@misc{9946, abstract = {We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs.}, author = {Mühlböck, Fabian and Henzinger, Thomas A}, issn = {2664-1690}, keywords = {run-time verification, software engineering, implicit specification}, pages = {17}, publisher = {IST Austria}, title = {{Differential monitoring}}, doi = {10.15479/AT:ISTA:9946}, year = {2021}, } @article{10073, abstract = {Thermoelectric materials enable the direct conversion between heat and electricity. SnTe is a promising candidate due to its high charge transport performance. Here, we prepared SnTe nanocomposites by employing an aqueous method to synthetize SnTe nanoparticles (NP), followed by a unique surface treatment prior NP consolidation. This synthetic approach allowed optimizing the charge and phonon transport synergistically. The novelty of this strategy was the use of a soluble PbS molecular complex prepared using a thiol-amine solvent mixture that upon blending is adsorbed on the SnTe NP surface. Upon consolidation with spark plasma sintering, SnTe-PbS nanocomposite is formed. The presence of PbS complexes significantly compensates for the Sn vacancy and increases the average grain size of the nanocomposite, thus improving the carrier mobility. Moreover, lattice thermal conductivity is also reduced by the Pb and S-induced mass and strain fluctuation. As a result, an enhanced ZT of ca. 0.8 is reached at 873 K. Our finding provides a novel strategy to conduct rational surface treatment on NP-based thermoelectrics.}, author = {Chang, Cheng and Ibáñez, Maria}, issn = {1996-1944}, journal = {Materials}, number = {18}, publisher = {MDPI}, title = {{Enhanced thermoelectric performance by surface engineering in SnTe-PbS nanocomposites}}, doi = {10.3390/ma14185416}, volume = {14}, year = {2021}, } @article{10167, abstract = {Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group.}, author = {Elkrewi, Marwan N and Moldovan, Mikhail A. and Picard, Marion A L and Vicoso, Beatriz}, issn = {1537-1719}, journal = {Molecular Biology and Evolution}, keywords = {sex chromosomes, evolutionary strata, W-linked gene, sex determining gene, schistosome parasites}, publisher = {Oxford University Press }, title = {{Schistosome W-Linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination}}, doi = {10.1093/molbev/msab178}, year = {2021}, } @article{10163, abstract = {The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.}, author = {Appel, Lisa-Marie and Franke, Vedran and Bruno, Melania and Grishkovskaya, Irina and Kasiliauskaite, Aiste and Kaufmann, Tanja and Schoeberl, Ursula E. and Puchinger, Martin G. and Kostrhon, Sebastian and Ebenwaldner, Carmen and Sebesta, Marek and Beltzung, Etienne and Mechtler, Karl and Lin, Gen and Vlasova, Anna and Leeb, Martin and Pavri, Rushad and Stark, Alexander and Akalin, Altuna and Stefl, Richard and Bernecky, Carrie A and Djinovic-Carugo, Kristina and Slade, Dea}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry}, number = {1}, publisher = {Springer Nature}, title = {{PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC}}, doi = {10.1038/s41467-021-26360-2}, volume = {12}, year = {2021}, } @article{9547, abstract = {With the wider availability of full-color 3D printers, color-accurate 3D-print preparation has received increased attention. A key challenge lies in the inherent translucency of commonly used print materials that blurs out details of the color texture. Previous work tries to compensate for these scattering effects through strategic assignment of colored primary materials to printer voxels. To date, the highest-quality approach uses iterative optimization that relies on computationally expensive Monte Carlo light transport simulation to predict the surface appearance from subsurface scattering within a given print material distribution; that optimization, however, takes in the order of days on a single machine. In our work, we dramatically speed up the process by replacing the light transport simulation with a data-driven approach. Leveraging a deep neural network to predict the scattering within a highly heterogeneous medium, our method performs around two orders of magnitude faster than Monte Carlo rendering while yielding optimization results of similar quality level. The network is based on an established method from atmospheric cloud rendering, adapted to our domain and extended by a physically motivated weight sharing scheme that substantially reduces the network size. We analyze its performance in an end-to-end print preparation pipeline and compare quality and runtime to alternative approaches, and demonstrate its generalization to unseen geometry and material values. This for the first time enables full heterogenous material optimization for 3D-print preparation within time frames in the order of the actual printing time.}, author = {Rittig, Tobias and Sumin, Denis and Babaei, Vahid and Didyk, Piotr and Voloboy, Alexey and Wilkie, Alexander and Bickel, Bernd and Myszkowski, Karol and Weyrich, Tim and Křivánek, Jaroslav}, issn = {1467-8659}, journal = {Computer Graphics Forum}, number = {2}, pages = {205--219}, publisher = {Wiley}, title = {{Neural acceleration of scattering-aware color 3D printing}}, doi = {10.1111/cgf.142626}, volume = {40}, year = {2021}, } @article{10177, abstract = {Phonon polaritons (PhPs)—light coupled to lattice vibrations—with in-plane hyperbolic dispersion exhibit ray-like propagation with large wave vectors and enhanced density of optical states along certain directions on a surface. As such, they have raised a surge of interest, promising unprecedented manipulation of infrared light at the nanoscale in a planar circuitry. Here, we demonstrate focusing of in-plane hyperbolic PhPs propagating along thin slabs of α-MoO3. To that end, we developed metallic nanoantennas of convex geometries for both efficient launching and focusing of the polaritons. The foci obtained exhibit enhanced near-field confinement and absorption compared to foci produced by in-plane isotropic PhPs. Foci sizes as small as λp/4.5 = λ0/50 were achieved (λp is the polariton wavelength and λ0 is the photon wavelength). Focusing of in-plane hyperbolic polaritons introduces a first and most basic building block developing planar polariton optics using in-plane anisotropic van der Waals materials.}, author = {Martín-Sánchez, Javier and Duan, Jiahua and Taboada-Gutiérrez, Javier and Álvarez-Pérez, Gonzalo and Voronin, Kirill V. and Prieto Gonzalez, Ivan and Ma, Weiliang and Bao, Qiaoliang and Volkov, Valentyn S. and Hillenbrand, Rainer and Nikitin, Alexey Y. and Alonso-González, Pablo}, issn = {23752548}, journal = {Science Advances}, number = {41}, publisher = {American Association for the Advancement of Science}, title = {{Focusing of in-plane hyperbolic polaritons in van der Waals crystals with tailored infrared nanoantennas}}, doi = {10.1126/sciadv.abj0127}, volume = {7}, year = {2021}, } @article{10146, abstract = {The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain.}, author = {Vercellino, Irene and Sazanov, Leonid A}, issn = {1476-4687}, journal = {Nature}, number = {7880}, pages = {364--367}, publisher = {Springer Nature}, title = {{Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV}}, doi = {10.1038/s41586-021-03927-z}, volume = {598}, year = {2021}, } @article{10176, abstract = {We give a combinatorial model for r-spin surfaces with parameterized boundary based on Novak (“Lattice topological field theories in two dimensions,” Ph.D. thesis, Universität Hamburg, 2015). The r-spin structure is encoded in terms of ℤ𝑟-valued indices assigned to the edges of a polygonal decomposition. This combinatorial model is designed for our state-sum construction of two-dimensional topological field theories on r-spin surfaces. We show that an example of such a topological field theory computes the Arf-invariant of an r-spin surface as introduced by Randal-Williams [J. Topol. 7, 155 (2014)] and Geiges et al. [Osaka J. Math. 49, 449 (2012)]. This implies, in particular, that the r-spin Arf-invariant is constant on orbits of the mapping class group, providing an alternative proof of that fact.}, author = {Runkel, Ingo and Szegedy, Lorant}, issn = {00222488}, journal = {Journal of Mathematical Physics}, number = {10}, publisher = {AIP Publishing}, title = {{Topological field theory on r-spin surfaces and the Arf-invariant}}, doi = {10.1063/5.0037826}, volume = {62}, year = {2021}, } @article{10179, abstract = {Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling.}, author = {Bajaj, Sunanjay and Bagley, Joshua A. and Sommer, Christoph M and Vertesy, Abel and Nagumo Wong, Sakurako and Krenn, Veronica and Lévi-Strauss, Julie and Knoblich, Juergen A.}, issn = {1460-2075}, journal = {EMBO Journal}, number = {23}, publisher = {Embo Press}, title = {{Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration}}, doi = {10.15252/embj.2021108714}, volume = {40}, year = {2021}, } @article{10203, abstract = {Single photon emitters in atomically-thin semiconductors can be deterministically positioned using strain induced by underlying nano-structures. Here, we couple monolayer WSe2 to high-refractive-index gallium phosphide dielectric nano-antennas providing both optical enhancement and monolayer deformation. For single photon emitters formed on such nano-antennas, we find very low (femto-Joule) saturation pulse energies and up to 104 times brighter photoluminescence than in WSe2 placed on low-refractive-index SiO2 pillars. We show that the key to these observations is the increase on average by a factor of 5 of the quantum efficiency of the emitters coupled to the nano-antennas. This further allows us to gain new insights into their photoluminescence dynamics, revealing the roles of the dark exciton reservoir and Auger processes. We also find that the coherence time of such emitters is limited by intrinsic dephasing processes. Our work establishes dielectric nano-antennas as a platform for high-efficiency quantum light generation in monolayer semiconductors.}, author = {Sortino, Luca and Zotev, Panaiot G. and Phillips, Catherine L. and Brash, Alistair J. and Cambiasso, Javier and Marensi, Elena and Fox, A. Mark and Maier, Stefan A. and Sapienza, Riccardo and Tartakovskii, Alexander I.}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Bright single photon emitters with enhanced quantum efficiency in a two-dimensional semiconductor coupled with dielectric nano-antennas}}, doi = {10.1038/s41467-021-26262-3}, volume = {12}, year = {2021}, } @article{10178, abstract = {In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features.}, author = {Sahu, Preeti and Schwarz, J. M. and Manning, M. Lisa}, issn = {13672630}, journal = {New Journal of Physics}, number = {9}, publisher = {IOP Publishing}, title = {{Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue}}, doi = {10.1088/1367-2630/ac23f1}, volume = {23}, year = {2021}, } @article{10181, abstract = {In this article we study some geometric properties of proximally smooth sets. First, we introduce a modification of the metric projection and prove its existence. Then we provide an algorithm for constructing a rectifiable curve between two sufficiently close points of a proximally smooth set in a uniformly convex and uniformly smooth Banach space, with the moduli of smoothness and convexity of power type. Our algorithm returns a reasonably short curve between two sufficiently close points of a proximally smooth set, is iterative and uses our modification of the metric projection. We estimate the length of the constructed curve and its deviation from the segment with the same endpoints. These estimates coincide up to a constant factor with those for the geodesics in a proximally smooth set in a Hilbert space.}, author = {Ivanov, Grigory and Lopushanski, Mariana S.}, issn = {1877-0541}, journal = {Set-Valued and Variational Analysis}, publisher = {Springer Nature}, title = {{Rectifiable curves in proximally smooth sets}}, doi = {10.1007/s11228-021-00612-1}, year = {2021}, } @article{10202, abstract = {Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.}, author = {Pradhan, Saurabh J. and Reddy, Puli Chandramouli and Smutny, Michael and Sharma, Ankita and Sako, Keisuke and Oak, Meghana S. and Shah, Rini and Pal, Mrinmoy and Deshpande, Ojas and Dsilva, Greg and Tang, Yin and Mishra, Rakesh and Deshpande, Girish and Giraldez, Antonio J. and Sonawane, Mahendra and Heisenberg, Carl-Philipp J and Galande, Sanjeev}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis}}, doi = {10.1038/s41467-021-26234-7}, volume = {12}, year = {2021}, } @article{10271, abstract = {Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions.}, author = {Qi, Qin and Angermayr, S. Andreas and Bollenbach, Mark Tobias}, issn = {1664-302X}, journal = {Frontiers in Microbiology}, keywords = {microbiology}, publisher = {Frontiers}, title = {{Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli}}, doi = {10.3389/fmicb.2021.760017}, volume = {12}, year = {2021}, } @article{10221, abstract = {We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020).}, author = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, number = {2}, pages = {1005–1048}, publisher = {Springer Nature}, title = {{Eigenstate thermalization hypothesis for Wigner matrices}}, doi = {10.1007/s00220-021-04239-z}, volume = {388}, year = {2021}, } @article{10224, abstract = {We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging.}, author = {Feliciangeli, Dario and Seiringer, Robert}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {1835–1906}, publisher = {Springer Nature}, title = {{The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics}}, doi = {10.1007/s00205-021-01715-7}, volume = {242}, year = {2021}, } @article{10281, abstract = {Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems}, author = {Vasic, Verica and Jones, Mattson S.O. and Haslinger, Denise and Knaus, Lisa and Schmeisser, Michael J. and Novarino, Gaia and Chiocchetti, Andreas G.