@article{7882, abstract = {A few-body cluster is a building block of a many-body system in a gas phase provided the temperature at most is of the order of the binding energy of this cluster. Here we illustrate this statement by considering a system of tubes filled with dipolar distinguishable particles. We calculate the partition function, which determines the probability to find a few-body cluster at a given temperature. The input for our calculations—the energies of few-body clusters—is estimated using the harmonic approximation. We first describe and demonstrate the validity of our numerical procedure. Then we discuss the results featuring melting of the zero-temperature many-body state into a gas of free particles and few-body clusters. For temperature higher than its binding energy threshold, the dimers overwhelmingly dominate the ensemble, where the remaining probability is in free particles. At very high temperatures free (harmonic oscillator trap-bound) particle dominance is eventually reached. This structure evolution appears both for one and two particles in each layer providing crucial information about the behavior of ultracold dipolar gases. The investigation addresses the transition region between few- and many-body physics as a function of temperature using a system of ten dipoles in five tubes.}, author = {Armstrong, Jeremy R. and Jensen, Aksel S. and Volosniev, Artem and Zinner, Nikolaj T.}, issn = {22277390}, journal = {Mathematics}, number = {4}, publisher = {MDPI}, title = {{Clusters in separated tubes of tilted dipoles}}, doi = {10.3390/math8040484}, volume = {8}, year = {2020}, } @article{7804, abstract = {Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.}, author = {Flynn, Sean M. and Chen, Changchun and Artan, Murat and Barratt, Stephen and Crisp, Alastair and Nelson, Geoffrey M. and Peak-Chew, Sew Yeu and Begum, Farida and Skehel, Mark and De Bono, Mario}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity}}, doi = {10.1038/s41467-020-15872-y}, volume = {11}, year = {2020}, } @article{7875, abstract = {Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.}, author = {Kopf, Aglaja and Renkawitz, Jörg and Hauschild, Robert and Girkontaite, Irute and Tedford, Kerry and Merrin, Jack and Thorn-Seshold, Oliver and Trauner, Dirk and Häcker, Hans and Fischer, Klaus Dieter and Kiermaier, Eva and Sixt, Michael K}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {6}, publisher = {Rockefeller University Press}, title = {{Microtubules control cellular shape and coherence in amoeboid migrating cells}}, doi = {10.1083/jcb.201907154}, volume = {219}, year = {2020}, } @article{7888, abstract = {Embryonic stem cell cultures are thought to self-organize into embryoid bodies, able to undergo symmetry-breaking, germ layer specification and even morphogenesis. Yet, it is unclear how to reconcile this remarkable self-organization capacity with classical experiments demonstrating key roles for extrinsic biases by maternal factors and/or extraembryonic tissues in embryogenesis. Here, we show that zebrafish embryonic tissue explants, prepared prior to germ layer induction and lacking extraembryonic tissues, can specify all germ layers and form a seemingly complete mesendoderm anlage. Importantly, explant organization requires polarized inheritance of maternal factors from dorsal-marginal regions of the blastoderm. Moreover, induction of endoderm and head-mesoderm, which require peak Nodal-signaling levels, is highly variable in explants, reminiscent of embryos with reduced Nodal signals from the extraembryonic tissues. Together, these data suggest that zebrafish explants do not undergo bona fide self-organization, but rather display features of genetically encoded self-assembly, where intrinsic genetic programs control the emergence of order.}, author = {Schauer, Alexandra and Nunes Pinheiro, Diana C and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Zebrafish embryonic explants undergo genetically encoded self-assembly}}, doi = {10.7554/elife.55190}, volume = {9}, year = {2020}, } @article{7877, abstract = {The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions.}, author = {Parenti, Ilaria and Diab, Farah and Gil, Sara Ruiz and Mulugeta, Eskeatnaf and Casa, Valentina and Berutti, Riccardo and Brouwer, Rutger W.W. and Dupé, Valerie and Eckhold, Juliane and Graf, Elisabeth and Puisac, Beatriz and Ramos, Feliciano and Schwarzmayr, Thomas and Gines, Macarena Moronta and Van Staveren, Thomas and Van Ijcken, Wilfred F.J. and Strom, Tim M. and Pié, Juan and Watrin, Erwan and Kaiser, Frank J. and Wendt, Kerstin S.}, issn = {22111247}, journal = {Cell Reports}, number = {7}, publisher = {Elsevier}, title = {{MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome}}, doi = {10.1016/j.celrep.2020.107647}, volume = {31}, year = {2020}, } @article{7878, abstract = {Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions.}, author = {Bao, Jin and Graupner, Michael and Astorga, Guadalupe and Collin, Thibault and Jalil, Abdelali and Indriati, Dwi Wahyu and Bradley, Jonathan and Shigemoto, Ryuichi and Llano, Isabel}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo}}, doi = {10.7554/eLife.56839}, volume = {9}, year = {2020}, } @article{7880, abstract = {Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. }, author = {Fagan, Rita R. and Kearney, Patrick J. and Sweeney, Carolyn G. and Luethi, Dino and Schoot Uiterkamp, Florianne E and Schicker, Klaus and Alejandro, Brian S. and O'Connor, Lauren C. and Sitte, Harald H. and Melikian, Haley E.}, issn = {1083351X}, journal = {Journal of Biological Chemistry}, number = {16}, pages = {5229--5244}, publisher = {ASBMB Publications}, title = {{Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact}}, doi = {10.1074/jbc.RA120.012628}, volume = {295}, year = {2020}, } @article{7876, abstract = {In contrast to lymph nodes, the lymphoid regions of the spleen—the white pulp—are located deep within the organ, yielding the trafficking paths of T cells in the white pulp largely invisible. In an intravital microscopy tour de force reported in this issue of Immunity, Chauveau et al. show that T cells perform unidirectional, perivascular migration through the enigmatic marginal zone bridging channels. }, author = {Sixt, Michael K and Lämmermann, Tim}, issn = {10974180}, journal = {Immunity}, number = {5}, pages = {721--723}, publisher = {Elsevier}, title = {{T cells: Bridge-and-channel commute to the white pulp}}, doi = {10.1016/j.immuni.2020.04.020}, volume = {52}, year = {2020}, } @article{7909, abstract = {Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.}, author = {Damiano-Guercio, Julia and Kurzawa, Laëtitia and Müller, Jan and Dimchev, Georgi A and Schaks, Matthias and Nemethova, Maria and Pokrant, Thomas and Brühmann, Stefan and Linkner, Joern and Blanchoin, Laurent and Sixt, Michael K and Rottner, Klemens and Faix, Jan}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion}}, doi = {10.7554/eLife.55351}, volume = {9}, year = {2020}, } @article{7908, abstract = {Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.}, author = {Wang, Han Ying and Eguchi, Kohgaku and Yamashita, Takayuki and Takahashi, Tomoyuki}, issn = {15292401}, journal = {Journal of Neuroscience}, number = {21}, pages = {4103--4115}, publisher = {Society for Neuroscience}, title = {{Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms}}, doi = {10.1523/JNEUROSCI.2946-19.2020}, volume = {40}, year = {2020}, } @article{7931, abstract = {In the course of sample preparation for Next Generation Sequencing (NGS), DNA is fragmented by various methods. Fragmentation shows a persistent bias with regard to the cleavage rates of various dinucleotides. With the exception of CpG dinucleotides the previously described biases were consistent with results of the DNA cleavage in solution. Here we computed cleavage rates of all dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data of the Whole Genome Sequencing datasets of the 1000 Genomes project. We found that the cleavage rate of CpG is significantly higher for the methylated CpG dinucleotides. Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their CpG islands statuses of the fragmentation. A simple Support Vector Machine classifier based on this algorithm shows an accuracy of 84%. The proposed method allows the detection of epigenetic markers purely based on mechanochemical DNA fragmentation, which can be detected by a simple analysis of the NGS sequencing data.}, author = {Uroshlev, Leonid A. and Abdullaev, Eldar T. and Umarova, Iren R. and Il’Icheva, Irina A. and Panchenko, Larisa A. and Polozov, Robert V. and Kondrashov, Fyodor and Nechipurenko, Yury D. and Grokhovsky, Sergei L.}, issn = {20452322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{A method for identification of the methylation level of CpG islands from NGS data}}, doi = {10.1038/s41598-020-65406-1}, volume = {10}, year = {2020}, } @article{7933, abstract = {We study a mobile quantum impurity, possessing internal rotational degrees of freedom, confined to a ring in the presence of a many-particle bosonic bath. By considering the recently introduced rotating polaron problem, we define the Hamiltonian and examine the energy spectrum. The weak-coupling regime is studied by means of a variational ansatz in the truncated Fock space. The corresponding spectrum indicates that there emerges a coupling between the internal and orbital angular momenta of the impurity as a consequence of the phonon exchange. We interpret the coupling as a phonon-mediated spin-orbit coupling and quantify it by using a correlation function between the internal and the orbital angular momentum operators. The strong-coupling regime is investigated within the Pekar approach, and it is shown that the correlation function of the ground state shows a kink at a critical coupling, that is explained by a sharp transition from the noninteracting state to the states that exhibit strong interaction with the surroundings. The results might find applications in such fields as spintronics or topological insulators where spin-orbit coupling is of crucial importance.}, author = {Maslov, Mikhail and Lemeshko, Mikhail and Yakaboylu, Enderalp}, issn = {24699969}, journal = {Physical Review B}, number = {18}, publisher = {American Physical Society}, title = {{Synthetic spin-orbit coupling mediated by a bosonic environment}}, doi = {10.1103/PhysRevB.101.184104}, volume = {101}, year = {2020}, } @article{7942, abstract = {An understanding of the missing antinodal electronic excitations in the pseudogap state is essential for uncovering the physics of the underdoped cuprate high-temperature superconductors1,2,3,4,5,6. The majority of high-temperature experiments performed thus far, however, have been unable to discern whether the antinodal states are rendered unobservable due to their damping or whether they vanish due to their gapping7,8,9,10,11,12,13,14,15,16,17,18. Here, we distinguish between these two scenarios by using quantum oscillations to examine whether the small Fermi surface pocket, found to occupy only 2% of the Brillouin zone in the underdoped cuprates19,20,21,22,23,24, exists in isolation against a majority of completely gapped density of states spanning the antinodes, or whether it is thermodynamically coupled to a background of ungapped antinodal states. We find that quantum oscillations associated with the small Fermi surface pocket exhibit a signature sawtooth waveform characteristic of an isolated two-dimensional Fermi surface pocket25,26,27,28,29,30,31,32. This finding reveals that the antinodal states are destroyed by a hard gap that extends over the majority of the Brillouin zone, placing strong constraints on a drastic underlying origin of quasiparticle disappearance over almost the entire Brillouin zone in the pseudogap regime7,8,9,10,11,12,13,14,15,16,17,18.