TY - GEN AB - We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs. AU - Mühlböck, Fabian AU - Henzinger, Thomas A ID - 9946 KW - run-time verification KW - software engineering KW - implicit specification SN - 2664-1690 TI - Differential monitoring ER - TY - JOUR AB - Thermoelectric materials enable the direct conversion between heat and electricity. SnTe is a promising candidate due to its high charge transport performance. Here, we prepared SnTe nanocomposites by employing an aqueous method to synthetize SnTe nanoparticles (NP), followed by a unique surface treatment prior NP consolidation. This synthetic approach allowed optimizing the charge and phonon transport synergistically. The novelty of this strategy was the use of a soluble PbS molecular complex prepared using a thiol-amine solvent mixture that upon blending is adsorbed on the SnTe NP surface. Upon consolidation with spark plasma sintering, SnTe-PbS nanocomposite is formed. The presence of PbS complexes significantly compensates for the Sn vacancy and increases the average grain size of the nanocomposite, thus improving the carrier mobility. Moreover, lattice thermal conductivity is also reduced by the Pb and S-induced mass and strain fluctuation. As a result, an enhanced ZT of ca. 0.8 is reached at 873 K. Our finding provides a novel strategy to conduct rational surface treatment on NP-based thermoelectrics. AU - Chang, Cheng AU - Ibáñez, Maria ID - 10073 IS - 18 JF - Materials TI - Enhanced thermoelectric performance by surface engineering in SnTe-PbS nanocomposites VL - 14 ER - TY - JOUR AB - Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group. AU - Elkrewi, Marwan N AU - Moldovan, Mikhail A. AU - Picard, Marion A L AU - Vicoso, Beatriz ID - 10167 JF - Molecular Biology and Evolution KW - sex chromosomes KW - evolutionary strata KW - W-linked gene KW - sex determining gene KW - schistosome parasites SN - 0737-4038 TI - Schistosome W-Linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination ER - TY - JOUR AB - The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay. AU - Appel, Lisa-Marie AU - Franke, Vedran AU - Bruno, Melania AU - Grishkovskaya, Irina AU - Kasiliauskaite, Aiste AU - Kaufmann, Tanja AU - Schoeberl, Ursula E. AU - Puchinger, Martin G. AU - Kostrhon, Sebastian AU - Ebenwaldner, Carmen AU - Sebesta, Marek AU - Beltzung, Etienne AU - Mechtler, Karl AU - Lin, Gen AU - Vlasova, Anna AU - Leeb, Martin AU - Pavri, Rushad AU - Stark, Alexander AU - Akalin, Altuna AU - Stefl, Richard AU - Bernecky, Carrie A AU - Djinovic-Carugo, Kristina AU - Slade, Dea ID - 10163 IS - 1 JF - Nature Communications KW - general physics and astronomy KW - general biochemistry KW - genetics and molecular biology KW - general chemistry TI - PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC VL - 12 ER - TY - JOUR AB - With the wider availability of full-color 3D printers, color-accurate 3D-print preparation has received increased attention. A key challenge lies in the inherent translucency of commonly used print materials that blurs out details of the color texture. Previous work tries to compensate for these scattering effects through strategic assignment of colored primary materials to printer voxels. To date, the highest-quality approach uses iterative optimization that relies on computationally expensive Monte Carlo light transport simulation to predict the surface appearance from subsurface scattering within a given print material distribution; that optimization, however, takes in the order of days on a single machine. In our work, we dramatically speed up the process by replacing the light transport simulation with a data-driven approach. Leveraging a deep neural network to predict the scattering within a highly heterogeneous medium, our method performs around two orders of magnitude faster than Monte Carlo rendering while yielding optimization results of similar quality level. The network is based on an established method from atmospheric cloud rendering, adapted to our domain and extended by a physically motivated weight sharing scheme that substantially reduces the network size. We analyze its performance in an end-to-end print preparation pipeline and compare quality and runtime to alternative approaches, and demonstrate its generalization to unseen geometry and material values. This for the first time enables full heterogenous material optimization for 3D-print preparation within time frames in the