}, issn = {2073-4425}, journal = {Genes}, number = {11}, publisher = {MDPI}, title = {{Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment}}, doi = {10.3390/genes12111746}, volume = {12}, year = {2021}, } @article{10282, abstract = {Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development.}, author = {Kashkan, Ivan and Hrtyan, Mónika and Retzer, Katarzyna and Humpolíčková, Jana and Jayasree, Aswathy and Filepová, Roberta and Vondráková, Zuzana and Simon, Sibu and Rombaut, Debbie and Jacobs, Thomas B. and Frilander, Mikko J. and Hejátko, Jan and Friml, Jiří and Petrášek, Jan and Růžička, Kamil}, issn = {1469-8137}, journal = {New Phytologist}, pages = {329--343}, publisher = {Wiley}, title = {{Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana}}, doi = {10.1111/nph.17792}, volume = {233}, year = {2021}, } @article{10220, abstract = {We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.}, author = {Avvakumov, Sergey and Mabillard, Isaac and Skopenkov, Arkadiy B. and Wagner, Uli}, issn = {1565-8511}, journal = {Israel Journal of Mathematics}, pages = {501–534 }, publisher = {Springer Nature}, title = {{Eliminating higher-multiplicity intersections. III. Codimension 2}}, doi = {10.1007/s11856-021-2216-z}, volume = {245}, year = {2021}, } @misc{13061, abstract = {Infections early in life can have enduring effects on an organism’s development and immunity. In this study, we show that this equally applies to developing “superorganisms” – incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen’s immune system to suppress pathogen proliferation. Early-life queen pathogen-exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen’s pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism.}, author = {Casillas Perez, Barbara E and Pull, Christopher and Naiser, Filip and Naderlinger, Elisabeth and Matas, Jiri and Cremer, Sylvia}, publisher = {Dryad}, title = {{Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies}}, doi = {10.5061/DRYAD.7PVMCVDTJ}, year = {2021}, } @article{10301, abstract = {De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.}, author = {Conde-Dusman, María J and Dey, Partha N and Elía-Zudaire, Óscar and Garcia Rabaneda, Luis E and García-Lira, Carmen and Grand, Teddy and Briz, Victor and Velasco, Eric R and Andero Galí, Raül and Niñerola, Sergio and Barco, Angel and Paoletti, Pierre and Wesseling, John F and Gardoni, Fabrizio and Tavalin, Steven J and Perez-Otaño, Isabel}, issn = {2050-084X}, journal = {eLife}, keywords = {general immunology and microbiology, general biochemistry, genetics and molecular biology, general medicine, general neuroscience}, publisher = {eLife Sciences Publications}, title = {{Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly}}, doi = {10.7554/elife.71575}, volume = {10}, year = {2021}, } @article{10283, abstract = {During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research.}, author = {Restivo, Leonardo and Gerlach, Björn and Tsoory, Michael and Bikovski, Lior and Badurek, Sylvia and Pitzer, Claudia and Kos-Braun, Isabelle C. and Mausset-Bonnefont, Anne Laure Mj and Ward, Jonathan and Schunn, Michael and Noldus, Lucas P.J.J. and Bespalov, Anton and Voikar, Vootele}, issn = {1469-3178}, journal = {EMBO Reports}, publisher = {EMBO Press}, title = {{Towards best practices in research: Role of academic core facilities}}, doi = {10.15252/embr.202153824}, volume = {22}, year = {2021}, } @article{10310, abstract = {A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.}, author = {Çoruh, Mehmet Orkun and Frank, Anna and Tanaka, Hideaki and Kawamoto, Akihiro and El-Mohsnawy, Eithar and Kato, Takayuki and Namba, Keiichi and Gerle, Christoph and Nowaczyk, Marc M. and Kurisu, Genji}, issn = {2399-3642}, journal = {Communications Biology}, keywords = {general agricultural and biological Sciences, general biochemistry, genetics and molecular biology, medicine (miscellaneous)}, number = {1}, publisher = {Springer }, title = {{Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster}}, doi = {10.1038/s42003-021-01808-9}, volume = {4}, year = {2021}, } @article{10270, abstract = {Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development.}, author = {Marconi, Marco and Gallemi, Marçal and Benková, Eva and Wabnik, Krzysztof}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{A coupled mechano-biochemical model for cell polarity guided anisotropic root growth}}, doi = {10.7554/elife.72132}, volume = {10}, year = {2021}, } @article{10299, abstract = {Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number.}, author = {Choueiri, George H and Lopez Alonso, Jose M and Varshney, Atul and Sankar, Sarath and Hof, Björn}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary, elastoinertial turbulence, viscoelastic flows, elastic instability, drag reduction}, number = {45}, publisher = {National Academy of Sciences}, title = {{Experimental observation of the origin and structure of elastoinertial turbulence}}, doi = {10.1073/pnas.2102350118}, volume = {118}, year = {2021}, } @article{10280, abstract = {Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials.}, author = {Aubret, Antoine and Martinet, Quentin and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Metamachines of pluripotent colloids}}, doi = {10.1038/s41467-021-26699-6}, volume = {12}, year = {2021}, } @article{10322, abstract = {To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.}, author = {Chauve, Laetitia and Hodge, Francesca and Murdoch, Sharlene and Masoudzadeh, Fatemah and Mann, Harry Jack and Lopez-Clavijo, Andrea and Okkenhaug, Hanneke and West, Greg and Sousa, Bebiana C. and Segonds-Pichon, Anne and Li, Cheryl and Wingett, Steven and Kienberger, Hermine and Kleigrewe, Karin and De Bono, Mario and Wakelam, Michael and Casanueva, Olivia}, issn = {1545-7885}, journal = {PLoS Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans}}, doi = {10.1371/journal.pbio.3001431}, volume = {19}, year = {2021}, } @article{10222, abstract = {Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density.}, author = {Akopyan, Arseniy and Edelsbrunner, Herbert and Nikitenko, Anton}, issn = {1944-950X}, journal = {Experimental Mathematics}, pages = {1--15}, publisher = {Taylor and Francis}, title = {{The beauty of random polytopes inscribed in the 2-sphere}}, doi = {10.1080/10586458.2021.1980459}, year = {2021}, } @article{10323, abstract = {Molecular chaperones are central to cellular protein homeostasis. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. We focus hereby on chaperone-client interactions that are independent of ATP. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity.}, author = {Sučec, Iva and Bersch, Beate and Schanda, Paul}, issn = {2296-889X}, journal = {Frontiers in Molecular Biosciences}, publisher = {Frontiers}, title = {{How do chaperones bind (partly) unfolded client proteins?}}, doi = {10.3389/fmolb.2021.762005}, volume = {8}, year = {2021}, } @article{10326, abstract = {Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.}, author = {Xu, Enjun and Chai, Liang and Zhang, Shiqi and Yu, Ruixue and Zhang, Xixi and Xu, Chongyi and Hu, Yuxin}, issn = {2055-0278}, journal = {Nature Plants}, pages = {1495–1504 }, publisher = {Springer Nature}, title = {{Catabolism of strigolactones by a carboxylesterase}}, doi = {10.1038/s41477-021-01011-y}, volume = {7}, year = {2021}, } @misc{13069, abstract = {To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell-autonomous. We have discovered that, in Caenorhabditis elegans, neuronal Heat shock Factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR)- causes extensive fat remodelling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine, and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodelling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least six TAX-2/TAX-4 cGMP gated channel expressing sensory neurons and TGF-β/BMP are required for signalling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodelling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell non-autonomously coordinate membrane saturation and composition across tissues in a multicellular animal.}, author = {Chauve, Laetitia and Hodge, Francesca and Murdoch, Sharlene and Masoudzadeh, Fatemah and Mann, Harry-Jack and Lopez-Clavijo, Andrea and Okkenhaug, Hanneke and West, Greg and Sousa, Bebiana C. and Segonds-Pichon, Anne and Li, Cheryl and Wingett, Steven and Kienberger, Hermine and Kleigrewe, Karin and de Bono, Mario and Wakelam, Michael and Casanueva, Olivia}, publisher = {Zenodo}, title = {{Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans}}, doi = {10.5281/ZENODO.5519410}, year = {2021}, } @inproceedings{10325, abstract = {Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains.}, author = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.}, booktitle = {25th International Conference on Financial Cryptography and Data Security}, isbn = {9-783-6626-4330-3}, issn = {1611-3349}, location = {Virtual}, pages = {3--36}, publisher = {Springer Nature}, title = {{SoK: Communication across distributed ledgers}}, doi = {10.1007/978-3-662-64331-0_1}, volume = {12675 }, year = {2021}, } @inproceedings{10324, abstract = {Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.}, author = {Avarikioti, Zeta and Kokoris Kogias, Eleftherios and Wattenhofer, Roger and Zindros, Dionysis}, booktitle = {25th International Conference on Financial Cryptography and Data Security}, isbn = {9-783-6626-4330-3}, issn = {1611-3349}, location = {Virtual}, pages = {209--230}, publisher = {Springer Nature}, title = {{Brick: Asynchronous incentive-compatible payment channels}}, doi = {10.1007/978-3-662-64331-0_11}, volume = {12675 }, year = {2021}, } @article{10363, abstract = {Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.}, author = {Lee, Jungmin and Vernet, Andyna and Gruber, Nathalie and Kready, Kasia M. and Burrill, Devin R. and Way, Jeffrey C. and Silver, Pamela A.}, issn = {1741-0134}, journal = {Protein Engineering, Design and Selection}, publisher = {Oxford University Press}, title = {{Rational engineering of an erythropoietin fusion protein to treat hypoxia}}, doi = {10.1093/protein/gzab025}, volume = {34}, year = {2021}, } @article{10366, author = {Heisenberg, Carl-Philipp J and Lennon, Ana Maria and Mayor, Roberto and Salbreux, Guillaume}, issn = {2667-2901}, journal = {Cells and Development}, number = {12}, publisher = {Elsevier}, title = {{Special rebranding issue: “Quantitative cell and developmental biology”}}, doi = {10.1016/j.cdev.2021.203758}, volume = {168}, year = {2021}, } @article{10402, abstract = {Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales.}, author = {Ucar, Mehmet C and Kamenev, Dmitrii and Sunadome, Kazunori and Fachet, Dominik C and Lallemend, Francois and Adameyko, Igor and Hadjab, Saida and Hannezo, Edouard B}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Theory of branching morphogenesis by local interactions and global guidance}}, doi = {10.1038/s41467-021-27135-5}, volume = {12}, year = {2021}, } @inproceedings{10407, abstract = {Digital hardware Trojans are integrated circuits whose implementation differ from the specification in an arbitrary and malicious way. For example, the circuit can differ from its specified input/output behavior after some fixed number of queries (known as “time bombs”) or on some particular input (known as “cheat codes”). To detect such Trojans, countermeasures using multiparty computation (MPC) or verifiable computation (VC) have been proposed. On a high level, to realize a circuit with specification F one has more sophisticated circuits F⋄ manufactured (where F⋄ specifies a MPC or VC of F ), and then embeds these F⋄ ’s into a master circuit which must be trusted but is relatively simple compared to F . Those solutions impose a significant overhead as F⋄ is much more complex than F , also the master circuits are not exactly trivial. In this work, we show that in restricted settings, where F has no evolving state and is queried on independent inputs, we can achieve a relaxed security notion using very simple constructions. In particular, we do not change the specification of the circuit at all (i.e., F=F⋄ ). Moreover the master circuit basically just queries a subset of its manufactured circuits and checks if they’re all the same. The security we achieve guarantees that, if the manufactured circuits are initially tested on up to T inputs, the master circuit will catch Trojans that try to deviate on significantly more than a 1/T fraction of the inputs. This bound is optimal for the type of construction considered, and we provably achieve it using a construction where 12 instantiations of F need to be embedded into the master. We also discuss an extremely simple construction with just 2 instantiations for which we conjecture that it already achieves the optimal bound.}, author = {Chakraborty, Suvradip and Dziembowski, Stefan and Gałązka, Małgorzata and Lizurej, Tomasz and Pietrzak, Krzysztof Z and Yeo, Michelle X}, isbn = {9-783-0309-0452-4}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {397--428}, publisher = {Springer Nature}, title = {{Trojan-resilience without cryptography}}, doi = {10.1007/978-3-030-90453-1_14}, volume = {13043}, year = {2021}, } @article{10403, abstract = {Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits.}, author = {Biane, Celia and Rückerl, Florian and Abrahamsson, Therese and Saint-Cloment, Cécile and Mariani, Jean and Shigemoto, Ryuichi and Digregorio, David A. and Sherrard, Rachel M. and Cathala, Laurence}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons}}, doi = {10.7554/eLife.65954}, volume = {10}, year = {2021}, } @article{10401, abstract = {Theoretical and experimental studies of the interaction between spins and temperature are vital for the development of spin caloritronics, as they dictate the design of future devices. In this work, we propose a two-terminal cold-atom simulator to study that interaction. The proposed quantum simulator consists of strongly interacting atoms that occupy two temperature reservoirs connected by a one-dimensional link. First, we argue that the dynamics in the link can be described using an inhomogeneous Heisenberg spin chain whose couplings are defined by the local temperature. Second, we show the existence of a spin current in a system with a temperature difference by studying the dynamics that follows the spin-flip of an atom in the link. A temperature gradient accelerates the impurity in one direction more than in the other, leading to an overall spin current similar to the spin Seebeck effect.