TY - JOUR AB - In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes. AU - Narasimhan, Madhumitha AU - Johnson, Alexander J AU - Prizak, Roshan AU - Kaufmann, Walter AU - Tan, Shutang AU - Casillas Perez, Barbara E AU - Friml, Jiří ID - 7490 JF - eLife TI - Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants VL - 9 ER - TY - JOUR AB - Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS. AU - Latorre-Pellicer, Ana AU - Ascaso, Ángela AU - Trujillano, Laura AU - Gil-Salvador, Marta AU - Arnedo, Maria AU - Lucia-Campos, Cristina AU - Antoñanzas-Pérez, Rebeca AU - Marcos-Alcalde, Iñigo AU - Parenti, Ilaria AU - Bueno-Lozano, Gloria AU - Musio, Antonio AU - Puisac, Beatriz AU - Kaiser, Frank J. AU - Ramos, Feliciano J. AU - Gómez-Puertas, Paulino AU - Pié, Juan ID - 7488 IS - 3 JF - International Journal of Molecular Sciences SN - 16616596 TI - Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes VL - 21 ER - TY - CONF AB - Neural networks have demonstrated unmatched performance in a range of classification tasks. Despite numerous efforts of the research community, novelty detection remains one of the significant limitations of neural networks. The ability to identify previously unseen inputs as novel is crucial for our understanding of the decisions made by neural networks. At runtime, inputs not falling into any of the categories learned during training cannot be classified correctly by the neural network. Existing approaches treat the neural network as a black box and try to detect novel inputs based on the confidence of the output predictions. However, neural networks are not trained to reduce their confidence for novel inputs, which limits the effectiveness of these approaches. We propose a framework to monitor a neural network by observing the hidden layers. We employ a common abstraction from program analysis - boxes - to identify novel behaviors in the monitored layers, i.e., inputs that cause behaviors outside the box. For each neuron, the boxes range over the values seen in training. The framework is efficient and flexible to achieve a desired trade-off between raising false warnings and detecting novel inputs. We illustrate the performance and the robustness to variability in the unknown classes on popular image-classification benchmarks. AU - Henzinger, Thomas A AU - Lukina, Anna AU - Schilling, Christian ID - 7505 T2 - 24th European Conference on Artificial Intelligence TI - Outside the box: Abstraction-based monitoring of neural networks VL - 325 ER - TY - JOUR AB - In this paper, we introduce a novel method for deriving higher order corrections to the mean-field description of the dynamics of interacting bosons. More precisely, we consider the dynamics of N d-dimensional bosons for large N. The bosons initially form a Bose–Einstein condensate and interact with each other via a pair potential of the form (N−1)−1Ndβv(Nβ·)forβ∈[0,14d). We derive a sequence of N-body functions which approximate the true many-body dynamics in L2(RdN)-norm to arbitrary precision in powers of N−1. The approximating functions are constructed as Duhamel expansions of finite order in terms of the first quantised analogue of a Bogoliubov time evolution. AU - Bossmann, Lea AU - Pavlović, Nataša AU - Pickl, Peter AU - Soffer, Avy ID - 7508 JF - Journal of Statistical Physics SN - 0022-4715 TI - Higher order corrections to the mean-field description of the dynamics of interacting bosons VL - 178 ER - TY - JOUR AB - Cryo electron tomography with subsequent subtomogram averaging is a powerful technique to structurally analyze macromolecular complexes in their native context. Although close to atomic resolution in principle can be obtained, it is not clear how individual experimental parameters contribute to the attainable resolution. Here, we have used immature HIV-1 lattice as a benchmarking sample to optimize the attainable resolution for subtomogram averaging. We systematically tested various experimental parameters such as the order of projections, different angular increments and the use of the Volta phase plate. We find that although any of the prominently used acquisition schemes is sufficient to obtain subnanometer resolution, dose-symmetric acquisition provides considerably better outcome. We discuss our findings in order to provide guidance for data acquisition. Our data is publicly available and might be used to further develop processing routines. AU - Turoňová, Beata AU - Hagen, Wim J.H. AU - Obr, Martin AU - Mosalaganti, Shyamal AU - Beugelink, J. Wouter AU - Zimmerli, Christian E. AU - Kräusslich, Hans Georg AU - Beck, Martin ID - 7511 JF - Nature Communications TI - Benchmarking tomographic acquisition schemes for high-resolution structural biology VL - 11 ER - TY - JOUR AB - Endophytic fungi can be beneficial to plant growth. However, the molecular mechanisms underlying colonization of Acremonium spp. remain unclear. In this study, a novel endophytic Acremonium strain was isolated from the buds of Panax notoginseng and named Acremonium sp. D212. The Acremonium sp. D212 could colonize the roots of P. notoginseng, enhance the resistance of P. notoginseng to root rot disease, and promote root growth and saponin biosynthesis in P. notoginseng. Acremonium sp. D212 could secrete indole‐3‐acetic acid (IAA) and jasmonic acid (JA), and inoculation with the fungus increased the endogenous levels of IAA and JA in P. notoginseng. Colonization of the Acremonium sp. D212 in the roots of the rice line Nipponbare was dependent on the concentration of methyl jasmonate (MeJA) (2 to 15 μM) and 1‐naphthalenacetic acid (NAA) (10 to 20 μM). Moreover, the roots of the JA signalling‐defective coi1‐18 mutant were colonized by Acremonium sp. D212 to a