research on common envelope evolution have not yet resulted in a satisfactory understanding of the multi-spatial multi-timescale evolution for the systems that lead to compact binaries. In this paper, we report on the first successful simulations of common envelope ejection leading to binary neutron star formation in 3D hydrodynamics. We simulate the dynamical inspiral phase of the interaction between a 12M⊙ red supergiant and a 1.4M⊙ neutron star for different initial separations and initial conditions. For all of our simulations, we find complete envelope ejection and final orbital separations of af≈1.3-5.1R⊙ depending on the simulation and criterion, leading to binary neutron stars that can merge within a Hubble time. We find αCE-equivalent efficiencies of ≈0.1-2.7 depending on the simulation and criterion, but this may be specific for these extended progenitors. We fully resolve the core of the star to ≲0.005R⊙ and our 3D hydrodynamics simulations are informed by an adjusted 1D analytic energy formalism and a 2D kinematics study in order to overcome the prohibitive computational cost of simulating these systems. The framework we develop in this paper can be used to simulate a wide variety of interactions between stars, from stellar mergers to common envelope episodes leading to GW sources. AU - Jamie A. P. Law-Smith, Jamie A. P. Law-Smith AU - Everson, Rosa Wallace AU - Enrico Ramirez-Ruiz, Enrico Ramirez-Ruiz AU - Mink, Selma E. de AU - Son, Lieke A. C. van AU - Götberg, Ylva Louise Linsdotter AU - Zellmann, Stefan AU - Alejandro Vigna-Gómez, Alejandro Vigna-Gómez AU - Renzo, Mathieu AU - Wu, Samantha AU - Schrøder, Sophie L. AU - Foley, Ryan J. AU - Tenley Hutchinson-Smith, Tenley Hutchinson-Smith ID - 14096 T2 - arXiv TI - Successful common envelope ejection and binary neutron star formation in 3D hydrodynamics ER - TY - JOUR AB - In the high spin–orbit-coupled Sr2IrO4, the high sensitivity of the ground state to the details of the local lattice structure shows a large potential for the manipulation of the functional properties by inducing local lattice distortions. We use epitaxial strain to modify the Ir–O bond geometry in Sr2IrO4 and perform momentum-dependent resonant inelastic X-ray scattering (RIXS) at the metal and at the ligand sites to unveil the response of the low-energy elementary excitations. We observe that the pseudospin-wave dispersion for tensile-strained Sr2IrO4 films displays large softening along the [h,0] direction, while along the [h,h] direction it shows hardening. This evolution reveals a renormalization of the magnetic interactions caused by a strain-driven cross-over from anisotropic to isotropic interactions between the magnetic moments. Moreover, we detect dispersive electron–hole pair excitations which shift to lower (higher) energies upon compressive (tensile) strain, manifesting a reduction (increase) in the size of the charge gap. This behavior shows an intimate coupling between charge excitations and lattice distortions in Sr2IrO4, originating from the modified hopping elements between the t2g orbitals. Our work highlights the central role played by the lattice degrees of freedom in determining both the pseudospin and charge excitations of Sr2IrO4 and provides valuable information toward the control of the ground state of complex oxides in the presence of high spin–orbit coupling. AU - Paris, Eugenio AU - Tseng, Yi AU - Paerschke, Ekaterina AU - Zhang, Wenliang AU - Upton, Mary H AU - Efimenko, Anna AU - Rolfs, Katharina AU - McNally, Daniel E AU - Maurel, Laura AU - Naamneh, Muntaser AU - Caputo, Marco AU - Strocov, Vladimir N AU - Wang, Zhiming AU - Casa, Diego AU - Schneider, Christof W AU - Pomjakushina, Ekaterina AU - Wohlfeld, Krzysztof AU - Radovic, Milan AU - Schmitt, Thorsten ID - 8699 IS - 40 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Strain engineering of the charge and spin-orbital interactions in Sr2IrO4 VL - 117 ER - TY - JOUR AB - Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here, we present cryo-electron microscopy structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3 to 2.5 angstroms. Resolved water molecules allowed us to experimentally define the proton translocation pathways. Quinone binds at three positions along the quinone cavity, as does the inhibitor rotenone that also binds within subunit ND4. Dramatic conformational changes around the quinone cavity couple the redox reaction to proton translocation during open-to-closed state transitions of the enzyme. In the induced deactive state, the open conformation is arrested by the ND6 subunit. We propose a detailed molecular coupling mechanism of complex I, which is an unexpected combination of conformational changes and electrostatic interactions. AU - Kampjut, Domen AU - Sazanov, Leonid A ID - 8737 IS - 6516 JF - Science TI - The coupling mechanism of mammalian respiratory complex I VL - 370 ER - TY - CONF AB - Load imbalance pervasively exists in distributed deep learning training systems, either caused by the inherent imbalance in learned tasks or by the system itself. Traditional synchronous Stochastic Gradient Descent (SGD) achieves good accuracy for a wide variety of tasks, but relies on global synchronization to accumulate the gradients at every training step. In this paper, we propose eager-SGD, which relaxes the global synchronization for decentralized accumulation. To implement eager-SGD, we propose to use two partial collectives: solo and majority. With solo allreduce, the faster processes contribute