order of the actual printing time. AU - Rittig, Tobias AU - Sumin, Denis AU - Babaei, Vahid AU - Didyk, Piotr AU - Voloboy, Alexey AU - Wilkie, Alexander AU - Bickel, Bernd AU - Myszkowski, Karol AU - Weyrich, Tim AU - Křivánek, Jaroslav ID - 9547 IS - 2 JF - Computer Graphics Forum SN - 0167-7055 TI - Neural acceleration of scattering-aware color 3D printing VL - 40 ER - TY - JOUR AB - Phonon polaritons (PhPs)—light coupled to lattice vibrations—with in-plane hyperbolic dispersion exhibit ray-like propagation with large wave vectors and enhanced density of optical states along certain directions on a surface. As such, they have raised a surge of interest, promising unprecedented manipulation of infrared light at the nanoscale in a planar circuitry. Here, we demonstrate focusing of in-plane hyperbolic PhPs propagating along thin slabs of α-MoO3. To that end, we developed metallic nanoantennas of convex geometries for both efficient launching and focusing of the polaritons. The foci obtained exhibit enhanced near-field confinement and absorption compared to foci produced by in-plane isotropic PhPs. Foci sizes as small as λp/4.5 = λ0/50 were achieved (λp is the polariton wavelength and λ0 is the photon wavelength). Focusing of in-plane hyperbolic polaritons introduces a first and most basic building block developing planar polariton optics using in-plane anisotropic van der Waals materials. AU - Martín-Sánchez, Javier AU - Duan, Jiahua AU - Taboada-Gutiérrez, Javier AU - Álvarez-Pérez, Gonzalo AU - Voronin, Kirill V. AU - Prieto Gonzalez, Ivan AU - Ma, Weiliang AU - Bao, Qiaoliang AU - Volkov, Valentyn S. AU - Hillenbrand, Rainer AU - Nikitin, Alexey Y. AU - Alonso-González, Pablo ID - 10177 IS - 41 JF - Science Advances TI - Focusing of in-plane hyperbolic polaritons in van der Waals crystals with tailored infrared nanoantennas VL - 7 ER - TY - JOUR AB - The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain. AU - Vercellino, Irene AU - Sazanov, Leonid A ID - 10146 IS - 7880 JF - Nature SN - 0028-0836 TI - Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV VL - 598 ER - TY - JOUR AB - We give a combinatorial model for r-spin surfaces with parameterized boundary based on Novak (“Lattice topological field theories in two dimensions,” Ph.D. thesis, Universität Hamburg, 2015). The r-spin structure is encoded in terms of ℤ𝑟-valued indices assigned to the edges of a polygonal decomposition. This combinatorial model is designed for our state-sum construction of two-dimensional topological field theories on r-spin surfaces. We show that an example of such a topological field theory computes the Arf-invariant of an r-spin surface as introduced by Randal-Williams [J. Topol. 7, 155 (2014)] and Geiges et al. [Osaka J. Math. 49, 449 (2012)]. This implies, in particular, that the r-spin Arf-invariant is constant on orbits of the mapping class group, providing an alternative proof of that fact. AU - Runkel, Ingo AU - Szegedy, Lorant ID - 10176 IS - 10 JF - Journal of Mathematical Physics SN - 00222488 TI - Topological field theory on r-spin surfaces and the Arf-invariant VL - 62 ER - TY - JOUR AB - Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling. AU - Bajaj, Sunanjay AU - Bagley, Joshua A. AU - Sommer, Christoph M AU - Vertesy, Abel AU - Nagumo Wong, Sakurako AU - Krenn, Veronica AU - Lévi-Strauss, Julie AU - Knoblich, Juergen A. ID - 10179 IS - 23 JF - EMBO Journal SN - 0261-4189 TI - Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration VL - 40 ER - TY - JOUR AB - Single photon emitters in atomically-thin semiconductors can be deterministically positioned using strain induced by underlying nano-structures. Here, we couple monolayer WSe2 to high-refractive-index gallium phosphide dielectric nano-antennas providing both optical enhancement and monolayer deformation. For single photon emitters formed on such nano-antennas, we find very low (femto-Joule) saturation pulse energies and up to 104 times brighter photoluminescence than in WSe2 placed on low-refractive-index SiO2 pillars. We show that the key to these observations is the increase on average by a factor of 5 of the quantum efficiency of the emitters coupled to the nano-antennas. This further allows us to gain new insights into their photoluminescence dynamics, revealing the roles of the dark exciton reservoir and Auger processes. We also find that the coherence time of such emitters is limited by intrinsic dephasing processes. Our