}, author = {Barfknecht, Rafael E. and Foerster, Angela and Zinner, Nikolaj T. and Volosniev, Artem}, issn = {23993650}, journal = {Communications Physics}, number = {1}, publisher = {Springer Nature}, title = {{Generation of spin currents by a temperature gradient in a two-terminal device}}, doi = {10.1038/s42005-021-00753-7}, volume = {4}, year = {2021}, } @article{10404, abstract = {While convolutional neural networks (CNNs) have found wide adoption as state-of-the-art models for image-related tasks, their predictions are often highly sensitive to small input perturbations, which the human vision is robust against. This paper presents Perturber, a web-based application that allows users to instantaneously explore how CNN activations and predictions evolve when a 3D input scene is interactively perturbed. Perturber offers a large variety of scene modifications, such as camera controls, lighting and shading effects, background modifications, object morphing, as well as adversarial attacks, to facilitate the discovery of potential vulnerabilities. Fine-tuned model versions can be directly compared for qualitative evaluation of their robustness. Case studies with machine learning experts have shown that Perturber helps users to quickly generate hypotheses about model vulnerabilities and to qualitatively compare model behavior. Using quantitative analyses, we could replicate users’ insights with other CNN architectures and input images, yielding new insights about the vulnerability of adversarially trained models.}, author = {Sietzen, Stefan and Lechner, Mathias and Borowski, Judy and Hasani, Ramin and Waldner, Manuela}, issn = {1467-8659}, journal = {Computer Graphics Forum}, number = {7}, pages = {253--264}, publisher = {Wiley}, title = {{Interactive analysis of CNN robustness}}, doi = {10.1111/cgf.14418}, volume = {40}, year = {2021}, } @article{10406, abstract = {Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future.}, author = {Mishra, Nikhil and Heisenberg, Carl-Philipp J}, issn = {1545-2948}, journal = {Annual Review of Genetics}, keywords = {morphogenesis, forward genetics, high-resolution microscopy, biophysics, biochemistry, patterning}, pages = {209--233}, publisher = {Annual Reviews}, title = {{Dissecting organismal morphogenesis by bridging genetics and biophysics}}, doi = {10.1146/annurev-genet-071819-103748}, volume = {55}, year = {2021}, } @misc{13058, abstract = {The zip file includes source data used in the main text of the manuscript "Theory of branching morphogenesis by local interactions and global guidance", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt.}, author = {Ucar, Mehmet C}, publisher = {Zenodo}, title = {{Source data for the manuscript "Theory of branching morphogenesis by local interactions and global guidance"}}, doi = {10.5281/ZENODO.5257160}, year = {2021}, } @inproceedings{10408, abstract = {Key trees are often the best solution in terms of transmission cost and storage requirements for managing keys in a setting where a group needs to share a secret key, while being able to efficiently rotate the key material of users (in order to recover from a potential compromise, or to add or remove users). Applications include multicast encryption protocols like LKH (Logical Key Hierarchies) or group messaging like the current IETF proposal TreeKEM. A key tree is a (typically balanced) binary tree, where each node is identified with a key: leaf nodes hold users’ secret keys while the root is the shared group key. For a group of size N, each user just holds log(N) keys (the keys on the path from its leaf to the root) and its entire key material can be rotated by broadcasting 2log(N) ciphertexts (encrypting each fresh key on the path under the keys of its parents). In this work we consider the natural setting where we have many groups with partially overlapping sets of users, and ask if we can find solutions where the cost of rotating a key is better than in the trivial one where we have a separate key tree for each group. We show that in an asymptotic setting (where the number m of groups is fixed while the number N of users grows) there exist more general key graphs whose cost converges to the cost of a single group, thus saving a factor linear in the number of groups over the trivial solution. As our asymptotic “solution” converges very slowly and performs poorly on concrete examples, we propose an algorithm that uses a natural heuristic to compute a key graph for any given group structure. Our algorithm combines two greedy algorithms, and is thus very efficient: it first converts the group structure into a “lattice graph”, which is then turned into a key graph by repeatedly applying the algorithm for constructing a Huffman code. To better understand how far our proposal is from an optimal solution, we prove lower bounds on the update cost of continuous group-key agreement and multicast encryption in a symbolic model admitting (asymmetric) encryption, pseudorandom generators, and secret sharing as building blocks.}, author = {Alwen, Joel F and Auerbach, Benedikt and Baig, Mirza Ahad and Cueto Noval, Miguel and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael}, booktitle = {19th International Conference}, isbn = {9-783-0309-0455-5}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {222--253}, publisher = {Springer Nature}, title = {{Grafting key trees: Efficient key management for overlapping groups}}, doi = {10.1007/978-3-030-90456-2_8}, volume = {13044}, year = {2021}, } @article{10527, abstract = {We show that in a two-dimensional electron gas with an annular Fermi surface, long-range Coulomb interactions can lead to unconventional superconductivity by the Kohn-Luttinger mechanism. Superconductivity is strongly enhanced when the inner and outer Fermi surfaces are close to each other. The most prevalent state has chiral p-wave symmetry, but d-wave and extended s-wave pairing are also possible. We discuss these results in the context of rhombohedral trilayer graphene, where superconductivity was recently discovered in regimes where the normal state has an annular Fermi surface. Using realistic parameters, our mechanism can account for the order of magnitude of Tc, as well as its trends as a function of electron density and perpendicular displacement field. Moreover, it naturally explains some of the outstanding puzzles in this material, that include the weak temperature dependence of the resistivity above Tc, and the proximity of spin singlet superconductivity to the ferromagnetic phase.}, author = {Ghazaryan, Areg and Holder, Tobias and Serbyn, Maksym and Berg, Erez}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {24}, publisher = {American Physical Society}, title = {{Unconventional superconductivity in systems with annular Fermi surfaces: Application to rhombohedral trilayer graphene}}, doi = {10.1103/physrevlett.127.247001}, volume = {127}, year = {2021}, } @article{10534, abstract = {For many years, fullerene derivatives have been the main n-type material of organic electronics and optoelectronics. Recently, fullerene derivatives functionalized with ethylene glycol (EG) side chains have been showing important properties such as enhanced dielectric constants, facile doping and enhanced self-assembly capabilities. Here, we have prepared field-effect transistors using a series of these fullerene derivatives equipped with EG side chains of different lengths. Transport data show the beneficial effect of increasing the EG side chain. In order to understand the material properties, full structural determination of these fullerene derivatives has been achieved by coupling the X-ray data with molecular dynamics (MD) simulations. The increase in transport properties is paired with the formation of extended layered structures, efficient molecular packing and an increase in the crystallite alignment. The layer-like structure is composed of conducting layers, containing of closely packed C60 balls approaching the inter-distance of 1 nm, that are separated by well-defined EG layers, where the EG chains are rather splayed with the chain direction almost perpendicular to the layer normal. Such a layered structure appears highly ordered and highly aligned with the C60 planes oriented parallel to the substrate in the thin film configuration. The order inside the thin film increases with the EG chain length, allowing the systems to achieve mobilities as high as 0.053 cm2 V−1 s−1. Our work elucidates the structure of these interesting semiconducting organic molecules and shows that the synergistic use of X-ray structural analysis and MD simulations is a powerful tool to identify the structure of thin organic films for optoelectronic applications.}, author = {Dong, Jingjin and Sami, Selim and Balazs, Daniel and Alessandri, Riccardo and Jahani, Fatimeh and Qiu, Li and Marrink, Siewert J. and Havenith, Remco W.A. and Hummelen, Jan C. and Loi, Maria A. and Portale, Giuseppe}, issn = {2050-7526}, journal = {Journal of Materials Chemistry C}, number = {45}, pages = {16217--16225}, publisher = {Royal Society of Chemistry}, title = {{Fullerene derivatives with oligoethylene-glycol side chains: An investigation on the origin of their outstanding transport properties}}, doi = {10.1039/d1tc02753k}, volume = {9}, year = {2021}, } @article{10533, abstract = {Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin.}, author = {Choi, Jaemyung and Lyons, David B and Zilberman, Daniel}, issn = {2050-084X}, journal = {eLife}, keywords = {genetics and molecular biology}, publisher = {eLife Sciences Publications}, title = {{Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin}}, doi = {10.7554/elife.72676}, volume = {10}, year = {2021}, } @article{10536, abstract = {TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner.}, author = {Stefanescu, Cristina and Van Gogh, Merel and Roblek, Marko and Heikenwalder, Mathias and Borsig, Lubor}, issn = {2234-943X}, journal = {Frontiers in Oncology}, publisher = {Frontiers}, title = {{TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms}}, doi = {10.3389/fonc.2021.765151}, volume = {11}, year = {2021}, } @article{10537, abstract = {We consider the quantum many-body evolution of a homogeneous Fermi gas in three dimensions in the coupled semiclassical and mean-field scaling regime. We study a class of initial data describing collective particle–hole pair excitations on the Fermi ball. Using a rigorous version of approximate bosonization, we prove that the many-body evolution can be approximated in Fock space norm by a quasi-free bosonic evolution of the collective particle–hole excitations.}, author = {Benedikter, Niels P and Nam, Phan Thành and Porta, Marcello and Schlein, Benjamin and Seiringer, Robert}, issn = {1424-0637}, journal = {Annales Henri Poincaré}, publisher = {Springer Nature}, title = {{Bosonization of fermionic many-body dynamics}}, doi = {10.1007/s00023-021-01136-y}, year = {2021}, } @article{10549, abstract = {We derive optimal-order homogenization rates for random nonlinear elliptic PDEs with monotone nonlinearity in the uniformly elliptic case. More precisely, for a random monotone operator on \mathbb {R}^d with stationary law (that is spatially homogeneous statistics) and fast decay of correlations on scales larger than the microscale \varepsilon >0, we establish homogenization error estimates of the order \varepsilon in case d\geqq 3, and of the order \varepsilon |\log \varepsilon |^{1/2} in case d=2. Previous results in nonlinear stochastic homogenization have been limited to a small algebraic rate of convergence \varepsilon ^\delta . We also establish error estimates for the approximation of the homogenized operator by the method of representative volumes of the order (L/\varepsilon )^{-d/2} for a representative volume of size L. Our results also hold in the case of systems for which a (small-scale) C^{1,\alpha } regularity theory is available.}, author = {Fischer, Julian L and Neukamm, Stefan}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, keywords = {Mechanical Engineering, Mathematics (miscellaneous), Analysis}, number = {1}, pages = {343--452}, publisher = {Springer Nature}, title = {{Optimal homogenization rates in stochastic homogenization of nonlinear uniformly elliptic equations and systems}}, doi = {10.1007/s00205-021-01686-9}, volume = {242}, year = {2021}, } @inproceedings{10409, abstract = {We show that Yao’s garbling scheme is adaptively indistinguishable for the class of Boolean circuits of size S and treewidth w with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity.}, author = {Kamath Hosdurg, Chethan and Klein, Karen and Pietrzak, Krzysztof Z}, booktitle = {19th International Conference}, isbn = {9-783-0309-0452-4}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {486--517}, publisher = {Springer Nature}, title = {{On treewidth, separators and Yao’s garbling}}, doi = {10.1007/978-3-030-90453-1_17}, volume = {13043 }, year = {2021}, } @article{10545, abstract = {Classical models with complex energy landscapes represent a perspective avenue for the near-term application of quantum simulators. Until now, many theoretical works studied the performance of quantum algorithms for models with a unique ground state. However, when the classical problem is in a so-called clustering phase, the ground state manifold is highly degenerate. As an example, we consider a 3-XORSAT model defined on simple hypergraphs. The degeneracy of classical ground state manifold translates into the emergence of an extensive number of Z2 symmetries, which remain intact even in the presence of a quantum transverse magnetic field. We establish a general duality approach that restricts the quantum problem to a given sector of conserved Z2 charges and use it to study how the outcome of the quantum adiabatic algorithm depends on the hypergraph geometry. We show that the tree hypergraph which corresponds to a classically solvable instance of the 3-XORSAT problem features a constant gap, whereas the closed hypergraph encounters a second-order phase transition with a gap vanishing as a power-law in the problem size. The duality developed in this work provides a practical tool for studies of quantum models with classically degenerate energy manifold and reveals potential connections between glasses and gauge theories.