}, author = {Hartstein, Máté and Hsu, Yu Te and Modic, Kimberly A and Porras, Juan and Loew, Toshinao and Tacon, Matthieu Le and Zuo, Huakun and Wang, Jinhua and Zhu, Zengwei and Chan, Mun K. and Mcdonald, Ross D. and Lonzarich, Gilbert G. and Keimer, Bernhard and Sebastian, Suchitra E. and Harrison, Neil}, issn = {17452481}, journal = {Nature Physics}, pages = {841--847}, publisher = {Springer Nature}, title = {{Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors}}, doi = {10.1038/s41567-020-0910-0}, volume = {16}, year = {2020}, } @article{7948, abstract = {In agricultural systems, nitrate is the main source of nitrogen available for plants. Besides its role as a nutrient, nitrate has been shown to act as a signal molecule for plant growth, development and stress responses. In Arabidopsis, the NRT1.1 nitrate transceptor represses lateral root (LR) development at low nitrate availability by promoting auxin basipetal transport out of the LR primordia (LRPs). In addition, our present study shows that NRT1.1 acts as a negative regulator of the TAR2 auxin biosynthetic gene expression in the root stele. This is expected to repress local auxin biosynthesis and thus to reduce acropetal auxin supply to the LRPs. Moreover, NRT1.1 also negatively affects expression of the LAX3 auxin influx carrier, thus preventing cell wall remodeling required for overlying tissues separation during LRP emergence. Both NRT1.1-mediated repression of TAR2 and LAX3 are suppressed at high nitrate availability, resulting in the nitrate induction of TAR2 and LAX3 expression that is required for optimal stimulation of LR development by nitrate. Altogether, our results indicate that the NRT1.1 transceptor coordinately controls several crucial auxin-associated processes required for LRP development, and as a consequence that NRT1.1 plays a much more integrated role than previously anticipated in regulating the nitrate response of root system architecture.}, author = {Maghiaoui, A and Bouguyon, E and Cuesta, Candela and Perrine-Walker, F and Alcon, C and Krouk, G and Benková, Eva and Nacry, P and Gojon, A and Bach, L}, issn = {1460-2431}, journal = {Journal of Experimental Botany}, number = {15}, pages = {4480--4494}, publisher = {Oxford University Press}, title = {{The Arabidopsis NRT1.1 transceptor coordinately controls auxin biosynthesis and transport to regulate root branching in response to nitrate}}, doi = {10.1093/jxb/eraa242}, volume = {71}, year = {2020}, } @article{7940, abstract = {We prove that the Yangian associated to an untwisted symmetric affine Kac–Moody Lie algebra is isomorphic to the Drinfeld double of a shuffle algebra. The latter is constructed in [YZ14] as an algebraic formalism of cohomological Hall algebras. As a consequence, we obtain the Poincare–Birkhoff–Witt (PBW) theorem for this class of affine Yangians. Another independent proof of the PBW theorem is given recently by Guay, Regelskis, and Wendlandt [GRW18].}, author = {Yang, Yaping and Zhao, Gufang}, issn = {1531586X}, journal = {Transformation Groups}, pages = {1371--1385}, publisher = {Springer Nature}, title = {{The PBW theorem for affine Yangians}}, doi = {10.1007/s00031-020-09572-6}, volume = {25}, year = {2020}, } @misc{9708, abstract = {This research data supports 'Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors'. A Readme file for plotting each figure is provided.}, author = {Hartstein, Mate and Hsu, Yu-Te and Modic, Kimberly A and Porras, Juan and Loew, Toshinao and Le Tacon, Matthieu and Zuo, Huakun and Wang, Jinhua and Zhu, Zengwei and Chan, Mun and McDonald, Ross and Lonzarich, Gilbert and Keimer, Bernhard and Sebastian, Suchitra and Harrison, Neil}, publisher = {Apollo - University of Cambridge}, title = {{Accompanying dataset for 'Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors'}}, doi = {10.17863/cam.50169}, year = {2020}, } @inproceedings{7955, abstract = {Simple stochastic games are turn-based 2½-player games with a reachability objective. The basic question asks whether one player can ensure reaching a given target with at least a given probability. A natural extension is games with a conjunction of such conditions as objective. Despite a plethora of recent results on the analysis of systems with multiple objectives, the decidability of this basic problem remains open. In this paper, we present an algorithm approximating the Pareto frontier of the achievable values to a given precision. Moreover, it is an anytime algorithm, meaning it can be stopped at any time returning the current approximation and its error bound.}, author = {Ashok, Pranav and Chatterjee, Krishnendu and Kretinsky, Jan and Weininger, Maximilian and Winkler, Tobias}, booktitle = {Proceedings of the 35th Annual ACM/IEEE Symposium on Logic in Computer Science }, isbn = {9781450371049}, location = {Saarbrücken, Germany}, pages = {102--115}, publisher = {Association for Computing Machinery}, title = {{Approximating values of generalized-reachability stochastic games}}, doi = {10.1145/3373718.3394761}, year = {2020}, } @article{7957, abstract = {Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.}, author = {Parenti, Ilaria and Garcia Rabaneda, Luis E and Schön, Hanna and Novarino, Gaia}, issn = {1878108X}, journal = {Trends in Neurosciences}, number = {8}, pages = {608--621}, publisher = {Elsevier}, title = {{Neurodevelopmental disorders: From genetics to functional pathways}}, doi = {10.1016/j.tins.2020.05.004}, volume = {43}, year = {2020}, } @article{7960, abstract = {Let A={A1,…,An} be a family of sets in the plane. For 0≤i2b be integers. We prove that if each k-wise or (k+1)-wise intersection of sets from A has at most b path-connected components, which all are open, then fk+1=0 implies fk≤cfk−1 for some positive constant c depending only on b and k. These results also extend to two-dimensional compact surfaces.}, author = {Kalai, Gil and Patakova, Zuzana}, issn = {14320444}, journal = {Discrete and Computational Geometry}, pages = {304--323}, publisher = {Springer Nature}, title = {{Intersection patterns of planar sets}}, doi = {10.1007/s00454-020-00205-z}, volume = {64}, year = {2020}, } @article{7962, abstract = {A string graph is the intersection graph of a family of continuous arcs in the plane. The intersection graph of a family of plane convex sets is a string graph, but not all string graphs can be obtained in this way. We prove the following structure theorem conjectured by Janson and Uzzell: The vertex set of almost all string graphs on n vertices can be partitioned into five cliques such that some pair of them is not connected by any edge (n→∞). We also show that every graph with the above property is an intersection graph of plane convex sets. As a corollary, we obtain that almost all string graphs on n vertices are intersection graphs of plane convex sets.}, author = {Pach, János and Reed, Bruce and Yuditsky, Yelena}, issn = {14320444}, journal = {Discrete and Computational Geometry}, number = {4}, pages = {888--917}, publisher = {Springer Nature}, title = {{Almost all string graphs are intersection graphs of plane convex sets}}, doi = {10.1007/s00454-020-00213-z}, volume = {63}, year = {2020}, } @article{13460, abstract = {Binary interaction can cause stellar envelopes to be stripped, which significantly reduces the radius of the star. The orbit of a binary composed of a stripped star and a compact object can therefore be so tight that the gravitational radiation the system produces reaches frequencies accessible to the Laser Interferometer Space Antenna (LISA). Two such stripped stars in tight orbits with white dwarfs are known so far (ZTF J2130+4420 and CD−30°11223), but many more are expected to exist. These binaries provide important constraints for binary evolution models and may be used as LISA verification sources. We develop a Monte Carlo code that uses detailed evolutionary models to simulate the Galactic population of stripped stars in tight orbits with either neutron star or white dwarf companions. We predict 0–100 stripped star + white dwarf binaries and 0–4 stripped star + neutron star binaries with a signal-to-noise ratio >5 after 10 yr of observations with LISA. More than 90% of these binaries are expected to show large radial velocity shifts of ≳200 $\,\mathrm{km}\,{{\rm{s}}}^{-1}$, which are spectroscopically detectable. Photometric variability due to tidal deformation of the stripped star is also expected and has been observed in ZTF J2130+4420 and CD−30°11223. In addition, the stripped star + neutron star binaries are expected to be X-ray bright with LX ≳ 1033–1036 $\,\mathrm{erg}\,{{\rm{s}}}^{-1}$. Our results show that stripped star binaries are promising multimessenger sources for the upcoming electromagnetic and gravitational wave facilities.}, author = {Götberg, Ylva Louise Linsdotter and Korol, V. and Lamberts, A. and Kupfer, T. and Breivik, K. and Ludwig, B. and Drout, M. R.}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {1}, publisher = {American Astronomical Society}, title = {{Stars stripped in binaries: The living gravitational-wave sources}}, doi = {10.3847/1538-4357/abbda5}, volume = {904}, year = {2020}, } @article{7999, abstract = {Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal. }, author = {Trejo Banos, D and McCartney, DL and Patxot, M and Anchieri, L and Battram, T and Christiansen, C and Costeira, R and Walker, RM and Morris, SW and Campbell, A and Zhang, Q and Porteous, DJ and McRae, AF and Wray, NR and Visscher, PM and Haley, CS and Evans, KL and Deary, IJ and McIntosh, AM and Hemani, G and Bell, JT and Marioni, RE and Robinson, Matthew Richard}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Bayesian reassessment of the epigenetic architecture of complex traits}}, doi = {10.1038/s41467-020-16520-1}, volume = {11}, year = {2020}, } @article{7995, abstract = {When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple‐effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis , occur in North Atlantic rocky‐shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size‐assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.}, author = {Perini, Samuel and Rafajlović, Marina and Westram, Anja M and Johannesson, Kerstin and Butlin, Roger K.