work establishes dielectric nano-antennas as a platform for high-efficiency quantum light generation in monolayer semiconductors. AU - Sortino, Luca AU - Zotev, Panaiot G. AU - Phillips, Catherine L. AU - Brash, Alistair J. AU - Cambiasso, Javier AU - Marensi, Elena AU - Fox, A. Mark AU - Maier, Stefan A. AU - Sapienza, Riccardo AU - Tartakovskii, Alexander I. ID - 10203 JF - Nature Communications TI - Bright single photon emitters with enhanced quantum efficiency in a two-dimensional semiconductor coupled with dielectric nano-antennas VL - 12 ER - TY - JOUR AB - In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features. AU - Sahu, Preeti AU - Schwarz, J. M. AU - Manning, M. Lisa ID - 10178 IS - 9 JF - New Journal of Physics TI - Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue VL - 23 ER - TY - JOUR AB - In this article we study some geometric properties of proximally smooth sets. First, we introduce a modification of the metric projection and prove its existence. Then we provide an algorithm for constructing a rectifiable curve between two sufficiently close points of a proximally smooth set in a uniformly convex and uniformly smooth Banach space, with the moduli of smoothness and convexity of power type. Our algorithm returns a reasonably short curve between two sufficiently close points of a proximally smooth set, is iterative and uses our modification of the metric projection. We estimate the length of the constructed curve and its deviation from the segment with the same endpoints. These estimates coincide up to a constant factor with those for the geodesics in a proximally smooth set in a Hilbert space. AU - Ivanov, Grigory AU - Lopushanski, Mariana S. ID - 10181 JF - Set-Valued and Variational Analysis SN - 0927-6947 TI - Rectifiable curves in proximally smooth sets ER - TY - JOUR AB - Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant. AU - Pradhan, Saurabh J. AU - Reddy, Puli Chandramouli AU - Smutny, Michael AU - Sharma, Ankita AU - Sako, Keisuke AU - Oak, Meghana S. AU - Shah, Rini AU - Pal, Mrinmoy AU - Deshpande, Ojas AU - Dsilva, Greg AU - Tang, Yin AU - Mishra, Rakesh AU - Deshpande, Girish AU - Giraldez, Antonio J. AU - Sonawane, Mahendra AU - Heisenberg, Carl-Philipp J AU - Galande, Sanjeev ID - 10202 IS - 1 JF - Nature Communications TI - Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis VL - 12 ER - TY - JOUR AB - Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions. AU - Qi, Qin AU - Angermayr, S. Andreas AU - Bollenbach, Mark Tobias ID - 10271 JF - Frontiers in Microbiology KW - microbiology TI - Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli VL - 12 ER - TY - JOUR AB - We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020). AU - Cipolloni, Giorgio AU - Erdös, László AU - Schröder, Dominik J ID - 10221 IS - 2 JF - Communications in Mathematical Physics SN - 0010-3616 TI - Eigenstate thermalization hypothesis for Wigner matrices VL - 388 ER - TY - JOUR AB - We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging. AU - Feliciangeli, Dario AU - Seiringer, Robert ID - 10224 IS - 3 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics VL - 242 ER - TY - JOUR AB - Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems AU - Vasic, Verica AU - Jones, Mattson S.O. AU - Haslinger, Denise AU - Knaus, Lisa AU - Schmeisser, Michael J. AU - Novarino, Gaia AU - Chiocchetti, Andreas G. ID - 10281 IS - 11 JF - Genes TI - Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment VL - 12 ER - TY - JOUR AB - Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development. AU - Kashkan, Ivan AU - Hrtyan, Mónika AU - Retzer, Katarzyna AU - Humpolíčková, Jana AU - Jayasree, Aswathy AU - Filepová, Roberta AU - Vondráková, Zuzana AU - Simon, Sibu AU - Rombaut, Debbie AU - Jacobs, Thomas B. AU - Frilander, Mikko J. AU - Hejátko, Jan AU - Friml, Jiří AU - Petrášek, Jan AU - Růžička, Kamil ID - 10282 JF - New Phytologist SN - 0028-646X TI - Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana VL - 233 ER - TY - JOUR AB - We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample. AU - Avvakumov, Sergey AU - Mabillard, Isaac AU - Skopenkov, Arkadiy B. AU - Wagner, Uli ID - 10220 JF - Israel Journal of Mathematics SN - 0021-2172 TI - Eliminating higher-multiplicity intersections. III. Codimension 2 VL - 245 ER - TY - GEN AB - Infections early in life can have enduring effects on an organism’s development and immunity. In this study, we