lesser degree than those of the wild‐type Nipponbare and miR393b‐overexpressing lines, and the colonization was rescued by MeJA but not by NAA. It suggests that the cross‐talk between JA signalling and the auxin biosynthetic pathway plays a crucial role in the colonization of Acremonium sp. D212 in host plants. AU - Han, L AU - Zhou, X AU - Zhao, Y AU - Zhu, S AU - Wu, L AU - He, Y AU - Ping, X AU - Lu, X AU - Huang, W AU - Qian, J AU - Zhang, L AU - Jiang, X AU - Zhu, D AU - Luo, C AU - Li, S AU - Dong, Q AU - Fu, Q AU - Deng, K AU - Wang, X AU - Wang, L AU - Peng, S AU - Wu, J AU - Li, W AU - Friml, Jiří AU - Zhu, Y AU - He, X AU - Du, Y ID - 7497 IS - 9 JF - Journal of Integrative Plant Biology SN - 1672-9072 TI - Colonization of endophyte Acremonium sp. D212 in Panax notoginseng and rice mediated by auxin and jasmonic acid VL - 62 ER - TY - JOUR AB - In the past two decades, our understanding of the transition to turbulence in shear flows with linearly stable laminar solutions has greatly improved. Regarding the susceptibility of the laminar flow, two concepts have been particularly useful: the edge states and the minimal seeds. In this nonlinear picture of the transition, the basin boundary of turbulence is set by the edge state's stable manifold and this manifold comes closest in energy to the laminar equilibrium at the minimal seed. We begin this paper by presenting numerical experiments in which three-dimensional perturbations are too energetic to trigger turbulence in pipe flow but they do lead to turbulence when their amplitude is reduced. We show that this seemingly counterintuitive observation is in fact consistent with the fully nonlinear description of the transition mediated by the edge state. In order to understand the physical mechanisms behind this process, we measure the turbulent kinetic energy production and dissipation rates as a function of the radial coordinate. Our main observation is that the transition to turbulence relies on the energy amplification away from the wall, as opposed to the turbulence itself, whose energy is predominantly produced near the wall. This observation is further supported by the similar analyses on the minimal seeds and the edge states. Furthermore, we show that the time evolution of production-over-dissipation curves provides a clear distinction between the different initial amplification stages of the transition to turbulence from the minimal seed. AU - Budanur, Nazmi B AU - Marensi, Elena AU - Willis, Ashley P. AU - Hof, Björn ID - 7534 IS - 2 JF - Physical Review Fluids SN - 2469-990X TI - Upper edge of chaos and the energetics of transition in pipe flow VL - 5 ER - TY - JOUR AB - We consider general self-adjoint polynomials in several independent random matrices whose entries are centered and have the same variance. We show that under certain conditions the local law holds up to the optimal scale, i.e., the eigenvalue density on scales just above the eigenvalue spacing follows the global density of states which is determined by free probability theory. We prove that these conditions hold for general homogeneous polynomials of degree two and for symmetrized products of independent matrices with i.i.d. entries, thus establishing the optimal bulk local law for these classes of ensembles. In particular, we generalize a similar result of Anderson for anticommutator. For more general polynomials our conditions are effectively checkable numerically. AU - Erdös, László AU - Krüger, Torben H AU - Nemish, Yuriy ID - 7512 IS - 12 JF - Journal of Functional Analysis SN - 00221236 TI - Local laws for polynomials of Wigner matrices VL - 278 ER - TY - JOUR AB - In this paper we study the joint convexity/concavity of the trace functions Ψp,q,s(A,B)=Tr(Bq2K∗ApKBq2)s, p,q,s∈R, where A and B are positive definite matrices and K is any fixed invertible matrix. We will give full range of (p,q,s)∈R3 for Ψp,q,s to be jointly convex/concave for all K. As a consequence, we confirm a conjecture of Carlen, Frank and Lieb. In particular, we confirm a weaker conjecture of Audenaert and Datta and obtain the full range of (α,z) for α-z Rényi relative entropies to be monotone under completely positive trace preserving maps. We also give simpler proofs of many known results, including the concavity of Ψp,0,1/p for 0
2b be integers. We prove that if each k-wise or (k+1)-wise intersection of sets from A has at most b path-connected components, which all are open, then fk+1=0 implies fk≤cfk−1 for some positive constant c depending only on b and k. These results also extend to two-dimensional compact surfaces.
AU - Kalai, Gil
AU - Patakova, Zuzana
ID - 7960
JF - Discrete and Computational Geometry
SN - 01795376
TI - Intersection patterns of planar sets
VL - 64
ER -
TY - JOUR
AB - A string graph is the intersection graph of a family of continuous arcs in the plane. The intersection graph of a family of plane convex sets is a string graph, but not all string graphs can be obtained in this way. We prove the following structure theorem conjectured by Janson and Uzzell: The vertex set of almost all string graphs on n vertices can be partitioned into five cliques such that some pair of them is not connected by any edge (n→∞). We also show that every graph with the above property is an intersection graph of plane convex sets. As a corollary, we obtain that almost all string graphs on n vertices are intersection graphs of plane convex sets.
AU - Pach, János
AU - Reed, Bruce
AU - Yuditsky, Yelena
ID - 7962
IS - 4
JF - Discrete and Computational Geometry
SN - 01795376
TI - Almost all string graphs are intersection graphs of plane convex sets
VL - 63
ER -
TY - JOUR
AB - Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal.