}, issn = {15585646}, journal = {Evolution}, number = {7}, pages = {1482--1497}, publisher = {Wiley}, title = {{Assortative mating, sexual selection, and their consequences for gene flow in Littorina}}, doi = {10.1111/evo.14027}, volume = {74}, year = {2020}, } @misc{8809, abstract = {When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple-effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis, occur in North Atlantic rocky-shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size-assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively-sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.}, author = {Perini, Samuel and Rafajlovic, Marina and Westram, Anja M and Johannesson, Kerstin and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Assortative mating, sexual selection and their consequences for gene flow in Littorina}}, doi = {10.5061/dryad.qrfj6q5cn}, year = {2020}, } @article{8001, abstract = {Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.}, author = {Vandael, David H and Borges Merjane, Carolina and Zhang, Xiaomin and Jonas, Peter M}, issn = {10974199}, journal = {Neuron}, number = {3}, pages = {509--521}, publisher = {Elsevier}, title = {{Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation}}, doi = {10.1016/j.neuron.2020.05.013}, volume = {107}, year = {2020}, } @article{13998, abstract = {The interaction of strong near-infrared (NIR) laser pulses with wide-bandgap dielectrics produces high harmonics in the extreme ultraviolet (XUV) wavelength range. These observations have opened up the possibility of attosecond metrology in solids, which would benefit from a precise measurement of the emission times of individual harmonics with respect to the NIR laser field. Here we show that, when high-harmonics are detected from the input surface of a magnesium oxide crystal, a bichromatic probing of the XUV emission shows a clear synchronization largely consistent with a semiclassical model of electron–hole recollisions in bulk solids. On the other hand, the bichromatic spectrogram of harmonics originating from the exit surface of the 200 μm-thick crystal is strongly modified, indicating the influence of laser field distortions during propagation. Our tracking of sub-cycle electron and hole re-collisions at XUV energies is relevant to the development of solid-state sources of attosecond pulses.}, author = {Vampa, Giulio and Lu, Jian and You, Yong Sing and Baykusheva, Denitsa Rangelova and Wu, Mengxi and Liu, Hanzhe and Schafer, Kenneth J and Gaarde, Mette B and Reis, David A and Ghimire, Shambhu}, issn = {1361-6455}, journal = {Journal of Physics B: Atomic, Molecular and Optical Physics}, keywords = {Condensed Matter Physics, Atomic and Molecular Physics, and Optics}, number = {14}, publisher = {IOP Publishing}, title = {{Attosecond synchronization of extreme ultraviolet high harmonics from crystals}}, doi = {10.1088/1361-6455/ab8e56}, volume = {53}, year = {2020}, } @article{8038, abstract = {Microelectromechanical systems and integrated photonics provide the basis for many reliable and compact circuit elements in modern communication systems. Electro-opto-mechanical devices are currently one of the leading approaches to realize ultra-sensitive, low-loss transducers for an emerging quantum information technology. Here we present an on-chip microwave frequency converter based on a planar aluminum on silicon nitride platform that is compatible with slot-mode coupled photonic crystal cavities. We show efficient frequency conversion between two propagating microwave modes mediated by the radiation pressure interaction with a metalized dielectric nanobeam oscillator. We achieve bidirectional coherent conversion with a total device efficiency of up to ~60%, a dynamic range of 2 × 10^9 photons/s and an instantaneous bandwidth of up to 1.7 kHz. A high fidelity quantum state transfer would be possible if the drive dependent output noise of currently ~14 photons s^−1 Hz^−1 is further reduced. Such a silicon nitride based transducer is in situ reconfigurable and could be used for on-chip classical and quantum signal routing and filtering, both for microwave and hybrid microwave-optical applications.}, author = {Fink, Johannes M and Kalaee, M. and Norte, R. and Pitanti, A. and Painter, O.}, issn = {20589565}, journal = {Quantum Science and Technology}, number = {3}, publisher = {IOP Publishing}, title = {{Efficient microwave frequency conversion mediated by a photonics compatible silicon nitride nanobeam oscillator}}, doi = {10.1088/2058-9565/ab8dce}, volume = {5}, year = {2020}, } @article{8037, abstract = {Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such perturbations interact with subsequent evolutionary adaptation to the drug? Here, we show that strong epistasis between resistance mutations and systematically identified genes can be exploited to control spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform that tightly controls population size and selection pressure. We find a global diminishing-returns epistasis pattern: strains that are initially more sensitive generally undergo larger resistance gains. However, some gene deletion strains deviate from this general trend and curtail the evolvability of resistance, including deletions of genes for membrane transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force evolution on inferior mutational paths, not explored in the wild type, and some of these essentially block resistance evolution. This effect is due to strong negative epistasis with resistance mutations. The identified genes and cellular functions provide potential targets for development of adjuvants that may block spontaneous resistance evolution when combined with antibiotics.}, author = {Lukacisinova, Marta and Fernando, Booshini and Bollenbach, Mark Tobias}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Highly parallel lab evolution reveals that epistasis can curb the evolution of antibiotic resistance}}, doi = {10.1038/s41467-020-16932-z}, volume = {11}, year = {2020}, } @article{8036, abstract = {When tiny soft ferromagnetic particles are placed along a liquid interface and exposed to a vertical magnetic field, the balance between capillary attraction and magnetic repulsion leads to self-organization into well-defined patterns. Here, we demonstrate experimentally that precessing magnetic fields induce metachronal waves on the periphery of these assemblies, similar to the ones observed in ciliates and some arthropods. The outermost layer of particles behaves like an array of cilia or legs whose sequential movement causes a net and controllable locomotion. This bioinspired many-particle swimming strategy is effective even at low Reynolds number, using only spatially uniform fields to generate the waves.}, author = {Collard, Ylona and Grosjean, Galien M and Vandewalle, Nicolas}, issn = {23993650}, journal = {Communications Physics}, publisher = {Springer Nature}, title = {{Magnetically powered metachronal waves induce locomotion in self-assemblies}}, doi = {10.1038/s42005-020-0380-9}, volume = {3}, year = {2020}, } @article{8043, abstract = {With decreasing Reynolds number, Re, turbulence in channel flow becomes spatio-temporally intermittent and self-organises into solitary stripes oblique to the mean flow direction. We report here the existence of localised nonlinear travelling wave solutions of the Navier–Stokes equations possessing this obliqueness property. Such solutions are identified numerically using edge tracking coupled with arclength continuation. All solutions emerge in saddle-node bifurcations at values of Re lower than the non-localised solutions. Relative periodic orbit solutions bifurcating from branches of travelling waves have also been computed. A complete parametric study is performed, including their stability, the investigation of their large-scale flow, and the robustness to changes of the numerical domain.}, author = {Paranjape, Chaitanya S and Duguet, Yohann and Hof, Björn}, issn = {14697645}, journal = {Journal of Fluid Mechanics}, publisher = {Cambridge University Press}, title = {{Oblique stripe solutions of channel flow}}, doi = {10.1017/jfm.2020.322}, volume = {897}, year = {2020}, } @misc{9326, abstract = {The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol forma design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.}, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun and Dehez, Francois and Shekhar, Mrinal and Gunner, M. R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, publisher = {American Chemical Society}, title = {{Charge transfer and chemo-mechanical coupling in respiratory complex I}}, doi = {10.1021/jacs.9b13450.s002}, year = {2020}, } @article{8042, abstract = {We consider systems of N bosons in a box of volume one, interacting through a repulsive two-body potential of the form κN3β−1V(Nβx). For all 0<β<1, and for sufficiently small coupling constant κ>0, we establish the validity of Bogolyubov theory, identifying the ground state energy and the low-lying excitation spectrum up to errors that vanish in the limit of large N.}, author = {Boccato, Chiara and Brennecke, Christian and Cenatiempo, Serena and Schlein, Benjamin}, issn = {14359855}, journal = {Journal of the European Mathematical Society}, number = {7}, pages = {2331--2403}, publisher = {European Mathematical Society}, title = {{The excitation spectrum of Bose gases interacting through singular potentials}}, doi = {10.4171/JEMS/966}, volume = {22}, year = {2020}, } @article{8093, abstract = {Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment. Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo. Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system. Conclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.}, author = {Hippe, Andreas and Braun, Stephan Alexander and Oláh, Péter and Gerber, Peter Arne and Schorr, Anne and Seeliger, Stephan and Holtz, Stephanie and Jannasch, Katharina and Pivarcsi, Andor and Buhren, Bettina and Schrumpf, Holger and Kislat, Andreas and Bünemann, Erich and Steinhoff, Martin and Fischer, Jens and Lira, Sérgio A. and Boukamp, Petra and Hevezi, Peter and Stoecklein, Nikolas Hendrik and Hoffmann, Thomas and Alves, Frauke and Sleeman, Jonathan and Bauer, Thomas and Klufa, Jörg and Amberg, Nicole and Sibilia, Maria and Zlotnik, Albert and Müller-Homey, Anja and Homey, Bernhard}, issn = {1532-1827}, journal = {British Journal of Cancer}, pages = {942--954}, publisher = {Springer Nature}, title = {{EGFR/Ras-induced CCL20 production modulates the tumour microenvironment}}, doi = {10.1038/s41416-020-0943-2}, volume = {123}, year = {2020}, } @article{8091, abstract = {In the setting of the fractional quantum Hall effect we study the effects of strong, repulsive two-body interaction potentials of short range. We prove that Haldane’s pseudo-potential operators, including their pre-factors, emerge as mathematically rigorous limits of such interactions when the range of the potential tends to zero while its strength tends to infinity. In a common approach the interaction potential is expanded in angular momentum eigenstates in the lowest Landau level, which amounts to taking the pre-factors to be the moments of the potential. Such a procedure is not appropriate for very strong interactions, however, in particular not in the case of hard spheres. We derive the formulas valid in the short-range case, which involve the scattering lengths of the interaction potential in different angular momentum channels rather than its moments. Our results hold for bosons and fermions alike and generalize previous results in [6], which apply to bosons in the lowest angular momentum channel. Our main theorem asserts the convergence in a norm-resolvent sense of the Hamiltonian on the whole Hilbert space, after appropriate energy scalings, to Hamiltonians with contact interactions in the lowest Landau level.