TY - JOUR
AB - The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems.
AU - Goodrich, Carl Peter
AU - King, Ella M.
AU - Schoenholz, Samuel S.
AU - Cubuk, Ekin D.
AU - Brenner, Michael P.
ID - 9257
IS - 10
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Designing self-assembling kinetics with differentiable statistical physics models
VL - 118
ER -
TY - JOUR
AU - Pinkard, Henry
AU - Stuurman, Nico
AU - Ivanov, Ivan E.
AU - Anthony, Nicholas M.
AU - Ouyang, Wei
AU - Li, Bin
AU - Yang, Bin
AU - Tsuchida, Mark A.
AU - Chhun, Bryant
AU - Zhang, Grace
AU - Mei, Ryan
AU - Anderson, Michael
AU - Shepherd, Douglas P.
AU - Hunt-Isaak, Ian
AU - Dunn, Raymond L.
AU - Jahr, Wiebke
AU - Kato, Saul
AU - Royer, Loïc A.
AU - Thiagarajah, Jay R.
AU - Eliceiri, Kevin W.
AU - Lundberg, Emma
AU - Mehta, Shalin B.
AU - Waller, Laura
ID - 9258
IS - 3
JF - Nature Methods
SN - 1548-7091
TI - Pycro-Manager: Open-source software for customized and reproducible microscope control
VL - 18
ER -
TY - JOUR
AB - Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient.
AU - Vaahtomeri, Kari
AU - Moussion, Christine
AU - Hauschild, Robert
AU - Sixt, Michael K
ID - 9259
JF - Frontiers in Immunology
TI - Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium
VL - 12
ER -
TY - JOUR
AB - We study the density of rational points on a higher-dimensional orbifold (Pn−1,Δ) when Δ is a Q-divisor involving hyperplanes. This allows us to address a question of Tanimoto about whether the set of rational points on such an orbifold constitutes a thin set. Our approach relies on the Hardy–Littlewood circle method to first study an asymptotic version of Waring’s problem for mixed powers. In doing so we make crucial use of the recent resolution of the main conjecture in Vinogradov’s mean value theorem, due to Bourgain–Demeter–Guth and Wooley.
AU - Browning, Timothy D
AU - Yamagishi, Shuntaro
ID - 9260
JF - Mathematische Zeitschrift
SN - 0025-5874
TI - Arithmetic of higher-dimensional orbifolds and a mixed Waring problem
VL - 299
ER -
TY - JOUR
AB - Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide.
AU - Mbianda, Johanne
AU - Bakail, May M
AU - André, Christophe
AU - Moal, Gwenaëlle
AU - Perrin, Marie E.
AU - Pinna, Guillaume
AU - Guerois, Raphaël
AU - Becher, Francois
AU - Legrand, Pierre
AU - Traoré, Seydou
AU - Douat, Céline
AU - Guichard, Gilles
AU - Ochsenbein, Françoise
ID - 9262
IS - 12
JF - Science Advances
SN - 2375-2548
TI - Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity
VL - 7
ER -
TY - GEN
AB - We comment on two formal proofs of Fermat's sum of two squares theorem, written using the Mathematical Components libraries of the Coq proof assistant. The first one follows Zagier's celebrated one-sentence proof; the second follows David Christopher's recent new proof relying on partition-theoretic arguments. Both formal proofs rely on a general property of involutions of finite sets, of independent interest. The proof technique consists for the most part of automating recurrent tasks (such as case distinctions and computations on natural numbers) via ad hoc tactics.
AU - Dubach, Guillaume
AU - Mühlböck, Fabian
ID - 9281
T2 - arXiv
TI - Formal verification of Zagier's one-sentence proof
ER -
TY - JOUR
AB - Several Ising-type magnetic van der Waals (vdW) materials exhibit stable magnetic ground states. Despite these clear experimental demonstrations, a complete theoretical and microscopic understanding of their magnetic anisotropy is still lacking. In particular, the validity limit of identifying their one-dimensional (1-D) Ising nature has remained uninvestigated in a quantitative way. Here we performed the complete mapping of magnetic anisotropy for a prototypical Ising vdW magnet FePS3 for the first time. Combining torque magnetometry measurements with their magnetostatic model analysis and the relativistic density functional total energy calculations, we successfully constructed the three-dimensional (3-D) mappings of the magnetic anisotropy in terms of magnetic torque and energy. The results not only quantitatively confirm that the easy axis is perpendicular to the ab plane, but also reveal the anisotropies within the ab, ac, and bc planes. Our approach can be applied to the detailed quantitative study of magnetism in vdW materials.
AU - Nauman, Muhammad
AU - Kiem, Do Hoon
AU - Lee, Sungmin
AU - Son, Suhan
AU - Park, J-G
AU - Kang, Woun
AU - Han, Myung Joon
AU - Jo, Youn Jung
ID - 9282
IS - 3
JF - 2D Materials
KW - Mechanical Engineering
KW - General Materials Science
KW - Mechanics of Materials
KW - General Chemistry
KW - Condensed Matter Physics
SN - 2053-1583
TI - Complete mapping of magnetic anisotropy for prototype Ising van der Waals FePS3
VL - 8
ER -
TY - JOUR
AB - Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.
AU - Nagy-Staron, Anna A
AU - Tomasek, Kathrin
AU - Caruso Carter, Caroline
AU - Sonnleitner, Elisabeth
AU - Kavcic, Bor
AU - Paixão, Tiago
AU - Guet, Calin C
ID - 9283
JF - eLife
KW - Genetics and Molecular Biology
SN - 2050-084X
TI - Local genetic context shapes the function of a gene regulatory network
VL - 10
ER -
TY - JOUR
AB - The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the
auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural (IAA) and synthetic (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network (EE/TGN), rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using Total Internal Reflection Fluorescence (TIRF) microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus contributing to its
polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments.
AU - Narasimhan, Madhumitha
AU - Gallei, Michelle C
AU - Tan, Shutang
AU - Johnson, Alexander J
AU - Verstraeten, Inge
AU - Li, Lanxin
AU - Rodriguez Solovey, Lesia
AU - Han, Huibin
AU - Himschoot, E
AU - Wang, R
AU - Vanneste, S
AU - Sánchez-Simarro, J
AU - Aniento, F
AU - Adamowski, Maciek
AU - Friml, Jiří
ID - 9287
IS - 2
JF - Plant Physiology
SN - 0032-0889
TI - Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking
VL - 186
ER -
TY - JOUR
AB - • The phenylpropanoid pathway serves a central role in plant metabolism, providing numerous compounds involved in diverse physiological processes. Most carbon entering the pathway is incorporated into lignin. Although several phenylpropanoid pathway mutants show seedling growth arrest, the role for lignin in seedling growth and development is unexplored.
• We use complementary pharmacological and genetic approaches to block CINNAMATE‐4‐HYDROXYLASE (C4H) functionality in Arabidopsis seedlings and a set of molecular and biochemical techniques to investigate the underlying phenotypes.
• Blocking C4H resulted in reduced lateral rooting and increased adventitious rooting apically in the hypocotyl. These phenotypes coincided with an inhibition in auxin transport. The upstream accumulation in cis‐cinnamic acid was found to likely cause polar auxin transport inhibition. Conversely, a downstream depletion in lignin perturbed phloem‐mediated auxin transport. Restoring lignin deposition effectively reestablished phloem transport and, accordingly, auxin homeostasis.
• Our results show that the accumulation of bioactive intermediates and depletion in lignin jointly cause the aberrant phenotypes upon blocking C4H, and demonstrate that proper deposition of lignin is essential for the establishment of auxin distribution in seedlings. Our data position the phenylpropanoid pathway and lignin in a new physiological framework, consolidating their importance in plant growth and development.
AU - El Houari, I
AU - Van Beirs, C
AU - Arents, HE
AU - Han, Huibin
AU - Chanoca, A
AU - Opdenacker, D
AU - Pollier, J
AU - Storme, V
AU - Steenackers, W
AU - Quareshy, M
AU - Napier, R
AU - Beeckman, T
AU - Friml, Jiří
AU - De Rybel, B
AU - Boerjan, W
AU - Vanholme, B
ID - 9288
IS - 6
JF - New Phytologist
SN - 0028-646x
TI - Seedling developmental defects upon blocking CINNAMATE-4-HYDROXYLASE are caused by perturbations in auxin transport
VL - 230
ER -
TY - CONF
AB - We present a faster symbolic algorithm for the following central problem in probabilistic verification: Compute the maximal end-component (MEC) decomposition of Markov decision processes (MDPs). This problem generalizes the SCC decomposition problem of graphs and closed recurrent sets of Markov chains. The model of symbolic algorithms is widely used in formal verification and model-checking, where access to the input model is restricted to only symbolic operations (e.g., basic set operations and computation of one-step neighborhood). For an input MDP with n vertices and m edges, the classical symbolic algorithm from the 1990s for the MEC decomposition requires O(n2) symbolic operations and O(1) symbolic space. The only other symbolic algorithm for the MEC decomposition requires O(nm−−√) symbolic operations and O(m−−√) symbolic space. A main open question is whether the worst-case O(n2) bound for symbolic operations can be beaten. We present a symbolic algorithm that requires O˜(n1.5) symbolic operations and O˜(n−−√) symbolic space. Moreover, the parametrization of our algorithm provides a trade-off between symbolic operations and symbolic space: for all 0<ϵ≤1/2 the symbolic algorithm requires O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space ( O˜ hides poly-logarithmic factors). Using our techniques we present faster algorithms for computing the almost-sure winning regions of ω -regular objectives for MDPs. We consider the canonical parity objectives for ω -regular objectives, and for parity objectives with d -priorities we present an algorithm that computes the almost-sure winning region with O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space, for all 0<ϵ≤1/2 .