AU - Trejo Banos, D
AU - McCartney, DL
AU - Patxot, M
AU - Anchieri, L
AU - Battram, T
AU - Christiansen, C
AU - Costeira, R
AU - Walker, RM
AU - Morris, SW
AU - Campbell, A
AU - Zhang, Q
AU - Porteous, DJ
AU - McRae, AF
AU - Wray, NR
AU - Visscher, PM
AU - Haley, CS
AU - Evans, KL
AU - Deary, IJ
AU - McIntosh, AM
AU - Hemani, G
AU - Bell, JT
AU - Marioni, RE
AU - Robinson, Matthew Richard
ID - 7999
JF - Nature Communications
SN - 2041-1723
TI - Bayesian reassessment of the epigenetic architecture of complex traits
VL - 11
ER -
TY - JOUR
AB - When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple‐effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis , occur in North Atlantic rocky‐shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size‐assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.
AU - Perini, Samuel
AU - Rafajlović, Marina
AU - Westram, Anja M
AU - Johannesson, Kerstin
AU - Butlin, Roger K.
ID - 7995
IS - 7
JF - Evolution
SN - 00143820
TI - Assortative mating, sexual selection, and their consequences for gene flow in Littorina
VL - 74
ER -
TY - GEN
AB - When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple-effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis, occur in North Atlantic rocky-shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size-assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively-sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.
AU - Perini, Samuel
AU - Rafajlovic, Marina
AU - Westram, Anja M
AU - Johannesson, Kerstin
AU - Butlin, Roger
ID - 8809
TI - Data from: Assortative mating, sexual selection and their consequences for gene flow in Littorina
ER -
TY - JOUR
AB - Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.
AU - Vandael, David H
AU - Borges Merjane, Carolina
AU - Zhang, Xiaomin
AU - Jonas, Peter M
ID - 8001
IS - 3
JF - Neuron
SN - 0896-6273
TI - Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation
VL - 107
ER -
TY - JOUR
AB - Microelectromechanical systems and integrated photonics provide the basis for many reliable and compact circuit elements in modern communication systems. Electro-opto-mechanical devices are currently one of the leading approaches to realize ultra-sensitive, low-loss transducers for an emerging quantum information technology. Here we present an on-chip microwave frequency converter based on a planar aluminum on silicon nitride platform that is compatible with slot-mode coupled photonic crystal cavities. We show efficient frequency conversion between two propagating microwave modes mediated by the radiation pressure interaction with a metalized dielectric nanobeam oscillator. We achieve bidirectional coherent conversion with a total device efficiency of up to ~60%, a dynamic range of 2 × 10^9 photons/s and an instantaneous bandwidth of up to 1.7 kHz. A high fidelity quantum state transfer would be possible if the drive dependent output noise of currently ~14 photons s^−1 Hz^−1 is further reduced. Such a silicon nitride based transducer is in situ reconfigurable and could be used for on-chip classical and quantum signal routing and filtering, both for microwave and hybrid microwave-optical applications.
AU - Fink, Johannes M
AU - Kalaee, M.
AU - Norte, R.
AU - Pitanti, A.
AU - Painter, O.
ID - 8038
IS - 3
JF - Quantum Science and Technology
TI - Efficient microwave frequency conversion mediated by a photonics compatible silicon nitride nanobeam oscillator
VL - 5
ER -
TY - JOUR
AB - When tiny soft ferromagnetic particles are placed along a liquid interface and exposed to a vertical magnetic field, the balance between capillary attraction and magnetic repulsion leads to self-organization into well-defined patterns. Here, we demonstrate experimentally that precessing magnetic fields induce metachronal waves on the periphery of these assemblies, similar to the ones observed in ciliates and some arthropods. The outermost layer of particles behaves like an array of cilia or legs whose sequential movement causes a net and controllable locomotion. This bioinspired many-particle swimming strategy is effective even at low Reynolds number, using only spatially uniform fields to generate the waves.
AU - Collard, Ylona
AU - Grosjean, Galien M
AU - Vandewalle, Nicolas
ID - 8036
JF - Communications Physics
TI - Magnetically powered metachronal waves induce locomotion in self-assemblies
VL - 3
ER -
TY - JOUR
AB - With decreasing Reynolds number, Re, turbulence in channel flow becomes spatio-temporally intermittent and self-organises into solitary stripes oblique to the mean flow direction. We report here the existence of localised nonlinear travelling wave solutions of the Navier–Stokes equations possessing this obliqueness property. Such solutions are identified numerically using edge tracking coupled with arclength continuation. All solutions emerge in saddle-node bifurcations at values of Re lower than the non-localised solutions. Relative periodic orbit solutions bifurcating from branches of travelling waves have also been computed. A complete parametric study is performed, including their stability, the investigation of their large-scale flow, and the robustness to changes of the numerical domain.
AU - Paranjape, Chaitanya S
AU - Duguet, Yohann
AU - Hof, Björn
ID - 8043
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Oblique stripe solutions of channel flow
VL - 897
ER -
TY - GEN
AB - The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol forma design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.
AU - Gupta, Chitrak
AU - Khaniya, Umesh
AU - Chan, Chun
AU - Dehez, Francois
AU - Shekhar, Mrinal
AU - Gunner, M. R.