their gradients eagerly without waiting for the slower processes, whereas with majority allreduce, at least half of the participants must contribute gradients before continuing, all without using a central parameter server. We theoretically prove the convergence of the algorithms and describe the partial collectives in detail. Experimental results on load-imbalanced environments (CIFAR-10, ImageNet, and UCF101 datasets) show that eager-SGD achieves 1.27x speedup over the state-of-the-art synchronous SGD, without losing accuracy. AU - Li, Shigang AU - Tal Ben-Nun, Tal Ben-Nun AU - Girolamo, Salvatore Di AU - Alistarh, Dan-Adrian AU - Hoefler, Torsten ID - 8722 T2 - Proceedings of the 25th ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming TI - Taming unbalanced training workloads in deep learning with partial collective operations ER - TY - JOUR AB - Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy, we show that thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding. AU - Schulte, Linda AU - Mao, Jiafei AU - Reitz, Julian AU - Sreeramulu, Sridhar AU - Kudlinzki, Denis AU - Hodirnau, Victor-Valentin AU - Meier-Credo, Jakob AU - Saxena, Krishna AU - Buhr, Florian AU - Langer, Julian D. AU - Blackledge, Martin AU - Frangakis, Achilleas S. AU - Glaubitz, Clemens AU - Schwalbe, Harald ID - 8744 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Cysteine oxidation and disulfide formation in the ribosomal exit tunnel VL - 11 ER - TY - JOUR AB - Appropriately designed nanocomposites allow improving the thermoelectric performance by several mechanisms, including phonon scattering, modulation doping and energy filtering, while additionally promoting better mechanical properties than those of crystalline materials. Here, a strategy for producing Bi2Te3–Cu2xTe nanocomposites based on the consolidation of heterostructured nanoparticles is described and the thermoelectric properties of the obtained materials are investigated. We first detail a two-step solution-based process to produce Bi2Te3–Cu2xTe heteronanostructures, based on the growth of Cu2xTe nanocrystals on the surface of Bi2Te3 nanowires. We characterize the structural and chemical properties of the synthesized nanostructures and of the nanocomposites produced by hot-pressing the particles at moderate temperatures. Besides, the transport properties of the nanocomposites are investigated as a function of the amount of Cu introduced. Overall, the presence of Cu decreases the material thermal conductivity through promotion of phonon scattering, modulates the charge carrier concentration through electron spillover, and increases the Seebeck coefficient through filtering of charge carriers at energy barriers. These effects result in an improvement of over 50% of the thermoelectric figure of merit of Bi2Te3. AU - Zhang, Yu AU - Liu, Yu AU - Calcabrini, Mariano AU - Xing, Congcong AU - Han, Xu AU - Arbiol, Jordi AU - Cadavid, Doris AU - Ibáñez, Maria AU - Cabot, Andreu ID - 8747 IS - 40 JF - Journal of Materials Chemistry C TI - Bismuth telluride-copper telluride nanocomposites from heterostructured building blocks VL - 8 ER - TY - GEN AB - The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument. AU - Gaudi, B. Scott AU - Seager, Sara AU - Mennesson, Bertrand AU - Kiessling, Alina AU - Warfield, Keith AU - Cahoy, Kerri AU - Clarke, John T. AU - Shawn Domagal-Goldman, Shawn Domagal-Goldman AU - Feinberg, Lee AU - Guyon, Olivier AU - Kasdin, Jeremy AU - Mawet, Dimitri AU - Plavchan, Peter AU - Robinson, Tyler AU - Rogers, Leslie AU - Scowen, Paul AU - Somerville, Rachel AU - Stapelfeldt, Karl AU - Stark, Christopher AU - Stern, Daniel AU - Turnbull, Margaret AU - Amini, Rashied AU - Kuan, Gary AU - Martin, Stefan AU - Morgan, Rhonda AU - Redding, David AU - Stahl, H. Philip AU - Webb, Ryan AU - Oscar Alvarez-Salazar, Oscar Alvarez-Salazar AU - Arnold, William L. AU - Arya, Manan AU - Balasubramanian, Bala AU - Baysinger, Mike AU - Bell, Ray AU - Below, Chris AU - Benson, Jonathan AU - Blais, Lindsey AU - Booth, Jeff AU - Bourgeois, Robert AU - Bradford, Case AU - Brewer, Alden AU - Brooks, Thomas AU - Cady, Eric AU - Caldwell, Mary AU - Calvet, Rob AU - Carr, Steven AU - Chan, Derek AU - Cormarkovic, Velibor AU - Coste, Keith AU - Cox, Charlie AU - Danner, Rolf AU - Davis, Jacqueline AU - Dewell, Larry AU - Dorsett, Lisa AU - Dunn, Daniel AU - East, Matthew AU - Effinger, Michael AU - Eng, Ron AU - Freebury, Greg AU - Garcia, Jay AU - Gaskin, Jonathan AU - Greene, Suzan AU - Hennessy, John AU - Hilgemann, Evan AU - Hood, Brad AU - Holota, Wolfgang AU - Howe, Scott AU - Huang, Pei AU - Hull, Tony AU - Hunt, Ron AU - Hurd, Kevin AU - Johnson, Sandra AU - Kissil, Andrew AU - Knight, Brent AU - Kolenz, Daniel AU - Kraus, Oliver AU - Krist, John AU - Li, Mary AU - Lisman, Doug AU - Mandic, Milan AU - Mann, John AU - Marchen, Luis AU - Colleen Marrese-Reading, Colleen Marrese-Reading AU - McCready, Jonathan AU - McGown, Jim AU - Missun, Jessica AU - Miyaguchi, Andrew AU - Moore, Bradley AU - Nemati, Bijan AU - Nikzad, Shouleh AU - Nissen, Joel AU - Novicki, Megan AU - Perrine, Todd AU - Pineda, Claudia AU - Polanco, Otto AU - Putnam, Dustin AU - Qureshi, Atif AU - Richards, Michael AU - Riggs, A. J. Eldorado AU - Rodgers, Michael AU - Rud, Mike AU - Saini, Navtej AU - Scalisi, Dan AU - Scharf, Dan AU - Schulz, Kevin AU - Serabyn, Gene AU - Sigrist, Norbert AU - Sikkia, Glory AU - Singleton, Andrew AU - Shaklan, Stuart AU - Smith, Scott AU - Southerd, Bart AU - Stahl, Mark AU - Steeves, John AU - Sturges, Brian AU - Sullivan, Chris AU - Tang, Hao AU - Taras, Neil AU - Tesch, Jonathan AU - Therrell, Melissa AU - Tseng, Howard AU - Valente, Marty AU - Buren, David Van AU - Villalvazo, Juan AU - Warwick, Steve AU - Webb, David AU - Westerhoff, Thomas AU - Wofford, Rush AU - Wu, Gordon AU - Woo, Jahning AU - Wood, Milana AU - Ziemer, John AU - Arney, Giada AU - Anderson, Jay AU - Jesús Maíz-Apellániz, Jesús Maíz-Apellániz AU - Bartlett, James AU - Belikov, Ruslan AU - Bendek, Eduardo AU - Cenko, Brad AU - Douglas, Ewan AU - Dulz, Shannon AU - Evans, Chris AU - Faramaz, Virginie AU - Feng, Y. Katherina AU - Ferguson, Harry AU - Follette, Kate AU - Ford, Saavik AU - García, Miriam AU - Geha, Marla AU - Gelino, Dawn AU - Götberg, Ylva Louise Linsdotter AU - Hildebrandt, Sergi AU - Hu, Renyu AU - Jahnke, Knud AU - Kennedy, Grant AU - Kreidberg, Laura AU - Isella, Andrea AU - Lopez, Eric AU - Marchis, Franck AU - Macri, Lucas AU - Marley, Mark AU - Matzko, William AU - Mazoyer, Johan AU - McCandliss, Stephan AU - Meshkat, Tiffany AU - Mordasini, Christoph AU - Morris, Patrick AU - Nielsen, Eric AU - Newman, Patrick AU - Petigura, Erik AU - Postman, Marc AU - Reines, Amy AU - Roberge, Aki AU - Roederer, Ian AU - Ruane, Garreth AU - Schwieterman, Edouard AU - Sirbu, Dan AU - Spalding, Christopher AU - Teplitz, Harry AU - Tumlinson, Jason AU - Turner, Neal AU - Werk, Jessica AU - Wofford, Aida AU - Wyatt, Mark AU - Young, Amber AU - Zellem, Rob ID - 14095 T2 - arXiv TI - The habitable exoplanet observatory (HabEx) mission concept study final report ER - TY - JOUR AB - Resources are rarely distributed uniformly within a population. Heterogeneity in the concentration of a drug, the quality of breeding sites, or wealth can all affect evolutionary dynamics. In this study, we represent a collection of properties affecting the fitness at a given location using a color. A green node is rich in resources while a red node is poorer. More colors can represent a broader spectrum of resource qualities. For a population evolving according to the birth-death Moran model, the first question we address is which structures, identified by graph connectivity and graph coloring, are evolutionarily equivalent. We prove that all properly two-colored, undirected, regular graphs are evolutionarily equivalent (where “properly colored” means that no two neighbors have the same color). We then compare the effects of background heterogeneity on properly two-colored graphs to those with alternative schemes in which the colors are permuted. Finally, we discuss dynamic coloring as a model for spatiotemporal resource fluctuations, and we illustrate that random dynamic colorings often diminish the effects of background heterogeneity relative to a proper two-coloring. AU - Kaveh, Kamran AU - McAvoy, Alex AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 8767 IS - 11 JF - PLOS Computational Biology KW - Ecology KW - Modelling and Simulation KW - Computational Theory and Mathematics KW - Genetics KW - Ecology KW - Evolution KW - Behavior and Systematics KW - Molecular Biology KW - Cellular and Molecular Neuroscience SN - 1553-734X TI - The Moran process on 2-chromatic graphs VL - 16 ER - TY - CONF AB - Efficiently handling time-triggered and possibly nondeterministic switches for hybrid systems reachability is a challenging task. In this paper we present an approach based on conservative set-based enclosure of the dynamics that can handle systems with uncertain parameters and inputs, where the uncertainties are bound to given intervals. The method is evaluated on the plant model of an experimental electro-mechanical braking system with periodic controller. In this model, the fast-switching controller dynamics requires simulation time scales of the order of nanoseconds. Accurate set-based computations for relatively large time horizons are known to be expensive. However, by appropriately decoupling the time variable with respect to the spatial variables, and enclosing the uncertain parameters using interval matrix maps acting on zonotopes, we show that the computation time can be lowered to 5000 times faster with respect to previous works. This is a step forward in formal verification of hybrid systems because reduced run-times allow engineers to introduce more expressiveness in their models with a relatively inexpensive computational cost. AU - Forets, Marcelo AU - Freire, Daniel AU - Schilling, Christian ID - 8750 SN - 9781728191485 T2 - 18th ACM-IEEE International Conference on Formal Methods and Models for System Design TI - Efficient reachability analysis of parametric linear hybrid systems with time-triggered transitions ER - TY - JOUR AB - We consider various modeling levels for spatially homogeneous chemical reaction systems, namely the chemical master equation, the chemical Langevin dynamics, and the reaction-rate equation. Throughout we restrict our study to the case where the microscopic system satisfies the detailed-balance condition. The latter allows us to enrich the systems with a gradient structure, i.e. the evolution is given by a gradient-flow equation. We present the arising links between the associated gradient structures that are driven by the relative entropy of the detailed-balance steady state. The limit of large volumes is studied in the sense of evolutionary Γ-convergence of gradient flows. Moreover, we use the gradient structures to derive hybrid models for coupling different modeling levels. AU - Maas, Jan AU - Mielke, Alexander ID - 8758 IS - 6 JF - Journal of Statistical Physics SN - 00224715 TI - Modeling of chemical reaction systems with detailed balance using gradient structures VL - 181 ER - TY - GEN AB - This dataset comprises all data shown in the figures of the submitted article "Surpassing the resistance quantum with a geometric superinductor". Additional raw data are available from the corresponding author on reasonable request. AU - Peruzzo, Matilda AU - Trioni, Andrea AU - Hassani, Farid AU - Zemlicka, Martin AU - Fink, Johannes M ID - 13070 TI - Surpassing the resistance quantum with a geometric superinductor ER - TY - JOUR AB - Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets. AU - Nicolai, Leo AU - Schiefelbein, Karin AU - Lipsky, Silvia AU - Leunig, Alexander AU - Hoffknecht, Marie AU - Pekayvaz, Kami AU - Raude, Ben AU - Marx, Charlotte AU - Ehrlich, Andreas AU - Pircher, Joachim AU - Zhang, Zhe AU - Saleh, Inas AU - Marel, Anna-Kristina AU - Löf, Achim AU - Petzold, Tobias AU - Lorenz, Michael AU - Stark, Konstantin AU - Pick, Robert AU - Rosenberger, Gerhild AU - Weckbach, Ludwig AU - Uhl, Bernd AU - Xia, Sheng AU - Reichel, Christoph Andreas AU - Walzog, Barbara AU - Schulz, Christian AU - Zheden, Vanessa AU - Bender, Markus AU - Li, Rong AU - Massberg, Steffen AU - Gärtner, Florian R ID - 8787 JF - Nature Communications TI - Vascular surveillance by haptotactic blood platelets in inflammation and infection VL - 11 ER - TY - JOUR AB - Cooperation is a ubiquitous and beneficial behavioural trait despite being prone to exploitation by free-riders. Hence, cooperative populations are prone to invasions by selfish individuals. However, a population consisting of only free-riders typically does not survive. Thus, cooperators and free-riders often coexist in some proportion. An evolutionary version of a Snowdrift Game proved its efficiency in analysing this phenomenon. However, what if the system has already reached its stable state but was perturbed due to a change in environmental conditions? Then, individuals may have to re-learn their effective strategies. To address this, we consider behavioural mistakes in strategic choice execution, which we refer to as incompetence. Parametrising the propensity to make such mistakes allows for a mathematical description of learning. We compare strategies based on their relative strategic advantage relying on both fitness and learning factors. When strategies are learned at distinct rates, allowing learning according to a prescribed order is optimal. Interestingly, the strategy with the lowest strategic advantage should be learnt first if we are to optimise fitness over the learning path. Then, the differences between strategies are balanced out in order to minimise the effect of behavioural uncertainty. AU - Kleshnina, Maria AU - Streipert, Sabrina AU - Filar, Jerzy AU - Chatterjee, Krishnendu ID - 8789 IS - 11 JF - Mathematics TI - Prioritised learning in snowdrift-type games VL - 8 ER - TY - CONF AB - Reachability analysis aims at identifying states reachable by a system within a given time horizon. This task is known to be computationally expensive for linear hybrid systems. Reachability analysis works by iteratively applying continuous and discrete post operators to compute states reachable according to continuous and discrete dynamics, respectively. In this paper, we enhance both of these operators and make sure that most of the involved computations are performed in low-dimensional state space. In particular, we improve the continuous-post operator by performing computations in high-dimensional state space only for time intervals relevant for the subsequent application of the discrete-post operator. Furthermore, the new discrete-post operator performs low-dimensional computations by leveraging the structure of the guard and assignment of a considered transition. We illustrate the potential of our approach on a number of challenging benchmarks. AU - Bogomolov, Sergiy AU - Forets, Marcelo AU - Frehse, Goran AU - Potomkin, Kostiantyn AU - Schilling, Christian ID - 8287 KW - reachability KW - hybrid systems KW - decomposition T2 - Proceedings of the International Conference on Embedded Software TI - Reachability analysis of linear hybrid systems via block decomposition ER - TY - JOUR AB - We consider a real-time setting where an environment releases sequences of firm-deadline tasks, and an online scheduler chooses on-the-fly the ones to execute on a single processor so as to maximize cumulated utility. The competitive ratio is a well-known performance measure for the scheduler: it gives the worst-case ratio, among all possible choices for the environment, of the cumulated utility of the online scheduler versus an offline scheduler that knows these choices in advance. Traditionally, competitive analysis is performed by hand, while automated techniques are rare and only handle static environments with independent tasks. We present a quantitative-verification framework for precedence-aware competitive analysis, where task releases may depend on preceding scheduling choices, i.e., the environment can respond to scheduling decisions dynamically . We consider two general classes of precedences: 1) follower precedences force the release of a dependent task upon the completion of a set of precursor tasks, while and 2) pairing precedences modify the characteristics of a dependent task provided the completion of a set of precursor tasks. Precedences make competitive analysis challenging, as the online and offline schedulers operate on