}, author = {Medina Ramos, Raimel A and Serbyn, Maksym}, issn = {2469-9934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Duality approach to quantum annealing of the 3-variable exclusive-or satisfiability problem (3-XORSAT)}}, doi = {10.1103/physreva.104.062423}, volume = {104}, year = {2021}, } @inproceedings{10554, abstract = {We present DAG-Rider, the first asynchronous Byzantine Atomic Broadcast protocol that achieves optimal resilience, optimal amortized communication complexity, and optimal time complexity. DAG-Rider is post-quantum safe and ensures that all values proposed by correct processes eventually get delivered. We construct DAG-Rider in two layers: In the first layer, processes reliably broadcast their proposals and build a structured Directed Acyclic Graph (DAG) of the communication among them. In the second layer, processes locally observe their DAGs and totally order all proposals with no extra communication.}, author = {Keidar, Idit and Kokoris Kogias, Eleftherios and Naor, Oded and Spiegelman, Alexander}, booktitle = {Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing}, isbn = {978-1-4503-8548-0}, location = {Virtual, Italy}, pages = {165--175}, publisher = {Association for Computing Machinery}, title = {{All You Need is DAG}}, doi = {10.1145/3465084.3467905}, year = {2021}, } @article{10568, abstract = {Genetic adaptation and phenotypic plasticity facilitate the migration into new habitats and enable organisms to cope with a rapidly changing environment. In contrast to genetic adaptation that spans multiple generations as an evolutionary process, phenotypic plasticity allows acclimation within the life-time of an organism. Genetic adaptation and phenotypic plasticity are usually studied in isolation, however, only by including their interactive impact, we can understand acclimation and adaptation in nature. We aimed to explore the contribution of adaptation and plasticity in coping with an abiotic (salinity) and a biotic (Vibrio bacteria) stressor using six different populations of the broad-nosed pipefish Syngnathus typhle that originated from either high [14–17 Practical Salinity Unit (PSU)] or low (7–11 PSU) saline environments along the German coastline of the Baltic Sea. We exposed wild caught animals, to either high (15 PSU) or low (7 PSU) salinity, representing native and novel salinity conditions and allowed animals to mate. After male pregnancy, offspring was split and each half was exposed to one of the two salinities and infected with Vibrio alginolyticus bacteria that were evolved at either of the two salinities in a fully reciprocal design. We investigated life-history traits of fathers and expression of 47 target genes in mothers and offspring. Pregnant males originating from high salinity exposed to low salinity were highly susceptible to opportunistic fungi infections resulting in decreased offspring size and number. In contrast, no signs of fungal infection were identified in fathers originating from low saline conditions suggesting that genetic adaptation has the potential to overcome the challenges encountered at low salinity. Offspring from parents with low saline origin survived better at low salinity suggesting genetic adaptation to low salinity. In addition, gene expression analyses of juveniles indicated patterns of local adaptation, trans-generational plasticity and developmental plasticity. In conclusion, our study suggests that pipefish are locally adapted to the low salinity in their environment, however, they are retaining phenotypic plasticity, which allows them to also cope with ancestral salinity levels and prevailing pathogens.}, author = {Goehlich, Henry and Sartoris, Linda and Wagner, Kim-Sara and Wendling, Carolin C. and Roth, Olivia}, issn = {2296-701X}, journal = {Frontiers in Ecology and Evolution}, keywords = {ecology, evolution, behavior and systematics, trans-generational plasticity, genetic adaptation, local adaptation, phenotypic plasticity, Baltic Sea, climate change, salinity, syngnathids}, publisher = {Frontiers Media}, title = {{Pipefish locally adapted to low salinity in the Baltic Sea retain phenotypic plasticity to cope with ancestral salinity levels}}, doi = {10.3389/fevo.2021.626442}, volume = {9}, year = {2021}, } @article{10586, abstract = {A facile approach for developing an interfacial solar evaporator by heat localization of solar-thermal energy conversion at water-air liquid composed by in-situ polymerization of Fe2O3 nanoparticles (Fe2O3@PPy) deposited over a facial sponge is proposed. The demonstrated system consists of a floating solar receiver having a vertically cross-linked microchannel for wicking up saline water. The in situ polymerized Fe2O3@PPy interfacial layer promotes diffuse reflection and its rough black surface allows Omni-directional solar absorption (94%) and facilitates efficient thermal localization at the water/air interface and offers a defect-rich surface to promote heat localization (41.9 °C) and excellent thermal management due to cellulosic content. The self-floating composite foam reveals continuous vapors generation at a rate of 1.52 kg m−2 h−1 under one 1 kW m−2 and profound evaporating efficiency (95%) without heat losses that dissipates in its surroundings. Indeed, long-term evaporation experiments reveal the negligible disparity in continuous evaporation rate (33.84 kg m−2/8.3 h) receiving two sun solar intensity, and ensures the stability of the device under intense seawater conditions synchronized with excellent salt rejection potential. More importantly, Raman spectroscopy investigation validates the orange dye rejection via Fe2O3@PPy solar evaporator. The combined advantages of high efficiency, self-floating capability, multimedia rejection, low cost, and this configuration are promising for producing large-scale solar steam generating systems appropriate for commercial clean water yield due to their scalable fabrication.}, author = {Lu, Yuzheng and Arshad, Naila and Irshad, Muhammad Sultan and Ahmed, Iftikhar and Ahmad, Shafiq and Alshahrani, Lina Abdullah and Yousaf, Muhammad and Sayed, Abdelaty Edrees and Nauman, Muhammad}, issn = {2073-4352}, journal = {Crystals}, number = {12}, publisher = {MDPI}, title = {{Fe2O3 nanoparticles deposited over self-floating facial sponge for facile interfacial seawater solar desalination}}, doi = {10.3390/cryst11121509}, volume = {11}, year = {2021}, } @article{10569, abstract = {For animals to survive until reproduction, it is crucial that juveniles successfully detect potential predators and respond with appropriate behavior. The recognition of cues originating from predators can be innate or learned. Cues of various modalities might be used alone or in multi-modal combinations to detect and distinguish predators but studies investigating multi-modal integration in predator avoidance are scarce. Here, we used wild, naive tadpoles of the Neotropical poison frog Allobates femoralis ( Boulenger, 1884) to test their reaction to cues with two modalities from two different sympatrically occurring potential predators: heterospecific predatory Dendrobates tinctorius tadpoles and dragonfly larvae. We presented A. femoralis tadpoles with olfactory or visual cues, or a combination of the two, and compared their reaction to a water control in a between-individual design. In our trials, A. femoralis tadpoles reacted to multi-modal stimuli (a combination of visual and chemical information) originating from dragonfly larvae with avoidance but showed no reaction to uni-modal cues or cues from heterospecific tadpoles. In addition, visual cues from conspecifics increased swimming activity while cues from predators had no effect on tadpole activity. Our results show that A. femoralis tadpoles can innately recognize some predators and probably need both visual and chemical information to effectively avoid them. This is the first study looking at anti-predator behavior in poison frog tadpoles. We discuss how parental care might influence the expression of predator avoidance responses in tadpoles.}, author = {Szabo, B and Mangione, R and Rath, M and Pašukonis, A and Reber, SA and Oh, Jinook and Ringler, M and Ringler, E}, issn = {1477-9145}, journal = {Journal of Experimental Biology}, number = {24}, publisher = {The Company of Biologists}, title = {{Naïve poison frog tadpoles use bi-modal cues to avoid insect predators but not heterospecific predatory tadpoles}}, doi = {10.1242/jeb.243647}, volume = {224}, year = {2021}, } @article{10575, abstract = {The choice of the boundary conditions in mechanical problems has to reflect the interaction of the considered material with the surface. Still the assumption of the no-slip condition is preferred in order to avoid boundary terms in the analysis and slipping effects are usually overlooked. Besides the “static slip models”, there are phenomena that are not accurately described by them, e.g. at the moment when the slip changes rapidly, the wall shear stress and the slip can exhibit a sudden overshoot and subsequent relaxation. When these effects become significant, the so-called dynamic slip phenomenon occurs. We develop a mathematical analysis of Navier–Stokes-like problems with a dynamic slip boundary condition, which requires a proper generalization of the Gelfand triplet and the corresponding function space setting.}, author = {Abbatiello, Anna and Bulíček, Miroslav and Maringová, Erika}, issn = {1793-6314}, journal = {Mathematical Models and Methods in Applied Sciences}, number = {11}, pages = {2165--2212}, publisher = {World Scientific Publishing}, title = {{On the dynamic slip boundary condition for Navier-Stokes-like problems}}, doi = {10.1142/S0218202521500470}, volume = {31}, year = {2021}, } @article{10574, abstract = {The understanding of material appearance perception is a complex problem due to interactions between material reflectance, surface geometry, and illumination. Recently, Serrano et al. collected the largest dataset to date with subjective ratings of material appearance attributes, including glossiness, metallicness, sharpness and contrast of reflections. In this work, we make use of their dataset to investigate for the first time the impact of the interactions between illumination, geometry, and eight different material categories in perceived appearance attributes. After an initial analysis, we select for further analysis the four material categories that cover the largest range for all perceptual attributes: fabric, plastic, ceramic, and metal. Using a cumulative link mixed model (CLMM) for robust regression, we discover interactions between these material categories and four representative illuminations and object geometries. We believe that our findings contribute to expanding the knowledge on material appearance perception and can be useful for many applications, such as scene design, where any particular material in a given shape can be aligned with dominant classes of illumination, so that a desired strength of appearance attributes can be achieved.}, author = {Chen, Bin and Wang, Chao and Piovarci, Michael and Seidel, Hans Peter and Didyk, Piotr and Myszkowski, Karol and Serrano, Ana}, issn = {1432-2315}, journal = {Visual Computer}, number = {12}, pages = {2975--2987}, publisher = {Springer Nature}, title = {{The effect of geometry and illumination on appearance perception of different material categories}}, doi = {10.1007/s00371-021-02227-x}, volume = {37}, year = {2021}, } @article{10573, abstract = {How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.}, author = {Munjal, Akankshi and Hannezo, Edouard B and Tsai, Tony Y.C. and Mitchison, Timothy J. and Megason, Sean G.}, issn = {1097-4172}, journal = {Cell}, number = {26}, pages = {6313--6325.e18}, publisher = {Elsevier ; Cell Press}, title = {{Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis}}, doi = {10.1016/j.cell.2021.11.025}, volume = {184}, year = {2021}, } @article{10674, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets.}, author = {Aghajohari, Milad and Avni, Guy and Henzinger, Thomas A}, issn = {1860-5974}, journal = {Logical Methods in Computer Science}, keywords = {computer science, computer science and game theory, logic in computer science}, number = {1}, pages = {10:1--10:23}, publisher = {International Federation for Computational Logic}, title = {{Determinacy in discrete-bidding infinite-duration games}}, doi = {10.23638/LMCS-17(1:10)2021}, volume = {17}, year = {2021}, } @inproceedings{10609, abstract = {We study Multi-party computation (MPC) in the setting of subversion, where the adversary tampers with the machines of honest parties. Our goal is to construct actively secure MPC protocols where parties are corrupted adaptively by an adversary (as in the standard adaptive security setting), and in addition, honest parties’ machines are compromised. The idea of reverse firewalls (RF) was introduced at EUROCRYPT’15 by Mironov and Stephens-Davidowitz as an approach to protecting protocols against corruption of honest parties’ devices. Intuitively, an RF for a party P is an external entity that sits between P and the outside world and whose scope is to sanitize P ’s incoming and outgoing messages in the face of subversion of their computer. Mironov and Stephens-Davidowitz constructed a protocol for passively-secure two-party computation. At CRYPTO’20, Chakraborty, Dziembowski and Nielsen constructed a protocol for secure computation with firewalls that improved on this result, both by extending it to multi-party computation protocol, and considering active security in the presence of static corruptions. In this paper, we initiate the study of RF for MPC in the adaptive setting. We put forward a definition for adaptively secure MPC in the reverse firewall setting, explore relationships among the security notions, and then construct reverse firewalls for MPC in this stronger setting of adaptive security. We also resolve the open question of Chakraborty, Dziembowski and Nielsen by removing the need for a trusted setup in constructing RF for MPC. Towards this end, we construct reverse firewalls for adaptively secure augmented coin tossing and adaptively secure zero-knowledge protocols and obtain a constant round adaptively secure MPC protocol in the reverse firewall setting without setup. Along the way, we propose a new multi-party adaptively secure coin tossing protocol in the plain model, that is of independent interest.