AU - Sazanov, Leonid A
AU - Chipot, Christophe
AU - Singharoy, Abhishek
ID - 9326
TI - Charge transfer and chemo-mechanical coupling in respiratory complex I
ER -
TY - JOUR
AB - We consider systems of N bosons in a box of volume one, interacting through a repulsive two-body potential of the form κN3β−1V(Nβx). For all 0<β<1, and for sufficiently small coupling constant κ>0, we establish the validity of Bogolyubov theory, identifying the ground state energy and the low-lying excitation spectrum up to errors that vanish in the limit of large N.
AU - Boccato, Chiara
AU - Brennecke, Christian
AU - Cenatiempo, Serena
AU - Schlein, Benjamin
ID - 8042
IS - 7
JF - Journal of the European Mathematical Society
SN - 14359855
TI - The excitation spectrum of Bose gases interacting through singular potentials
VL - 22
ER -
TY - JOUR
AB - Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.
Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.
Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.
Conclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.
AU - Hippe, Andreas
AU - Braun, Stephan Alexander
AU - Oláh, Péter
AU - Gerber, Peter Arne
AU - Schorr, Anne
AU - Seeliger, Stephan
AU - Holtz, Stephanie
AU - Jannasch, Katharina
AU - Pivarcsi, Andor
AU - Buhren, Bettina
AU - Schrumpf, Holger
AU - Kislat, Andreas
AU - Bünemann, Erich
AU - Steinhoff, Martin
AU - Fischer, Jens
AU - Lira, Sérgio A.
AU - Boukamp, Petra
AU - Hevezi, Peter
AU - Stoecklein, Nikolas Hendrik
AU - Hoffmann, Thomas
AU - Alves, Frauke
AU - Sleeman, Jonathan
AU - Bauer, Thomas
AU - Klufa, Jörg
AU - Amberg, Nicole
AU - Sibilia, Maria
AU - Zlotnik, Albert
AU - Müller-Homey, Anja
AU - Homey, Bernhard
ID - 8093
JF - British Journal of Cancer
SN - 0007-0920
TI - EGFR/Ras-induced CCL20 production modulates the tumour microenvironment
VL - 123
ER -
TY - JOUR
AB - In the setting of the fractional quantum Hall effect we study the effects of strong, repulsive two-body interaction potentials of short range. We prove that Haldane’s pseudo-potential operators, including their pre-factors, emerge as mathematically rigorous limits of such interactions when the range of the potential tends to zero while its strength tends to infinity. In a common approach the interaction potential is expanded in angular momentum eigenstates in the lowest Landau level, which amounts to taking the pre-factors to be the moments of the potential. Such a procedure is not appropriate for very strong interactions, however, in particular not in the case of hard spheres. We derive the formulas valid in the short-range case, which involve the scattering lengths of the interaction potential in different angular momentum channels rather than its moments. Our results hold for bosons and fermions alike and generalize previous results in [6], which apply to bosons in the lowest angular momentum channel. Our main theorem asserts the convergence in a norm-resolvent sense of the Hamiltonian on the whole Hilbert space, after appropriate energy scalings, to Hamiltonians with contact interactions in the lowest Landau level.
AU - Seiringer, Robert
AU - Yngvason, Jakob
ID - 8091
JF - Journal of Statistical Physics
SN - 00224715
TI - Emergence of Haldane pseudo-potentials in systems with short-range interactions
VL - 181
ER -
TY - JOUR
AB - The projection methods with vanilla inertial extrapolation step for variational inequalities have been of interest to many authors recently due to the improved convergence speed contributed by the presence of inertial extrapolation step. However, it is discovered that these projection methods with inertial steps lose the Fejér monotonicity of the iterates with respect to the solution, which is being enjoyed by their corresponding non-inertial projection methods for variational inequalities. This lack of Fejér monotonicity makes projection methods with vanilla inertial extrapolation step for variational inequalities not to converge faster than their corresponding non-inertial projection methods at times. Also, it has recently been proved that the projection methods with vanilla inertial extrapolation step may provide convergence rates that are worse than the classical projected gradient methods for strongly convex functions. In this paper, we introduce projection methods with alternated inertial extrapolation step for solving variational inequalities. We show that the sequence of iterates generated by our methods converges weakly to a solution of the variational inequality under some appropriate conditions. The Fejér monotonicity of even subsequence is recovered in these methods and linear rate of convergence is obtained. The numerical implementations of our methods compared with some other inertial projection methods show that our method is more efficient and outperforms some of these inertial projection methods.
AU - Shehu, Yekini
AU - Iyiola, Olaniyi S.
ID - 8077
JF - Applied Numerical Mathematics
SN - 0168-9274
TI - Projection methods with alternating inertial steps for variational inequalities: Weak and linear convergence
VL - 157
ER -
TY - JOUR
AB - The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn’s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
AU - Hillary, Robert F.
AU - Trejo-Banos, Daniel
AU - Kousathanas, Athanasios
AU - Mccartney, Daniel L.
AU - Harris, Sarah E.
AU - Stevenson, Anna J.
AU - Patxot, Marion
AU - Ojavee, Sven Erik
AU - Zhang, Qian
AU - Liewald, David C.
AU - Ritchie, Craig W.
AU - Evans, Kathryn L.
AU - Tucker-Drob, Elliot M.
AU - Wray, Naomi R.
AU - Mcrae, Allan F.
AU - Visscher, Peter M.
AU - Deary, Ian J.
AU - Robinson, Matthew Richard
AU - Marioni, Riccardo E.