AU - Chatterjee, Krishnendu
AU - Dvorak, Wolfgang
AU - Henzinger, Monika
AU - Svozil, Alexander
ID - 10002
KW - Computer science
KW - Computational modeling
KW - Markov processes
KW - Probabilistic logic
KW - Formal verification
KW - Game Theory
SN - 1043-6871
T2 - Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Symbolic time and space tradeoffs for probabilistic verification
ER -
TY - CONF
AB - Markov chains are the de facto finite-state model for stochastic dynamical systems, and Markov decision processes (MDPs) extend Markov chains by incorporating non-deterministic behaviors. Given an MDP and rewards on states, a classical optimization criterion is the maximal expected total reward where the MDP stops after T steps, which can be computed by a simple dynamic programming algorithm. We consider a natural generalization of the problem where the stopping times can be chosen according to a probability distribution, such that the expected stopping time is T, to optimize the expected total reward. Quite surprisingly we establish inter-reducibility of the expected stopping-time problem for Markov chains with the Positivity problem (which is related to the well-known Skolem problem), for which establishing either decidability or undecidability would be a major breakthrough. Given the hardness of the exact problem, we consider the approximate version of the problem: we show that it can be solved in exponential time for Markov chains and in exponential space for MDPs.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 10004
KW - Computer science
KW - Heuristic algorithms
KW - Memory management
KW - Automata
KW - Markov processes
KW - Probability distribution
KW - Complexity theory
SN - 1043-6871
T2 - Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Stochastic processes with expected stopping time
ER -
TY - JOUR
AB - We study systems of nonlinear partial differential equations of parabolic type, in which the elliptic operator is replaced by the first-order divergence operator acting on a flux function, which is related to the spatial gradient of the unknown through an additional implicit equation. This setting, broad enough in terms of applications, significantly expands the paradigm of nonlinear parabolic problems. Formulating four conditions concerning the form of the implicit equation, we first show that these conditions describe a maximal monotone p-coercive graph. We then establish the global-in-time and large-data existence of a (weak) solution and its uniqueness. To this end, we adopt and significantly generalize Minty’s method of monotone mappings. A unified theory, containing several novel tools, is developed in a way to be tractable from the point of view of numerical approximations.
AU - Bulíček, Miroslav
AU - Maringová, Erika
AU - Málek, Josef
ID - 10005
IS - 09
JF - Mathematical Models and Methods in Applied Sciences
KW - Nonlinear parabolic systems
KW - implicit constitutive theory
KW - weak solutions
KW - existence
KW - uniqueness
SN - 0218-2025
TI - On nonlinear problems of parabolic type with implicit constitutive equations involving flux
VL - 31
ER -
TY - THES
AB - The present thesis is concerned with the derivation of weak-strong uniqueness principles for curvature driven interface evolution problems not satisfying a comparison principle. The specific examples being treated are two-phase Navier-Stokes flow with surface tension, modeling the evolution of two incompressible, viscous and immiscible fluids separated by a sharp interface, and multiphase mean curvature flow, which serves as an idealized model for the motion of grain boundaries in an annealing polycrystalline material. Our main results - obtained in joint works with Julian Fischer, Tim Laux and Theresa M. Simon - state that prior to the formation of geometric singularities due to topology changes, the weak solution concept of Abels (Interfaces Free Bound. 9, 2007) to two-phase Navier-Stokes flow with surface tension and the weak solution concept of Laux and Otto (Calc. Var. Partial Differential Equations 55, 2016) to multiphase mean curvature flow (for networks in R^2 or double bubbles in R^3) represents the unique solution to these interface evolution problems within the class of classical solutions, respectively. To the best of the author's knowledge, for interface evolution problems not admitting a geometric comparison principle the derivation of a weak-strong uniqueness principle represented an open problem, so that the works contained in the present thesis constitute the first positive results in this direction. The key ingredient of our approach consists of the introduction of a novel concept of relative entropies for a class of curvature driven interface evolution problems, for which the associated energy contains an interfacial contribution being proportional to the surface area of the evolving (network of) interface(s). The interfacial part of the relative entropy gives sufficient control on the interface error between a weak and a classical solution, and its time evolution can be computed, at least in principle, for any energy dissipating weak solution concept. A resulting stability estimate for the relative entropy essentially entails the above mentioned weak-strong uniqueness principles. The present thesis contains a detailed introduction to our relative entropy approach, which in particular highlights potential applications to other problems in curvature driven interface evolution not treated in this thesis.
AU - Hensel, Sebastian
ID - 10007
SN - 2663-337X
TI - Curvature driven interface evolution: Uniqueness properties of weak solution concepts
ER -
TY - GEN
AB - We propose a new weak solution concept for (two-phase) mean curvature flow which enjoys both (unconditional) existence and (weak-strong) uniqueness properties. These solutions are evolving varifolds, just as in Brakke's formulation, but are coupled to the phase volumes by a simple transport equation. First, we show that, in the exact same setup as in Ilmanen's proof [J. Differential Geom. 38, 417-461, (1993)], any limit point of solutions to the Allen-Cahn equation is a varifold solution in our sense. Second, we prove that any calibrated flow in the sense of Fischer et al. [arXiv:2003.05478] - and hence any classical solution to mean curvature flow - is unique in the class of our new varifold solutions. This is in sharp contrast to the case of Brakke flows, which a priori may disappear at any given time and are therefore fatally non-unique. Finally, we propose an extension of the solution concept to the multi-phase case which is at least guaranteed to satisfy a weak-strong uniqueness principle.
AU - Hensel, Sebastian
AU - Laux, Tim
ID - 10011
KW - Mean curvature flow
KW - gradient flows
KW - varifolds
KW - weak solutions
KW - weak-strong uniqueness
KW - calibrated geometry
KW - gradient-flow calibrations
T2 - arXiv
TI - A new varifold solution concept for mean curvature flow: Convergence of the Allen-Cahn equation and weak-strong uniqueness
ER -
TY - GEN
AB - We derive a weak-strong uniqueness principle for BV solutions to multiphase mean curvature flow of triple line clusters in three dimensions. Our proof is based on the explicit construction of a gradient-flow calibration in the sense of the recent work of Fischer et al. [arXiv:2003.05478] for any such cluster. This extends the two-dimensional construction to the three-dimensional case of surfaces meeting along triple junctions.
AU - Hensel, Sebastian
AU - Laux, Tim
ID - 10013
T2 - arXiv
TI - Weak-strong uniqueness for the mean curvature flow of double bubbles
ER -
TY - JOUR
AB - Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxincontrolled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2
Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.
AU - Nikonorova, N
AU - Murphy, E
AU - Fonseca de Lima, CF
AU - Zhu, S
AU - van de Cotte, B
AU - Vu, LD
AU - Balcerowicz, D
AU - Li, Lanxin
AU - Kong, X
AU - De Rop, G
AU - Beeckman, T
AU - Friml, Jiří
AU - Vissenberg, K
AU - Morris, PC
AU - Ding, Z
AU - De Smet, I
ID - 10015
JF - Cells
KW - primary root
KW - (phospho)proteomics
KW - auxin
KW - (receptor) kinase
SN - 2073-4409
TI - The Arabidopsis root tip (phospho)proteomes at growth-promoting versus growth-repressing conditions reveal novel root growth regulators
VL - 10
ER -
TY - JOUR
AB - Auxin has always been at the forefront of research in plant physiology and development. Since the earliest contemplations by Julius von Sachs and Charles Darwin, more than a century-long struggle has been waged to understand its function. This largely reflects the failures, successes, and inevitable progress in the entire field of plant signaling and development. Here I present 14 stations on our long and sometimes mystical journey to understand auxin. These highlights were selected to give a flavor of the field and to show the scope and limits of our current knowledge. A special focus is put on features that make auxin unique among phytohormones, such as its dynamic, directional transport network, which integrates external and internal signals, including self-organizing feedback. Accented are persistent mysteries and controversies. The unexpected discoveries related to rapid auxin responses and growth regulation recently disturbed our contentment regarding understanding of the auxin signaling mechanism. These new revelations, along with advances in technology, usher us into a new, exciting era in auxin research.
AU - Friml, Jiří
ID - 10016
JF - Cold Spring Harbor Perspectives in Biology
SN - 1943-0264
TI - Fourteen stations of auxin
ER -
TY - GEN
AB - In order to study integral points of bounded log-anticanonical height on weak del Pezzo surfaces, we classify weak del Pezzo pairs. As a representative example, we consider a quartic del Pezzo surface of singularity type A1 + A3 and prove an analogue of Manin's conjecture for integral points with respect to its singularities and its lines.
AU - Derenthal, Ulrich
AU - Wilsch, Florian Alexander
ID - 10018
KW - Integral points
KW - del Pezzo surface
KW - universal torsor
KW - Manin’s conjecture
T2 - arXiv
TI - Integral points on singular del Pezzo surfaces
ER -
TY - JOUR
AB - We study the temporal dissipation of variance and relative entropy for ergodic Markov Chains in continuous time, and compute explicitly the corresponding dissipation rates. These are identified, as is well known, in the case of the variance in terms of an appropriate Hilbertian norm; and in the case of the relative entropy, in terms of a Dirichlet form which morphs into a version of the familiar Fisher information under conditions of detailed balance. Here we obtain trajectorial versions of these results, valid along almost every path of the random motion and most transparent in the backwards direction of time. Martingale arguments and time reversal play crucial roles, as in the recent work of Karatzas, Schachermayer and Tschiderer for conservative diffusions. Extensions are developed to general “convex divergences” and to countable state-spaces. The steepest descent and gradient flow properties for the variance, the relative entropy, and appropriate generalizations, are studied along with their respective geometries under conditions of detailed balance, leading to a very direct proof for the HWI inequality of Otto and Villani in the present context.