}, author = {Seiringer, Robert and Yngvason, Jakob}, issn = {15729613}, journal = {Journal of Statistical Physics}, pages = {448--464}, publisher = {Springer}, title = {{Emergence of Haldane pseudo-potentials in systems with short-range interactions}}, doi = {10.1007/s10955-020-02586-0}, volume = {181}, year = {2020}, } @article{8077, abstract = {The projection methods with vanilla inertial extrapolation step for variational inequalities have been of interest to many authors recently due to the improved convergence speed contributed by the presence of inertial extrapolation step. However, it is discovered that these projection methods with inertial steps lose the Fejér monotonicity of the iterates with respect to the solution, which is being enjoyed by their corresponding non-inertial projection methods for variational inequalities. This lack of Fejér monotonicity makes projection methods with vanilla inertial extrapolation step for variational inequalities not to converge faster than their corresponding non-inertial projection methods at times. Also, it has recently been proved that the projection methods with vanilla inertial extrapolation step may provide convergence rates that are worse than the classical projected gradient methods for strongly convex functions. In this paper, we introduce projection methods with alternated inertial extrapolation step for solving variational inequalities. We show that the sequence of iterates generated by our methods converges weakly to a solution of the variational inequality under some appropriate conditions. The Fejér monotonicity of even subsequence is recovered in these methods and linear rate of convergence is obtained. The numerical implementations of our methods compared with some other inertial projection methods show that our method is more efficient and outperforms some of these inertial projection methods.}, author = {Shehu, Yekini and Iyiola, Olaniyi S.}, issn = {0168-9274}, journal = {Applied Numerical Mathematics}, pages = {315--337}, publisher = {Elsevier}, title = {{Projection methods with alternating inertial steps for variational inequalities: Weak and linear convergence}}, doi = {10.1016/j.apnum.2020.06.009}, volume = {157}, year = {2020}, } @article{8133, abstract = {The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn’s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.}, author = {Hillary, Robert F. and Trejo-Banos, Daniel and Kousathanas, Athanasios and Mccartney, Daniel L. and Harris, Sarah E. and Stevenson, Anna J. and Patxot, Marion and Ojavee, Sven Erik and Zhang, Qian and Liewald, David C. and Ritchie, Craig W. and Evans, Kathryn L. and Tucker-Drob, Elliot M. and Wray, Naomi R. and Mcrae, Allan F. and Visscher, Peter M. and Deary, Ian J. and Robinson, Matthew Richard and Marioni, Riccardo E.}, issn = {1756994X}, journal = {Genome Medicine}, number = {1}, publisher = {Springer Nature}, title = {{Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults}}, doi = {10.1186/s13073-020-00754-1}, volume = {12}, year = {2020}, } @article{8127, abstract = {Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.}, author = {Gonçalves, Pedro J. and Lueckmann, Jan-Matthis and Deistler, Michael and Nonnenmacher, Marcel and Öcal, Kaan and Bassetto, Giacomo and Chintaluri, Chaitanya and Podlaski, William F. and Haddad, Sara A. and Vogels, Tim P and Greenberg, David S. and Macke, Jakob H.}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Training deep neural density estimators to identify mechanistic models of neural dynamics}}, doi = {10.7554/eLife.56261}, volume = {9}, year = {2020}, } @article{8126, abstract = {Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.}, author = {Agnes, Everton J. and Luppi, Andrea I. and Vogels, Tim P}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {50}, pages = {9634--9649}, publisher = {Society for Neuroscience}, title = {{Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields}}, doi = {10.1523/JNEUROSCI.0276-20.2020}, volume = {40}, year = {2020}, } @misc{9706, abstract = {Additional file 2: Supplementary Tables. The association of pre-adjusted protein levels with biological and technical covariates. Protein levels were adjusted for age, sex, array plate and four genetic principal components (population structure) prior to analyses. Significant associations are emboldened. (Table S1). pQTLs associated with inflammatory biomarker levels from Bayesian penalised regression model (Posterior Inclusion Probability > 95%). (Table S2). All pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S3). Summary of lambda values relating to ordinary least squares GWAS and EWAS performed on inflammatory protein levels (n = 70) in Lothian Birth Cohort 1936 study. (Table S4). Conditionally significant pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S5). Comparison of variance explained by ordinary least squares and Bayesian penalised regression models for concordantly identified SNPs. (Table S6). Estimate of heritability for blood protein levels as well as proportion of variance explained attributable to different prior mixtures. (Table S7). Comparison of heritability estimates from Ahsan et al. (maximum likelihood) and Hillary et al. (Bayesian penalised regression). (Table S8). List of concordant SNPs identified by linear model and Bayesian penalised regression and whether they have been previously identified as eQTLs. (Table S9). Bayesian tests of colocalisation for cis pQTLs and cis eQTLs. (Table S10). Sherlock algorithm: Genes whose expression are putatively associated with circulating inflammatory proteins that harbour pQTLs. (Table S11). CpGs associated with inflammatory protein biomarkers as identified by Bayesian model (Bayesian model; Posterior Inclusion Probability > 95%). (Table S12). CpGs associated with inflammatory protein biomarkers as identified by linear model (limma) at P < 5.14 × 10− 10. (Table S13). CpGs associated with inflammatory protein biomarkers as identified by mixed linear model (OSCA) at P < 5.14 × 10− 10. (Table S14). Estimate of variance explained for blood protein levels by DNA methylation as well as proportion of explained attributable to different prior mixtures - BayesR+. (Table S15). Comparison of variance in protein levels explained by genome-wide DNA methylation data by mixed linear model (OSCA) and Bayesian penalised regression model (BayesR+). (Table S16). Variance in circulating inflammatory protein biomarker levels explained by common genetic and methylation data (joint and conditional estimates from BayesR+). Ordered by combined variance explained by genetic and epigenetic data - smallest to largest. Significant results from t-tests comparing distributions for variance explained by methylation or genetics alone versus combined estimate are emboldened. (Table S17). Genetic and epigenetic factors identified by BayesR+ when conditioning on all SNPs and CpGs together. (Table S18). Mendelian Randomisation analyses to assess whether proteins with concordantly identified genetic signals are causally associated with Alzheimer’s disease risk. (Table S19).}, author = {Hillary, Robert F. and Trejo-Banos, Daniel and Kousathanas, Athanasios and McCartney, Daniel L. and Harris, Sarah E. and Stevenson, Anna J. and Patxot, Marion and Ojavee, Sven Erik and Zhang, Qian and Liewald, David C. and Ritchie, Craig W. and Evans, Kathryn L. and Tucker-Drob, Elliot M. and Wray, Naomi R. and McRae, Allan F. and Visscher, Peter M. and Deary, Ian J. and Robinson, Matthew Richard and Marioni, Riccardo E. }, publisher = {Springer Nature}, title = {{Additional file 2 of multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults}}, doi = {10.6084/m9.figshare.12629697.v1}, year = {2020}, } @article{8134, abstract = {We prove an upper bound on the free energy of a two-dimensional homogeneous Bose gas in the thermodynamic limit. We show that for a2ρ ≪ 1 and βρ ≳ 1, the free energy per unit volume differs from the one of the non-interacting system by at most 4πρ2|lna2ρ|−1(2−[1−βc/β]2+) to leading order, where a is the scattering length of the two-body interaction potential, ρ is the density, β is the inverse temperature, and βc is the inverse Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity. In combination with the corresponding matching lower bound proved by Deuchert et al. [Forum Math. Sigma 8, e20 (2020)], this shows equality in the asymptotic expansion.}, author = {Mayer, Simon and Seiringer, Robert}, issn = {00222488}, journal = {Journal of Mathematical Physics}, number = {6}, publisher = {AIP Publishing}, title = {{The free energy of the two-dimensional dilute Bose gas. II. Upper bound}}, doi = {10.1063/5.0005950}, volume = {61}, year = {2020}, } @article{8162, abstract = {In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity.}, author = {Laukoter, Susanne and Pauler, Florian and Beattie, Robert J and Amberg, Nicole and Hansen, Andi H and Streicher, Carmen and Penz, Thomas and Bock, Christoph and Hippenmeyer, Simon}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1160--1179.e9}, publisher = {Elsevier}, title = {{Cell-type specificity of genomic imprinting in cerebral cortex}}, doi = {10.1016/j.neuron.2020.06.031}, volume = {107}, year = {2020}, } @article{8138, abstract = {Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.}, author = {Zhang, J and Mazur, E and Balla, J and Gallei, Michelle C and Kalousek, P and Medveďová, Z and Li, Y and Wang, Y and Prat, Tomas and Vasileva, Mina K and Reinöhl, V and Procházka, S and Halouzka, R and Tarkowski, P and Luschnig, C and Brewer, PB and Friml, Jiří}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, pages = {3508}, publisher = {Springer Nature}, title = {{Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization}}, doi = {10.1038/s41467-020-17252-y}, volume = {11}, year = {2020}, } @article{8168, abstract = {Speciation, that is, the evolution of reproductive barriers eventually leading to complete isolation, is a crucial process generating biodiversity. Recent work has contributed much to our understanding of how reproductive barriers begin to evolve, and how they are maintained in the face of gene flow. However, little is known about the transition from partial to strong reproductive isolation (RI) and the completion of speciation. We argue that the evolution of strong RI is likely to involve different processes, or new interactions among processes, compared with the evolution of the first reproductive barriers. Transition to strong RI may be brought about by changing external conditions, for example, following secondary contact. However, the increasing levels of RI themselves create opportunities for new barriers to evolve and, and interaction or coupling among barriers. These changing processes may depend on genomic architecture and leave detectable signals in the genome. We outline outstanding questions and suggest more theoretical and empirical work, considering both patterns and processes associated with strong RI, is needed to understand how speciation is completed.