ID - 8133
IS - 1
JF - Genome Medicine
TI - Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults
VL - 12
ER -
TY - JOUR
AB - Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.
AU - Gonçalves, Pedro J.
AU - Lueckmann, Jan-Matthis
AU - Deistler, Michael
AU - Nonnenmacher, Marcel
AU - Öcal, Kaan
AU - Bassetto, Giacomo
AU - Chintaluri, Chaitanya
AU - Podlaski, William F.
AU - Haddad, Sara A.
AU - Vogels, Tim P
AU - Greenberg, David S.
AU - Macke, Jakob H.
ID - 8127
JF - eLife
TI - Training deep neural density estimators to identify mechanistic models of neural dynamics
VL - 9
ER -
TY - JOUR
AB - Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.
AU - Agnes, Everton J.
AU - Luppi, Andrea I.
AU - Vogels, Tim P
ID - 8126
IS - 50
JF - The Journal of Neuroscience
TI - Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields
VL - 40
ER -
TY - GEN
AB - Additional file 2: Supplementary Tables. The association of pre-adjusted protein levels with biological and technical covariates. Protein levels were adjusted for age, sex, array plate and four genetic principal components (population structure) prior to analyses. Significant associations are emboldened. (Table S1). pQTLs associated with inflammatory biomarker levels from Bayesian penalised regression model (Posterior Inclusion Probability > 95%). (Table S2). All pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S3). Summary of lambda values relating to ordinary least squares GWAS and EWAS performed on inflammatory protein levels (n = 70) in Lothian Birth Cohort 1936 study. (Table S4). Conditionally significant pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S5). Comparison of variance explained by ordinary least squares and Bayesian penalised regression models for concordantly identified SNPs. (Table S6). Estimate of heritability for blood protein levels as well as proportion of variance explained attributable to different prior mixtures. (Table S7). Comparison of heritability estimates from Ahsan et al. (maximum likelihood) and Hillary et al. (Bayesian penalised regression). (Table S8). List of concordant SNPs identified by linear model and Bayesian penalised regression and whether they have been previously identified as eQTLs. (Table S9). Bayesian tests of colocalisation for cis pQTLs and cis eQTLs. (Table S10). Sherlock algorithm: Genes whose expression are putatively associated with circulating inflammatory proteins that harbour pQTLs. (Table S11). CpGs associated with inflammatory protein biomarkers as identified by Bayesian model (Bayesian model; Posterior Inclusion Probability > 95%). (Table S12). CpGs associated with inflammatory protein biomarkers as identified by linear model (limma) at P < 5.14 × 10− 10. (Table S13). CpGs associated with inflammatory protein biomarkers as identified by mixed linear model (OSCA) at P < 5.14 × 10− 10. (Table S14). Estimate of variance explained for blood protein levels by DNA methylation as well as proportion of explained attributable to different prior mixtures - BayesR+. (Table S15). Comparison of variance in protein levels explained by genome-wide DNA methylation data by mixed linear model (OSCA) and Bayesian penalised regression model (BayesR+). (Table S16). Variance in circulating inflammatory protein biomarker levels explained by common genetic and methylation data (joint and conditional estimates from BayesR+). Ordered by combined variance explained by genetic and epigenetic data - smallest to largest. Significant results from t-tests comparing distributions for variance explained by methylation or genetics alone versus combined estimate are emboldened. (Table S17). Genetic and epigenetic factors identified by BayesR+ when conditioning on all SNPs and CpGs together. (Table S18). Mendelian Randomisation analyses to assess whether proteins with concordantly identified genetic signals are causally associated with Alzheimer’s disease risk. (Table S19).
AU - Hillary, Robert F.
AU - Trejo-Banos, Daniel
AU - Kousathanas, Athanasios
AU - McCartney, Daniel L.
AU - Harris, Sarah E.
AU - Stevenson, Anna J.
AU - Patxot, Marion
AU - Ojavee, Sven Erik
AU - Zhang, Qian
AU - Liewald, David C.
AU - Ritchie, Craig W.
AU - Evans, Kathryn L.
AU - Tucker-Drob, Elliot M.
AU - Wray, Naomi R.
AU - McRae, Allan F.
AU - Visscher, Peter M.
AU - Deary, Ian J.
AU - Robinson, Matthew Richard
AU - Marioni, Riccardo E.
ID - 9706
TI - Additional file 2 of multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults
ER -
TY - JOUR
AB - We prove an upper bound on the free energy of a two-dimensional homogeneous Bose gas in the thermodynamic limit. We show that for a2ρ ≪ 1 and βρ ≳ 1, the free energy per unit volume differs from the one of the non-interacting system by at most 4πρ2|lna2ρ|−1(2−[1−βc/β]2+) to leading order, where a is the scattering length of the two-body interaction potential, ρ is the density, β is the inverse temperature, and βc is the inverse Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity. In combination with the corresponding matching lower bound proved by Deuchert et al. [Forum Math. Sigma 8, e20 (2020)], this shows equality in the asymptotic expansion.
AU - Mayer, Simon
AU - Seiringer, Robert
ID - 8134
IS - 6
JF - Journal of Mathematical Physics
SN - 00222488
TI - The free energy of the two-dimensional dilute Bose gas. II. Upper bound
VL - 61
ER -
TY - JOUR
AB - In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity.