AU - Karatzas, Ioannis
AU - Maas, Jan
AU - Schachermayer, Walter
ID - 10023
IS - 4
JF - Communications in Information and Systems
KW - Markov Chain
KW - relative entropy
KW - time reversal
KW - steepest descent
KW - gradient flow
SN - 1526-7555
TI - Trajectorial dissipation and gradient flow for the relative entropy in Markov chains
VL - 21
ER -
TY - JOUR
AB - Ferromagnetism is most common in transition metal compounds but may also arise in low-density two-dimensional electron systems, with signatures observed in silicon, III-V semiconductor systems, and graphene moiré heterostructures. Here we show that gate-tuned van Hove singularities in rhombohedral trilayer graphene drive the spontaneous ferromagnetic polarization of the electron system into one or more spin- and valley flavors. Using capacitance measurements on graphite-gated van der Waals heterostructures, we find a cascade of density- and electronic displacement field tuned phase transitions marked by negative electronic compressibility. The transitions define the boundaries between phases where quantum oscillations have either four-fold, two-fold, or one-fold degeneracy, associated with a spin and valley degenerate normal metal, spin-polarized `half-metal', and spin and valley polarized `quarter metal', respectively. For electron doping, the salient features are well captured by a phenomenological Stoner model with a valley-anisotropic Hund's coupling, likely arising from interactions at the lattice scale. For hole filling, we observe a richer phase diagram featuring a delicate interplay of broken symmetries and transitions in the Fermi surface topology. Finally, by rotational alignment of a hexagonal boron nitride substrate to induce a moiré superlattice, we find that the superlattice perturbs the preexisting isospin order only weakly, leaving the basic phase diagram intact while catalyzing the formation of topologically nontrivial gapped states whenever itinerant half- or quarter metal states occur at half- or quarter superlattice band filling. Our results show that rhombohedral trilayer graphene is an ideal platform for well-controlled tests of many-body theory and reveal magnetism in moiré materials to be fundamentally itinerant in nature.
AU - Zhou, Haoxin
AU - Xie, Tian
AU - Ghazaryan, Areg
AU - Holder, Tobias
AU - Ehrets, James R.
AU - Spanton, Eric M.
AU - Taniguchi, Takashi
AU - Watanabe, Kenji
AU - Berg, Erez
AU - Serbyn, Maksym
AU - Young, Andrea F.
ID - 10025
JF - Nature
KW - condensed matter - mesoscale and nanoscale physics
KW - condensed matter - strongly correlated electrons
KW - multidisciplinary
SN - 0028-0836
TI - Half and quarter metals in rhombohedral trilayer graphene
ER -
TY - GEN
AB - Superconductor-semiconductor hybrids are platforms for realizing effective p-wave superconductivity. Spin-orbit coupling, combined with the proximity effect, causes the two-dimensional semiconductor to inherit p±ip intraband pairing, and application of magnetic field can then result in transitions to the normal state, partial Bogoliubov Fermi surfaces, or topological phases with Majorana modes. Experimentally probing the hybrid superconductor-semiconductor interface is challenging due to the shunting effect of the conventional superconductor. Consequently, the nature of induced pairing remains an open question. Here, we use the circuit quantum electrodynamics architecture to probe induced superconductivity in a two dimensional Al-InAs hybrid system. We observe a strong suppression of superfluid density and enhanced dissipation driven by magnetic field, which cannot be accounted for by the depairing theory of an s-wave superconductor. These observations are explained by a picture of independent intraband p±ip superconductors giving way to partial Bogoliubov Fermi surfaces, and allow for the first characterization of key properties of the hybrid superconducting system.
AU - Phan, Duc T
AU - Senior, Jorden L
AU - Ghazaryan, Areg
AU - Hatefipour, M.
AU - Strickland, W. M.
AU - Shabani, J.
AU - Serbyn, Maksym
AU - Higginbotham, Andrew P
ID - 10029
T2 - arXiv
TI - Breakdown of induced p±ip pairing in a superconductor-semiconductor hybrid
ER -
TY - THES
AB - This PhD thesis is primarily focused on the study of discrete transport problems, introduced for the first time in the seminal works of Maas [Maa11] and Mielke [Mie11] on finite state Markov chains and reaction-diffusion equations, respectively. More in detail, my research focuses on the study of transport costs on graphs, in particular the convergence and the stability of such problems in the discrete-to-continuum limit. This thesis also includes some results concerning
non-commutative optimal transport. The first chapter of this thesis consists of a general introduction to the optimal transport problems, both in the discrete, the continuous, and the non-commutative setting. Chapters 2 and 3 present the content of two works, obtained in collaboration with Peter Gladbach, Eva Kopfer, and Jan Maas, where we have been able to show the convergence of discrete transport costs on periodic graphs to suitable continuous ones, which can be described by means of a homogenisation result. We first focus on the particular case of quadratic costs on the real line and then extending the result to more general costs in arbitrary dimension. Our results are the first complete characterisation of limits of transport costs on periodic graphs in arbitrary dimension which do not rely on any additional symmetry. In Chapter 4 we turn our attention to one of the intriguing connection between evolution equations and optimal transport, represented by the theory of gradient flows. We show that discrete gradient flow structures associated to a finite volume approximation of a certain class of diffusive equations (Fokker–Planck) is stable in the limit of vanishing meshes, reproving the convergence of the scheme via the method of evolutionary Γ-convergence and exploiting a more variational point of view on the problem. This is based on a collaboration with Dominik Forkert and Jan Maas. Chapter 5 represents a change of perspective, moving away from the discrete world and reaching the non-commutative one. As in the discrete case, we discuss how classical tools coming from the commutative optimal transport can be translated into the setting of density matrices. In particular, in this final chapter we present a non-commutative version of the Schrödinger problem (or entropic regularised optimal transport problem) and discuss existence and characterisation of minimisers, a duality result, and present a non-commutative version of the well-known Sinkhorn algorithm to compute the above mentioned optimisers. This is based on a joint work with Dario Feliciangeli and Augusto Gerolin. Finally, Appendix A and B contain some additional material and discussions, with particular attention to Harnack inequalities and the regularity of flows on discrete spaces.
AU - Portinale, Lorenzo
ID - 10030
SN - 2663-337X
TI - Discrete-to-continuum limits of transport problems and gradient flows in the space of measures
ER -
TY - THES
AB - Many security definitions come in two flavors: a stronger “adaptive” flavor, where the adversary can arbitrarily make various choices during the course of the attack, and a weaker “selective” flavor where the adversary must commit to some or all of their choices a-priori. For example, in the context of identity-based encryption, selective security requires the adversary to decide on the identity of the attacked party at the very beginning of the game whereas adaptive security allows the attacker to first see the master public key and some secret keys before making this choice. Often, it appears to be much easier to achieve selective security than it is to achieve adaptive security. A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption [Pan07][FJP15], constrained PRFs [FKPR14], and Yao’s garbled circuits [JW16]. Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework (published at Crypto ’17 [JKK+17a]) that connects all of these works and allows us to present them in a unified and simplified fashion. Having the framework in place, we show how to achieve adaptive security for proxy re-encryption schemes (published at PKC ’19 [FKKP19]) and provide the first adaptive security proofs for continuous group key agreement protocols (published at S&P ’21 [KPW+21]). Questioning optimality of our framework, we then show that currently used proof techniques cannot lead to significantly better security guarantees for "graph-building" games (published at TCC ’21 [KKPW21a]). These games cover generalized selective decryption, as well as the security of prominent constructions for constrained PRFs, continuous group key agreement, and proxy re-encryption. Finally, we revisit the adaptive security of Yao’s garbled circuits and extend the analysis of Jafargholi and Wichs in two directions: While they prove adaptive security only for a modified construction with increased online complexity, we provide the first positive results for the original construction by Yao (published at TCC ’21 [KKP21a]). On the negative side, we prove that the results of Jafargholi and Wichs are essentially optimal by showing that no black-box reduction can provide a significantly better security bound (published at Crypto ’21 [KKPW21c]).
AU - Klein, Karen
ID - 10035
SN - 2663-337X
TI - On the adaptive security of graph-based games
ER -
TY - CONF
AB - Yao’s garbling scheme is one of the most fundamental cryptographic constructions. Lindell and Pinkas (Journal of Cryptograhy 2009) gave a formal proof of security in the selective setting where the adversary chooses the challenge inputs before seeing the garbled circuit assuming secure symmetric-key encryption (and hence one-way functions). This was followed by results, both positive and negative, concerning its security in the, stronger, adaptive setting. Applebaum et al. (Crypto 2013) showed that it cannot satisfy adaptive security as is, due to a simple incompressibility argument. Jafargholi and Wichs (TCC 2017) considered a natural adaptation of Yao’s scheme (where the output mapping is sent in the online phase, together with the garbled input) that circumvents this negative result, and proved that it is adaptively secure, at least for shallow circuits. In particular, they showed that for the class of circuits of depth δ , the loss in security is at most exponential in δ . The above results all concern the simulation-based notion of security. In this work, we show that the upper bound of Jafargholi and Wichs is basically optimal in a strong sense. As our main result, we show that there exists a family of Boolean circuits, one for each depth δ∈N , such that any black-box reduction proving the adaptive indistinguishability of the natural adaptation of Yao’s scheme from any symmetric-key encryption has to lose a factor that is exponential in δ√ . Since indistinguishability is a weaker notion than simulation, our bound also applies to adaptive simulation. To establish our results, we build on the recent approach of Kamath et al. (Eprint 2021), which uses pebbling lower bounds in conjunction with oracle separations to prove fine-grained lower bounds on loss in cryptographic security.
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ID - 10041
SN - 0302-9743
T2 - 41st Annual International Cryptology Conference, Part II
TI - Limits on the Adaptive Security of Yao’s Garbling
VL - 12826
ER -
TY - CONF
AB - We show that Yao’s garbling scheme is adaptively indistinguishable for the class of Boolean circuits of size S and treewidth w with only a S^O(w) loss in security. For instance, circuits with constant treewidth are as a result adaptively indistinguishable with only a polynomial loss. This (partially) complements a negative result of Applebaum et al. (Crypto 2013), which showed (assuming one-way functions) that Yao’s garbling scheme cannot be adaptively simulatable. As main technical contributions, we introduce a new pebble game that abstracts out our security reduction and then present a pebbling strategy for this game where the number of pebbles used is roughly O(d w log(S)), d being the fan-out of the circuit. The design of the strategy relies on separators, a graph-theoretic notion with connections to circuit complexity.