}, author = {Kulmuni, Jonna and Butlin, Roger K. and Lucek, Kay and Savolainen, Vincent and Westram, Anja M}, issn = {1471-2970}, journal = {Philosophical Transactions of the Royal Society. Series B: Biological sciences}, number = {1806}, publisher = {The Royal Society}, title = {{Towards the completion of speciation: The evolution of reproductive isolation beyond the first barriers}}, doi = {10.1098/rstb.2019.0528}, volume = {375}, year = {2020}, } @article{8167, abstract = {The evolution of strong reproductive isolation (RI) is fundamental to the origins and maintenance of biological diversity, especially in situations where geographical distributions of taxa broadly overlap. But what is the history behind strong barriers currently acting in sympatry? Using whole-genome sequencing and single nucleotide polymorphism genotyping, we inferred (i) the evolutionary relationships, (ii) the strength of RI, and (iii) the demographic history of divergence between two broadly sympatric taxa of intertidal snail. Despite being cryptic, based on external morphology, Littorina arcana and Littorina saxatilis differ in their mode of female reproduction (egg-laying versus brooding), which may generate a strong post-zygotic barrier. We show that egg-laying and brooding snails are closely related, but genetically distinct. Genotyping of 3092 snails from three locations failed to recover any recent hybrid or backcrossed individuals, confirming that RI is strong. There was, however, evidence for a very low level of asymmetrical introgression, suggesting that isolation remains incomplete. The presence of strong, asymmetrical RI was further supported by demographic analysis of these populations. Although the taxa are currently broadly sympatric, demographic modelling suggests that they initially diverged during a short period of geographical separation involving very low gene flow. Our study suggests that some geographical separation may kick-start the evolution of strong RI, facilitating subsequent coexistence of taxa in sympatry. The strength of RI needed to achieve sympatry and the subsequent effect of sympatry on RI remain open questions.}, author = {Stankowski, Sean and Westram, Anja M and Zagrodzka, Zuzanna B. and Eyres, Isobel and Broquet, Thomas and Johannesson, Kerstin and Butlin, Roger K.}, issn = {1471-2970}, journal = {Philosophical Transactions of the Royal Society. Series B: Biological Sciences}, number = {1806}, publisher = {The Royal Society}, title = {{The evolution of strong reproductive isolation between sympatric intertidal snails}}, doi = {10.1098/rstb.2019.0545}, volume = {375}, year = {2020}, } @article{8170, abstract = {Alignment of OCS, CS2, and I2 molecules embedded in helium nanodroplets is measured as a function of time following rotational excitation by a nonresonant, comparatively weak ps laser pulse. The distinct peaks in the power spectra, obtained by Fourier analysis, are used to determine the rotational, B, and centrifugal distortion, D, constants. For OCS, B and D match the values known from IR spectroscopy. For CS2 and I2, they are the first experimental results reported. The alignment dynamics calculated from the gas-phase rotational Schrödinger equation, using the experimental in-droplet B and D values, agree in detail with the measurement for all three molecules. The rotational spectroscopy technique for molecules in helium droplets introduced here should apply to a range of molecules and complexes.}, author = {Chatterley, Adam S. and Christiansen, Lars and Schouder, Constant A. and Jørgensen, Anders V. and Shepperson, Benjamin and Cherepanov, Igor and Bighin, Giacomo and Zillich, Robert E. and Lemeshko, Mikhail and Stapelfeldt, Henrik}, issn = {10797114}, journal = {Physical Review Letters}, number = {1}, publisher = {American Physical Society}, title = {{Rotational coherence spectroscopy of molecules in Helium nanodroplets: Reconciling the time and the frequency domains}}, doi = {10.1103/PhysRevLett.125.013001}, volume = {125}, year = {2020}, } @inproceedings{8194, abstract = {Fixed-point arithmetic is a popular alternative to floating-point arithmetic on embedded systems. Existing work on the verification of fixed-point programs relies on custom formalizations of fixed-point arithmetic, which makes it hard to compare the described techniques or reuse the implementations. In this paper, we address this issue by proposing and formalizing an SMT theory of fixed-point arithmetic. We present an intuitive yet comprehensive syntax of the fixed-point theory, and provide formal semantics for it based on rational arithmetic. We also describe two decision procedures for this theory: one based on the theory of bit-vectors and the other on the theory of reals. We implement the two decision procedures, and evaluate our implementations using existing mature SMT solvers on a benchmark suite we created. Finally, we perform a case study of using the theory we propose to verify properties of quantized neural networks.}, author = {Baranowski, Marek and He, Shaobo and Lechner, Mathias and Nguyen, Thanh Son and Rakamarić, Zvonimir}, booktitle = {Automated Reasoning}, isbn = {9783030510732}, issn = {16113349}, location = {Paris, France}, pages = {13--31}, publisher = {Springer Nature}, title = {{An SMT theory of fixed-point arithmetic}}, doi = {10.1007/978-3-030-51074-9_2}, volume = {12166}, year = {2020}, } @article{8220, abstract = {Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common (“universal”) functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings.}, author = {Corominas-Murtra, Bernat and Scheele, Colinda L.G.J. and Kishi, Kasumi and Ellenbroek, Saskia I.J. and Simons, Benjamin D. and Van Rheenen, Jacco and Hannezo, Edouard B}, issn = {10916490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {29}, pages = {16969--16975}, publisher = {National Academy of Sciences}, title = {{Stem cell lineage survival as a noisy competition for niche access}}, doi = {10.1073/pnas.1921205117}, volume = {117}, year = {2020}, } @article{8199, abstract = {We investigate a mechanism to transiently stabilize topological phenomena in long-lived quasi-steady states of isolated quantum many-body systems driven at low frequencies. We obtain an analytical bound for the lifetime of the quasi-steady states which is exponentially large in the inverse driving frequency. Within this lifetime, the quasi-steady state is characterized by maximum entropy subject to the constraint of fixed number of particles in the system's Floquet-Bloch bands. In such a state, all the non-universal properties of these bands are washed out, hence only the topological properties persist.}, author = {Gulden, Tobias and Berg, Erez and Rudner, Mark Spencer and Lindner, Netanel}, issn = {2542-4653}, journal = {SciPost Physics}, publisher = {SciPost Foundation}, title = {{Exponentially long lifetime of universal quasi-steady states in topological Floquet pumps}}, doi = {10.21468/scipostphys.9.1.015}, volume = {9}, year = {2020}, } @article{8261, abstract = {Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.}, author = {Zhang, Xiaomin and Schlögl, Alois and Jonas, Peter M}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1212--1225}, publisher = {Elsevier}, title = {{Selective routing of spatial information flow from input to output in hippocampal granule cells}}, doi = {10.1016/j.neuron.2020.07.006}, volume = {107}, year = {2020}, } @article{8268, abstract = {Modern scientific instruments produce vast amounts of data, which can overwhelm the processing ability of computer systems. Lossy compression of data is an intriguing solution, but comes with its own drawbacks, such as potential signal loss, and the need for careful optimization of the compression ratio. In this work, we focus on a setting where this problem is especially acute: compressive sensing frameworks for interferometry and medical imaging. We ask the following question: can the precision of the data representation be lowered for all inputs, with recovery guarantees and practical performance Our first contribution is a theoretical analysis of the normalized Iterative Hard Thresholding (IHT) algorithm when all input data, meaning both the measurement matrix and the observation vector are quantized aggressively. We present a variant of low precision normalized IHT that, under mild conditions, can still provide recovery guarantees. The second contribution is the application of our quantization framework to radio astronomy and magnetic resonance imaging. We show that lowering the precision of the data can significantly accelerate image recovery. We evaluate our approach on telescope data and samples of brain images using CPU and FPGA implementations achieving up to a 9x speedup with negligible loss of recovery quality.}, author = {Gurel, Nezihe Merve and Kara, Kaan and Stojanov, Alen and Smith, Tyler and Lemmin, Thomas and Alistarh, Dan-Adrian and Puschel, Markus and Zhang, Ce}, issn = {19410476}, journal = {IEEE Transactions on Signal Processing}, pages = {4268--4282}, publisher = {IEEE}, title = {{Compressive sensing using iterative hard thresholding with low precision data representation: Theory and applications}}, doi = {10.1109/TSP.2020.3010355}, volume = {68}, year = {2020}, } @article{8101, abstract = {By rigorously accounting for mesoscale spatial correlations in donor/acceptor surface properties, we develop a scale-spanning model for same-material tribocharging. We find that mesoscale correlations affect not only the magnitude of charge transfer but also the fluctuations—suppressing otherwise overwhelming charge-transfer variability that is not observed experimentally. We furthermore propose a generic theoretical mechanism by which the mesoscale features might emerge, which is qualitatively consistent with other proposals in the literature.