AU - Laukoter, Susanne
AU - Pauler, Florian
AU - Beattie, Robert J
AU - Amberg, Nicole
AU - Hansen, Andi H
AU - Streicher, Carmen
AU - Penz, Thomas
AU - Bock, Christoph
AU - Hippenmeyer, Simon
ID - 8162
IS - 6
JF - Neuron
SN - 0896-6273
TI - Cell-type specificity of genomic imprinting in cerebral cortex
VL - 107
ER -
TY - JOUR
AB - Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.
AU - Zhang, J
AU - Mazur, E
AU - Balla, J
AU - Gallei, Michelle C
AU - Kalousek, P
AU - Medveďová, Z
AU - Li, Y
AU - Wang, Y
AU - Prat, Tomas
AU - Vasileva, Mina K
AU - Reinöhl, V
AU - Procházka, S
AU - Halouzka, R
AU - Tarkowski, P
AU - Luschnig, C
AU - Brewer, PB
AU - Friml, Jiří
ID - 8138
IS - 1
JF - Nature Communications
SN - 2041-1723
TI - Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization
VL - 11
ER -
TY - JOUR
AB - Speciation, that is, the evolution of reproductive barriers eventually leading to complete isolation, is a crucial process generating biodiversity. Recent work has contributed much to our understanding of how reproductive barriers begin to evolve, and how they are maintained in the face of gene flow. However, little is known about the transition from partial to strong reproductive isolation (RI) and the completion of speciation. We argue that the evolution of strong RI is likely to involve different processes, or new interactions among processes, compared with the evolution of the first reproductive barriers. Transition to strong RI may be brought about by changing external conditions, for example, following secondary contact. However, the increasing levels of RI themselves create opportunities for new barriers to evolve and, and interaction or coupling among barriers. These changing processes may depend on genomic architecture and leave detectable signals in the genome. We outline outstanding questions and suggest more theoretical and empirical work, considering both patterns and processes associated with strong RI, is needed to understand how speciation is completed.
AU - Kulmuni, Jonna
AU - Butlin, Roger K.
AU - Lucek, Kay
AU - Savolainen, Vincent
AU - Westram, Anja M
ID - 8168
IS - 1806
JF - Philosophical Transactions of the Royal Society. Series B: Biological sciences
SN - 0962-8436
TI - Towards the completion of speciation: The evolution of reproductive isolation beyond the first barriers
VL - 375
ER -
TY - JOUR
AB - The evolution of strong reproductive isolation (RI) is fundamental to the origins and maintenance of biological diversity, especially in situations where geographical distributions of taxa broadly overlap. But what is the history behind strong barriers currently acting in sympatry? Using whole-genome sequencing and single nucleotide polymorphism genotyping, we inferred (i) the evolutionary relationships, (ii) the strength of RI, and (iii) the demographic history of divergence between two broadly sympatric taxa of intertidal snail. Despite being cryptic, based on external morphology, Littorina arcana and Littorina saxatilis differ in their mode of female reproduction (egg-laying versus brooding), which may generate a strong post-zygotic barrier. We show that egg-laying and brooding snails are closely related, but genetically distinct. Genotyping of 3092 snails from three locations failed to recover any recent hybrid or backcrossed individuals, confirming that RI is strong. There was, however, evidence for a very low level of asymmetrical introgression, suggesting that isolation remains incomplete. The presence of strong, asymmetrical RI was further supported by demographic analysis of these populations. Although the taxa are currently broadly sympatric, demographic modelling suggests that they initially diverged during a short period of geographical separation involving very low gene flow. Our study suggests that some geographical separation may kick-start the evolution of strong RI, facilitating subsequent coexistence of taxa in sympatry. The strength of RI needed to achieve sympatry and the subsequent effect of sympatry on RI remain open questions.
AU - Stankowski, Sean
AU - Westram, Anja M
AU - Zagrodzka, Zuzanna B.
AU - Eyres, Isobel
AU - Broquet, Thomas
AU - Johannesson, Kerstin
AU - Butlin, Roger K.
ID - 8167
IS - 1806
JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences
TI - The evolution of strong reproductive isolation between sympatric intertidal snails
VL - 375
ER -
TY - JOUR
AB - Alignment of OCS, CS2, and I2 molecules embedded in helium nanodroplets is measured as a function
of time following rotational excitation by a nonresonant, comparatively weak ps laser pulse. The distinct
peaks in the power spectra, obtained by Fourier analysis, are used to determine the rotational, B, and
centrifugal distortion, D, constants. For OCS, B and D match the values known from IR spectroscopy. For
CS2 and I2, they are the first experimental results reported. The alignment dynamics calculated from the
gas-phase rotational Schrödinger equation, using the experimental in-droplet B and D values, agree in
detail with the measurement for all three molecules. The rotational spectroscopy technique for molecules in
helium droplets introduced here should apply to a range of molecules and complexes.
AU - Chatterley, Adam S.
AU - Christiansen, Lars
AU - Schouder, Constant A.
AU - Jørgensen, Anders V.
AU - Shepperson, Benjamin
AU - Cherepanov, Igor
AU - Bighin, Giacomo
AU - Zillich, Robert E.