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Pietrzak, Krzysztof Z
ID - 10044
T2 - 19th Theory of Cryptography Conference 2021
TI - On treewidth, separators and Yao's garbling
ER -
TY - GEN
AB - Given a fixed finite metric space (V,μ), the {\em minimum 0-extension problem}, denoted as 0-Ext[μ], is equivalent to the following optimization problem: minimize function of the form minx∈Vn∑ifi(xi)+∑ijcijμ(xi,xj) where cij,cvi are given nonnegative costs and fi:V→R are functions given by fi(xi)=∑v∈Vcviμ(xi,v). The computational complexity of 0-Ext[μ] has been recently established by Karzanov and by Hirai: if metric μ is {\em orientable modular} then 0-Ext[μ] can be solved in polynomial time, otherwise 0-Ext[μ] is NP-hard. To prove the tractability part, Hirai developed a theory of discrete convex functions on orientable modular graphs generalizing several known classes of functions in discrete convex analysis, such as L♮-convex functions. We consider a more general version of the problem in which unary functions fi(xi) can additionally have terms of the form cuv;iμ(xi,{u,v}) for {u,v}∈F, where set F⊆(V2) is fixed. We extend the complexity classification above by providing an explicit condition on (μ,F) for the problem to be tractable. In order to prove the tractability part, we generalize Hirai's theory and define a larger class of discrete convex functions. It covers, in particular, another well-known class of functions, namely submodular functions on an integer lattice. Finally, we improve the complexity of Hirai's algorithm for solving 0-Ext on orientable modular graphs.
AU - Dvorak, Martin
AU - Kolmogorov, Vladimir
ID - 10045
KW - minimum 0-extension problem
KW - metric labeling problem
KW - discrete metric spaces
KW - metric extensions
KW - computational complexity
KW - valued constraint satisfaction problems
KW - discrete convex analysis
KW - L-convex functions
T2 - arXiv
TI - Generalized minimum 0-extension problem and discrete convexity
ER -
TY - CONF
AB - The security of cryptographic primitives and protocols against adversaries that are allowed to make adaptive choices (e.g., which parties to corrupt or which queries to make) is notoriously difficult to establish. A broad theoretical
framework was introduced by Jafargholi et al. [Crypto’17] for this purpose. In this paper we initiate the study of lower bounds on loss in adaptive security for certain cryptographic protocols considered in the framework. We prove lower
bounds that almost match the upper bounds (proven using the framework) for proxy re-encryption, prefix-constrained PRFs and generalized selective decryption, a security game that captures the security of certain group messaging and
broadcast encryption schemes. Those primitives have in common that their security game involves an underlying graph that can be adaptively built by the adversary. Some of our lower bounds only apply to a restricted class of black-box reductions which we term “oblivious” (the existing upper bounds are of this restricted type), some apply to the broader but still restricted class of non-rewinding reductions, while our lower bound for proxy re-encryption applies to all black-box reductions. The fact that some of our lower bounds seem to crucially rely on obliviousness or at least a non-rewinding reduction hints to the exciting possibility that the existing upper bounds can be improved by using more sophisticated reductions. Our main conceptual contribution is a two-player multi-stage game called the Builder-Pebbler Game. We can translate bounds on the winning probabilities for various instantiations of this game into cryptographic lower bounds for the above-mentioned primitives using oracle separation techniques.
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Pietrzak, Krzysztof Z
AU - Walter, Michael
ID - 10048
T2 - 19th Theory of Cryptography Conference 2021
TI - The cost of adaptivity in security games on graphs
ER -
TY - CONF
AB - While messaging systems with strong security guarantees are widely used in practice, designing a protocol that scales efficiently to large groups and enjoys similar security guarantees remains largely open. The two existing proposals to date are ART (Cohn-Gordon et al., CCS18) and TreeKEM (IETF, The Messaging Layer Security Protocol, draft). TreeKEM is the currently considered candidate by the IETF MLS working group, but dynamic group operations (i.e. adding and removing users) can cause efficiency issues. In this paper we formalize and analyze a variant of TreeKEM which we term Tainted TreeKEM (TTKEM for short). The basic idea underlying TTKEM was suggested by Millican (MLS mailing list, February 2018). This version is more efficient than TreeKEM for some natural distributions of group operations, we quantify this through simulations.Our second contribution is two security proofs for TTKEM which establish post compromise and forward secrecy even against adaptive attackers. The security loss (to the underlying PKE) in the Random Oracle Model is a polynomial factor, and a quasipolynomial one in the Standard Model. Our proofs can be adapted to TreeKEM as well. Before our work no security proof for any TreeKEM-like protocol establishing tight security against an adversary who can adaptively choose the sequence of operations was known. We also are the first to prove (or even formalize) active security where the server can arbitrarily deviate from the protocol specification. Proving fully active security – where also the users can arbitrarily deviate – remains open.
AU - Klein, Karen
AU - Pascual Perez, Guillermo
AU - Walter, Michael
AU - Kamath Hosdurg, Chethan
AU - Capretto, Margarita
AU - Cueto Noval, Miguel
AU - Markov, Ilia
AU - Yeo, Michelle X
AU - Alwen, Joel F
AU - Pietrzak, Krzysztof Z
ID - 10049
T2 - 2021 IEEE Symposium on Security and Privacy
TI - Keep the dirt: tainted TreeKEM, adaptively and actively secure continuous group key agreement
ER -
TY - JOUR
AB - Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.
AU - Butola, Tanvi
AU - Alvanos, Theocharis
AU - Hintze, Anika
AU - Koppensteiner, Peter
AU - Kleindienst, David
AU - Shigemoto, Ryuichi
AU - Wichmann, Carolin
AU - Moser, Tobias
ID - 10051
IS - 37
JF - Journal of Neuroscience
SN - 0270-6474
TI - RIM-binding protein 2 organizes Ca^{21} channel topography and regulates release probability and vesicle replenishment at a fast central synapse
VL - 41
ER -
TY - CONF
AB - This paper characterizes the latency of the simplified successive-cancellation (SSC) decoding scheme for polar codes under hardware resource constraints. In particular, when the number of processing elements P that can perform SSC decoding operations in parallel is limited, as is the case in practice, the latency of SSC decoding is O(N1−1 μ+NPlog2log2NP), where N is the block length of the code and μ is the scaling exponent of polar codes for the channel. Three direct consequences of this bound are presented. First, in a fully-parallel implementation where P=N2 , the latency of SSC decoding is O(N1−1/μ) , which is sublinear in the block length. This recovers a result from an earlier work. Second, in a fully-serial implementation where P=1 , the latency of SSC decoding scales as O(Nlog2log2N) . The multiplicative constant is also calculated: we show that the latency of SSC decoding when P=1 is given by (2+o(1))Nlog2log2N . Third, in a semi-parallel implementation, the smallest P that gives the same latency as that of the fully-parallel implementation is P=N1/μ . The tightness of our bound on SSC decoding latency and the applicability of the foregoing results is validated through extensive simulations.
AU - Hashemi, Seyyed Ali
AU - Mondelli, Marco
AU - Fazeli, Arman
AU - Vardy, Alexander
AU - Cioffi, John
AU - Goldsmith, Andrea
ID - 10053
SN - 2157-8095
T2 - 2021 IEEE International Symposium on Information Theory
TI - Parallelism versus latency in simplified successive-cancellation decoding of polar codes
ER -
TY - GEN
AB - The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions. We give a key step towards tackling this variability with an algorithm that, without modification, is capable of tuning a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate SiGe heterostructure double quantum dot device from scratch. We achieve tuning times of 30, 10, and 92 minutes, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning.
AU - Severin, B.
AU - Lennon, D. T.
AU - Camenzind, L. C.
AU - Vigneau, F.
AU - Fedele, F.
AU - Jirovec, Daniel
AU - Ballabio, A.
AU - Chrastina, D.
AU - Isella, G.
AU - Kruijf, M. de
AU - Carballido, M. J.
AU - Svab, S.
AU - Kuhlmann, A. V.
AU - Braakman, F. R.
AU - Geyer, S.
AU - Froning, F. N. M.
AU - Moon, H.
AU - Osborne, M. A.
AU - Sejdinovic, D.
AU - Katsaros, Georgios
AU - Zumbühl, D. M.
AU - Briggs, G. A. D.
AU - Ares, N.
ID - 10066
T2 - arXiv
TI - Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning
ER -
TY - JOUR
AB - The search for novel entangled phases of matter has lead to the recent discovery of a new class of “entanglement transitions,” exemplified by random tensor networks and monitored quantum circuits. Most known examples can be understood as some classical ordering transitions in an underlying statistical mechanics model, where entanglement maps onto the free-energy cost of inserting a domain wall. In this paper we study the possibility of entanglement transitions driven by physics beyond such statistical mechanics mappings. Motivated by recent applications of neural-network-inspired variational Ansätze, we investigate under what conditions on the variational parameters these Ansätze can capture an entanglement transition. We study the entanglement scaling of short-range restricted Boltzmann machine (RBM) quantum states with random phases. For uncorrelated random phases, we analytically demonstrate the absence of an entanglement transition and reveal subtle finite-size effects in finite-size numerical simulations. Introducing phases with correlations decaying as 1/r^α in real space, we observe three regions with a different scaling of entanglement entropy depending on the exponent α. We study the nature of the transition between these regions, finding numerical evidence for critical behavior. Our work establishes the presence of long-range correlated phases in RBM-based wave functions as a required ingredient for entanglement transitions.
AU - Medina Ramos, Raimel A
AU - Vasseur, Romain
AU - Serbyn, Maksym
ID - 10067
IS - 10
JF - Physical Review B
SN - 2469-9950
TI - Entanglement transitions from restricted Boltzmann machines
VL - 104
ER -
TY - JOUR
AB - The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a [Formula: see text] level, among women in how blood count values change through pregnancy for mean corpuscular hemoglobin, mean corpuscular volume, mean platelet volume, platelet count and red cell distribution width. We find evidence that almost all complete blood count values show trimester-specific associations with PPH. For example, high platelet count (OR 1.20, 95% CI 1.01-1.53), high mean platelet volume (OR 1.58, 95% CI 1.04-2.08), and high erythrocyte levels (OR 1.36, 95% CI 1.01-1.57) in trimester 1 increased PPH, but high values in trimester 3 decreased PPH risk (OR 0.85, 0.79, 0.67 respectively). We show that differences among women in the course of blood cell counts throughout pregnancy have an important role in shaping pregnancy outcome and tracking blood count value changes through pregnancy improves identification of women at increased risk of postpartum hemorrhage. This study provides greater understanding of the complex changes in blood count values that occur through pregnancy and provides indicators to guide the stratification of patients into risk groups.