diverging sequences. We make a formal presentation of our framework, and use a GPU-based implementation to analyze ten well-known schedulers on precedence-based application examples taken from the existing literature: 1) a handshake protocol (HP); 2) network packet-switching; 3) query scheduling (QS); and 4) a sporadic-interrupt setting. Our experimental results show that precedences and task parameters can vary drastically the best scheduler. Our framework thus supports application designers in choosing the best scheduler among a given set automatically. AU - Pavlogiannis, Andreas AU - Schaumberger, Nico AU - Schmid, Ulrich AU - Chatterjee, Krishnendu ID - 8788 IS - 11 JF - IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems SN - 02780070 TI - Precedence-aware automated competitive analysis of real-time scheduling VL - 39 ER - TY - JOUR AB - Reachability analysis aims at identifying states reachable by a system within a given time horizon. This task is known to be computationally expensive for linear hybrid systems. Reachability analysis works by iteratively applying continuous and discrete post operators to compute states reachable according to continuous and discrete dynamics, respectively. In this article, we enhance both of these operators and make sure that most of the involved computations are performed in low-dimensional state space. In particular, we improve the continuous-post operator by performing computations in high-dimensional state space only for time intervals relevant for the subsequent application of the discrete-post operator. Furthermore, the new discrete-post operator performs low-dimensional computations by leveraging the structure of the guard and assignment of a considered transition. We illustrate the potential of our approach on a number of challenging benchmarks. AU - Bogomolov, Sergiy AU - Forets, Marcelo AU - Frehse, Goran AU - Potomkin, Kostiantyn AU - Schilling, Christian ID - 8790 IS - 11 JF - IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems SN - 02780070 TI - Reachability analysis of linear hybrid systems via block decomposition VL - 39 ER - TY - JOUR AB - Maintaining fertility in a fluctuating environment is key to the reproductive success of flowering plants. Meiosis and pollen formation are particularly sensitive to changes in growing conditions, especially temperature. We have previously identified cyclin-dependent kinase G1 (CDKG1) as a master regulator of temperature-dependent meiosis and this may involve the regulation of alternative splicing (AS), including of its own transcript. CDKG1 mRNA can undergo several AS events, potentially producing two protein variants: CDKG1L and CDKG1S, differing in their N-terminal domain which may be involved in co-factor interaction. In leaves, both isoforms have distinct temperature-dependent functions on target mRNA processing, but their role in pollen development is unknown. In the present study, we characterize the role of CDKG1L and CDKG1S in maintaining Arabidopsis fertility. We show that the long (L) form is necessary and sufficient to rescue the fertility defects of the cdkg1-1 mutant, while the short (S) form is unable to rescue fertility. On the other hand, an extra copy of CDKG1L reduces fertility. In addition, mutation of the ATP binding pocket of the kinase indicates that kinase activity is necessary for the function of CDKG1. Kinase mutants of CDKG1L and CDKG1S correctly localize to the cell nucleus and nucleus and cytoplasm, respectively, but are unable to rescue either the fertility or the splicing defects of the cdkg1-1 mutant. Furthermore, we show that there is partial functional overlap between CDKG1 and its paralog CDKG2 that could in part be explained by overlapping gene expression. AU - Nibau, Candida AU - Dadarou, Despoina AU - Kargios, Nestoras AU - Mallioura, Areti AU - Fernandez-Fuentes, Narcis AU - Cavallari, Nicola AU - Doonan, John H. ID - 8924 JF - Frontiers in Plant Science TI - A functional kinase is necessary for cyclin-dependent kinase G1 (CDKG1) to maintain fertility at high ambient temperature in Arabidopsis VL - 11 ER - TY - JOUR AB - Bimetallic nanoparticles with tailored size and specific composition have shown promise as stable and selective catalysts for electrochemical reduction of CO2 (CO2R) in batch systems. Yet, limited effort was devoted to understand the effect of ligand coverage and postsynthesis treatments on CO2 reduction, especially under industrially applicable conditions, such as at high currents (>100 mA/cm2) using gas diffusion electrodes (GDE) and flow reactors. In this work, Cu–Ag core–shell nanoparticles (11 ± 2 nm) were prepared with three different surface modes: (i) capped with oleylamine, (ii) capped with monoisopropylamine, and (iii) surfactant-free with a reducing borohydride agent; Cu–Ag (OAm), Cu–Ag (MIPA), and Cu–Ag (NaBH4), respectively. The ligand exchange and removal was evidenced by infrared spectroscopy (ATR-FTIR) analysis, whereas high-resolution scanning transmission electron microscopy (HAADF-STEM) showed their effect on the interparticle distance and nanoparticle rearrangement. Later on, we developed a process-on-substrate method to track these effects on CO2R. Cu–Ag (OAm) gave a lower on-set potential for hydrocarbon production, whereas Cu–Ag (MIPA) and Cu–Ag (NaBH4) promoted syngas production. The electrochemical impedance and surface area analysis on the well-controlled electrodes showed gradual increases in the electrical conductivity and active surface area after each surface