show that this equally applies to developing “superorganisms” – incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen’s immune system to suppress pathogen proliferation. Early-life queen pathogen-exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen’s pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism. AU - Casillas Perez, Barbara E AU - Pull, Christopher AU - Naiser, Filip AU - Naderlinger, Elisabeth AU - Matas, Jiri AU - Cremer, Sylvia ID - 13061 TI - Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies ER - TY - JOUR AB - De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement. AU - Conde-Dusman, María J AU - Dey, Partha N AU - Elía-Zudaire, Óscar AU - Garcia Rabaneda, Luis E AU - García-Lira, Carmen AU - Grand, Teddy AU - Briz, Victor AU - Velasco, Eric R AU - Andero Galí, Raül AU - Niñerola, Sergio AU - Barco, Angel AU - Paoletti, Pierre AU - Wesseling, John F AU - Gardoni, Fabrizio AU - Tavalin, Steven J AU - Perez-Otaño, Isabel ID - 10301 JF - eLife KW - general immunology and microbiology KW - general biochemistry KW - genetics and molecular biology KW - general medicine KW - general neuroscience SN - 2050-084X TI - Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly VL - 10 ER - TY - JOUR AB - During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research. AU - Restivo, Leonardo AU - Gerlach, Björn AU - Tsoory, Michael AU - Bikovski, Lior AU - Badurek, Sylvia AU - Pitzer, Claudia AU - Kos-Braun, Isabelle C. AU - Mausset-Bonnefont, Anne Laure Mj AU - Ward, Jonathan AU - Schunn, Michael AU - Noldus, Lucas P.J.J. AU - Bespalov, Anton AU - Voikar, Vootele ID - 10283 JF - EMBO Reports SN - 1469-221X TI - Towards best practices in research: Role of academic core facilities VL - 22 ER - TY - JOUR AB - A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700. AU - Çoruh, Mehmet Orkun AU - Frank, Anna AU - Tanaka, Hideaki AU - Kawamoto, Akihiro AU - El-Mohsnawy, Eithar AU - Kato, Takayuki AU - Namba, Keiichi AU - Gerle, Christoph AU - Nowaczyk, Marc M. AU - Kurisu, Genji ID - 10310 IS - 1 JF - Communications Biology KW - general agricultural and biological Sciences KW - general biochemistry KW - genetics and molecular biology KW - medicine (miscellaneous) SN - 2399-3642 TI - Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster VL - 4 ER - TY - JOUR AB - Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development. AU - Marconi, Marco AU - Gallemi, Marçal AU - Benková, Eva AU - Wabnik, Krzysztof ID - 10270 JF - eLife SN - 2050-084X TI - A coupled mechano-biochemical model for cell polarity guided anisotropic root growth VL - 10 ER - TY - JOUR AB - Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number. AU - Choueiri, George H AU - Lopez Alonso, Jose M AU - Varshney, Atul AU - Sankar, Sarath AU - Hof, Björn ID - 10299 IS - 45 JF - Proceedings of the National Academy of Sciences KW - multidisciplinary KW - elastoinertial turbulence KW - viscoelastic flows KW - elastic instability KW - drag reduction SN - 0027-8424 TI - Experimental observation of the origin and structure of elastoinertial turbulence VL - 118 ER - TY - JOUR AB - Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials. AU - Aubret, Antoine AU - Martinet, Quentin AU - Palacci, Jérémie A ID - 10280 IS - 1 JF - Nature Communications TI - Metamachines of pluripotent colloids VL - 12 ER - TY - JOUR AB - To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - De Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 10322 IS - 11 JF - PLoS Biology SN - 1544-9173 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans VL - 19 ER - TY - JOUR AB - Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density. AU - Akopyan, Arseniy AU - Edelsbrunner, Herbert AU - Nikitenko, Anton ID - 10222 JF - Experimental Mathematics SN - 1058-6458 TI - The beauty of random polytopes inscribed in the 2-sphere ER - TY - JOUR AB - Molecular chaperones are central to cellular protein homeostasis. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. We focus hereby on chaperone-client interactions that are independent of ATP. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity. AU - Sučec, Iva AU - Bersch, Beate AU - Schanda, Paul ID - 10323 JF - Frontiers in Molecular Biosciences TI - How do chaperones bind (partly) unfolded client proteins? VL - 8 ER - TY - JOUR AB - Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants. AU - Xu, Enjun AU - Chai, Liang AU - Zhang, Shiqi AU - Yu, Ruixue AU - Zhang, Xixi AU - Xu, Chongyi AU - Hu, Yuxin ID - 10326 JF - Nature Plants TI - Catabolism of strigolactones by a carboxylesterase VL - 7 ER - TY - GEN AB - To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell-autonomous. We have discovered that, in Caenorhabditis elegans, neuronal Heat shock Factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR)- causes extensive fat remodelling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine, and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodelling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least six TAX-2/TAX-4 cGMP gated channel expressing sensory neurons and TGF-β/BMP are required for signalling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodelling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell non-autonomously coordinate membrane saturation and composition across tissues in a multicellular animal. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry-Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - de Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 13069 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans ER - TY - CONF AB - Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains. AU - Zamyatin, Alexei AU - Al-Bassam, Mustafa AU - Zindros, Dionysis AU - Kokoris Kogias, Eleftherios AU - Moreno-Sanchez, Pedro AU - Kiayias, Aggelos AU - Knottenbelt, William J. ID - 10325 SN - 0302-9743 T2 - 25th International Conference on Financial Cryptography and Data Security TI - SoK: Communication across distributed ledgers VL - 12675 ER - TY - CONF AB - Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity. AU - Avarikioti, Zeta AU - Kokoris Kogias, Eleftherios AU - Wattenhofer, Roger AU - Zindros, Dionysis ID - 10324 SN - 0302-9743 T2 - 25th International Conference on Financial Cryptography and Data Security TI - Brick: Asynchronous incentive-compatible payment channels VL - 12675 ER - TY - JOUR AB - Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia. AU - Lee, Jungmin AU - Vernet, Andyna AU - Gruber, Nathalie AU - Kready, Kasia M. AU - Burrill, Devin R. AU - Way, Jeffrey C. AU - Silver, Pamela A. ID - 10363 JF - Protein Engineering, Design and Selection SN - 1741-0126 TI - Rational engineering of an erythropoietin fusion protein to treat hypoxia VL - 34 ER - TY - JOUR AU - Heisenberg, Carl-Philipp J AU - Lennon, Ana Maria AU - Mayor, Roberto AU - Salbreux, Guillaume ID - 10366 IS - 12 JF - Cells and Development SN - 2667-2901 TI - Special rebranding issue: “Quantitative cell and developmental biology” VL - 168 ER - TY - JOUR AB - Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales. AU - Ucar, Mehmet C AU - Kamenev, Dmitrii AU - Sunadome, Kazunori AU - Fachet, Dominik C AU - Lallemend, Francois AU - Adameyko, Igor AU - Hadjab, Saida AU - Hannezo, Edouard B ID - 10402 JF - Nature Communications TI - Theory of branching morphogenesis by local interactions and global guidance VL - 12 ER - TY - CONF AB - Digital hardware Trojans are integrated circuits whose implementation differ from the specification in an arbitrary and malicious way. For example, the circuit can differ from its specified input/output behavior after some fixed number of queries (known as “time bombs”) or on some particular input (known as “cheat codes”). To detect such Trojans, countermeasures using multiparty computation (MPC) or verifiable computation (VC) have been proposed. On a high level, to realize a circuit with specification F one has more sophisticated circuits F⋄ manufactured (where F⋄ specifies a MPC or VC of F ), and then embeds these F⋄ ’s into a master circuit which must be trusted but is relatively simple compared to F . Those solutions impose a significant overhead as F⋄ is much more complex than F , also the master circuits are not exactly trivial. In this work, we show that in restricted settings, where F has no evolving state and is queried on independent inputs, we can achieve a relaxed security notion using very simple constructions. In particular, we do not change the specification of the circuit at all (i.e., F=F⋄ ). Moreover the master circuit basically just queries a subset of its manufactured circuits and checks if they’re all the same. The security we achieve guarantees that, if the manufactured circuits are initially tested on up to T inputs, the master circuit will catch Trojans that try to deviate on significantly more than a 1/T fraction of the inputs. This bound is optimal for the type of