TY - JOUR AB - Let A={A1,…,An} be a family of sets in the plane. For 0≤i2b be integers. We prove that if each k-wise or (k+1)-wise intersection of sets from A has at most b path-connected components, which all are open, then fk+1=0 implies fk≤cfk−1 for some positive constant c depending only on b and k. These results also extend to two-dimensional compact surfaces. 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 - Binary interaction can cause stellar envelopes to be stripped, which significantly reduces the radius of the star. The orbit of a binary composed of a stripped star and a compact object can therefore be so tight that the gravitational radiation the system produces reaches frequencies accessible to the Laser Interferometer Space Antenna (LISA). Two such stripped stars in tight orbits with white dwarfs are known so far (ZTF J2130+4420 and CD−30°11223), but many more are expected to exist. These binaries provide important constraints for binary evolution models and may be used as LISA verification sources. We develop a Monte Carlo code that uses detailed evolutionary models to simulate the Galactic population of stripped stars in tight orbits with either neutron star or white dwarf companions. We predict 0–100 stripped star + white dwarf binaries and 0–4 stripped star + neutron star binaries with a signal-to-noise ratio >5 after 10 yr of observations with LISA. More than 90% of these binaries are expected to show large radial velocity shifts of ≳200 $\,\mathrm{km}\,{{\rm{s}}}^{-1}$, which are spectroscopically detectable. Photometric variability due to tidal deformation of the stripped star is also expected and has been observed in ZTF J2130+4420 and CD−30°11223. In addition, the stripped star + neutron star binaries are expected to be X-ray bright with LX ≳ 1033–1036 $\,\mathrm{erg}\,{{\rm{s}}}^{-1}$. Our results show that stripped star binaries are promising multimessenger sources for the upcoming electromagnetic and gravitational wave facilities. AU - Götberg, Ylva Louise Linsdotter AU - Korol, V. AU - Lamberts, A. AU - Kupfer, T. AU - Breivik, K. AU - Ludwig, B. AU - Drout, M. R. ID - 13460 IS - 1 JF - The Astrophysical Journal KW - Space and Planetary Science KW - Astronomy and Astrophysics SN - 0004-637X TI - Stars stripped in binaries: The living gravitational-wave sources VL - 904 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 - The interaction of strong near-infrared (NIR) laser pulses with wide-bandgap dielectrics produces high harmonics in the extreme ultraviolet (XUV) wavelength range. These observations have opened up the possibility of attosecond metrology in solids, which would benefit from a precise measurement of the emission times of individual harmonics with respect to the NIR laser field. Here we show that, when high-harmonics are detected from the input surface of a magnesium oxide crystal, a bichromatic probing of the XUV emission shows a clear synchronization largely consistent with a semiclassical model of electron–hole recollisions in bulk solids. On the other hand, the bichromatic spectrogram of harmonics originating from the exit surface of the 200 μm-thick crystal is strongly modified, indicating the influence of laser field distortions during propagation. Our tracking of sub-cycle electron and hole re-collisions at XUV energies is relevant to the development of solid-state sources of attosecond pulses. AU - Vampa, Giulio AU - Lu, Jian AU - You, Yong Sing AU - Baykusheva, Denitsa Rangelova AU - Wu, Mengxi AU - Liu, Hanzhe AU - Schafer, Kenneth J AU - Gaarde, Mette B AU - Reis, David A AU - Ghimire, Shambhu ID - 13998 IS - 14 JF - Journal of Physics B: Atomic, Molecular and Optical Physics KW - Condensed Matter Physics KW - Atomic and Molecular Physics KW - and Optics SN - 0953-4075 TI - Attosecond synchronization of extreme ultraviolet high harmonics from crystals VL - 53 ER - TY - JOUR AB - Attosecond chronoscopy has revealed small but measurable delays in photoionization, characterized by the ejection of an electron on absorption of a single photon. Ionization-delay measurements in atomic targets provide a wealth of information about the timing of the photoelectric effect, resonances, electron correlations and transport. However, extending this approach to molecules presents challenges, such as identifying the correct ionization channels and the effect of the anisotropic molecular landscape on the measured delays. Here, we measure ionization delays from ethyl iodide around a giant dipole resonance. By using the theoretical value for the iodine atom as a reference, we disentangle the contribution from the functional ethyl group, which is responsible for the characteristic chemical reactivity of a molecule. We find a substantial additional delay caused by the presence of a functional group, which encodes the effect of the molecular potential on the departing electron. Such information is inaccessible to the conventional approach of measuring photoionization cross-sections. The results establish ionization-delay measurements as a valuable tool in investigating the electronic properties of molecules. AU - Biswas, Shubhadeep AU - Förg, Benjamin AU - Ortmann, Lisa AU - Schötz, Johannes AU - Schweinberger, Wolfgang AU - Zimmermann, Tomáš AU - Pi, Liangwen AU - Baykusheva, Denitsa Rangelova AU - Masood, Hafiz A. AU - Liontos, Ioannis AU - Kamal, Amgad M. AU - Kling, Nora G. AU - Alharbi, Abdullah F. AU - Alharbi, Meshaal AU - Azzeer, Abdallah M. AU - Hartmann, Gregor AU - Wörner, Hans J. AU - Landsman, Alexandra S. AU - Kling, Matthias F. ID - 13999 IS - 7 JF - Nature Physics KW - General Physics and Astronomy SN - 1745-2473 TI - Probing molecular environment through photoemission delays VL - 16 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 - Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such perturbations interact with subsequent evolutionary adaptation to the drug? Here, we show that strong epistasis between resistance mutations and systematically identified genes can be exploited to control spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform that tightly controls population size and selection pressure. We find a global diminishing-returns epistasis pattern: strains that are initially more sensitive generally undergo larger resistance gains. However, some gene deletion strains deviate from this general trend and curtail the evolvability of resistance, including deletions of genes for membrane transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force evolution on inferior mutational paths, not explored in the wild type, and some of these essentially block resistance evolution. This effect is due to strong negative epistasis with resistance mutations. The identified genes and cellular functions provide potential targets for development of adjuvants that may block spontaneous resistance evolution when combined with antibiotics. AU - Lukacisinova, Marta AU - Fernando, Booshini AU - Bollenbach, Mark Tobias ID - 8037 JF - Nature Communications TI - Highly parallel lab evolution reveals that epistasis can curb the evolution of antibiotic resistance VL - 11 ER - TY - JOUR 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 form—a design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I. AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M. R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 8040 IS - 20 JF - Journal of the American Chemical Society SN - 00027863 TI - Charge transfer and chemo-mechanical coupling in respiratory complex I VL - 142 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 forma design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I. 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 - GEN AB - Additional analyses of the trajectories AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M.R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 9713 TI - Supporting information ER - TY - GEN AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M.R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 9878 TI - Movies 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 - In the present work, we report a solution-based strategy to produce crystallographically textured SnSe bulk nanomaterials and printed layers with optimized thermoelectric performance in the direction normal to the substrate. Our strategy is based on the formulation of a molecular precursor that can be continuously decomposed to produce a SnSe powder or printed into predefined patterns. The precursor formulation and decomposition conditions are optimized to produce pure phase 2D SnSe nanoplates. The printed layer and the bulk material obtained after hot press displays a clear preferential orientation of the crystallographic domains, resulting in an ultralow thermal conductivity of 0.55 W m–1 K–1 in the direction normal to the substrate. Such textured nanomaterials present highly anisotropic properties with the best thermoelectric performance in plane, i.e., in the directions parallel to the substrate, which coincide with the crystallographic bc plane of SnSe. This is an unfortunate characteristic because thermoelectric devices are designed to create/harvest temperature gradients in the direction normal to the substrate. We further demonstrate that this limitation can be overcome with the introduction of small amounts of tellurium in the precursor. The presence of tellurium allows one to reduce the band gap and increase both the charge carrier concentration and the mobility, especially the cross plane, with a minimal decrease of the Seebeck coefficient. These effects translate into record out of plane ZT values at 800 K. AU - Zhang, Yu AU - Liu, Yu AU - Xing, Congcong AU - Zhang, Ting AU - Li, Mengyao AU - Pacios, Mercè AU - Yu, Xiaoting AU - Arbiol, Jordi AU - Llorca, Jordi AU - Cadavid, Doris AU - Ibáñez, Maria AU - Cabot, Andreu ID - 8039 IS - 24 JF - ACS Applied Materials and Interfaces TI - Tin selenide molecular precursor for the solution processing of thermoelectric materials and devices VL - 12 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 - JOUR AB - The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity. AU - Salzer, Elisabeth AU - Zoghi, Samaneh AU - Kiss, Máté G. AU - Kage, Frieda AU - Rashkova, Christina AU - Stahnke, Stephanie AU - Haimel, Matthias AU - Platzer, René AU - Caldera, Michael AU - Ardy, Rico Chandra AU - Hoeger, Birgit AU - Block, Jana AU - Medgyesi, David AU - Sin, Celine AU - Shahkarami, Sepideh AU - Kain, Renate AU - Ziaee, Vahid AU - Hammerl, Peter AU - Bock, Christoph AU - Menche, Jörg AU - Dupré, Loïc AU - Huppa, Johannes B. AU - Sixt, Michael K AU - Lomakin, Alexis AU - Rottner, Klemens AU - Binder, Christoph J. AU - Stradal, Theresia E.B. AU - Rezaei, Nima AU - Boztug, Kaan ID - 8132 IS - 49 JF - Science Immunology TI - The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity VL - 5 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 AU - Barton, Nicholas H ID - 8112 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences SN - 0962-8436 TI - On the completion of speciation VL - 375 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 - Many recent studies have addressed the mechanisms operating during the early stages of speciation, but surprisingly few studies have tested theoretical predictions on the evolution of strong reproductive isolation (RI). To help address this gap, we first undertook a quantitative review of the hybrid zone literature for flowering plants in relation to reproductive barriers. Then, using Populus as an exemplary model group, we analysed genome-wide variation for phylogenetic tree topologies in both early- and late-stage speciation taxa to determine how these patterns may be related to the genomic architecture of RI. Our plant literature survey revealed variation in barrier complexity and an association between barrier number and introgressive gene flow. Focusing on Populus, our genome-wide analysis of tree topologies in speciating poplar taxa points to unusually complex genomic architectures of RI, consistent with earlier genome-wide association studies. These architectures appear to facilitate the ‘escape’ of introgressed genome segments from polygenic barriers even with strong RI, thus affecting their relationships with recombination rates. Placed within the context of the broader literature, our data illustrate how phylogenomic approaches hold great promise for addressing the evolution and temporary breakdown of RI during late stages of speciation. AU - Shang, Huiying AU - Hess, Jaqueline AU - Pickup, Melinda AU - Field, David AU - Ingvarsson, Pär K. AU - Liu, Jianquan AU - Lexer, Christian ID - 8169 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences TI - Evolution of strong reproductive isolation in plants: Broad-scale patterns and lessons from a perennial model group VL - 375 ER - TY - JOUR AB - Direct ethanol fuel cells (DEFCs) show a huge potential to power future electric vehicles and portable electronics, but their deployment is currently limited by the unavailability of proper electrocatalysis for the ethanol oxidation reaction (EOR). In this work, we engineer a new electrocatalyst by incorporating phosphorous into a palladium-tin alloy and demonstrate a significant performance improvement toward EOR. We first detail a synthetic method to produce Pd2Sn:P nanocrystals that incorporate 35% of phosphorus. These nanoparticles are supported on carbon black and tested for EOR. Pd2Sn:P/C catalysts exhibit mass current densities up to 5.03 A mgPd−1, well above those of Pd2Sn/C, PdP2/C and Pd/C reference catalysts. Furthermore, a twofold lower Tafel slope and a much longer durability are revealed for the Pd2Sn:P/C catalyst compared with Pd/C. The performance improvement is rationalized with the aid of density functional theory (DFT) calculations considering different phosphorous chemical environments. Depending on its oxidation state, surface phosphorus introduces sites with low energy OH− adsorption and/or strongly influences the electronic structure of palladium and tin to facilitate the oxidation of the acetyl to acetic acid, which is considered the EOR rate limiting step. DFT calculations also points out that the durability improvement of Pd2Sn:P/C catalyst is associated to the promotion of OH adsorption that accelerates the oxidation of intermediate poisoning COads, reactivating the catalyst surface. AU - Yu, Xiaoting AU - Liu, Junfeng AU - Li, Junshan AU - Luo, Zhishan AU - Zuo, Yong AU - Xing, Congcong AU - Llorca, Jordi AU - Nasiou, Déspina AU - Arbiol, Jordi AU - Pan, Kai AU - Kleinhanns, Tobias AU - Xie, Ying AU - Cabot, Andreu ID - 8189 IS - 11 JF - Nano Energy SN - 2211-2855 TI - Phosphorous incorporation in Pd2Sn alloys for electrocatalytic ethanol oxidation VL - 77 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 AU - He, Peng AU - Zhang, Yuzhou AU - Xiao, Guanghui ID - 8271 IS - 9 JF - Molecular Plant SN - 16742052 TI - Origin of a subgenome and genome evolution of allotetraploid cotton species VL - 13 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 AB - The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications. AU - Mukba, S. A. AU - Vlasov, Petr AU - Kolosov, P. M. AU - Shuvalova, E. Y. AU - Egorova, T. V. AU - Alkalaeva, E. Z. ID - 8320 IS - 4 JF - Molecular Biology SN - 00268933 TI - Expanding the genetic code: Unnatural base pairs in biological systems VL - 54 ER - TY - JOUR AB - The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications. AU - Mukba, S. A. AU - Vlasov, Petr AU - Kolosov, P. M. AU - Shuvalova, E. Y. AU - Egorova, T. V. AU - Alkalaeva, E. Z. ID - 8321 IS - 4 JF - Molekuliarnaia biologiia SN - 00268984 TI - Expanding the genetic code: Unnatural base pairs in biological systems VL - 54 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 -