}, author = {Grosjean, Galien M and Wald, Sebastian and Sobarzo Ponce, Juan Carlos A and Waitukaitis, Scott R}, issn = {2475-9953}, journal = {Physical Review Materials}, keywords = {electric charge, tribocharging, soft matter, granular materials, polymers}, number = {8}, publisher = {American Physical Society}, title = {{Quantitatively consistent scale-spanning model for same-material tribocharging}}, doi = {10.1103/PhysRevMaterials.4.082602}, volume = {4}, year = {2020}, } @article{8325, abstract = {Let 𝐹:ℤ2→ℤ be the pointwise minimum of several linear functions. The theory of smoothing allows us to prove that under certain conditions there exists the pointwise minimal function among all integer-valued superharmonic functions coinciding with F “at infinity”. We develop such a theory to prove existence of so-called solitons (or strings) in a sandpile model, studied by S. Caracciolo, G. Paoletti, and A. Sportiello. Thus we made a step towards understanding the phenomena of the identity in the sandpile group for planar domains where solitons appear according to experiments. We prove that sandpile states, defined using our smoothing procedure, move changeless when we apply the wave operator (that is why we call them solitons), and can interact, forming triads and nodes. }, author = {Kalinin, Nikita and Shkolnikov, Mikhail}, issn = {14320916}, journal = {Communications in Mathematical Physics}, number = {9}, pages = {1649--1675}, publisher = {Springer Nature}, title = {{Sandpile solitons via smoothing of superharmonic functions}}, doi = {10.1007/s00220-020-03828-8}, volume = {378}, year = {2020}, } @article{8318, abstract = {Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.}, author = {Gutierrez-Fernandez, Javier and Kaszuba, Karol and Minhas, Gurdeep S. and Baradaran, Rozbeh and Tambalo, Margherita and Gallagher, David T. and Sazanov, Leonid A}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Key role of quinone in the mechanism of respiratory complex I}}, doi = {10.1038/s41467-020-17957-0}, volume = {11}, year = {2020}, } @article{8323, author = {Pach, János}, issn = {14320444}, journal = {Discrete and Computational Geometry}, pages = {571--574}, publisher = {Springer Nature}, title = {{A farewell to Ricky Pollack}}, doi = {10.1007/s00454-020-00237-5}, volume = {64}, year = {2020}, } @article{8336, abstract = {Plant hormone cytokinins are perceived by a subfamily of sensor histidine kinases (HKs), which via a two-component phosphorelay cascade activate transcriptional responses in the nucleus. Subcellular localization of the receptors proposed the endoplasmic reticulum (ER) membrane as a principal cytokinin perception site, while study of cytokinin transport pointed to the plasma membrane (PM)-mediated cytokinin signalling. Here, by detailed monitoring of subcellular localizations of the fluorescently labelled natural cytokinin probe and the receptor ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/AHK4) fused to GFP reporter, we show that pools of the ER-located cytokinin receptors can enter the secretory pathway and reach the PM in cells of the root apical meristem, and the cell plate of dividing meristematic cells. Brefeldin A (BFA) experiments revealed vesicular recycling of the receptor and its accumulation in BFA compartments. We provide a revised view on cytokinin signalling and the possibility of multiple sites of perception at PM and ER.}, author = {Kubiasova, Karolina and Montesinos López, Juan C and Šamajová, Olga and Nisler, Jaroslav and Mik, Václav and Semeradova, Hana and Plíhalová, Lucie and Novák, Ondřej and Marhavý, Peter and Cavallari, Nicola and Zalabák, David and Berka, Karel and Doležal, Karel and Galuszka, Petr and Šamaj, Jozef and Strnad, Miroslav and Benková, Eva and Plíhal, Ondřej and Spíchal, Lukáš}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Cytokinin fluoroprobe reveals multiple sites of cytokinin perception at plasma membrane and endoplasmic reticulum}}, doi = {10.1038/s41467-020-17949-0}, volume = {11}, year = {2020}, } @article{8337, abstract = {Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.}, author = {Antoniadi, Ioanna and Novák, Ondřej and Gelová, Zuzana and Johnson, Alexander J and Plíhal, Ondřej and Simerský, Radim and Mik, Václav and Vain, Thomas and Mateo-Bonmatí, Eduardo and Karady, Michal and Pernisová, Markéta and Plačková, Lenka and Opassathian, Korawit and Hejátko, Jan and Robert, Stéphanie and Friml, Jiří and Doležal, Karel and Ljung, Karin and Turnbull, Colin}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Cell-surface receptors enable perception of extracellular cytokinins}}, doi = {10.1038/s41467-020-17700-9}, volume = {11}, year = {2020}, } @misc{8067, abstract = {With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, lithium metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (polymeric and inorganic), Lithium-sulphur and Li-O2 (air) batteries. A particular attention is paid to review recent developments in regard of prototype manufacturing and current state-ofthe-art of these battery technologies with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7.}, author = {Varzi, Alberto and Thanner, Katharina and Scipioni, Roberto and Di Lecce, Daniele and Hassoun, Jusef and Dörfler, Susanne and Altheus, Holger and Kaskel, Stefan and Prehal, Christian and Freunberger, Stefan Alexander}, issn = {2664-1690}, keywords = {Battery, Lithium metal, Lithium-sulphur, Lithium-air, All-solid-state}, pages = {63}, publisher = {IST Austria}, title = {{Current status and future perspectives of Lithium metal batteries}}, doi = {10.15479/AT:ISTA:8067}, year = {2020}, } @article{8361, abstract = {With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, Li metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (inorganic and polymeric), Lithium–Sulfur (Li–S) and Lithium-O2 (air) batteries. A particular attention is paid to recent developments of these battery technologies and their current state with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7.}, author = {Varzi, Alberto and Thanner, Katharina and Scipioni, Roberto and Di Lecce, Daniele and Hassoun, Jusef and Dörfler, Susanne and Altheus, Holger and Kaskel, Stefan and Prehal, Christian and Freunberger, Stefan Alexander}, issn = {0378-7753}, journal = {Journal of Power Sources}, number = {12}, publisher = {Elsevier}, title = {{Current status and future perspectives of lithium metal batteries}}, doi = {10.1016/j.jpowsour.2020.228803}, volume = {480}, year = {2020}, } @unpublished{14028, abstract = {The present review addresses the technical advances and the theoretical developments to realize and rationalize attosecond-science experiments that reveal a new dynamical time scale (10−15-10−18 s), with a particular emphasis on molecular systems and the implications of attosecond processes for chemical dynamics. After a brief outline of the theoretical framework for treating non-perturbative phenomena in Section 2, we introduce the physical mechanisms underlying high-harmonic generation and attosecond technology. The relevant technological developments and experimental schemes are covered in Section 3. Throughout the remainder of the chapter, we report on selected applications in molecular attosecond physics, thereby addressing specific phenomena mediated by purely electronic dynamics: charge localization in molecular hydrogen, charge migration in biorelevant molecules, high-harmonic spectroscopy, and delays in molecular photoionization.}, author = {Baykusheva, Denitsa Rangelova and Wörner, Hans Jakob}, pages = {2002.02111}, title = {{Attosecond molecular spectroscopy and dynamics}}, doi = {10.48550/arXiv.2002.02111}, year = {2020}, } @article{8529, abstract = {Practical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a Vπ as low as 16 μV for sub-nanowatt pump powers. Without the associated optomechanical gain, we achieve a total (internal) pure conversion efficiency of up to 0.019% (1.6%), relevant for future noise-free operation on this qubit-compatible platform.}, author = {Arnold, Georg M and Wulf, Matthias and Barzanjeh, Shabir and Redchenko, Elena and Rueda Sanchez, Alfredo R and Hease, William J and Hassani, Farid and Fink, Johannes M}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Converting microwave and telecom photons with a silicon photonic nanomechanical interface}}, doi = {10.1038/s41467-020-18269-z}, volume = {11}, year = {2020}, } @article{8535, abstract = {We propose a method to enhance the visual detail of a water surface simulation. Our method works as a post-processing step which takes a simulation as input and increases its apparent resolution by simulating many detailed Lagrangian water waves on top of it. We extend linear water wave theory to work in non-planar domains which deform over time, and we discretize the theory using Lagrangian wave packets attached to spline curves. The method is numerically stable and trivially parallelizable, and it produces high frequency ripples with dispersive wave-like behaviors customized to the underlying fluid simulation.}, author = {Skrivan, Tomas and Soderstrom, Andreas and Johansson, John and Sprenger, Christoph and Museth, Ken and Wojtan, Christopher J}, issn = {15577368}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {Association for Computing Machinery}, title = {{Wave curves: Simulating Lagrangian water waves on dynamically deforming surfaces}}, doi = {10.1145/3386569.3392466}, volume = {39}, year = {2020}, } @article{8539, abstract = {Cohomological and K-theoretic stable bases originated from the study of quantum cohomology and quantum K-theory. Restriction formula for cohomological stable bases played an important role in computing the quantum connection of cotangent bundle of partial flag varieties. In this paper we study the K-theoretic stable bases of cotangent bundles of flag varieties. We describe these bases in terms of the action of the affine Hecke algebra and the twisted group algebra of KostantKumar. Using this algebraic description and the method of root polynomials, we give a restriction formula of the stable bases. We apply it to obtain the restriction formula for partial flag varieties. We also build a relation between the stable basis and the Casselman basis in the principal series representations of the Langlands dual group. As an application, we give a closed formula for the transition matrix between Casselman basis and the characteristic functions.}, author = {Su, C. and Zhao, Gufang and Zhong, C.}, issn = {0012-9593}, journal = {Annales Scientifiques de l'Ecole Normale Superieure}, number = {3}, pages = {663--671}, publisher = {Société Mathématique de France}, title = {{On the K-theory stable bases of the springer resolution}}, doi = {10.24033/asens.2431}, volume = {53}, year = {2020}, } @misc{13056, abstract = {This datasets comprises all data shown in plots of the submitted article "Converting microwave and telecom photons with a silicon photonic nanomechanical interface". Additional raw data are available from the corresponding author on reasonable request.}, author = {Arnold, Georg M and Wulf, Matthias and Barzanjeh, Shabir and Redchenko, Elena and Rueda Sanchez, Alfredo R and Hease, William J and Hassani, Farid and Fink, Johannes M}, publisher = {Zenodo}, title = {{Converting microwave and telecom photons with a silicon photonic nanomechanical interface}}, doi = {10.5281/ZENODO.3961561}, year = {2020}, } @article{8579, abstract = {Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells.}, author = {Andrei, Andreea and Öztürk, Yavuz and Khalfaoui-Hassani, Bahia and Rauch, Juna and Marckmann, Dorian and Trasnea, Petru Iulian and Daldal, Fevzi and Koch, Hans-Georg}, issn = {20770375}, journal = {Membranes}, number = {9}, publisher = {MDPI}, title = {{Cu homeostasis in bacteria: The ins and outs}}, doi = {10.3390/membranes10090242}, volume = {10}, year = {2020}, } @article{8592, abstract = {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.}, author = {Tian, Anhao and Kang, Bo and Li, Baizhou and Qiu, Biying and Jiang, Wenhong and Shao, Fangjie and Gao, Qingqing and Liu, Rui and Cai, Chengwei and Jing, Rui and Wang, Wei and Chen, Pengxiang and Liang, Qinghui and Bao, Lili and Man, Jianghong and Wang, Yan and Shi, Yu and Li, Jin and Yang, Minmin and Wang, Lisha and Zhang, Jianmin and Hippenmeyer, Simon and Zhu, Junming and Bian, Xiuwu and Wang, Ying‐Jie and Liu, Chong}, issn = {2198-3844}, journal = {Advanced Science}, keywords = {General Engineering, General Physics and Astronomy, General Materials Science, Medicine (miscellaneous), General Chemical Engineering, Biochemistry, Genetics and Molecular Biology (miscellaneous)}, number = {21}, publisher = {Wiley}, title = {{Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting}}, doi = {10.1002/advs.202001724}, volume = {7}, year = {2020}, } @article{8568, abstract = {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.}, author = {Prehal, Christian and Fitzek, Harald and Kothleitner, Gerald and Presser, Volker and Gollas, Bernhard and Freunberger, Stefan Alexander and Abbas, Qamar}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Persistent and reversible solid iodine electrodeposition in nanoporous carbons}}, doi = {10.1038/s41467-020-18610-6}, volume = {11}, year = {2020}, } @article{8643, abstract = {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.}, author = {Deichler, Alfonso and Carrasco, Denisse and Lopez-Jury, Luciana and Vega Zuniga, Tomas A and Marquez, Natalia and Mpodozis, Jorge and Marin, Gonzalo}, issn = {20452322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{A specialized reciprocal connectivity suggests a link between the mechanisms by which the superior colliculus and parabigeminal nucleus produce defensive behaviors in rodents}}, doi = {10.1038/s41598-020-72848-0}, volume = {10}, year = {2020}, } @article{8645, abstract = {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.}, author = {Esteban, Laura A and Lonishin, Lyubov R and Bobrovskiy, Daniil M and Leleytner, Gregory and Bogatyreva, Natalya S and Kondrashov, Fyodor and Ivankov, Dmitry N }, issn = {1460-2059}, journal = {Bioinformatics}, number = {6}, pages = {1960--1962}, publisher = {Oxford Academic}, title = {{HypercubeME: Two hundred million combinatorially complete datasets from a single experiment}}, doi = {10.1093/bioinformatics/btz841}, volume = {36}, year = {2020}, } @article{8597, abstract = {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.}, author = {Merrin, Jack}, issn = {14783975}, journal = {Physical Biology}, number = {6}, publisher = {IOP Publishing}, title = {{Differences in power law growth over time and indicators of COVID-19 pandemic progression worldwide}}, doi = {10.1088/1478-3975/abb2db}, volume = {17}, year = {2020}, } @article{8674, abstract = {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.}, author = {Henneberger, Christian and Bard, Lucie and Panatier, Aude and Reynolds, James P. and Kopach, Olga and Medvedev, Nikolay I. and Minge, Daniel and Herde, Michel K. and Anders, Stefanie and Kraev, Igor and Heller, Janosch P. and Rama, Sylvain and Zheng, Kaiyu and Jensen, Thomas P. and Sanchez-Romero, Inmaculada and Jackson, Colin J. and Janovjak, Harald L and Ottersen, Ole Petter and Nagelhus, Erlend Arnulf and Oliet, Stephane H.R. and Stewart, Michael G. and Nägerl, U. VAlentin and Rusakov, Dmitri A. }, issn = {10974199}, journal = {Neuron}, number = {5}, pages = {P919--936.E11}, publisher = {Elsevier}, title = {{LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia}}, doi = {10.1016/j.neuron.2020.08.030}, volume = {108}, year = {2020}, } @article{8652, abstract = {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.}, author = {Ghazaryan, Areg and Lemeshko, Mikhail and Volosniev, Artem}, issn = {2399-3650}, journal = {Communications Physics}, publisher = {Springer Nature}, title = {{Filtering spins by scattering from a lattice of point magnets}}, doi = {10.1038/s42005-020-00445-8}, volume = {3}, year = {2020}, } @article{8669, abstract = {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.}, author = {Sznurkowska, Magdalena K. and Hannezo, Edouard B and Azzarelli, Roberta and Chatzeli, Lemonia and Ikeda, Tatsuro and Yoshida, Shosei and Philpott, Anna and Simons, Benjamin D}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Tracing the cellular basis of islet specification in mouse pancreas}}, doi = {10.1038/s41467-020-18837-3}, volume = {11}, year = {2020}, } @article{8672, abstract = {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.}, author = {Chaigne, Agathe and Labouesse, Céline and White, Ian J. and Agnew, Meghan and Hannezo, Edouard B and Chalut, Kevin J. and Paluch, Ewa K.}, issn = {18781551}, journal = {Developmental Cell}, number = {2}, pages = {195--208}, publisher = {Elsevier}, title = {{Abscission couples cell division to embryonic stem cell fate}}, doi = {10.1016/j.devcel.2020.09.001}, volume = {55}, year = {2020}, } @article{8697, abstract = {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.}, author = {Fischer, Julian L and Kniely, Michael}, issn = {13616544}, journal = {Nonlinearity}, number = {11}, pages = {5733--5772}, publisher = {IOP Publishing}, title = {{Variance reduction for effective energies of random lattices in the Thomas-Fermi-von Weizsäcker model}}, doi = {10.1088/1361-6544/ab9728}, volume = {33}, year = {2020}, } @article{8680, abstract = {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.}, author = {Tsai, Tony Y.-C. and Sikora, Mateusz K and Xia, Peng and Colak-Champollion, Tugba and Knaut, Holger and Heisenberg, Carl-Philipp J and Megason, Sean G.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6512}, pages = {113--116}, publisher = {American Association for the Advancement of Science}, title = {{An adhesion code ensures robust pattern formation during tissue morphogenesis}}, doi = {10.1126/science.aba6637}, volume = {370}, year = {2020}, } @article{8670, abstract = {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)].}, author = {Zhang, Haonan}, issn = {00222488}, journal = {Journal of Mathematical Physics}, number = {10}, publisher = {AIP Publishing}, title = {{Equality conditions of data processing inequality for α-z Rényi relative entropies}}, doi = {10.1063/5.0022787}, volume = {61}, year = {2020}, } @article{8698, abstract = {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.}, author = {Maoz, Ori and Tkačik, Gašper and Esteki, Mohamad Saleh and Kiani, Roozbeh and Schneidman, Elad}, issn = {10916490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {40}, pages = {25066--25073}, publisher = {National Academy of Sciences}, title = {{Learning probabilistic neural representations with randomly connected circuits}}, doi = {10.1073/pnas.1912804117}, volume = {117}, year = {2020}, } @inproceedings{8704, abstract = {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.}, author = {Lechner, Mathias and Hasani, Ramin and Rus, Daniela and Grosu, Radu}, booktitle = {Proceedings - IEEE International Conference on Robotics and Automation}, isbn = {9781728173955}, issn = {10504729}, location = {Paris, France}, pages = {5446--5452}, publisher = {IEEE}, title = {{Gershgorin loss stabilizes the recurrent neural network compartment of an end-to-end robot learning scheme}}, doi = {10.1109/ICRA40945.2020.9196608}, year = {2020}, } @unpublished{14096, abstract = {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.}, author = {Jamie A. P. Law-Smith, Jamie A. P. Law-Smith and Everson, Rosa Wallace and Enrico Ramirez-Ruiz, Enrico Ramirez-Ruiz and Mink, Selma E. de and Son, Lieke A. C. van and Götberg, Ylva Louise Linsdotter and Zellmann, Stefan and Alejandro Vigna-Gómez, Alejandro Vigna-Gómez and Renzo, Mathieu and Wu, Samantha and Schrøder, Sophie L. and Foley, Ryan J. and Tenley Hutchinson-Smith, Tenley Hutchinson-Smith}, booktitle = {arXiv}, title = {{Successful common envelope ejection and binary neutron star formation in 3D hydrodynamics}}, doi = {10.48550/arXiv.2011.06630}, year = {2020}, } @article{8699, abstract = {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.}, author = {Paris, Eugenio and Tseng, Yi and Paerschke, Ekaterina and Zhang, Wenliang and Upton, Mary H and Efimenko, Anna and Rolfs, Katharina and McNally, Daniel E and Maurel, Laura and Naamneh, Muntaser and Caputo, Marco and Strocov, Vladimir N and Wang, Zhiming and Casa, Diego and Schneider, Christof W and Pomjakushina, Ekaterina and Wohlfeld, Krzysztof and Radovic, Milan and Schmitt, Thorsten}, issn = {10916490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {40}, pages = {24764--24770}, publisher = {National Academy of Sciences}, title = {{Strain engineering of the charge and spin-orbital interactions in Sr2IrO4}}, doi = {10.1073/pnas.2012043117}, volume = {117}, year = {2020}, } @article{8737, abstract = {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.}, author = {Kampjut, Domen and Sazanov, Leonid A}, issn = {10959203}, journal = {Science}, number = {6516}, publisher = {American Association for the Advancement of Science}, title = {{The coupling mechanism of mammalian respiratory complex I}}, doi = {10.1126/science.abc4209}, volume = {370}, year = {2020}, } @inproceedings{8722, abstract = {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.}, author = {Li, Shigang and Tal Ben-Nun, Tal Ben-Nun and Girolamo, Salvatore Di and Alistarh, Dan-Adrian and Hoefler, Torsten}, booktitle = {Proceedings of the 25th ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming}, location = {San Diego, CA, United States}, pages = {45--61}, publisher = {Association for Computing Machinery}, title = {{Taming unbalanced training workloads in deep learning with partial collective operations}}, doi = {10.1145/3332466.3374528}, year = {2020}, } @article{8744, abstract = {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.}, author = {Schulte, Linda and Mao, Jiafei and Reitz, Julian and Sreeramulu, Sridhar and Kudlinzki, Denis and Hodirnau, Victor-Valentin and Meier-Credo, Jakob and Saxena, Krishna and Buhr, Florian and Langer, Julian D. and Blackledge, Martin and Frangakis, Achilleas S. and Glaubitz, Clemens and Schwalbe, Harald}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Cysteine oxidation and disulfide formation in the ribosomal exit tunnel}}, doi = {10.1038/s41467-020-19372-x}, volume = {11}, year = {2020}, } @unpublished{14095, abstract = {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.