construction considered, and we provably achieve it using a construction where 12 instantiations of F need to be embedded into the master. We also discuss an extremely simple construction with just 2 instantiations for which we conjecture that it already achieves the optimal bound. AU - Chakraborty, Suvradip AU - Dziembowski, Stefan AU - Gałązka, Małgorzata AU - Lizurej, Tomasz AU - Pietrzak, Krzysztof Z AU - Yeo, Michelle X ID - 10407 SN - 0302-9743 TI - Trojan-resilience without cryptography VL - 13043 ER - TY - JOUR AB - Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits. AU - Biane, Celia AU - Rückerl, Florian AU - Abrahamsson, Therese AU - Saint-Cloment, Cécile AU - Mariani, Jean AU - Shigemoto, Ryuichi AU - Digregorio, David A. AU - Sherrard, Rachel M. AU - Cathala, Laurence ID - 10403 JF - eLife TI - Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons VL - 10 ER - TY - JOUR AB - Theoretical and experimental studies of the interaction between spins and temperature are vital for the development of spin caloritronics, as they dictate the design of future devices. In this work, we propose a two-terminal cold-atom simulator to study that interaction. The proposed quantum simulator consists of strongly interacting atoms that occupy two temperature reservoirs connected by a one-dimensional link. First, we argue that the dynamics in the link can be described using an inhomogeneous Heisenberg spin chain whose couplings are defined by the local temperature. Second, we show the existence of a spin current in a system with a temperature difference by studying the dynamics that follows the spin-flip of an atom in the link. A temperature gradient accelerates the impurity in one direction more than in the other, leading to an overall spin current similar to the spin Seebeck effect. AU - Barfknecht, Rafael E. AU - Foerster, Angela AU - Zinner, Nikolaj T. AU - Volosniev, Artem ID - 10401 IS - 1 JF - Communications Physics TI - Generation of spin currents by a temperature gradient in a two-terminal device VL - 4 ER - TY - JOUR AB - While convolutional neural networks (CNNs) have found wide adoption as state-of-the-art models for image-related tasks, their predictions are often highly sensitive to small input perturbations, which the human vision is robust against. This paper presents Perturber, a web-based application that allows users to instantaneously explore how CNN activations and predictions evolve when a 3D input scene is interactively perturbed. Perturber offers a large variety of scene modifications, such as camera controls, lighting and shading effects, background modifications, object morphing, as well as adversarial attacks, to facilitate the discovery of potential vulnerabilities. Fine-tuned model versions can be directly compared for qualitative evaluation of their robustness. Case studies with machine learning experts have shown that Perturber helps users to quickly generate hypotheses about model vulnerabilities and to qualitatively compare model behavior. Using quantitative analyses, we could replicate users’ insights with other CNN architectures and input images, yielding new insights about the vulnerability of adversarially trained models. AU - Sietzen, Stefan AU - Lechner, Mathias AU - Borowski, Judy AU - Hasani, Ramin AU - Waldner, Manuela ID - 10404 IS - 7 JF - Computer Graphics Forum SN - 0167-7055 TI - Interactive analysis of CNN robustness VL - 40 ER - TY - JOUR AB - Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future. AU - Mishra, Nikhil AU - Heisenberg, Carl-Philipp J ID - 10406 JF - Annual Review of Genetics KW - morphogenesis KW - forward genetics KW - high-resolution microscopy KW - biophysics KW - biochemistry KW - patterning SN - 0066-4197 TI - Dissecting organismal morphogenesis by bridging genetics and biophysics VL - 55 ER - TY - GEN AB - The zip file includes source data used in the main text of the manuscript "Theory of branching morphogenesis by local interactions and global guidance", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt. AU - Ucar, Mehmet C ID - 13058 TI - Source data for the manuscript "Theory of branching morphogenesis by local interactions and global guidance" ER - TY - CONF AB - Key trees are often the best solution in terms of transmission cost and storage requirements for managing keys in a setting where a group needs to share a secret key, while being able to efficiently rotate the key material of users (in order to recover