AU - Robinson, Matthew Richard
AU - Patxot, Marion
AU - Stojanov, Miloš
AU - Blum, Sabine
AU - Baud, David
ID - 10069
JF - Scientific Reports
TI - Postpartum hemorrhage risk is driven by changes in blood composition through pregnancy
VL - 11
ER -
TY - JOUR
AB - We extensively discuss the Rademacher and Sobolev-to-Lipschitz properties for generalized intrinsic distances on strongly local Dirichlet spaces possibly without square field operator. We present many non-smooth and infinite-dimensional examples. As an application, we prove the integral Varadhan short-time asymptotic with respect to a given distance function for a large class of strongly local Dirichlet forms.
AU - Dello Schiavo, Lorenzo
AU - Suzuki, Kohei
ID - 10070
IS - 11
JF - Journal of Functional Analysis
SN - 0022-1236
TI - Rademacher-type theorems and Sobolev-to-Lipschitz properties for strongly local Dirichlet spaces
VL - 281
ER -
TY - JOUR
AU - Adams, Henry
AU - Kourimska, Hana
AU - Heiss, Teresa
AU - Percival, Sarah
AU - Ziegelmeier, Lori
ID - 10071
IS - 9
JF - Notices of the American Mathematical Society
SN - 0002-9920
TI - How to tutorial-a-thon
VL - 68
ER -
TY - CONF
AB - The Lovász Local Lemma (LLL) is a powerful tool in probabilistic combinatorics which can be used to establish the existence of objects that satisfy certain properties. The breakthrough paper of Moser and Tardos and follow-up works revealed that the LLL has intimate connections with a class of stochastic local search algorithms for finding such desirable objects. In particular, it can be seen as a sufficient condition for this type of algorithms to converge fast. Besides conditions for existence of and fast convergence to desirable objects, one may naturally ask further questions regarding properties of these algorithms. For instance, "are they parallelizable?", "how many solutions can they output?", "what is the expected "weight" of a solution?", etc. These questions and more have been answered for a class of LLL-inspired algorithms called commutative. In this paper we introduce a new, very natural and more general notion of commutativity (essentially matrix commutativity) which allows us to show a number of new refined properties of LLL-inspired local search algorithms with significantly simpler proofs.
AU - Harris, David G.
AU - Iliopoulos, Fotis
AU - Kolmogorov, Vladimir
ID - 10072
SN - 1868-8969
T2 - Approximation, Randomization, and Combinatorial Optimization. Algorithms and Techniques
TI - A new notion of commutativity for the algorithmic Lovász Local Lemma
VL - 207
ER -
TY - JOUR
AB - Thermoelectric materials enable the direct conversion between heat and electricity. SnTe is a promising candidate due to its high charge transport performance. Here, we prepared SnTe nanocomposites by employing an aqueous method to synthetize SnTe nanoparticles (NP), followed by a unique surface treatment prior NP consolidation. This synthetic approach allowed optimizing the charge and phonon transport synergistically. The novelty of this strategy was the use of a soluble PbS molecular complex prepared using a thiol-amine solvent mixture that upon blending is adsorbed on the SnTe NP surface. Upon consolidation with spark plasma sintering, SnTe-PbS nanocomposite is formed. The presence of PbS complexes significantly compensates for the Sn vacancy and increases the average grain size of the nanocomposite, thus improving the carrier mobility. Moreover, lattice thermal conductivity is also reduced by the Pb and S-induced mass and strain fluctuation. As a result, an enhanced ZT of ca. 0.8 is reached at 873 K. Our finding provides a novel strategy to conduct rational surface treatment on NP-based thermoelectrics.
AU - Chang, Cheng
AU - Ibáñez, Maria
ID - 10073
IS - 18
JF - Materials
TI - Enhanced thermoelectric performance by surface engineering in SnTe-PbS nanocomposites
VL - 14
ER -
TY - CONF
AB - We present a novel approach for blockchain asset owners to reclaim their funds in case of accidental private-key loss or transfer to a mistyped address. Our solution can be deployed upon failure or absence of proactively implemented backup mechanisms, such as secret sharing and cold storage. The main advantages against previous proposals is it does not require any prior action from users and works with both single-key and multi-sig accounts. We achieve this by a 3-phase Commit()→Reveal()→Claim()−or−Challenge() smart contract that enables accessing funds of addresses for which the spending key is not available. We provide an analysis of the threat and incentive models and formalize the concept of reactive KEy-Loss Protection (KELP).
AU - Blackshear, Sam
AU - Chalkias, Konstantinos
AU - Chatzigiannis, Panagiotis
AU - Faizullabhoy, Riyaz
AU - Khaburzaniya, Irakliy
AU - Kokoris Kogias, Eleftherios
AU - Lind, Joshua
AU - Wong, David
AU - Zakian, Tim
ID - 10076
SN - 0302-9743
T2 - FC 2021 Workshops
TI - Reactive key-loss protection in blockchains
VL - 12676
ER -
TY - GEN
AB - Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.
AU - Nardin, Michele
AU - Csicsvari, Jozsef L
AU - Tkačik, Gašper
AU - Savin, Cristina
ID - 10077
T2 - bioRxiv
TI - The structure of hippocampal CA1 interactions optimizes spatial coding across experience
ER -
TY - GEN
AB - Hippocampal and neocortical neural activity is modulated by the position of the individual in space. While hippocampal neurons provide the basis for a spatial map, prefrontal cortical neurons generalize over environmental features. Whether these generalized representations result from a bidirectional interaction with, or are mainly derived from hippocampal spatial representations is not known. By examining simultaneously recorded hippocampal and medial prefrontal neurons, we observed that prefrontal spatial representations show a delayed coherence with hippocampal ones. We also identified subpopulations of cells in the hippocampus and medial prefrontal cortex that formed functional cross-area couplings; these resembled the optimal connections predicted by a probabilistic model of spatial information transfer and generalization. Moreover, cross-area couplings were strongest and had the shortest delay preceding spatial decision-making. Our results suggest that generalized spatial coding in the medial prefrontal cortex is inherited from spatial representations in the hippocampus, and that the routing of information can change dynamically with behavioral demands.
AU - Nardin, Michele
AU - Käfer, Karola
AU - Csicsvari, Jozsef L
ID - 10080
T2 - bioRxiv
TI - The generalized spatial representation in the prefrontal cortex is inherited from the hippocampus
ER -
TY - THES
AB - Plant motions occur across a wide spectrum of timescales, ranging from seed dispersal through bursting (milliseconds) and stomatal opening (minutes) to long-term adaptation of gross architecture. Relatively fast motions include water-driven growth as exemplified by root cell expansion under abiotic/biotic stresses or during gravitropism. A showcase is a root growth inhibition in 30 seconds triggered by the phytohormone auxin. However, the cellular and molecular mechanisms are still largely unknown. This thesis covers the studies about this topic as follows. By taking advantage of microfluidics combined with live imaging, pharmaceutical tools, and transgenic lines, we examined the kinetics of and causal relationship among various auxininduced rapid cellular changes in root growth, apoplastic pH, cytosolic Ca2+, cortical microtubule (CMT) orientation, and vacuolar morphology. We revealed that CMT reorientation and vacuolar constriction are the consequence of growth itself instead of responding directly to auxin. In contrast, auxin induces apoplast alkalinization to rapidly inhibit root growth in 30 seconds. This auxin-triggered apoplast alkalinization results from rapid H+- influx that is contributed by Ca2+ inward channel CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14)-dependent Ca2+ signaling. To dissect which auxin signaling mediates the rapid apoplast alkalinization, we
combined microfluidics and genetic engineering to verify that TIR1/AFB receptors conduct a non-transcriptional regulation on Ca2+ and H+ -influx. This non-canonical pathway is mostly mediated by the cytosolic portion of TIR1/AFB. On the other hand, we uncovered, using biochemical and phospho-proteomic analysis, that auxin cell surface signaling component TRANSMEMBRANE KINASE 1 (TMK1) plays a negative role during auxin-trigger apoplast
alkalinization and root growth inhibition through directly activating PM H+ -ATPases. Therefore, we discovered that PM H+ -ATPases counteract instead of mediate the auxintriggered rapid H+ -influx, and that TIR1/AFB and TMK1 regulate root growth antagonistically. This opposite effect of TIR1/AFB and TMK1 is consistent during auxin-induced hypocotyl elongation, leading us to explore the relation of two signaling pathways. Assisted with biochemistry and fluorescent imaging, we verified for the first time that TIR1/AFB and TMK1 can interact with each other. The ability of TIR1/AFB binding to membrane lipid provides a basis for the interaction of plasma membrane- and cytosol-localized proteins.
Besides, transgenic analysis combined with genetic engineering and biochemistry showed that vi
they do function in the same pathway. Particularly, auxin-induced TMK1 increase is TIR1/AFB dependent, suggesting TIR1/AFB regulation on TMK1. Conversely, TMK1 also regulates TIR1/AFB protein levels and thus auxin canonical signaling. To follow the study of rapid growth regulation, we analyzed another rapid growth regulator, signaling peptide RALF1. We showed that RALF1 also triggers a rapid and reversible growth inhibition caused by H + influx, highly resembling but not dependent on auxin. Besides, RALF1 promotes auxin biosynthesis by increasing expression of auxin biosynthesis enzyme YUCCAs and thus induces auxin signaling in ca. 1 hour, contributing to the sustained RALF1-triggered growth inhibition. These studies collectively contribute to understanding rapid regulation on plant cell
growth, novel auxin signaling pathway as well as auxin-peptide crosstalk.
AU - Li, Lanxin
ID - 10083
SN - 2663-337X
TI - Rapid cell growth regulation in Arabidopsis
ER -
TY - GEN
AB - Growth regulation tailors plant development to its environment. A showcase is response to gravity, where shoots bend up and roots down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots, while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phospho-proteomics in Arabidopsis thaliana, we advance our understanding how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on the rapid regulation of the apoplastic pH, a causative growth determinant. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+-influx, causing apoplast alkalinisation. The simultaneous activation of these two counteracting mechanisms poises the root for a rapid, fine-tuned growth modulation while navigating complex soil environment.