treatment. We found that the increasing amount of the triple phase boundaries (the meeting point for the electron–electrolyte–CO2 reactant) affect the required electrode potential and eventually the C+2e̅/C2e̅ product ratio. This study highlights the importance of the electron transfer to those active sites affected by the capping agents—particularly on larger substrates that are crucial for their industrial application. AU - Irtem, Erdem AU - Arenas Esteban, Daniel AU - Duarte, Miguel AU - Choukroun, Daniel AU - Lee, Seungho AU - Ibáñez, Maria AU - Bals, Sara AU - Breugelmans, Tom ID - 8926 IS - 22 JF - ACS Catalysis TI - Ligand-mode directed selectivity in Cu-Ag core-shell based gas diffusion electrodes for CO2 electroreduction VL - 10 ER - TY - JOUR AB - Superconductor insulator transition in transverse magnetic field is studied in the highly disordered MoC film with the product of the Fermi momentum and the mean free path kF*l close to unity. Surprisingly, the Zeeman paramagnetic effects dominate over orbital coupling on both sides of the transition. In superconducting state it is evidenced by a high upper critical magnetic field 𝐵𝑐2, by its square root dependence on temperature, as well as by the Zeeman splitting of the quasiparticle density of states (DOS) measured by scanning tunneling microscopy. At 𝐵𝑐2 a logarithmic anomaly in DOS is observed. This anomaly is further enhanced in increasing magnetic field, which is explained by the Zeeman splitting of the Altshuler-Aronov DOS driving the system into a more insulating or resistive state. Spin dependent Altshuler-Aronov correction is also needed to explain the transport behavior above 𝐵𝑐2. AU - Zemlicka, Martin AU - Kopčík, M. AU - Szabó, P. AU - Samuely, T. AU - Kačmarčík, J. AU - Neilinger, P. AU - Grajcar, M. AU - Samuely, P. ID - 8944 IS - 18 JF - Physical Review B SN - 24699950 TI - Zeeman-driven superconductor-insulator transition in strongly disordered MoC films: Scanning tunneling microscopy and transport studies in a transverse magnetic field VL - 102 ER - TY - JOUR AB - Skeletal muscle activity is continuously modulated across physiologic states to provide coordination, flexibility and responsiveness to body tasks and external inputs. Despite the central role the muscular system plays in facilitating vital body functions, the network of brain-muscle interactions required to control hundreds of muscles and synchronize their activation in relation to distinct physiologic states has not been investigated. Recent approaches have focused on general associations between individual brain rhythms and muscle activation during movement tasks. However, the specific forms of coupling, the functional network of cortico-muscular coordination, and how network structure and dynamics are modulated by autonomic regulation across physiologic states remains unknown. To identify and quantify the cortico-muscular interaction network and uncover basic features of neuro-autonomic control of muscle function, we investigate the coupling between synchronous bursts in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing the concept of time delay stability and a novel network physiology approach, we find that the brain-muscle network exhibits complex dynamic patterns of communication involving multiple brain rhythms across cortical locations and different electromyographic frequency bands. Moreover, our results show that during each physiologic state the cortico-muscular network is characterized by a specific profile of network links strength, where particular brain rhythms play role of main mediators of interaction and control. Further, we discover a hierarchical reorganization in network structure across physiologic states, with high connectivity and network link strength during wake, intermediate during REM and light sleep, and low during deep sleep, a sleep-stage stratification that demonstrates a unique association between physiologic states and cortico-muscular network structure. The reported empirical observations are consistent across individual subjects, indicating universal behavior in network structure and dynamics, and high sensitivity of cortico-muscular control to changes in autonomic regulation, even at low levels of physical activity and muscle tone during sleep. Our findings demonstrate previously unrecognized basic principles of brain-muscle network communication and control, and provide new perspectives on the regulatory mechanisms of brain dynamics and locomotor activation, with potential clinical implications for neurodegenerative, movement and sleep disorders, and for developing efficient treatment strategies. AU - Rizzo, Rossella AU - Zhang, Xiyun AU - Wang, Jilin W.J.L. AU - Lombardi, Fabrizio AU - Ivanov, Plamen Ch ID - 8955 JF - Frontiers in Physiology TI - Network physiology of cortico–muscular interactions VL - 11 ER - TY - JOUR AB - Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis. AU - Zhang, Xuying AU - Mennicke, Christine V. AU - Xiao, Guanxi AU - Beattie, Robert J AU - Haider, Mansoor AU - Hippenmeyer, Simon AU - Ghashghaei, H. Troy ID - 8949 IS - 12 JF - Cells SN - 2073-4409 TI - Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage VL - 9 ER - TY - JOUR AB - The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves complex structural rearrangements and actin filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging. This allows us to generate an accurate model of the active Arp2/3 complex in the branch junction and its interaction with actin filaments. Notably, our