}, author = {Chakraborty, Suvradip and Ganesh, Chaya and Pancholi, Mahak and Sarkar, Pratik}, booktitle = {27th International Conference on the Theory and Application of Cryptology and Information Security}, isbn = {978-3-030-92074-6}, issn = {1611-3349}, location = {Virtual, Singapore}, pages = {335--364}, publisher = {Springer Nature}, title = {{Reverse firewalls for adaptively secure MPC without setup}}, doi = {10.1007/978-3-030-92075-3_12}, volume = {13091}, year = {2021}, } @article{10606, abstract = {Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s).}, author = {Godard, Benoit G and Dumollard, Remi and Heisenberg, Carl-Philipp J and Mcdougall, Alex}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Combined effect of cell geometry and polarity domains determines the orientation of unequal division}}, doi = {10.7554/eLife.75639}, volume = {10}, year = {2021}, } @article{10607, abstract = {The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders.}, author = {Venezia, Serena and Kaufmann, Walter and Wenning, Gregor K. and Stefanova, Nadia}, issn = {1873-5126}, journal = {Parkinsonism & Related Disorders}, pages = {59--65}, publisher = {Elsevier}, title = {{Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease}}, doi = {10.1016/j.parkreldis.2021.09.007}, volume = {91}, year = {2021}, } @article{10628, abstract = {The surface states of 3D topological insulators in general have negligible quantum oscillations (QOs) when the chemical potential is tuned to the Dirac points. In contrast, we find that topological Kondo insulators (TKIs) can support surface states with an arbitrarily large Fermi surface (FS) when the chemical potential is pinned to the Dirac point. We illustrate that these FSs give rise to finite-frequency QOs, which can become comparable to the extremal area of the unhybridized bulk bands. We show that this occurs when the crystal symmetry is lowered from cubic to tetragonal in a minimal two-orbital model. We label such surface modes as 'shadow surface states'. Moreover, we show that the sufficient next-nearest neighbor out-of-plane hybridization leading to shadow surface states can be self-consistently stabilized for tetragonal TKIs. Consequently, shadow surface states provide an important example of high-frequency QOs beyond the context of cubic TKIs.}, author = {Ghazaryan, Areg and Nica, Emilian M. and Erten, Onur and Ghaemi, Pouyan}, issn = {1367-2630}, journal = {New Journal of Physics}, number = {12}, publisher = {IOP Publishing}, title = {{Shadow surface states in topological Kondo insulators}}, doi = {10.1088/1367-2630/ac4124}, volume = {23}, year = {2021}, } @article{10631, abstract = {We combine experimental and theoretical approaches to explore excited rotational states of molecules embedded in helium nanodroplets using CS2 and I2 as examples. Laser-induced nonadiabatic molecular alignment is employed to measure spectral lines for rotational states extending beyond those initially populated at the 0.37 K droplet temperature. We construct a simple quantum-mechanical model, based on a linear rotor coupled to a single-mode bosonic bath, to determine the rotational energy structure in its entirety. The calculated and measured spectral lines are in good agreement. We show that the effect of the surrounding superfluid on molecular rotation can be rationalized by a single quantity, the angular momentum, transferred from the molecule to the droplet.}, author = {Cherepanov, Igor and Bighin, Giacomo and Schouder, Constant A. and Chatterley, Adam S. and Albrechtsen, Simon H. and Muñoz, Alberto Viñas and Christiansen, Lars and Stapelfeldt, Henrik and Lemeshko, Mikhail}, issn = {2469-9934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Excited rotational states of molecules in a superfluid}}, doi = {10.1103/PhysRevA.104.L061303}, volume = {104}, year = {2021}, } @inproceedings{10597, abstract = {We thank Emmanuel Abbe and Min Ye for providing us the implementation of RPA decoding. D. Fathollahi and M. Mondelli are partially supported by the 2019 Lopez-Loreta Prize. N. Farsad is supported by Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Canada Foundation for Innovation (CFI), John R. Evans Leader Fund. S. A. Hashemi is supported by a Postdoctoral Fellowship from NSERC.}, author = {Fathollahi, Dorsa and Farsad, Nariman and Hashemi, Seyyed Ali and Mondelli, Marco}, booktitle = {2021 IEEE International Symposium on Information Theory}, isbn = {978-1-5386-8210-4}, location = {Virtual, Melbourne, Australia}, pages = {1082--1087}, publisher = {Institute of Electrical and Electronics Engineers}, title = {{Sparse multi-decoder recursive projection aggregation for Reed-Muller codes}}, doi = {10.1109/isit45174.2021.9517887}, year = {2021}, } @inproceedings{10666, abstract = {Adversarial training is an effective method to train deep learning models that are resilient to norm-bounded perturbations, with the cost of nominal performance drop. While adversarial training appears to enhance the robustness and safety of a deep model deployed in open-world decision-critical applications, counterintuitively, it induces undesired behaviors in robot learning settings. In this paper, we show theoretically and experimentally that neural controllers obtained via adversarial training are subjected to three types of defects, namely transient, systematic, and conditional errors. We first generalize adversarial training to a safety-domain optimization scheme allowing for more generic specifications. We then prove that such a learning process tends to cause certain error profiles. We support our theoretical results by a thorough experimental safety analysis in a robot-learning task. Our results suggest that adversarial training is not yet ready for robot learning.}, author = {Lechner, Mathias and Hasani, Ramin and Grosu, Radu and Rus, Daniela and Henzinger, Thomas A}, booktitle = {2021 IEEE International Conference on Robotics and Automation}, isbn = {978-1-7281-9078-5}, issn = {2577-087X}, location = {Xi'an, China}, pages = {4140--4147}, title = {{Adversarial training is not ready for robot learning}}, doi = {10.1109/ICRA48506.2021.9561036}, year = {2021}, } @article{10711, abstract = {In this paper, we investigate the distribution of the maximum of partial sums of families of m -periodic complex-valued functions satisfying certain conditions. We obtain precise uniform estimates for the distribution function of this maximum in a near-optimal range. Our results apply to partial sums of Kloosterman sums and other families of ℓ -adic trace functions, and are as strong as those obtained by Bober, Goldmakher, Granville and Koukoulopoulos for character sums. In particular, we improve on the recent work of the third author for Birch sums. However, unlike character sums, we are able to construct families of m -periodic complex-valued functions which satisfy our conditions, but for which the Pólya–Vinogradov inequality is sharp.}, author = {Autissier, Pascal and Bonolis, Dante and Lamzouri, Youness}, issn = {1570-5846}, journal = {Compositio Mathematica}, keywords = {Algebra and Number Theory}, number = {7}, pages = {1610--1651}, publisher = {Cambridge University Press}, title = {{The distribution of the maximum of partial sums of Kloosterman sums and other trace functions}}, doi = {10.1112/s0010437x21007351}, volume = {157}, year = {2021}, } @article{10809, abstract = {Thermoelectric materials are engines that convert heat into an electrical current. Intuitively, the efficiency of this process depends on how many electrons (charge carriers) can move and how easily they do so, how much energy those moving electrons transport, and how easily the temperature gradient is maintained. In terms of material properties, an excellent thermoelectric material requires a high electrical conductivity σ, a high Seebeck coefficient S (a measure of the induced thermoelectric voltage as a function of temperature gradient), and a low thermal conductivity κ. The challenge is that these three properties are strongly interrelated in a conflicting manner (1). On page 722 of this issue, Roychowdhury et al. (2) have found a way to partially break these ties in silver antimony telluride (AgSbTe2) with the addition of cadmium (Cd) cations, which increase the ordering in this inherently disordered thermoelectric material.}, author = {Liu, Yu and Ibáñez, Maria}, issn = {1095-9203}, journal = {Science}, keywords = {multidisciplinary}, number = {6530}, pages = {678--679}, publisher = {American Association for the Advancement of Science}, title = {{Tidying up the mess}}, doi = {10.1126/science.abg0886}, volume = {371}, year = {2021}, } @article{10858, abstract = {The cost-effective conversion of low-grade heat into electricity using thermoelectric devices requires developing alternative materials and material processing technologies able to reduce the currently high device manufacturing costs. In this direction, thermoelectric materials that do not rely on rare or toxic elements such as tellurium or lead need to be produced using high-throughput technologies not involving high temperatures and long processes. Bi2Se3 is an obvious possible Te-free alternative to Bi2Te3 for ambient temperature thermoelectric applications, but its performance is still low for practical applications, and additional efforts toward finding proper dopants are required. Here, we report a scalable method to produce Bi2Se3 nanosheets at low synthesis temperatures. We studied the influence of different dopants on the thermoelectric properties of this material. Among the elements tested, we demonstrated that Sn doping resulted in the best performance. Sn incorporation resulted in a significant improvement to the Bi2Se3 Seebeck coefficient and a reduction in the thermal conductivity in the direction of the hot-press axis, resulting in an overall 60% improvement in the thermoelectric figure of merit of Bi2Se3.}, author = {Li, Mengyao and Zhang, Yu and Zhang, Ting and Zuo, Yong and Xiao, Ke and Arbiol, Jordi and Llorca, Jordi and Liu, Yu and Cabot, Andreu}, issn = {2079-4991}, journal = {Nanomaterials}, keywords = {General Materials Science, General Chemical Engineering}, number = {7}, publisher = {MDPI}, title = {{Enhanced thermoelectric performance of n-type Bi2Se3 nanosheets through Sn doping}}, doi = {10.3390/nano11071827}, volume = {11}, year = {2021}, } @article{10834, abstract = {Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis.}, author = {Stahnke, Stephanie and Döring, Hermann and Kusch, Charly and de Gorter, David J.J. and Dütting, Sebastian and Guledani, Aleks and Pleines, Irina and Schnoor, Michael and Sixt, Michael K and Geffers, Robert and Rohde, Manfred and Müsken, Mathias and Kage, Frieda and Steffen, Anika and Faix, Jan and Nieswandt, Bernhard and Rottner, Klemens and Stradal, Theresia E.B.}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {2051--2064.e8}, publisher = {Elsevier}, title = {{Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion}}, doi = {10.1016/j.cub.2021.02.043}, volume = {31}, year = {2021}, } @inproceedings{9935, abstract = {We present a deterministic O(log log log n)-round low-space Massively Parallel Computation (MPC) algorithm for the classical problem of (Δ+1)-coloring on n-vertex graphs. In this model, every machine has sublinear local space of size n^φ for any arbitrary constant φ \in (0,1). Our algorithm works under the relaxed setting where each machine is allowed to perform exponential local computations, while respecting the n^φ space and bandwidth limitations. Our key technical contribution is a novel derandomization of the ingenious (Δ+1)-coloring local algorithm by Chang-Li-Pettie (STOC 2018, SIAM J. Comput. 2020). The Chang-Li-Pettie algorithm runs in T_local =poly(loglog n) rounds, which sets the state-of-the-art randomized round complexity for the problem in the local model. Our derandomization employs a combination of tools, notably pseudorandom generators (PRG) and bounded-independence hash functions. The achieved round complexity of O(logloglog n) rounds matches the bound of log(T_local ), which currently serves an upper bound barrier for all known randomized algorithms for locally-checkable problems in this model. Furthermore, no deterministic sublogarithmic low-space MPC algorithms for the (Δ+1)-coloring problem have been known before.}, author = {Czumaj, Artur and Davies, Peter and Parter, Merav}, booktitle = {Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing}, isbn = {978-1-4503-8548-0}, location = {Virtual, Italy}, pages = {469–479}, publisher = {Association for Computing Machinery}, title = {{Improved deterministic (Δ+1) coloring in low-space MPC}}, doi = {10.1145/3465084.3467937}, year = {2021}, } @article{10856, abstract = {We study the properties of the maximal volume k-dimensional sections of the n-dimensional cube [−1, 1]n. We obtain a first order necessary condition for a k-dimensional subspace to be a local maximizer of the volume of such sections, which we formulate in a geometric way. We estimate the length of the projection of a vector of the standard basis of Rn onto a k-dimensional subspace that maximizes the volume of the intersection. We nd the optimal upper bound on the volume of a planar section of the cube [−1, 1]n , n ≥ 2.