AU - Li, Lanxin
AU - Verstraeten, Inge
AU - Roosjen, Mark
AU - Takahashi, Koji
AU - Rodriguez Solovey, Lesia
AU - Merrin, Jack
AU - Chen, Jian
AU - Shabala, Lana
AU - Smet, Wouter
AU - Ren, Hong
AU - Vanneste, Steffen
AU - Shabala, Sergey
AU - De Rybel, Bert
AU - Weijers, Dolf
AU - Kinoshita, Toshinori
AU - Gray, William M.
AU - Friml, Jiří
ID - 10095
T2 - Research Square
TI - Cell surface and intracellular auxin signalling for H+-fluxes in root growth
ER -
TY - JOUR
AB - The small cellular molecule inositol hexakisphosphate (IP6) has been known for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like particles. However, the molecular details underlying this effect have been determined only recently, with the identification of the IP6 binding site in the immature Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice via a second IP6 binding site, and enhances core stability, creating a favorable environment for reverse transcription. IP6 also enhances assembly of other retroviruses, from both the Lentivirus and the Alpharetrovirus genera. These findings suggest that IP6 may have a conserved function throughout the family Retroviridae. Here, we discuss the different steps in the viral life cycle that are influenced by IP6, and describe in detail how IP6 interacts with the immature and mature lattices of different retroviruses.
AU - Obr, Martin
AU - Schur, Florian KM
AU - Dick, Robert A.
ID - 10103
IS - 9
JF - Viruses
KW - virology
KW - infectious diseases
SN - 1999-4915
TI - A structural perspective of the role of IP6 in immature and mature retroviral assembly
VL - 13
ER -
TY - CONF
AB - We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs.
AU - Mühlböck, Fabian
AU - Henzinger, Thomas A
ID - 10108
KW - run-time verification
KW - software engineering
KW - implicit specification
SN - 0302-9743
T2 - International Conference on Runtime Verification
TI - Differential monitoring
VL - 12974
ER -
TY - COMP
AB - Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.
AU - Guzmán, José
AU - Schlögl, Alois
AU - Espinoza Martinez, Claudia
AU - Zhang, Xiaomin
AU - Suter, Benjamin
AU - Jonas, Peter M
ID - 10110
TI - How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network
ER -
TY - JOUR
AB - Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism.
AU - Artan, Murat
AU - Barratt, Stephen
AU - Flynn, Sean M.
AU - Begum, Farida
AU - Skehel, Mark
AU - Nicolas, Armel
AU - De Bono, Mario
ID - 10117
IS - 3
JF - Journal of Biological Chemistry
SN - 0021-9258
TI - Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling
VL - 297
ER -
TY - JOUR
AB - Solution synthesis of particles emerged as an alternative to prepare thermoelectric materials with less demanding processing conditions than conventional solid-state synthetic methods. However, solution synthesis generally involves the presence of additional molecules or ions belonging to the precursors or added to enable solubility and/or regulate nucleation and growth. These molecules or ions can end up in the particles as surface adsorbates and interfere in the material properties. This work demonstrates that ionic adsorbates, in particular Na⁺ ions, are electrostatically adsorbed in SnSe particles synthesized in water and play a crucial role not only in directing the material nano/microstructure but also in determining the transport properties of the consolidated material. In dense pellets prepared by sintering SnSe particles, Na remains within the crystal lattice as dopant, in dislocations, precipitates, and forming grain boundary complexions. These results highlight the importance of considering all the possible unintentional impurities to establish proper structure-property relationships and control material properties in solution-processed thermoelectric materials.
AU - Liu, Yu
AU - Calcabrini, Mariano
AU - Yu, Yuan
AU - Genç, Aziz
AU - Chang, Cheng
AU - Costanzo, Tommaso
AU - Kleinhanns, Tobias
AU - Lee, Seungho
AU - Llorca, Jordi
AU - Cojocaru‐Mirédin, Oana
AU - Ibáñez, Maria
ID - 10123
IS - 52
JF - Advanced Materials
KW - mechanical engineering
KW - mechanics of materials
KW - general materials science
SN - 0935-9648
TI - The importance of surface adsorbates in solution‐processed thermoelectric materials: The case of SnSe
VL - 33
ER -
TY - JOUR
AB - We investigate the effect of coupling between translational and internal degrees of freedom of composite quantum particles on their localization in a random potential. We show that entanglement between the two degrees of freedom weakens localization due to the upper bound imposed on the inverse participation ratio by purity of a quantum state. We perform numerical calculations for a two-particle system bound by a harmonic force in a 1D disordered lattice and a rigid rotor in a 2D disordered lattice. We illustrate that the coupling has a dramatic effect on localization properties, even with a small number of internal states participating in quantum dynamics.
AU - Suzuki, Fumika
AU - Lemeshko, Mikhail
AU - Zurek, Wojciech H.
AU - Krems, Roman V.
ID - 10134
IS - 16
JF - Physical Review Letters
KW - General Physics and Astronomy
SN - 0031-9007
TI - Anderson localization of composite particles
VL - 127
ER -
TY - THES
AB - Plants maintain the capacity to develop new organs e.g. lateral roots post-embryonically throughout their whole life and thereby flexibly adapt to ever-changing environmental conditions. Plant hormones auxin and cytokinin are the main regulators of the lateral root organogenesis. Additionally to their solo activities, the interaction between auxin and
cytokinin plays crucial role in fine-tuning of lateral root development and growth. In particular, cytokinin modulates auxin distribution within the developing lateral root by affecting the endomembrane trafficking of auxin transporter PIN1 and promoting its vacuolar degradation (Marhavý et al., 2011, 2014). This effect is independent of transcription and
translation. Therefore, it suggests novel, non-canonical cytokinin activity occuring possibly on the posttranslational level. Impact of cytokinin and other plant hormones on auxin transporters (including PIN1) on the posttranslational level is described in detail in the introduction part of this thesis in a form of a review (Semeradova et al., 2020). To gain insights into the molecular machinery underlying cytokinin effect on the endomembrane trafficking in the plant cell, in particular on the PIN1 degradation, we conducted two large proteomic screens: 1) Identification of cytokinin binding proteins using
chemical proteomics. 2) Monitoring of proteomic and phosphoproteomic changes upon cytokinin treatment. In the first screen, we identified DYNAMIN RELATED PROTEIN 2A (DRP2A). We found that DRP2A plays a role in cytokinin regulated processes during the plant growth and that cytokinin treatment promotes destabilization of DRP2A protein. However, the role of DRP2A in the PIN1 degradation remains to be elucidated. In the second screen, we found VACUOLAR PROTEIN SORTING 9A (VPS9A). VPS9a plays crucial role in plant’s response to cytokin and in cytokinin mediated PIN1 degradation. Altogether, we identified proteins, which bind to cytokinin and proteins that in response to
cytokinin exhibit significantly changed abundance or phosphorylation pattern. By combining information from these two screens, we can pave our way towards understanding of noncanonical cytokinin effects.
AU - Semerádová, Hana
ID - 10135
SN - 2663-337X
TI - Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis
ER -
TY - JOUR
AB - FGFs and their high-affinity receptors (FGFRs) play key roles in development, tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their individual functions cannot be determined using ligand stimulation. Here, we generated a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by the major FGFR in keratinocytes. Illumination of OptoR2-expressing HEK 293T cells activated FGFR signaling with remarkable temporal precision and promoted cell migration and proliferation. In murine and human keratinocytes, OptoR2 activation rapidly induced the classical FGFR signaling pathways and expression of FGF target genes. Surprisingly, multi-level counter-regulation occurred in keratinocytes in vitro and in transgenic mice in vivo, including OptoR2 down-regulation and loss of responsiveness to light activation. These results demonstrate unexpected cell type-specific limitations of optogenetic FGFRs in long-term in vitro and in vivo settings and highlight the complex consequences of transferring optogenetic cell signaling tools into their relevant cellular contexts.
AU - Rauschendorfer, Theresa
AU - Gurri, Selina
AU - Heggli, Irina
AU - Maddaluno, Luigi
AU - Meyer, Michael
AU - Inglés Prieto, Álvaro
AU - Janovjak, Harald L
AU - Werner, Sabine
ID - 10144
IS - 11
JF - Life Science Alliance
TI - Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice
VL - 4
ER -
TY - JOUR
AB - We study direct integrals of quadratic and Dirichlet forms. We show that each quasi-regular Dirichlet space over a probability space admits a unique representation as a direct integral of irreducible Dirichlet spaces, quasi-regular for the same underlying topology. The same holds for each quasi-regular strongly local Dirichlet space over a metrizable Luzin σ-finite Radon measure space, and admitting carré du champ operator. In this case, the representation is only projectively unique.
AU - Dello Schiavo, Lorenzo
ID - 10145
JF - Potential Analysis
SN - 0926-2601
TI - Ergodic decomposition of Dirichlet forms via direct integrals and applications
ER -
TY - JOUR
AB - The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and plants13, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain.
AU - Vercellino, Irene
AU - Sazanov, Leonid A
ID - 10146
IS - 7880
JF - Nature
SN - 0028-0836
TI - Structure and assembly of the mammalian mitochondrial supercomplex CIII_{2}CIV
VL - 598
ER -
TY - CONF
AB - Tactile feedback of an object’s surface enables us to discern its material properties and affordances. This understanding is used in digital fabrication processes by creating objects with high-resolution surface variations to influence a user’s tactile perception. As the design of such surface haptics commonly relies on knowledge from real-life experiences, it is unclear how to adapt this information for digital design methods. In this work, we investigate replicating the haptics of real materials. Using an existing process for capturing an object’s microgeometry, we digitize and reproduce the stable surface information of a set of 15 fabric samples. In a psychophysical experiment, we evaluate the tactile qualities of our set of original samples and their replicas. From our results, we see that direct reproduction of surface variations is able to influence different psychophysical dimensions of the tactile perception of surface textures. While the fabrication process did not preserve all properties, our approach underlines that replication of surface microgeometries benefits fabrication methods in terms of haptic perception by covering a large range of tactile variations. Moreover, by changing the surface structure of a single fabricated material, its material perception can be influenced. We conclude by proposing strategies for capturing and reproducing digitized textures to better resemble the perceived haptics of the originals.