from a potential compromise, or to add or remove users). Applications include multicast encryption protocols like LKH (Logical Key Hierarchies) or group messaging like the current IETF proposal TreeKEM. A key tree is a (typically balanced) binary tree, where each node is identified with a key: leaf nodes hold users’ secret keys while the root is the shared group key. For a group of size N, each user just holds log(N) keys (the keys on the path from its leaf to the root) and its entire key material can be rotated by broadcasting 2log(N) ciphertexts (encrypting each fresh key on the path under the keys of its parents). In this work we consider the natural setting where we have many groups with partially overlapping sets of users, and ask if we can find solutions where the cost of rotating a key is better than in the trivial one where we have a separate key tree for each group. We show that in an asymptotic setting (where the number m of groups is fixed while the number N of users grows) there exist more general key graphs whose cost converges to the cost of a single group, thus saving a factor linear in the number of groups over the trivial solution. As our asymptotic “solution” converges very slowly and performs poorly on concrete examples, we propose an algorithm that uses a natural heuristic to compute a key graph for any given group structure. Our algorithm combines two greedy algorithms, and is thus very efficient: it first converts the group structure into a “lattice graph”, which is then turned into a key graph by repeatedly applying the algorithm for constructing a Huffman code. To better understand how far our proposal is from an optimal solution, we prove lower bounds on the update cost of continuous group-key agreement and multicast encryption in a symbolic model admitting (asymmetric) encryption, pseudorandom generators, and secret sharing as building blocks. AU - Alwen, Joel F AU - Auerbach, Benedikt AU - Baig, Mirza Ahad AU - Cueto Noval, Miguel AU - Klein, Karen AU - Pascual Perez, Guillermo AU - Pietrzak, Krzysztof Z AU - Walter, Michael ID - 10408 SN - 0302-9743 T2 - 19th International Conference TI - Grafting key trees: Efficient key management for overlapping groups VL - 13044 ER - TY - JOUR AB - We show that in a two-dimensional electron gas with an annular Fermi surface, long-range Coulomb interactions can lead to unconventional superconductivity by the Kohn-Luttinger mechanism. Superconductivity is strongly enhanced when the inner and outer Fermi surfaces are close to each other. The most prevalent state has chiral p-wave symmetry, but d-wave and extended s-wave pairing are also possible. We discuss these results in the context of rhombohedral trilayer graphene, where superconductivity was recently discovered in regimes where the normal state has an annular Fermi surface. Using realistic parameters, our mechanism can account for the order of magnitude of Tc, as well as its trends as a function of electron density and perpendicular displacement field. Moreover, it naturally explains some of the outstanding puzzles in this material, that include the weak temperature dependence of the resistivity above Tc, and the proximity of spin singlet superconductivity to the ferromagnetic phase. AU - Ghazaryan, Areg AU - Holder, Tobias AU - Serbyn, Maksym AU - Berg, Erez ID - 10527 IS - 24 JF - Physical Review Letters KW - general physics and astronomy SN - 0031-9007 TI - Unconventional superconductivity in systems with annular Fermi surfaces: Application to rhombohedral trilayer graphene VL - 127 ER - TY - JOUR AB - For many years, fullerene derivatives have been the main n-type material of organic electronics and optoelectronics. Recently, fullerene derivatives functionalized with ethylene glycol (EG) side chains have been showing important properties such as enhanced dielectric constants, facile doping and enhanced self-assembly capabilities. Here, we have prepared field-effect transistors using a series of these fullerene derivatives equipped with EG side chains of different lengths. Transport data show the beneficial effect of increasing the EG side chain. In order to understand the material properties, full structural determination of these fullerene derivatives has been achieved by coupling the X-ray data with molecular dynamics (MD) simulations. The increase in transport properties is paired with the formation of extended layered structures, efficient molecular packing