model reveals a previously undescribed set of interactions of the Arp2/3 complex with the mother filament, significantly different to the previous branch junction model. Our structure also indicates a central role for the ArpC3 subunit in stabilizing the active conformation. AU - Fäßler, Florian AU - Dimchev, Georgi A AU - Hodirnau, Victor-Valentin AU - Wan, William AU - Schur, Florian KM ID - 8971 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction VL - 11 ER - TY - CONF AB - Currently several projects aim at designing and implementing protocols for privacy preserving automated contact tracing to help fight the current pandemic. Those proposal are quite similar, and in their most basic form basically propose an app for mobile phones which broadcasts frequently changing pseudorandom identifiers via (low energy) Bluetooth, and at the same time, the app stores IDs broadcast by phones in its proximity. Only if a user is tested positive, they upload either the beacons they did broadcast (which is the case in decentralized proposals as DP-3T, east and west coast PACT or Covid watch) or received (as in Popp-PT or ROBERT) during the last two weeks or so. Vaudenay [eprint 2020/399] observes that this basic scheme (he considers the DP-3T proposal) succumbs to relay and even replay attacks, and proposes more complex interactive schemes which prevent those attacks without giving up too many privacy aspects. Unfortunately interaction is problematic for this application for efficiency and security reasons. The countermeasures that have been suggested so far are either not practical or give up on key privacy aspects. We propose a simple non-interactive variant of the basic protocol that (security) Provably prevents replay and (if location data is available) relay attacks. (privacy) The data of all parties (even jointly) reveals no information on the location or time where encounters happened. (efficiency) The broadcasted message can fit into 128 bits and uses only basic crypto (commitments and secret key authentication). Towards this end we introduce the concept of “delayed authentication”, which basically is a message authentication code where verification can be done in two steps, where the first doesn’t require the key, and the second doesn’t require the message. AU - Pietrzak, Krzysztof Z ID - 8987 SN - 03029743 T2 - Progress in Cryptology TI - Delayed authentication: Preventing replay and relay attacks in private contact tracing VL - 12578 ER - TY - JOUR AB - Global tissue tension anisotropy has been shown to trigger stereotypical cell division orientation by elongating mitotic cells along the main tension axis. Yet, how tissue tension elongates mitotic cells despite those cells undergoing mitotic rounding (MR) by globally upregulating cortical actomyosin tension remains unclear. We addressed this question by taking advantage of ascidian embryos, consisting of a small number of interphasic and mitotic blastomeres and displaying an invariant division pattern. We found that blastomeres undergo MR by locally relaxing cortical tension at their apex, thereby allowing extrinsic pulling forces from neighboring interphasic blastomeres to polarize their shape and thus division orientation. Consistently, interfering with extrinsic forces by reducing the contractility of interphasic blastomeres or disrupting the establishment of asynchronous mitotic domains leads to aberrant mitotic cell division orientations. Thus, apical relaxation during MR constitutes a key mechanism by which tissue tension anisotropy controls stereotypical cell division orientation. AU - Godard, Benoit G AU - Dumollard, Rémi AU - Munro, Edwin AU - Chenevert, Janet AU - Hebras, Céline AU - Mcdougall, Alex AU - Heisenberg, Carl-Philipp J ID - 8957 IS - 6 JF - Developmental Cell SN - 15345807 TI - Apical relaxation during mitotic rounding promotes tension-oriented cell division VL - 55 ER - TY - JOUR AB - In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In nonequilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal nonequilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity, and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate,” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in nonequilibrium models is in a trade-off with gene-expression noise, predicting bursty dynamics—an experimentally observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space of nonequilibrium enhancer models to a much smaller subspace that optimally realizes biological function, we deliver a rich class of models that could be tractably inferred from data in the near future. AU - Grah, Rok AU - Zoller, Benjamin AU - Tkačik, Gašper ID - 9000 IS - 50 JF - PNAS SN - 00278424 TI - Nonequilibrium models of optimal enhancer function VL - 117 ER - TY - JOUR AB - Quantum illumination uses entangled signal-idler photon pairs to boost the detection efficiency of low-reflectivity objects in environments with bright thermal noise. Its advantage is particularly evident at low signal powers, a promising feature for applications such as noninvasive biomedical scanning or low-power short-range radar. Here, we experimentally investigate the concept of quantum illumination at microwave frequencies. We generate entangled fields to illuminate a room-temperature object at a distance of 1 m in a free-space detection setup. We implement a digital phase-conjugate receiver based on linear quadrature measurements that outperforms a symmetric classical noise radar in the same conditions, despite the entanglement-breaking