}, author = {Ivanov, Grigory and Tsiutsiurupa, Igor}, issn = {2299-3274}, journal = {Analysis and Geometry in Metric Spaces}, keywords = {Applied Mathematics, Geometry and Topology, Analysis}, number = {1}, pages = {1--18}, publisher = {De Gruyter}, title = {{On the volume of sections of the cube}}, doi = {10.1515/agms-2020-0103}, volume = {9}, year = {2021}, } @inproceedings{9933, abstract = {In this paper, we study the power and limitations of component-stable algorithms in the low-space model of Massively Parallel Computation (MPC). Recently Ghaffari, Kuhn and Uitto (FOCS 2019) introduced the class of component-stable low-space MPC algorithms, which are, informally, defined as algorithms for which the outputs reported by the nodes in different connected components are required to be independent. This very natural notion was introduced to capture most (if not all) of the known efficient MPC algorithms to date, and it was the first general class of MPC algorithms for which one can show non-trivial conditional lower bounds. In this paper we enhance the framework of component-stable algorithms and investigate its effect on the complexity of randomized and deterministic low-space MPC. Our key contributions include: 1) We revise and formalize the lifting approach of Ghaffari, Kuhn and Uitto. This requires a very delicate amendment of the notion of component stability, which allows us to fill in gaps in the earlier arguments. 2) We also extend the framework to obtain conditional lower bounds for deterministic algorithms and fine-grained lower bounds that depend on the maximum degree Δ. 3) We demonstrate a collection of natural graph problems for which non-component-stable algorithms break the conditional lower bound obtained for component-stable algorithms. This implies that, for both deterministic and randomized algorithms, component-stable algorithms are conditionally weaker than the non-component-stable ones. Altogether our results imply that component-stability might limit the computational power of the low-space MPC model, paving the way for improved upper bounds that escape the conditional lower bound setting of Ghaffari, Kuhn, and Uitto.}, author = {Czumaj, Artur and Davies, Peter and Parter, Merav}, booktitle = {Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing}, isbn = {9781450385480}, location = {Virtual, Italy}, pages = {481–491}, publisher = {Association for Computing Machinery}, title = {{Component stability in low-space massively parallel computation}}, doi = {10.1145/3465084.3467903}, year = {2021}, } @article{9627, abstract = {We compute the deficiency spaces of operators of the form 𝐻𝐴⊗̂ 𝐼+𝐼⊗̂ 𝐻𝐵, for symmetric 𝐻𝐴 and self-adjoint 𝐻𝐵. This enables us to construct self-adjoint extensions (if they exist) by means of von Neumann's theory. The structure of the deficiency spaces for this case was asserted already in Ibort et al. [Boundary dynamics driven entanglement, J. Phys. A: Math. Theor. 47(38) (2014) 385301], but only proven under the restriction of 𝐻𝐵 having discrete, non-degenerate spectrum.}, author = {Lenz, Daniel and Weinmann, Timon and Wirth, Melchior}, issn = {1464-3839}, journal = {Proceedings of the Edinburgh Mathematical Society}, number = {3}, pages = {443--447}, publisher = {Cambridge University Press}, title = {{Self-adjoint extensions of bipartite Hamiltonians}}, doi = {10.1017/S0013091521000080}, volume = {64}, year = {2021}, } @article{7901, abstract = {We derive rigorously the leading order of the correlation energy of a Fermi gas in a scaling regime of high density and weak interaction. The result verifies the prediction of the random-phase approximation. Our proof refines the method of collective bosonization in three dimensions. We approximately diagonalize an effective Hamiltonian describing approximately bosonic collective excitations around the Hartree–Fock state, while showing that gapless and non-collective excitations have only a negligible effect on the ground state energy.}, author = {Benedikter, Niels P and Nam, Phan Thành and Porta, Marcello and Schlein, Benjamin and Seiringer, Robert}, issn = {1432-1297}, journal = {Inventiones Mathematicae}, pages = {885--979}, publisher = {Springer}, title = {{Correlation energy of a weakly interacting Fermi gas}}, doi = {10.1007/s00222-021-01041-5}, volume = {225}, year = {2021}, } @article{13455, abstract = {The majority of massive stars live in binary or multiple systems and will interact with a companion during their lifetimes, which helps to explain the observed diversity of core-collapse supernovae. Donor stars in binary systems can lose most of their hydrogen-rich envelopes through mass transfer. As a result, not only are the surface properties affected, but so is the core structure. However, most calculations of the core-collapse properties of massive stars rely on single-star models. We present a systematic study of the difference between the pre-supernova structures of single stars and stars of the same initial mass (11–21 M⊙) that have been stripped due to stable post-main-sequence mass transfer at solar metallicity. We present the pre-supernova core composition with novel diagrams that give an intuitive representation of the isotope distribution. As shown in previous studies, at the edge of the carbon-oxygen core, the binary-stripped star models contain an extended gradient of carbon, oxygen, and neon. This layer remains until core collapse and is more extended in mass for higher initial stellar masses. It originates from the receding of the convective helium core during core helium burning in binary-stripped stars, which does not occur in single-star models. We find that this same evolutionary phase leads to systematic differences in the final density and nuclear energy generation profiles. Binary-stripped star models have systematically higher total masses of carbon at the moment of core collapse compared to single-star models, which likely results in systematically different supernova yields. In about half of our models, the silicon-burning and oxygen-rich layers merge after core silicon burning. We discuss the implications of our findings for the “explodability”, supernova observations, and nucleosynthesis of these stars. Our models are publicly available and can be readily used as input for detailed supernova simulations.}, author = {Laplace, E. and Justham, S. and Renzo, M. and Götberg, Ylva Louise Linsdotter and Farmer, R. and Vartanyan, D. and de Mink, S. E.}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, publisher = {EDP Sciences}, title = {{Different to the core: The pre-supernova structures of massive single and binary-stripped stars}}, doi = {10.1051/0004-6361/202140506}, volume = {656}, year = {2021}, } @article{10005, abstract = {We study systems of nonlinear partial differential equations of parabolic type, in which the elliptic operator is replaced by the first-order divergence operator acting on a flux function, which is related to the spatial gradient of the unknown through an additional implicit equation. This setting, broad enough in terms of applications, significantly expands the paradigm of nonlinear parabolic problems. Formulating four conditions concerning the form of the implicit equation, we first show that these conditions describe a maximal monotone p-coercive graph. We then establish the global-in-time and large-data existence of a (weak) solution and its uniqueness. To this end, we adopt and significantly generalize Minty’s method of monotone mappings. A unified theory, containing several novel tools, is developed in a way to be tractable from the point of view of numerical approximations.}, author = {Bulíček, Miroslav and Maringová, Erika and Málek, Josef}, issn = {1793-6314}, journal = {Mathematical Models and Methods in Applied Sciences}, keywords = {Nonlinear parabolic systems, implicit constitutive theory, weak solutions, existence, uniqueness}, number = {09}, publisher = {World Scientific}, title = {{On nonlinear problems of parabolic type with implicit constitutive equations involving flux}}, doi = {10.1142/S0218202521500457}, volume = {31}, year = {2021}, } @inproceedings{10553, abstract = {The popularity of permissioned blockchain systems demands BFT SMR protocols that are efficient under good network conditions (synchrony) and robust under bad network conditions (asynchrony). The state-of-the-art partially synchronous BFT SMR protocols provide optimal linear communication cost per decision under synchrony and good leaders, but lose liveness under asynchrony. On the other hand, the state-of-the-art asynchronous BFT SMR protocols are live even under asynchrony, but always pay quadratic cost even under synchrony. In this paper, we propose a BFT SMR protocol that achieves the best of both worlds -- optimal linear cost per decision under good networks and leaders, optimal quadratic cost per decision under bad networks, and remains always live.}, author = {Gelashvili, Rati and Kokoris Kogias, Eleftherios and Spiegelman, Alexander and Xiang, Zhuolun}, booktitle = {Proceedings of the 2021 ACM Symposium on Principles of Distributed Computing}, isbn = {9-781-4503-8548-0}, keywords = {optimal, state machine replication, fallback, asynchrony, byzantine faults}, location = {Virtual, Italy}, pages = {187--190}, publisher = {Association for Computing Machinery}, title = {{Brief announcement: Be prepared when network goes bad: An asynchronous view-change protocol}}, doi = {10.1145/3465084.3467941}, year = {2021}, } @article{9048, abstract = {The analogy between an equilibrium partition function and the return probability in many-body unitary dynamics has led to the concept of dynamical quantum phase transition (DQPT). DQPTs are defined by nonanalyticities in the return amplitude and are present in many models. In some cases, DQPTs can be related to equilibrium concepts, such as order parameters, yet their universal description is an open question. In this Letter, we provide first steps toward a classification of DQPTs by using a matrix product state description of unitary dynamics in the thermodynamic limit. This allows us to distinguish the two limiting cases of “precession” and “entanglement” DQPTs, which are illustrated using an analytical description in the quantum Ising model. While precession DQPTs are characterized by a large entanglement gap and are semiclassical in their nature, entanglement DQPTs occur near avoided crossings in the entanglement spectrum and can be distinguished by a complex pattern of nonlocal correlations. We demonstrate the existence of precession and entanglement DQPTs beyond Ising models, discuss observables that can distinguish them, and relate their interplay to complex DQPT phenomenology.}, author = {De Nicola, Stefano and Michailidis, Alexios and Serbyn, Maksym}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {4}, publisher = {American Physical Society}, title = {{Entanglement view of dynamical quantum phase transitions}}, doi = {10.1103/physrevlett.126.040602}, volume = {126}, year = {2021}, } @article{9368, abstract = {The quality control system for messenger RNA (mRNA) is fundamental for cellular activities in eukaryotes. To elucidate the molecular mechanism of 3'-Phosphoinositide-Dependent Protein Kinase1 (PDK1), a master regulator that is essential throughout eukaryotic growth and development, we employed a forward genetic approach to screen for suppressors of the loss-of-function T-DNA insertion double mutant pdk1.1 pdk1.2 in Arabidopsis thaliana. Notably, the severe growth attenuation of pdk1.1 pdk1.2 was rescued by sop21 (suppressor of pdk1.1 pdk1.2), which harbours a loss-of-function mutation in PELOTA1 (PEL1). PEL1 is a homologue of mammalian PELOTA and yeast (Saccharomyces cerevisiae) DOM34p, which each form a heterodimeric complex with the GTPase HBS1 (HSP70 SUBFAMILY B SUPPRESSOR1, also called SUPERKILLER PROTEIN7, SKI7), a protein that is responsible for ribosomal rescue and thereby assures the quality and fidelity of mRNA molecules during translation. Genetic analysis further revealed that a dysfunctional PEL1-HBS1 complex failed to degrade the T-DNA-disrupted PDK1 transcripts, which were truncated but functional, and thus rescued the growth and developmental defects of pdk1.1 pdk1.2. Our studies demonstrated the functionality of a homologous PELOTA-HBS1 complex and identified its essential regulatory role in plants, providing insights into the mechanism of mRNA quality control.}, author = {Kong, W and Tan, Shutang and Zhao, Q and Lin, DL and Xu, ZH and Friml, Jiří and Xue, HW}, issn = {1532-2548}, journal = {Plant Physiology}, number = {4}, pages = {2003--2020}, publisher = {American Society of Plant Biologists}, title = {{mRNA surveillance complex PELOTA-HBS1 eegulates phosphoinositide-sependent protein kinase1 and plant growth}}, doi = {10.1093/plphys/kiab199}, volume = {186}, year = {2021}, } @article{10860, abstract = {A tight frame is the orthogonal projection of some orthonormal basis of Rn onto Rk. We show that a set of vectors is a tight frame if and only if the set of all cross products of these vectors is a tight frame. We reformulate a range of problems on the volume of projections (or sections) of regular polytopes in terms of tight frames and write a first-order necessary condition for local extrema of these problems. As applications, we prove new results for the problem of maximization of the volume of zonotopes.