and an increase in the crystallite alignment. The layer-like structure is composed of conducting layers, containing of closely packed C60 balls approaching the inter-distance of 1 nm, that are separated by well-defined EG layers, where the EG chains are rather splayed with the chain direction almost perpendicular to the layer normal. Such a layered structure appears highly ordered and highly aligned with the C60 planes oriented parallel to the substrate in the thin film configuration. The order inside the thin film increases with the EG chain length, allowing the systems to achieve mobilities as high as 0.053 cm2 V−1 s−1. Our work elucidates the structure of these interesting semiconducting organic molecules and shows that the synergistic use of X-ray structural analysis and MD simulations is a powerful tool to identify the structure of thin organic films for optoelectronic applications. AU - Dong, Jingjin AU - Sami, Selim AU - Balazs, Daniel AU - Alessandri, Riccardo AU - Jahani, Fatimeh AU - Qiu, Li AU - Marrink, Siewert J. AU - Havenith, Remco W.A. AU - Hummelen, Jan C. AU - Loi, Maria A. AU - Portale, Giuseppe ID - 10534 IS - 45 JF - Journal of Materials Chemistry C SN - 2050-7534 TI - Fullerene derivatives with oligoethylene-glycol side chains: An investigation on the origin of their outstanding transport properties VL - 9 ER - TY - JOUR AB - Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin. AU - Choi, Jaemyung AU - Lyons, David B AU - Zilberman, Daniel ID - 10533 JF - eLife KW - genetics and molecular biology SN - 2050-084X TI - Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin VL - 10 ER - TY - JOUR AB - TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner. AU - Stefanescu, Cristina AU - Van Gogh, Merel AU - Roblek, Marko AU - Heikenwalder, Mathias AU - Borsig, Lubor ID - 10536 JF - Frontiers in Oncology TI - TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms VL - 11 ER - TY - JOUR AB - We consider the quantum many-body evolution of a homogeneous Fermi gas in three dimensions in the coupled semiclassical and mean-field scaling regime. We study a class of initial data describing collective particle–hole pair excitations on the Fermi ball. Using a rigorous version of approximate bosonization, we prove that the many-body evolution can be approximated in Fock space norm by a quasi-free bosonic evolution of the collective particle–hole excitations. AU - Benedikter, Niels P AU - Nam, Phan Thành AU - Porta, Marcello AU - Schlein, Benjamin AU - Seiringer, Robert ID - 10537 JF - Annales Henri Poincaré SN - 1424-0637 TI - Bosonization of fermionic many-body dynamics ER - TY - JOUR AB - We derive optimal-order homogenization rates for random nonlinear elliptic PDEs with monotone nonlinearity in the uniformly elliptic case. More precisely, for a random monotone operator on \mathbb {R}^d with stationary law (that is spatially homogeneous statistics) and fast decay of correlations on scales larger than the microscale \varepsilon >0, we establish homogenization error estimates of the order \varepsilon in case d\geqq 3, and of the order \varepsilon |\log \varepsilon |^{1/2} in case d=2. Previous results in nonlinear stochastic homogenization have been limited to a small algebraic rate of convergence \varepsilon ^\delta . We also establish error estimates for the approximation of the homogenized operator by the method of representative volumes of the order (L/\varepsilon )^{-d/2} for a representative volume of size L. Our results also hold in the case of systems for which a (small-scale) C^{1,\alpha } regularity theory is available. AU - Fischer, Julian L AU - Neukamm, Stefan ID - 10549 IS - 1 JF - Archive for Rational Mechanics and Analysis KW - Mechanical Engineering KW - Mathematics (miscellaneous) KW - Analysis SN - 0003-9527 TI - Optimal homogenization rates in stochastic homogenization of nonlinear uniformly elliptic equations and systems VL - 242 ER - TY - CONF AB - We show that Yao’s garbling scheme is adaptively indistinguishable for the class of Boolean circuits of size S and treewidth w with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. with only a SO(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(δwlog(S)) , δ being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity. AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z ID - 10409 SN - 0302-9743 T2 - 19th International Conference TI - On treewidth, separators and Yao’s garbling VL - 13043 ER -