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 8170
IS - 1
JF - Physical Review Letters
SN - 00319007
TI - Rotational coherence spectroscopy of molecules in Helium nanodroplets: Reconciling the time and the frequency domains
VL - 125
ER -
TY - CONF
AB - Fixed-point arithmetic is a popular alternative to floating-point arithmetic on embedded systems. Existing work on the verification of fixed-point programs relies on custom formalizations of fixed-point arithmetic, which makes it hard to compare the described techniques or reuse the implementations. In this paper, we address this issue by proposing and formalizing an SMT theory of fixed-point arithmetic. We present an intuitive yet comprehensive syntax of the fixed-point theory, and provide formal semantics for it based on rational arithmetic. We also describe two decision procedures for this theory: one based on the theory of bit-vectors and the other on the theory of reals. We implement the two decision procedures, and evaluate our implementations using existing mature SMT solvers on a benchmark suite we created. Finally, we perform a case study of using the theory we propose to verify properties of quantized neural networks.
AU - Baranowski, Marek
AU - He, Shaobo
AU - Lechner, Mathias
AU - Nguyen, Thanh Son
AU - Rakamarić, Zvonimir
ID - 8194
SN - 03029743
T2 - Automated Reasoning
TI - An SMT theory of fixed-point arithmetic
VL - 12166
ER -
TY - JOUR
AB - Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common (“universal”) functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings.
AU - Corominas-Murtra, Bernat
AU - Scheele, Colinda L.G.J.
AU - Kishi, Kasumi
AU - Ellenbroek, Saskia I.J.
AU - Simons, Benjamin D.
AU - Van Rheenen, Jacco
AU - Hannezo, Edouard B
ID - 8220
IS - 29
JF - Proceedings of the National Academy of Sciences of the United States of America
TI - Stem cell lineage survival as a noisy competition for niche access
VL - 117
ER -
TY - JOUR
AB - We investigate a mechanism to transiently stabilize topological phenomena in long-lived quasi-steady states of isolated quantum many-body systems driven at low frequencies. We obtain an analytical bound for the lifetime of the quasi-steady states which is exponentially large in the inverse driving frequency. Within this lifetime, the quasi-steady state is characterized by maximum entropy subject to the constraint of fixed number of particles in the system's Floquet-Bloch bands. In such a state, all the non-universal properties of these bands are washed out, hence only the topological properties persist.
AU - Gulden, Tobias
AU - Berg, Erez
AU - Rudner, Mark Spencer
AU - Lindner, Netanel
ID - 8199
JF - SciPost Physics
SN - 2542-4653
TI - Exponentially long lifetime of universal quasi-steady states in topological Floquet pumps
VL - 9
ER -
TY - JOUR
AB - Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.
AU - Zhang, Xiaomin
AU - Schlögl, Alois
AU - Jonas, Peter M
ID - 8261
IS - 6
JF - Neuron
SN - 0896-6273
TI - Selective routing of spatial information flow from input to output in hippocampal granule cells
VL - 107
ER -
TY - JOUR
AB - Modern scientific instruments produce vast amounts of data, which can overwhelm the processing ability of computer systems. Lossy compression of data is an intriguing solution, but comes with its own drawbacks, such as potential signal loss, and the need for careful optimization of the compression ratio. In this work, we focus on a setting where this problem is especially acute: compressive sensing frameworks for interferometry and medical imaging. We ask the following question: can the precision of the data representation be lowered for all inputs, with recovery guarantees and practical performance Our first contribution is a theoretical analysis of the normalized Iterative Hard Thresholding (IHT) algorithm when all input data, meaning both the measurement matrix and the observation vector are quantized aggressively. We present a variant of low precision normalized IHT that, under mild conditions, can still provide recovery guarantees. The second contribution is the application of our quantization framework to radio astronomy and magnetic resonance imaging. We show that lowering the precision of the data can significantly accelerate image recovery. We evaluate our approach on telescope data and samples of brain images using CPU and FPGA implementations achieving up to a 9x speedup with negligible loss of recovery quality.
AU - Gurel, Nezihe Merve
AU - Kara, Kaan
AU - Stojanov, Alen
AU - Smith, Tyler
AU - Lemmin, Thomas
AU - Alistarh, Dan-Adrian
AU - Puschel, Markus
AU - Zhang, Ce
ID - 8268
JF - IEEE Transactions on Signal Processing
SN - 1053587X
TI - Compressive sensing using iterative hard thresholding with low precision data representation: Theory and applications
VL - 68
ER -
TY - JOUR
AB - By rigorously accounting for mesoscale spatial correlations in donor/acceptor surface properties, we develop a scale-spanning model for same-material tribocharging. We find that mesoscale correlations affect not only the magnitude of charge transfer but also the fluctuations—suppressing otherwise overwhelming charge-transfer variability that is not observed experimentally. We furthermore propose a generic theoretical mechanism by which the mesoscale features might emerge, which is qualitatively consistent with other proposals in the literature.
AU - Grosjean, Galien M
AU - Wald, Sebastian
AU - Sobarzo Ponce, Juan Carlos A
AU - Waitukaitis, Scott R
ID - 8101
IS - 8
JF - Physical Review Materials
KW - electric charge
KW - tribocharging
KW - soft matter
KW - granular materials
KW - polymers
SN - 2475-9953
TI - Quantitatively consistent scale-spanning model for same-material tribocharging
VL - 4
ER -
TY - JOUR
AB - Let 𝐹:ℤ2→ℤ be the pointwise minimum of several linear functions. The theory of smoothing allows us to prove that under certain conditions there exists the pointwise minimal function among all integer-valued superharmonic functions coinciding with F “at infinity”. We develop such a theory to prove existence of so-called solitons (or strings) in a sandpile model, studied by S. Caracciolo, G. Paoletti, and A. Sportiello. Thus we made a step towards understanding the phenomena of the identity in the sandpile group for planar domains where solitons appear according to experiments. We prove that sandpile states, defined using our smoothing procedure, move changeless when we apply the wave operator (that is why we call them solitons), and can interact, forming triads and nodes.