}, author = {Ivanov, Grigory}, issn = {1496-4287}, journal = {Canadian Mathematical Bulletin}, keywords = {General Mathematics, Tight frame, Grassmannian, zonotope}, number = {4}, pages = {942--963}, publisher = {Canadian Mathematical Society}, title = {{Tight frames and related geometric problems}}, doi = {10.4153/s000843952000096x}, volume = {64}, year = {2021}, } @article{9290, abstract = {Polar subcellular localization of the PIN exporters of the phytohormone auxin is a key determinant of directional, intercellular auxin transport and thus a central topic of both plant cell and developmental biology. Arabidopsis mutants lacking PID, a kinase that phosphorylates PINs, or the MAB4/MEL proteins of unknown molecular function display PIN polarity defects and phenocopy pin mutants, but mechanistic insights into how these factors convey PIN polarity are missing. Here, by combining protein biochemistry with quantitative live-cell imaging, we demonstrate that PINs, MAB4/MELs, and AGC kinases interact in the same complex at the plasma membrane. MAB4/MELs are recruited to the plasma membrane by the PINs and in concert with the AGC kinases maintain PIN polarity through limiting lateral diffusion-based escape of PINs from the polar domain. The PIN-MAB4/MEL-PID protein complex has self-reinforcing properties thanks to positive feedback between AGC kinase-mediated PIN phosphorylation and MAB4/MEL recruitment. We thus uncover the molecular mechanism by which AGC kinases and MAB4/MEL proteins regulate PIN localization and plant development.}, author = {Glanc, Matous and Van Gelderen, K and Hörmayer, Lukas and Tan, Shutang and Naramoto, S and Zhang, Xixi and Domjan, David and Vcelarova, L and Hauschild, Robert and Johnson, Alexander J and de Koning, E and van Dop, M and Rademacher, E and Janson, S and Wei, X and Molnar, Gergely and Fendrych, Matyas and De Rybel, B and Offringa, R and Friml, Jiří}, issn = {1879-0445}, journal = {Current Biology}, number = {9}, pages = {1918--1930}, publisher = {Elsevier}, title = {{AGC kinases and MAB4/MEL proteins maintain PIN polarity by limiting lateral diffusion in plant cells}}, doi = {10.1016/j.cub.2021.02.028}, volume = {31}, year = {2021}, } @article{8824, abstract = {Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface.}, author = {Marquès-Bueno, MM and Armengot, L and Noack, LC and Bareille, J and Rodriguez Solovey, Lesia and Platre, MP and Bayle, V and Liu, M and Opdenacker, D and Vanneste, S and Möller, BK and Nimchuk, ZL and Beeckman, T and Caño-Delgado, AI and Friml, Jiří and Jaillais, Y}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, publisher = {Elsevier}, title = {{Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism}}, doi = {10.1016/j.cub.2020.10.011}, volume = {31}, year = {2021}, } @article{9301, abstract = {Electrodepositing insulating lithium peroxide (Li2O2) is the key process during discharge of aprotic Li–O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and dissolved lithium superoxide governs whether Li2O2 grows as a conformal surface film or larger particles, leading to low or high capacities, respectively. However, better understanding governing factors for Li2O2 packing density and capacity requires structural sensitive in situ metrologies. Here, we establish in situ small- and wide-angle X-ray scattering (SAXS/WAXS) as a suitable method to record the Li2O2 phase evolution with atomic to submicrometer resolution during cycling a custom-built in situ Li–O2 cell. Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative structural information from complex multiphase systems. Surprisingly, we find that features are absent that would point at a Li2O2 surface film formed via two consecutive electron transfers, even in poorly solvating electrolytes thought to be prototypical for surface growth. All scattering data can be modeled by stacks of thin Li2O2 platelets potentially forming large toroidal particles. Li2O2 solution growth is further justified by rotating ring-disk electrode measurements and electron microscopy. Higher discharge overpotentials lead to smaller Li2O2 particles, but there is no transition to an electronically passivating, conformal Li2O2 coating. Hence, mass transport of reactive species rather than electronic transport through a Li2O2 film limits the discharge capacity. Provided that species mobilities and carbon surface areas are high, this allows for high discharge capacities even in weakly solvating electrolytes. The currently accepted Li–O2 reaction mechanism ought to be reconsidered.}, author = {Prehal, Christian and Samojlov, Aleksej and Nachtnebel, Manfred and Lovicar, Ludek and Kriechbaum, Manfred and Amenitsch, Heinz and Freunberger, Stefan Alexander}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {small-angle X-ray scattering, oxygen reduction, disproportionation, Li-air battery}, number = {14}, publisher = {National Academy of Sciences}, title = {{In situ small-angle X-ray scattering reveals solution phase discharge of Li–O2 batteries with weakly solvating electrolytes}}, doi = {10.1073/pnas.2021893118}, volume = {118}, year = {2021}, } @article{9447, abstract = {Lithium bis(trifluoromethylsulfonyl)imide (LiTFSI) based water-in-salt electrolytes (WiSEs) has recently emerged as a new promising class of electrolytes, primarily owing to their wide electrochemical stability windows (~3–4 V), that by far exceed the thermodynamic stability window of water (1.23 V). Upon increasing the salt concentration towards superconcentration the onset of the oxygen evolution reaction (OER) shifts more significantly than the hydrogen evolution reaction (HER) does. The OER shift has been explained by the accumulation of hydrophobic anions blocking water access to the electrode surface, hence by double layer theory. Here we demonstrate that the processes during oxidation are much more complex, involving OER, carbon and salt decomposition by OER intermediates, and salt precipitation upon local oversaturation. The positive shift in the onset potential of oxidation currents was elucidated by combining several advanced analysis techniques: rotating ring-disk electrode voltammetry, online electrochemical mass spectrometry, and X-ray photoelectron spectroscopy, using both dilute and superconcentrated electrolytes. The results demonstrate the importance of reactive OER intermediates and surface films for electrolyte and electrode stability and motivate further studies of the nature of the electrode.}, author = {Maffre, Marion and Bouchal, Roza and Freunberger, Stefan Alexander and Lindahl, Niklas and Johansson, Patrik and Favier, Frédéric and Fontaine, Olivier and Bélanger, Daniel}, issn = {1945-7111}, journal = {Journal of The Electrochemical Society}, keywords = {Renewable Energy, Sustainability and the Environment, Electrochemistry, Materials Chemistry, Electronic, Optical and Magnetic Materials, Surfaces, Coatings and Films, Condensed Matter Physics}, number = {5}, publisher = {IOP Publishing}, title = {{Investigation of electrochemical and chemical processes occurring at positive potentials in “Water-in-Salt” electrolytes}}, doi = {10.1149/1945-7111/ac0300}, volume = {168}, year = {2021}, } @article{9094, abstract = {Dendritic cells (DCs) are crucial for the priming of naive T cells and the initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell contact, the immunological synapse (IS). While it is established that F-actin dynamics regulates signaling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. Here, we show that the DC actin cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. DC actin at the IS appears in transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of activated and proliferating T cells, demonstrating an important role for DC actin in the regulation of immune synapse functionality.}, author = {Leithner, Alexander F and Altenburger, LM and Hauschild, R and Assen, Frank P and Rottner, K and TEB, Stradal and Diz-Muñoz, A and Stein, JV and Sixt, Michael K}, issn = {1540-8140}, journal = {Journal of Cell Biology}, number = {4}, publisher = {Rockefeller University Press}, title = {{Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse}}, doi = {10.1083/jcb.202006081}, volume = {220}, year = {2021}, } @article{9073, abstract = {The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention.}, author = {Hanganu-Opatz, Ileana L. and Butt, Simon J. B. and Hippenmeyer, Simon and De Marco García, Natalia V. and Cardin, Jessica A. and Voytek, Bradley and Muotri, Alysson R.}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, keywords = {General Neuroscience}, number = {5}, pages = {813--822}, publisher = {Society for Neuroscience}, title = {{The logic of developing neocortical circuits in health and disease}}, doi = {10.1523/jneurosci.1655-20.2020}, volume = {41}, year = {2021}, } @article{10211, abstract = {We study the problem of recovering an unknown signal 𝑥𝑥 given measurements obtained from a generalized linear model with a Gaussian sensing matrix. Two popular solutions are based on a linear estimator 𝑥𝑥^L and a spectral estimator 𝑥𝑥^s. The former is a data-dependent linear combination of the columns of the measurement matrix, and its analysis is quite simple. The latter is the principal eigenvector of a data-dependent matrix, and a recent line of work has studied its performance. In this paper, we show how to optimally combine 𝑥𝑥^L and 𝑥𝑥^s. At the heart of our analysis is the exact characterization of the empirical joint distribution of (𝑥𝑥,𝑥𝑥^L,𝑥𝑥^s) in the high-dimensional limit. This allows us to compute the Bayes-optimal combination of 𝑥𝑥^L and 𝑥𝑥^s, given the limiting distribution of the signal 𝑥𝑥. When the distribution of the signal is Gaussian, then the Bayes-optimal combination has the form 𝜃𝑥𝑥^L+𝑥𝑥^s and we derive the optimal combination coefficient. In order to establish the limiting distribution of (𝑥𝑥,𝑥𝑥^L,𝑥𝑥^s), we design and analyze an approximate message passing algorithm whose iterates give 𝑥𝑥^L and approach 𝑥𝑥^s. Numerical simulations demonstrate the improvement of the proposed combination with respect to the two methods considered separately.}, author = {Mondelli, Marco and Thrampoulidis, Christos and Venkataramanan, Ramji}, issn = {1615-3383}, journal = {Foundations of Computational Mathematics}, keywords = {Applied Mathematics, Computational Theory and Mathematics, Computational Mathematics, Analysis}, publisher = {Springer}, title = {{Optimal combination of linear and spectral estimators for generalized linear models}}, doi = {10.1007/s10208-021-09531-x}, year = {2021}, } @article{8940, abstract = {We quantise Whitney’s construction to prove the existence of a triangulation for any C^2 manifold, so that we get an algorithm with explicit bounds. We also give a new elementary proof, which is completely geometric.}, author = {Boissonnat, Jean-Daniel and Kachanovich, Siargey and Wintraecken, Mathijs}, issn = {1432-0444}, journal = {Discrete & Computational Geometry}, keywords = {Theoretical Computer Science, Computational Theory and Mathematics, Geometry and Topology, Discrete Mathematics and Combinatorics}, number = {1}, pages = {386--434}, publisher = {Springer Nature}, title = {{Triangulating submanifolds: An elementary and quantified version of Whitney’s method}}, doi = {10.1007/s00454-020-00250-8}, volume = {66}, year = {2021}, } @article{9121, abstract = {We show that the energy gap for the BCS gap equation is Ξ=μ(8e−2+o(1))exp(π2μ−−√a) in the low density limit μ→0. Together with the similar result for the critical temperature by Hainzl and Seiringer (Lett Math Phys 84: 99–107, 2008), this shows that, in the low density limit, the ratio of the energy gap and critical temperature is a universal constant independent of the interaction potential V. The results hold for a class of potentials with negative scattering length a and no bound states.}, author = {Lauritsen, Asbjørn Bækgaard}, issn = {1573-0530}, journal = {Letters in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, publisher = {Springer Nature}, title = {{The BCS energy gap at low density}}, doi = {10.1007/s11005-021-01358-5}, volume = {111}, year = {2021}, } @article{9234, abstract = {In this paper, we present two new inertial projection-type methods for solving multivalued variational inequality problems in finite-dimensional spaces. We establish the convergence of the sequence generated by these methods when the multivalued mapping associated with the problem is only required to be locally bounded without any monotonicity assumption. Furthermore, the inertial techniques that we employ in this paper are quite different from the ones used in most papers. Moreover, based on the weaker assumptions on the inertial factor in our methods, we derive several special cases of our methods. Finally, we present some experimental results to illustrate the profits that we gain by introducing the inertial extrapolation steps.}, author = {Izuchukwu, Chinedu and Shehu, Yekini}, issn = {1572-9427}, journal = {Networks and Spatial Economics}, keywords = {Computer Networks and Communications, Software, Artificial Intelligence}, number = {2}, pages = {291--323}, publisher = {Springer Nature}, title = {{New inertial projection methods for solving multivalued variational inequality problems beyond monotonicity}}, doi = {10.1007/s11067-021-09517-w}, volume = {21}, year = {2021}, } @article{9111, abstract = {We study the probabilistic convergence between the mapper graph and the Reeb graph of a topological space X equipped with a continuous function f:X→R. We first give a categorification of the mapper graph and the Reeb graph by interpreting them in terms of cosheaves and stratified covers of the real line R. We then introduce a variant of the classic mapper graph of Singh et al. (in: Eurographics symposium on point-based graphics, 2007), referred to as the enhanced mapper graph, and demonstrate that such a construction approximates the Reeb graph of (X,f) when it is applied to points randomly sampled from a probability density function concentrated on (X,f). Our techniques are based on the interleaving distance of constructible cosheaves and topological estimation via kernel density estimates. Following Munch and Wang (In: 32nd international symposium on computational geometry, volume 51 of Leibniz international proceedings in informatics (LIPIcs), Dagstuhl, Germany, pp 53:1–53:16, 2016), we first show that the mapper graph of (X,f), a constructible R-space (with a fixed open cover), approximates the Reeb graph of the same space. We then construct an isomorphism between the mapper of (X,f) to the mapper of a super-level set of a probability density function concentrated on (X,f). Finally, building on the approach of Bobrowski et al. (Bernoulli 23(1):288–328, 2017b), we show that, with high probability, we can recover the mapper of the super-level set given a sufficiently large sample. Our work is the first to consider the mapper construction using the theory of cosheaves in a probabilistic setting. It is part of an ongoing effort to combine sheaf theory, probability, and statistics, to support topological data analysis with random data.