signal path. Starting from experimental data, we also simulate the case of perfect idler photon number detection, which results in a quantum advantage compared with the relative classical benchmark. Our results highlight the opportunities and challenges in the way toward a first room-temperature application of microwave quantum circuits. AU - Barzanjeh, Shabir AU - Pirandola, S. AU - Vitali, D AU - Fink, Johannes M ID - 7910 IS - 19 JF - Science Advances TI - Microwave quantum illumination using a digital receiver VL - 6 ER - TY - CONF AB - Quantum illumination is a sensing technique that employs entangled signal-idler beams to improve the detection efficiency of low-reflectivity objects in environments with large thermal noise. The advantage over classical strategies is evident at low signal brightness, a feature which could make the protocol an ideal prototype for non-invasive scanning or low-power short-range radar. Here we experimentally investigate the concept of quantum illumination at microwave frequencies, by generating entangled fields using a Josephson parametric converter which are then amplified to illuminate a room-temperature object at a distance of 1 meter. Starting from experimental data, we simulate the case of perfect idler photon number detection, which results in a quantum advantage compared to the relative classical benchmark. Our results highlight the opportunities and challenges on the way towards a first room-temperature application of microwave quantum circuits. AU - Barzanjeh, Shabir AU - Pirandola, Stefano AU - Vitali, David AU - Fink, Johannes M ID - 9001 IS - 9 SN - 1097-5659 T2 - IEEE National Radar Conference - Proceedings TI - Microwave quantum illumination with a digital phase-conjugated receiver VL - 2020 ER - TY - JOUR AB - Motivated by a recent question of Peyre, we apply the Hardy–Littlewood circle method to count “sufficiently free” rational points of bounded height on arbitrary smooth projective hypersurfaces of low degree that are defined over the rationals. AU - Browning, Timothy D AU - Sawin, Will ID - 9007 IS - 4 JF - Commentarii Mathematici Helvetici SN - 00102571 TI - Free rational points on smooth hypersurfaces VL - 95 ER - TY - JOUR AB - Microwave photonics lends the advantages of fiber optics to electronic sensing and communication systems. In contrast to nonlinear optics, electro-optic devices so far require classical modulation fields whose variance is dominated by electronic or thermal noise rather than quantum fluctuations. Here we demonstrate bidirectional single-sideband conversion of X band microwave to C band telecom light with a microwave mode occupancy as low as 0.025 ± 0.005 and an added output noise of less than or equal to 0.074 photons. This is facilitated by radiative cooling and a triply resonant ultra-low-loss transducer operating at millikelvin temperatures. The high bandwidth of 10.7 MHz and total (internal) photon conversion efficiency of 0.03% (0.67%) combined with the extremely slow heating rate of 1.1 added output noise photons per second for the highest available pump power of 1.48 mW puts near-unity efficiency pulsed quantum transduction within reach. Together with the non-Gaussian resources of superconducting qubits this might provide the practical foundation to extend the range and scope of current quantum networks in analogy to electrical repeaters in classical fiber optic communication. AU - Hease, William J AU - Rueda Sanchez, Alfredo R AU - Sahu, Rishabh AU - Wulf, Matthias AU - Arnold, Georg M AU - Schwefel, Harald G.L. AU - Fink, Johannes M ID - 9114 IS - 2 JF - PRX Quantum SN - 2691-3399 TI - Bidirectional electro-optic wavelength conversion in the quantum ground state VL - 1 ER - TY - JOUR AB - Quantum transduction, the process of converting quantum signals from one form of energy to another, is an important area of quantum science and technology. The present perspective article reviews quantum transduction between microwave and optical photons, an area that has recently seen a lot of activity and progress because of its relevance for connecting superconducting quantum processors over long distances, among other applications. Our review covers the leading approaches to achieving such transduction, with an emphasis on those based on atomic ensembles, opto-electro-mechanics, and electro-optics. We briefly discuss relevant metrics from the point of view of different applications, as well as challenges for the future. AU - Lauk, Nikolai AU - Sinclair, Neil AU - Barzanjeh, Shabir AU - Covey, Jacob P AU - Saffman, Mark AU - Spiropulu, Maria AU - Simon, Christoph ID - 9194 IS - 2 JF - Quantum Science and Technology SN - 2058-9565 TI - Perspectives on quantum transduction VL - 5 ER - TY - JOUR AB - We give a short and self-contained proof for rates of convergence of the Allen--Cahn equation towards mean curvature flow, assuming that a classical (smooth) solution to the latter exists and starting from well-prepared initial data. Our approach is based on a relative entropy technique. In particular, it does not require a stability analysis for the linearized Allen--Cahn operator. As our analysis also does not rely on the comparison principle, we expect it to be applicable to more complex equations and systems. AU - Fischer, Julian L AU - Laux, Tim AU - Simon, Theresa M. ID - 9039 IS - 6 JF - SIAM Journal on Mathematical Analysis SN - 00361410 TI - Convergence rates of the Allen-Cahn equation to mean curvature flow: A short proof based on relative entropies VL - 52 ER -