AU - Degraen, Donald
AU - Piovarci, Michael
AU - Bickel, Bernd
AU - Kruger, Antonio
ID - 10148
SN - 978-1-4503-8635-7
T2 - 34th Annual ACM Symposium
TI - Capturing tactile properties of real surfaces for haptic reproduction
ER -
TY - JOUR
AB - Gradual typing is a principled means for mixing typed and untyped code. But typed and untyped code often exhibit different programming patterns. There is already substantial research investigating gradually giving types to code exhibiting typical untyped patterns, and some research investigating gradually removing types from code exhibiting typical typed patterns. This paper investigates how to extend these established gradual-typing concepts to give formal guarantees not only about how to change types as code evolves but also about how to change such programming patterns as well.
In particular, we explore mixing untyped "structural" code with typed "nominal" code in an object-oriented language. But whereas previous work only allowed "nominal" objects to be treated as "structural" objects, we also allow "structural" objects to dynamically acquire certain nominal types, namely interfaces. We present a calculus that supports such "cross-paradigm" code migration and interoperation in a manner satisfying both the static and dynamic gradual guarantees, and demonstrate that the calculus can be implemented efficiently.
AU - Mühlböck, Fabian
AU - Tate, Ross
ID - 10153
JF - Proceedings of the ACM on Programming Languages
KW - gradual typing
KW - gradual guarantee
KW - nominal
KW - structural
KW - call tags
TI - Transitioning from structural to nominal code with efficient gradual typing
VL - 5
ER -
TY - JOUR
AB - The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.
AU - Appel, Lisa-Marie
AU - Franke, Vedran
AU - Bruno, Melania
AU - Grishkovskaya, Irina
AU - Kasiliauskaite, Aiste
AU - Kaufmann, Tanja
AU - Schoeberl, Ursula E.
AU - Puchinger, Martin G.
AU - Kostrhon, Sebastian
AU - Ebenwaldner, Carmen
AU - Sebesta, Marek
AU - Beltzung, Etienne
AU - Mechtler, Karl
AU - Lin, Gen
AU - Vlasova, Anna
AU - Leeb, Martin
AU - Pavri, Rushad
AU - Stark, Alexander
AU - Akalin, Altuna
AU - Stefl, Richard
AU - Bernecky, Carrie A
AU - Djinovic-Carugo, Kristina
AU - Slade, Dea
ID - 10163
IS - 1
JF - Nature Communications
KW - general physics and astronomy
KW - general biochemistry
KW - genetics and molecular biology
KW - general chemistry
TI - PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
VL - 12
ER -
TY - JOUR
AB - While sexual reproduction is widespread among many taxa, asexual lineages have repeatedly evolved from sexual ancestors. Despite extensive research on the evolution of sex, it is still unclear whether this switch represents a major transition requiring major molecular reorganization, and how convergent the changes involved are. In this study, we investigated the phylogenetic relationship and patterns of gene expression of sexual and asexual lineages of Eurasian Artemia brine shrimp, to assess how gene expression patterns are affected by the transition to asexuality. We find only a few genes that are consistently associated with the evolution of asexuality, suggesting that this shift may not require an extensive overhauling of the meiotic machinery. While genes with sex-biased expression have high rates of expression divergence within Eurasian Artemia, neither female- nor male-biased genes appear to show unusual evolutionary patterns after sexuality is lost, contrary to theoretical expectations.
AU - Huylmans, Ann K
AU - Macon, Ariana
AU - Hontoria, Francisco
AU - Vicoso, Beatriz
ID - 10166
IS - 1959
JF - Proceedings of the Royal Society B: Biological Sciences
KW - asexual reproduction
KW - parthenogenesis
KW - sex-biased genes
KW - sexual conflict
KW - automixis
KW - crustaceans
SN - 0962-8452
TI - Transitions to asexuality and evolution of gene expression in Artemia brine shrimp
VL - 288
ER -
TY - JOUR
AB - Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group.
AU - Elkrewi, Marwan N
AU - Moldovan, Mikhail A.
AU - Picard, Marion A L
AU - Vicoso, Beatriz
ID - 10167
JF - Molecular Biology and Evolution
KW - sex chromosomes
KW - evolutionary strata
KW - W-linked gene
KW - sex determining gene
KW - schistosome parasites
SN - 0737-4038
TI - Schistosome W-Linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination
ER -
TY - GEN
AB - We study the large scale behavior of elliptic systems with stationary random coefficient that have only slowly decaying correlations. To this aim we analyze the so-called corrector equation, a degenerate elliptic equation posed in the probability space. In this contribution, we use a parabolic approach and optimally quantify the time decay of the semigroup. For the theoretical point of view, we prove an optimal decay estimate of the gradient and flux of the corrector when spatially averaged over a scale R larger than 1. For the numerical point of view, our results provide convenient tools for the analysis of various numerical methods.
AU - Clozeau, Nicolas
ID - 10173
T2 - arXiv
TI - Optimal decay of the parabolic semigroup in stochastic homogenization for correlated coefficient fields
ER -
TY - GEN
AB - Quantitative stochastic homogenization of linear elliptic operators is by now well-understood. In this contribution we move forward to the nonlinear setting of monotone operators with p-growth. This first work is dedicated to a quantitative two-scale expansion result. Fluctuations will be addressed in companion articles. By treating the range of exponents 2≤p<∞ in dimensions d≤3, we are able to consider genuinely nonlinear elliptic equations and systems such as −∇⋅A(x)(1+|∇u|p−2)∇u=f (with A random, non-necessarily symmetric) for the first time. When going from p=2 to p>2, the main difficulty is to analyze the associated linearized operator, whose coefficients are degenerate, unbounded, and depend on the random input A via the solution of a nonlinear equation. One of our main achievements is the control of this intricate nonlinear dependence, leading to annealed Meyers' estimates for the linearized operator, which are key to the quantitative two-scale expansion result.
AU - Clozeau, Nicolas
AU - Gloria, Antoine
ID - 10174
T2 - arXiv
TI - Quantitative nonlinear homogenization: control of oscillations
ER -
TY - JOUR
AB - We give a combinatorial model for r-spin surfaces with parameterized boundary based on Novak (“Lattice topological field theories in two dimensions,” Ph.D. thesis, Universität Hamburg, 2015). The r-spin structure is encoded in terms of ℤ𝑟-valued indices assigned to the edges of a polygonal decomposition. This combinatorial model is designed for our state-sum construction of two-dimensional topological field theories on r-spin surfaces. We show that an example of such a topological field theory computes the Arf-invariant of an r-spin surface as introduced by Randal-Williams [J. Topol. 7, 155 (2014)] and Geiges et al. [Osaka J. Math. 49, 449 (2012)]. This implies, in particular, that the r-spin Arf-invariant is constant on orbits of the mapping class group, providing an alternative proof of that fact.
AU - Runkel, Ingo
AU - Szegedy, Lorant
ID - 10176
IS - 10
JF - Journal of Mathematical Physics
SN - 00222488
TI - Topological field theory on r-spin surfaces and the Arf-invariant
VL - 62
ER -
TY - JOUR
AB - Phonon polaritons (PhPs)—light coupled to lattice vibrations—with in-plane hyperbolic dispersion exhibit ray-like propagation with large wave vectors and enhanced density of optical states along certain directions on a surface. As such, they have raised a surge of interest, promising unprecedented manipulation of infrared light at the nanoscale in a planar circuitry. Here, we demonstrate focusing of in-plane hyperbolic PhPs propagating along thin slabs of α-MoO3. To that end, we developed metallic nanoantennas of convex geometries for both efficient launching and focusing of the polaritons. The foci obtained exhibit enhanced near-field confinement and absorption compared to foci produced by in-plane isotropic PhPs. Foci sizes as small as λp/4.5 = λ0/50 were achieved (λp is the polariton wavelength and λ0 is the photon wavelength). Focusing of in-plane hyperbolic polaritons introduces a first and most basic building block developing planar polariton optics using in-plane anisotropic van der Waals materials.
AU - Martín-Sánchez, Javier
AU - Duan, Jiahua
AU - Taboada-Gutiérrez, Javier
AU - Álvarez-Pérez, Gonzalo
AU - Voronin, Kirill V.
AU - Prieto Gonzalez, Ivan
AU - Ma, Weiliang
AU - Bao, Qiaoliang
AU - Volkov, Valentyn S.
AU - Hillenbrand, Rainer
AU - Nikitin, Alexey Y.
AU - Alonso-González, Pablo
ID - 10177
IS - 41
JF - Science Advances
TI - Focusing of in-plane hyperbolic polaritons in van der Waals crystals with tailored infrared nanoantennas
VL - 7
ER -
TY - JOUR
AB - In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features.
AU - Sahu, Preeti
AU - Schwarz, J. M.
AU - Manning, M. Lisa
ID - 10178
IS - 9
JF - New Journal of Physics
TI - Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue
VL - 23
ER -
TY - JOUR
AB - In this article we study some geometric properties of proximally smooth sets. First, we introduce a modification of the metric projection and prove its existence. Then we provide an algorithm for constructing a rectifiable curve between two sufficiently close points of a proximally smooth set in a uniformly convex and uniformly smooth Banach space, with the moduli of smoothness and convexity of power type. Our algorithm returns a reasonably short curve between two sufficiently close points of a proximally smooth set, is iterative and uses our modification of the metric projection. We estimate the length of the constructed curve and its deviation from the segment with the same endpoints. These estimates coincide up to a constant factor with those for the geodesics in a proximally smooth set in a Hilbert space.
AU - Ivanov, Grigory
AU - Lopushanski, Mariana S.