}, author = {Gaudi, B. Scott and Seager, Sara and Mennesson, Bertrand and Kiessling, Alina and Warfield, Keith and Cahoy, Kerri and Clarke, John T. and Shawn Domagal-Goldman, Shawn Domagal-Goldman and Feinberg, Lee and Guyon, Olivier and Kasdin, Jeremy and Mawet, Dimitri and Plavchan, Peter and Robinson, Tyler and Rogers, Leslie and Scowen, Paul and Somerville, Rachel and Stapelfeldt, Karl and Stark, Christopher and Stern, Daniel and Turnbull, Margaret and Amini, Rashied and Kuan, Gary and Martin, Stefan and Morgan, Rhonda and Redding, David and Stahl, H. Philip and Webb, Ryan and Oscar Alvarez-Salazar, Oscar Alvarez-Salazar and Arnold, William L. and Arya, Manan and Balasubramanian, Bala and Baysinger, Mike and Bell, Ray and Below, Chris and Benson, Jonathan and Blais, Lindsey and Booth, Jeff and Bourgeois, Robert and Bradford, Case and Brewer, Alden and Brooks, Thomas and Cady, Eric and Caldwell, Mary and Calvet, Rob and Carr, Steven and Chan, Derek and Cormarkovic, Velibor and Coste, Keith and Cox, Charlie and Danner, Rolf and Davis, Jacqueline and Dewell, Larry and Dorsett, Lisa and Dunn, Daniel and East, Matthew and Effinger, Michael and Eng, Ron and Freebury, Greg and Garcia, Jay and Gaskin, Jonathan and Greene, Suzan and Hennessy, John and Hilgemann, Evan and Hood, Brad and Holota, Wolfgang and Howe, Scott and Huang, Pei and Hull, Tony and Hunt, Ron and Hurd, Kevin and Johnson, Sandra and Kissil, Andrew and Knight, Brent and Kolenz, Daniel and Kraus, Oliver and Krist, John and Li, Mary and Lisman, Doug and Mandic, Milan and Mann, John and Marchen, Luis and Colleen Marrese-Reading, Colleen Marrese-Reading and McCready, Jonathan and McGown, Jim and Missun, Jessica and Miyaguchi, Andrew and Moore, Bradley and Nemati, Bijan and Nikzad, Shouleh and Nissen, Joel and Novicki, Megan and Perrine, Todd and Pineda, Claudia and Polanco, Otto and Putnam, Dustin and Qureshi, Atif and Richards, Michael and Riggs, A. J. Eldorado and Rodgers, Michael and Rud, Mike and Saini, Navtej and Scalisi, Dan and Scharf, Dan and Schulz, Kevin and Serabyn, Gene and Sigrist, Norbert and Sikkia, Glory and Singleton, Andrew and Shaklan, Stuart and Smith, Scott and Southerd, Bart and Stahl, Mark and Steeves, John and Sturges, Brian and Sullivan, Chris and Tang, Hao and Taras, Neil and Tesch, Jonathan and Therrell, Melissa and Tseng, Howard and Valente, Marty and Buren, David Van and Villalvazo, Juan and Warwick, Steve and Webb, David and Westerhoff, Thomas and Wofford, Rush and Wu, Gordon and Woo, Jahning and Wood, Milana and Ziemer, John and Arney, Giada and Anderson, Jay and Jesús Maíz-Apellániz, Jesús Maíz-Apellániz and Bartlett, James and Belikov, Ruslan and Bendek, Eduardo and Cenko, Brad and Douglas, Ewan and Dulz, Shannon and Evans, Chris and Faramaz, Virginie and Feng, Y. Katherina and Ferguson, Harry and Follette, Kate and Ford, Saavik and García, Miriam and Geha, Marla and Gelino, Dawn and Götberg, Ylva Louise Linsdotter and Hildebrandt, Sergi and Hu, Renyu and Jahnke, Knud and Kennedy, Grant and Kreidberg, Laura and Isella, Andrea and Lopez, Eric and Marchis, Franck and Macri, Lucas and Marley, Mark and Matzko, William and Mazoyer, Johan and McCandliss, Stephan and Meshkat, Tiffany and Mordasini, Christoph and Morris, Patrick and Nielsen, Eric and Newman, Patrick and Petigura, Erik and Postman, Marc and Reines, Amy and Roberge, Aki and Roederer, Ian and Ruane, Garreth and Schwieterman, Edouard and Sirbu, Dan and Spalding, Christopher and Teplitz, Harry and Tumlinson, Jason and Turner, Neal and Werk, Jessica and Wofford, Aida and Wyatt, Mark and Young, Amber and Zellem, Rob}, booktitle = {arXiv}, title = {{The habitable exoplanet observatory (HabEx) mission concept study final report}}, doi = {10.48550/arXiv.2001.06683}, year = {2020}, } @article{8767, abstract = {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.}, author = {Kaveh, Kamran and McAvoy, Alex and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience}, number = {11}, publisher = {Public Library of Science}, title = {{The Moran process on 2-chromatic graphs}}, doi = {10.1371/journal.pcbi.1008402}, volume = {16}, year = {2020}, } @inproceedings{8750, abstract = {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.}, author = {Forets, Marcelo and Freire, Daniel and Schilling, Christian}, booktitle = {18th ACM-IEEE International Conference on Formal Methods and Models for System Design}, isbn = {9781728191485}, location = {Virtual Conference}, publisher = {IEEE}, title = {{Efficient reachability analysis of parametric linear hybrid systems with time-triggered transitions}}, doi = {10.1109/MEMOCODE51338.2020.9314994}, year = {2020}, } @article{8758, abstract = {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.}, author = {Maas, Jan and Mielke, Alexander}, issn = {15729613}, journal = {Journal of Statistical Physics}, number = {6}, pages = {2257--2303}, publisher = {Springer Nature}, title = {{Modeling of chemical reaction systems with detailed balance using gradient structures}}, doi = {10.1007/s10955-020-02663-4}, volume = {181}, year = {2020}, } @misc{13070, abstract = {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.}, author = {Peruzzo, Matilda and Trioni, Andrea and Hassani, Farid and Zemlicka, Martin and Fink, Johannes M}, publisher = {Zenodo}, title = {{Surpassing the resistance quantum with a geometric superinductor}}, doi = {10.5281/ZENODO.4052882}, year = {2020}, } @article{8787, abstract = {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.}, author = {Nicolai, Leo and Schiefelbein, Karin and Lipsky, Silvia and Leunig, Alexander and Hoffknecht, Marie and Pekayvaz, Kami and Raude, Ben and Marx, Charlotte and Ehrlich, Andreas and Pircher, Joachim and Zhang, Zhe and Saleh, Inas and Marel, Anna-Kristina and Löf, Achim and Petzold, Tobias and Lorenz, Michael and Stark, Konstantin and Pick, Robert and Rosenberger, Gerhild and Weckbach, Ludwig and Uhl, Bernd and Xia, Sheng and Reichel, Christoph Andreas and Walzog, Barbara and Schulz, Christian and Zheden, Vanessa and Bender, Markus and Li, Rong and Massberg, Steffen and Gärtner, Florian R}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Vascular surveillance by haptotactic blood platelets in inflammation and infection}}, doi = {10.1038/s41467-020-19515-0}, volume = {11}, year = {2020}, } @article{8789, abstract = {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.}, author = {Kleshnina, Maria and Streipert, Sabrina and Filar, Jerzy and Chatterjee, Krishnendu}, issn = {22277390}, journal = {Mathematics}, number = {11}, publisher = {MDPI}, title = {{Prioritised learning in snowdrift-type games}}, doi = {10.3390/math8111945}, volume = {8}, year = {2020}, } @inproceedings{8287, abstract = {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.}, author = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian}, booktitle = {Proceedings of the International Conference on Embedded Software}, keywords = {reachability, hybrid systems, decomposition}, location = {Virtual }, title = {{Reachability analysis of linear hybrid systems via block decomposition}}, year = {2020}, } @article{8790, abstract = {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.}, author = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian}, issn = {19374151}, journal = {IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems}, number = {11}, pages = {4018--4029}, publisher = {IEEE}, title = {{Reachability analysis of linear hybrid systems via block decomposition}}, doi = {10.1109/TCAD.2020.3012859}, volume = {39}, year = {2020}, } @article{8924, abstract = {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.}, author = {Nibau, Candida and Dadarou, Despoina and Kargios, Nestoras and Mallioura, Areti and Fernandez-Fuentes, Narcis and Cavallari, Nicola and Doonan, John H.}, issn = {1664-462X}, journal = {Frontiers in Plant Science}, publisher = {Frontiers}, title = {{A functional kinase is necessary for cyclin-dependent kinase G1 (CDKG1) to maintain fertility at high ambient temperature in Arabidopsis}}, doi = {10.3389/fpls.2020.586870}, volume = {11}, year = {2020}, } @article{8944, abstract = {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.}, author = {Zemlicka, Martin and Kopčík, M. and Szabó, P. and Samuely, T. and Kačmarčík, J. and Neilinger, P. and Grajcar, M. and Samuely, P.}, issn = {24699969}, journal = {Physical Review B}, number = {18}, publisher = {American Physical Society}, title = {{Zeeman-driven superconductor-insulator transition in strongly disordered MoC films: Scanning tunneling microscopy and transport studies in a transverse magnetic field}}, doi = {10.1103/PhysRevB.102.180508}, volume = {102}, year = {2020}, } @article{8955, abstract = {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.}, author = {Rizzo, Rossella and Zhang, Xiyun and Wang, Jilin W.J.L. and Lombardi, Fabrizio and Ivanov, Plamen Ch}, issn = {1664042X}, journal = {Frontiers in Physiology}, publisher = {Frontiers}, title = {{Network physiology of cortico–muscular interactions}}, doi = {10.3389/fphys.2020.558070}, volume = {11}, year = {2020}, } @article{8949, abstract = {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.}, author = {Zhang, Xuying and Mennicke, Christine V. and Xiao, Guanxi and Beattie, Robert J and Haider, Mansoor and Hippenmeyer, Simon and Ghashghaei, H. Troy}, issn = {2073-4409}, journal = {Cells}, number = {12}, publisher = {MDPI}, title = {{Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage}}, doi = {10.3390/cells9122662}, volume = {9}, year = {2020}, } @article{8971, abstract = {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.}, author = {Fäßler, Florian and Dimchev, Georgi A and Hodirnau, Victor-Valentin and Wan, William and Schur, Florian KM}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction}}, doi = {10.1038/s41467-020-20286-x}, volume = {11}, year = {2020}, } @inproceedings{8987, abstract = {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.}, author = {Pietrzak, Krzysztof Z}, booktitle = {Progress in Cryptology}, isbn = {9783030652760}, issn = {16113349}, location = {Bangalore, India}, pages = {3--15}, publisher = {Springer Nature}, title = {{Delayed authentication: Preventing replay and relay attacks in private contact tracing}}, doi = {10.1007/978-3-030-65277-7_1}, volume = {12578}, year = {2020}, } @article{9000, abstract = {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.}, author = {Grah, Rok and Zoller, Benjamin and Tkačik, Gašper}, issn = {10916490}, journal = {PNAS}, number = {50}, pages = {31614--31622}, publisher = {National Academy of Sciences}, title = {{Nonequilibrium models of optimal enhancer function}}, doi = {10.1073/pnas.2006731117}, volume = {117}, year = {2020}, } @article{7910, abstract = {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.}, author = {Barzanjeh, Shabir and Pirandola, S. and Vitali, D and Fink, Johannes M}, issn = {23752548}, journal = {Science Advances}, number = {19}, publisher = {AAAS}, title = {{Microwave quantum illumination using a digital receiver}}, doi = {10.1126/sciadv.abb0451}, volume = {6}, year = {2020}, }