AU - Kalinin, Nikita
AU - Shkolnikov, Mikhail
ID - 8325
IS - 9
JF - Communications in Mathematical Physics
SN - 00103616
TI - Sandpile solitons via smoothing of superharmonic functions
VL - 378
ER -
TY - JOUR
AB - Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.
AU - Gutierrez-Fernandez, Javier
AU - Kaszuba, Karol
AU - Minhas, Gurdeep S.
AU - Baradaran, Rozbeh
AU - Tambalo, Margherita
AU - Gallagher, David T.
AU - Sazanov, Leonid A
ID - 8318
IS - 1
JF - Nature Communications
TI - Key role of quinone in the mechanism of respiratory complex I
VL - 11
ER -
TY - JOUR
AU - Pach, János
ID - 8323
JF - Discrete and Computational Geometry
SN - 01795376
TI - A farewell to Ricky Pollack
VL - 64
ER -
TY - JOUR
AB - Plant hormone cytokinins are perceived by a subfamily of sensor histidine kinases (HKs), which via a two-component phosphorelay cascade activate transcriptional responses in the nucleus. Subcellular localization of the receptors proposed the endoplasmic reticulum (ER) membrane as a principal cytokinin perception site, while study of cytokinin transport pointed to the plasma membrane (PM)-mediated cytokinin signalling. Here, by detailed monitoring of subcellular localizations of the fluorescently labelled natural cytokinin probe and the receptor ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/AHK4) fused to GFP reporter, we show that pools of the ER-located cytokinin receptors can enter the secretory pathway and reach the PM in cells of the root apical meristem, and the cell plate of dividing meristematic cells. Brefeldin A (BFA) experiments revealed vesicular recycling of the receptor and its accumulation in BFA compartments. We provide a revised view on cytokinin signalling and the possibility of multiple sites of perception at PM and ER.
AU - Kubiasova, Karolina
AU - Montesinos López, Juan C
AU - Šamajová, Olga
AU - Nisler, Jaroslav
AU - Mik, Václav
AU - Semeradova, Hana
AU - Plíhalová, Lucie
AU - Novák, Ondřej
AU - Marhavý, Peter
AU - Cavallari, Nicola
AU - Zalabák, David
AU - Berka, Karel
AU - Doležal, Karel
AU - Galuszka, Petr
AU - Šamaj, Jozef
AU - Strnad, Miroslav
AU - Benková, Eva
AU - Plíhal, Ondřej
AU - Spíchal, Lukáš
ID - 8336
JF - Nature Communications
TI - Cytokinin fluoroprobe reveals multiple sites of cytokinin perception at plasma membrane and endoplasmic reticulum
VL - 11
ER -
TY - JOUR
AB - Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.
AU - Antoniadi, Ioanna
AU - Novák, Ondřej
AU - Gelová, Zuzana
AU - Johnson, Alexander J
AU - Plíhal, Ondřej
AU - Simerský, Radim
AU - Mik, Václav
AU - Vain, Thomas
AU - Mateo-Bonmatí, Eduardo
AU - Karady, Michal
AU - Pernisová, Markéta
AU - Plačková, Lenka
AU - Opassathian, Korawit
AU - Hejátko, Jan
AU - Robert, Stéphanie
AU - Friml, Jiří
AU - Doležal, Karel
AU - Ljung, Karin
AU - Turnbull, Colin
ID - 8337
JF - Nature Communications
TI - Cell-surface receptors enable perception of extracellular cytokinins
VL - 11
ER -
TY - GEN
AB - With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, lithium metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the
mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (polymeric and inorganic), Lithium-sulphur and Li-O2 (air) batteries. A particular attention is paid to review recent developments in regard of prototype manufacturing and current state-ofthe-art of these battery technologies with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7.
AU - Varzi, Alberto
AU - Thanner, Katharina
AU - Scipioni, Roberto
AU - Di Lecce, Daniele
AU - Hassoun, Jusef
AU - Dörfler, Susanne
AU - Altheus, Holger
AU - Kaskel, Stefan
AU - Prehal, Christian
AU - Freunberger, Stefan Alexander
ID - 8067
KW - Battery
KW - Lithium metal
KW - Lithium-sulphur
KW - Lithium-air
KW - All-solid-state
SN - 2664-1690
TI - Current status and future perspectives of Lithium metal batteries
ER -
TY - JOUR
AB - With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, Li metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (inorganic and polymeric), Lithium–Sulfur (Li–S) and Lithium-O2 (air) batteries. A particular attention is paid to recent developments of these battery technologies and their current state with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7.
AU - Varzi, Alberto
AU - Thanner, Katharina
AU - Scipioni, Roberto
AU - Di Lecce, Daniele
AU - Hassoun, Jusef
AU - Dörfler, Susanne
AU - Altheus, Holger
AU - Kaskel, Stefan
AU - Prehal, Christian
AU - Freunberger, Stefan Alexander
ID - 8361
IS - 12
JF - Journal of Power Sources
SN - 0378-7753
TI - Current status and future perspectives of lithium metal batteries
VL - 480
ER -
TY - JOUR
AB - Practical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a