}, author = {Brown, Adam and Bobrowski, Omer and Munch, Elizabeth and Wang, Bei}, issn = {2367-1734}, journal = {Journal of Applied and Computational Topology}, number = {1}, pages = {99--140}, publisher = {Springer Nature}, title = {{Probabilistic convergence and stability of random mapper graphs}}, doi = {10.1007/s41468-020-00063-x}, volume = {5}, year = {2021}, } @article{9252, abstract = {This paper analyses the conditions for local adaptation in a metapopulation with infinitely many islands under a model of hard selection, where population size depends on local fitness. Each island belongs to one of two distinct ecological niches or habitats. Fitness is influenced by an additive trait which is under habitat‐dependent directional selection. Our analysis is based on the diffusion approximation and accounts for both genetic drift and demographic stochasticity. By neglecting linkage disequilibria, it yields the joint distribution of allele frequencies and population size on each island. We find that under hard selection, the conditions for local adaptation in a rare habitat are more restrictive for more polygenic traits: even moderate migration load per locus at very many loci is sufficient for population sizes to decline. This further reduces the efficacy of selection at individual loci due to increased drift and because smaller populations are more prone to swamping due to migration, causing a positive feedback between increasing maladaptation and declining population sizes. Our analysis also highlights the importance of demographic stochasticity, which exacerbates the decline in numbers of maladapted populations, leading to population collapse in the rare habitat at significantly lower migration than predicted by deterministic arguments.}, author = {Szep, Eniko and Sachdeva, Himani and Barton, Nicholas H}, issn = {1558-5646}, journal = {Evolution}, keywords = {Genetics, Ecology, Evolution, Behavior and Systematics, General Agricultural and Biological Sciences}, number = {5}, pages = {1030--1045}, publisher = {Wiley}, title = {{Polygenic local adaptation in metapopulations: A stochastic eco‐evolutionary model}}, doi = {10.1111/evo.14210}, volume = {75}, year = {2021}, } @article{9374, abstract = {If there are no constraints on the process of speciation, then the number of species might be expected to match the number of available niches and this number might be indefinitely large. One possible constraint is the opportunity for allopatric divergence. In 1981, Felsenstein used a simple and elegant model to ask if there might also be genetic constraints. He showed that progress towards speciation could be described by the build‐up of linkage disequilibrium among divergently selected loci and between these loci and those contributing to other forms of reproductive isolation. Therefore, speciation is opposed by recombination, because it tends to break down linkage disequilibria. Felsenstein then introduced a crucial distinction between “two‐allele” models, which are subject to this effect, and “one‐allele” models, which are free from the recombination constraint. These fundamentally important insights have been the foundation for both empirical and theoretical studies of speciation ever since.}, author = {Butlin, Roger K. and Servedio, Maria R. and Smadja, Carole M. and Bank, Claudia and Barton, Nicholas H and Flaxman, Samuel M. and Giraud, Tatiana and Hopkins, Robin and Larson, Erica L. and Maan, Martine E. and Meier, Joana and Merrill, Richard and Noor, Mohamed A. F. and Ortiz‐Barrientos, Daniel and Qvarnström, Anna}, issn = {1558-5646}, journal = {Evolution}, keywords = {Genetics, Ecology, Evolution, Behavior and Systematics, General Agricultural and Biological Sciences}, number = {5}, pages = {978--988}, publisher = {Wiley}, title = {{Homage to Felsenstein 1981, or why are there so few/many species?}}, doi = {10.1111/evo.14235}, volume = {75}, year = {2021}, } @misc{13062, abstract = {This paper analyzes the conditions for local adaptation in a metapopulation with infinitely many islands under a model of hard selection, where population size depends on local fitness. Each island belongs to one of two distinct ecological niches or habitats. Fitness is influenced by an additive trait which is under habitat-dependent directional selection. Our analysis is based on the diffusion approximation and accounts for both genetic drift and demographic stochasticity. By neglecting linkage disequilibria, it yields the joint distribution of allele frequencies and population size on each island. We find that under hard selection, the conditions for local adaptation in a rare habitat are more restrictive for more polygenic traits: even moderate migration load per locus at very many loci is sufficient for population sizes to decline. This further reduces the efficacy of selection at individual loci due to increased drift and because smaller populations are more prone to swamping due to migration, causing a positive feedback between increasing maladaptation and declining population sizes. Our analysis also highlights the importance of demographic stochasticity, which exacerbates the decline in numbers of maladapted populations, leading to population collapse in the rare habitat at significantly lower migration than predicted by deterministic arguments.}, author = {Szep, Eniko and Sachdeva, Himani and Barton, Nicholas H}, publisher = {Dryad}, title = {{Supplementary code for: Polygenic local adaptation in metapopulations: A stochastic eco-evolutionary model}}, doi = {10.5061/DRYAD.8GTHT76P1}, year = {2021}, } @article{10838, abstract = {Combining hybrid zone analysis with genomic data is a promising approach to understanding the genomic basis of adaptive divergence. It allows for the identification of genomic regions underlying barriers to gene flow. It also provides insights into spatial patterns of allele frequency change, informing about the interplay between environmental factors, dispersal and selection. However, when only a single hybrid zone is analysed, it is difficult to separate patterns generated by selection from those resulting from chance. Therefore, it is beneficial to look for repeatable patterns across replicate hybrid zones in the same system. We applied this approach to the marine snail Littorina saxatilis, which contains two ecotypes, adapted to wave-exposed rocks vs. high-predation boulder fields. The existence of numerous hybrid zones between ecotypes offered the opportunity to test for the repeatability of genomic architectures and spatial patterns of divergence. We sampled and phenotyped snails from seven replicate hybrid zones on the Swedish west coast and genotyped them for thousands of single nucleotide polymorphisms. Shell shape and size showed parallel clines across all zones. Many genomic regions showing steep clines and/or high differentiation were shared among hybrid zones, consistent with a common evolutionary history and extensive gene flow between zones, and supporting the importance of these regions for divergence. In particular, we found that several large putative inversions contribute to divergence in all locations. Additionally, we found evidence for consistent displacement of clines from the boulder–rock transition. Our results demonstrate patterns of spatial variation that would not be accessible without continuous spatial sampling, a large genomic data set and replicate hybrid zones.}, author = {Westram, Anja M and Faria, Rui and Johannesson, Kerstin and Butlin, Roger}, issn = {1365-294X}, journal = {Molecular Ecology}, keywords = {Genetics, Ecology, Evolution, Behavior and Systematics}, number = {15}, pages = {3797--3814}, publisher = {Wiley}, title = {{Using replicate hybrid zones to understand the genomic basis of adaptive divergence}}, doi = {10.1111/mec.15861}, volume = {30}, year = {2021}, } @article{9288, abstract = {• The phenylpropanoid pathway serves a central role in plant metabolism, providing numerous compounds involved in diverse physiological processes. Most carbon entering the pathway is incorporated into lignin. Although several phenylpropanoid pathway mutants show seedling growth arrest, the role for lignin in seedling growth and development is unexplored. • We use complementary pharmacological and genetic approaches to block CINNAMATE‐4‐HYDROXYLASE (C4H) functionality in Arabidopsis seedlings and a set of molecular and biochemical techniques to investigate the underlying phenotypes. • Blocking C4H resulted in reduced lateral rooting and increased adventitious rooting apically in the hypocotyl. These phenotypes coincided with an inhibition in auxin transport. The upstream accumulation in cis‐cinnamic acid was found to likely cause polar auxin transport inhibition. Conversely, a downstream depletion in lignin perturbed phloem‐mediated auxin transport. Restoring lignin deposition effectively reestablished phloem transport and, accordingly, auxin homeostasis. • Our results show that the accumulation of bioactive intermediates and depletion in lignin jointly cause the aberrant phenotypes upon blocking C4H, and demonstrate that proper deposition of lignin is essential for the establishment of auxin distribution in seedlings. Our data position the phenylpropanoid pathway and lignin in a new physiological framework, consolidating their importance in plant growth and development.}, author = {El Houari, I and Van Beirs, C and Arents, HE and Han, Huibin and Chanoca, A and Opdenacker, D and Pollier, J and Storme, V and Steenackers, W and Quareshy, M and Napier, R and Beeckman, T and Friml, Jiří and De Rybel, B and Boerjan, W and Vanholme, B}, issn = {1469-8137}, journal = {New Phytologist}, number = {6}, pages = {2275--2291}, publisher = {Wiley}, title = {{Seedling developmental defects upon blocking CINNAMATE-4-HYDROXYLASE are caused by perturbations in auxin transport}}, doi = {10.1111/nph.17349}, volume = {230}, year = {2021}, } @article{10836, author = {Pranger, Christina L. and Fazekas-Singer, Judit and Köhler, Verena K. and Pali‐Schöll, Isabella and Fiocchi, Alessandro and Karagiannis, Sophia N. and Zenarruzabeitia, Olatz and Borrego, Francisco and Jensen‐Jarolim, Erika}, issn = {1398-9995}, journal = {Allergy}, keywords = {Immunology, Immunology and Allergy}, number = {5}, pages = {1553--1556}, publisher = {Wiley}, title = {{PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow's milk allergy and tolerance}}, doi = {10.1111/all.14604}, volume = {76}, year = {2021}, } @article{8608, abstract = {To adapt to the diverse array of biotic and abiotic cues, plants have evolved sophisticated mechanisms to sense changes in environmental conditions and modulate their growth. Growth-promoting hormones and defence signalling fine tune plant development antagonistically. During host-pathogen interactions, this defence-growth trade-off is mediated by the counteractive effects of the defence hormone salicylic acid (SA) and the growth hormone auxin. Here we revealed an underlying mechanism of SA regulating auxin signalling by constraining the plasma membrane dynamics of PIN2 auxin efflux transporter in Arabidopsis thaliana roots. The lateral diffusion of PIN2 proteins is constrained by SA signalling, during which PIN2 proteins are condensed into hyperclusters depending on REM1.2-mediated nanodomain compartmentalisation. Furthermore, membrane nanodomain compartmentalisation by SA or Remorin (REM) assembly significantly suppressed clathrin-mediated endocytosis. Consequently, SA-induced heterogeneous surface condensation disrupted asymmetric auxin distribution and the resultant gravitropic response. Our results demonstrated a defence-growth trade-off mechanism by which SA signalling crosstalked with auxin transport by concentrating membrane-resident PIN2 into heterogeneous compartments.}, author = {Ke, M and Ma, Z and Wang, D and Sun, Y and Wen, C and Huang, D and Chen, Z and Yang, L and Tan, Shutang and Li, R and Friml, Jiří and Miao, Y and Chen, X}, issn = {1469-8137}, journal = {New Phytologist}, number = {2}, pages = {963--978}, publisher = {Wiley}, title = {{Salicylic acid regulates PIN2 auxin transporter hyper-clustering and root gravitropic growth via Remorin-dependent lipid nanodomain organization in Arabidopsis thaliana}}, doi = {10.1111/nph.16915}, volume = {229}, year = {2021}, } @article{7900, abstract = {Hartree–Fock theory has been justified as a mean-field approximation for fermionic systems. However, it suffers from some defects in predicting physical properties, making necessary a theory of quantum correlations. Recently, bosonization of many-body correlations has been rigorously justified as an upper bound on the correlation energy at high density with weak interactions. We review the bosonic approximation, deriving an effective Hamiltonian. We then show that for systems with Coulomb interaction this effective theory predicts collective excitations (plasmons) in accordance with the random phase approximation of Bohm and Pines, and with experimental observation.}, author = {Benedikter, Niels P}, issn = {1793-6659}, journal = {Reviews in Mathematical Physics}, number = {1}, publisher = {World Scientific}, title = {{Bosonic collective excitations in Fermi gases}}, doi = {10.1142/s0129055x20600090}, volume = {33}, year = {2021}, }