ID - 10181
JF - Set-Valued and Variational Analysis
SN - 0927-6947
TI - Rectifiable curves in proximally smooth sets
ER -
TY - JOUR
AB - The mitochondrial oxidative phosphorylation system is central to cellular metabolism. It comprises five enzymatic complexes and two mobile electron carriers that work in a mitochondrial respiratory chain. By coupling the oxidation of reducing equivalents coming into mitochondria to the generation and subsequent dissipation of a proton gradient across the inner mitochondrial membrane, this electron transport chain drives the production of ATP, which is then used as a primary energy carrier in virtually all cellular processes. Minimal perturbations of the respiratory chain activity are linked to diseases; therefore, it is necessary to understand how these complexes are assembled and regulated and how they function. In this Review, we outline the latest assembly models for each individual complex, and we also highlight the recent discoveries indicating that the formation of larger assemblies, known as respiratory supercomplexes, originates from the association of the intermediates of individual complexes. We then discuss how recent cryo-electron microscopy structures have been key to answering open questions on the function of the electron transport chain in mitochondrial respiration and how supercomplexes and other factors, including metabolites, can regulate the activity of the single complexes. When relevant, we discuss how these mechanisms contribute to physiology and outline their deregulation in human diseases.
AU - Vercellino, Irene
AU - Sazanov, Leonid A
ID - 10182
JF - Nature Reviews Molecular Cell Biology
SN - 1471-0072
TI - The assembly, regulation and function of the mitochondrial respiratory chain
ER -
TY - JOUR
AB - We introduce a novel technique to automatically decompose an input object’s volume into a set of parts that can be represented by two opposite height fields. Such decomposition enables the manufacturing of individual parts using two-piece reusable rigid molds. Our decomposition strategy relies on a new energy formulation that utilizes a pre-computed signal on the mesh volume representing the accessibility for a predefined set of extraction directions. Thanks to this novel formulation, our method allows for efficient optimization of a fabrication-aware partitioning of volumes in a completely
automatic way. We demonstrate the efficacy of our approach by generating valid volume partitionings for a wide range of complex objects and physically reproducing several of them.
AU - Alderighi, Thomas
AU - Malomo, Luigi
AU - Bickel, Bernd
AU - Cignoni, Paolo
AU - Pietroni, Nico
ID - 10184
IS - 6
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - Volume decomposition for two-piece rigid casting
VL - 40
ER -
TY - JOUR
AB - In this work we solve the algorithmic problem of consistency verification for the TSO and PSO memory models given a reads-from map, denoted VTSO-rf and VPSO-rf, respectively. For an execution of n events over k threads and d variables, we establish novel bounds that scale as nk+1 for TSO and as nk+1· min(nk2, 2k· d) for PSO. Moreover, based on our solution to these problems, we develop an SMC algorithm under TSO and PSO that uses the RF equivalence. The algorithm is exploration-optimal, in the sense that it is guaranteed to explore each class of the RF partitioning exactly once, and spends polynomial time per class when k is bounded. Finally, we implement all our algorithms in the SMC tool Nidhugg, and perform a large number of experiments over benchmarks from existing literature. Our experimental results show that our algorithms for VTSO-rf and VPSO-rf provide significant scalability improvements over standard alternatives. Moreover, when used for SMC, the RF partitioning is often much coarser than the standard Shasha-Snir partitioning for TSO/PSO, which yields a significant speedup in the model checking task.
AU - Bui, Truc Lam
AU - Chatterjee, Krishnendu
AU - Gautam, Tushar
AU - Pavlogiannis, Andreas
AU - Toman, Viktor
ID - 10191
IS - OOPSLA
JF - Proceedings of the ACM on Programming Languages
KW - safety
KW - risk
KW - reliability and quality
KW - software
TI - The reads-from equivalence for the TSO and PSO memory models
VL - 5
ER -
TY - JOUR
AB - Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.
AU - Pradhan, Saurabh J.
AU - Reddy, Puli Chandramouli
AU - Smutny, Michael
AU - Sharma, Ankita
AU - Sako, Keisuke
AU - Oak, Meghana S.
AU - Shah, Rini
AU - Pal, Mrinmoy
AU - Deshpande, Ojas
AU - Dsilva, Greg
AU - Tang, Yin
AU - Mishra, Rakesh
AU - Deshpande, Girish
AU - Giraldez, Antonio J.
AU - Sonawane, Mahendra
AU - Heisenberg, Carl-Philipp J
AU - Galande, Sanjeev
ID - 10202
IS - 1
JF - Nature Communications
TI - Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis
VL - 12
ER -
TY - JOUR
AB - Two common representations of close packings of identical spheres consisting of hexagonal layers, called Barlow stackings, appear abundantly in minerals and metals. These motifs, however, occupy an identical portion of space and bear identical first-order topological signatures as measured by persistent homology. Here we present a novel method based on k-fold covers that unambiguously distinguishes between these patterns. Moreover, our approach provides topological evidence that the FCC motif is the more stable of the two in the context of evolving experimental sphere packings during the transition from disordered to an ordered state. We conclude that our approach can be generalised to distinguish between various Barlow stackings manifested in minerals and metals.
AU - Osang, Georg F
AU - Edelsbrunner, Herbert
AU - Saadatfar, Mohammad
ID - 10204
IS - 40
JF - Soft Matter
SN - 1744-683X
TI - Topological signatures and stability of hexagonal close packing and Barlow stackings
VL - 17
ER -
TY - CONF
AB - Neural-network classifiers achieve high accuracy when predicting the class of an input that they were trained to identify. Maintaining this accuracy in dynamic environments, where inputs frequently fall outside the fixed set of initially known classes, remains a challenge. The typical approach is to detect inputs from novel classes and retrain the classifier on an augmented dataset. However, not only the classifier but also the detection mechanism needs to adapt in order to distinguish between newly learned and yet unknown input classes. To address this challenge, we introduce an algorithmic framework for active monitoring of a neural network. A monitor wrapped in our framework operates in parallel with the neural network and interacts with a human user via a series of interpretable labeling queries for incremental adaptation. In addition, we propose an adaptive quantitative monitor to improve precision. An experimental evaluation on a diverse set of benchmarks with varying numbers of classes confirms the benefits of our active monitoring framework in dynamic scenarios.
AU - Lukina, Anna
AU - Schilling, Christian
AU - Henzinger, Thomas A
ID - 10206
KW - monitoring
KW - neural networks
KW - novelty detection
SN - 0302-9743
T2 - 21st International Conference on Runtime Verification
TI - Into the unknown: active monitoring of neural networks
VL - 12974
ER -
TY - JOUR
AB - It is practical to collect a huge amount of movement data and environmental context information along with the health signals of individuals because there is the emergence of new generations of positioning and tracking technologies and rapid advancements of health sensors. The study of the relations between these datasets and their sequence similarity analysis is of interest to many applications such as health monitoring and recommender systems. However, entering all movement parameters and health signals can lead to the complexity of the problem and an increase in its computational load. In this situation, dimension reduction techniques can be used to avoid consideration of simultaneous dependent parameters in the process of similarity measurement of the trajectories. The present study provides a framework, named CaDRAW, to use spatial–temporal data and movement parameters along with independent context information in the process of measuring the similarity of trajectories. In this regard, the omission of dependent movement characteristic signals is conducted by using an unsupervised feature selection dimension reduction technique. To evaluate the effectiveness of the proposed framework, it was applied to a real contextualized movement and related health signal datasets of individuals. The results indicated the capability of the proposed framework in measuring the similarity and in decreasing the characteristic signals in such a way that the similarity results -before and after reduction of dependent characteristic signals- have small differences. The mean differences between the obtained results before and after reducing the dimension were 0.029 and 0.023 for the round path, respectively.
AU - Goudarzi, Samira
AU - Sharif, Mohammad
AU - Karimipour, Farid
ID - 10208
JF - Journal of Ambient Intelligence and Humanized Computing
KW - general computer science
SN - 1868-5137
TI - A context-aware dimension reduction framework for trajectory and health signal analyses
ER -
TY - CONF
AB - This paper reports a new concurrent graph data structure that supports updates of both edges and vertices and queries: Breadth-first search, Single-source shortest-path, and Betweenness centrality. The operations are provably linearizable and non-blocking.
AU - Chatterjee, Bapi
AU - Peri, Sathya
AU - Sa, Muktikanta
ID - 10216
SN - 1868-8969
T2 - 35th International Symposium on Distributed Computing
TI - Brief announcement: Non-blocking dynamic unbounded graphs with worst-case amortized bounds
VL - 209
ER -
TY - CONF
AB - Let G be a graph on n nodes. In the stochastic population protocol model, a collection of n indistinguishable, resource-limited nodes collectively solve tasks via pairwise interactions. In each interaction, two randomly chosen neighbors first read each other’s states, and then update their local states. A rich line of research has established tight upper and lower bounds on the complexity of fundamental tasks, such as majority and leader election, in this model, when G is a clique. Specifically, in the clique, these tasks can be solved fast, i.e., in n polylog n pairwise interactions, with high probability, using at most polylog n states per node. In this work, we consider the more general setting where G is an arbitrary graph, and present a technique for simulating protocols designed for fully-connected networks in any connected regular graph. Our main result is a simulation that is efficient on many interesting graph families: roughly, the simulation overhead is polylogarithmic in the number of nodes, and quadratic in the conductance of the graph. As an example, this implies that, in any regular graph with conductance φ, both leader election and exact majority can be solved in φ^{-2} ⋅ n polylog n pairwise interactions, with high probability, using at most φ^{-2} ⋅ polylog n states per node. This shows that there are fast and space-efficient population protocols for leader election and exact majority on graphs with good expansion properties.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
AU - Rybicki, Joel
ID - 10218
SN - 1868-8969
T2 - 35th International Symposium on Distributed Computing
TI - Brief announcement: Fast graphical population protocols
VL - 209
ER -
TY - CONF
AB - We show that any algorithm that solves the sinkless orientation problem in the supported LOCAL model requires Ω(log n) rounds, and this is tight. The supported LOCAL is at least as strong as the usual LOCAL model, and as a corollary this also gives a new, short and elementary proof that shows that the round complexity of the sinkless orientation problem in the deterministic LOCAL model is Ω(log n).
AU - Korhonen, Janne
AU - Paz, Ami
AU - Rybicki, Joel
AU - Schmid, Stefan
AU - Suomela, Jukka
ID - 10219
SN - 1868-8969
T2 - 35th International Symposium on Distributed Computing
TI - Brief announcement: Sinkless orientation is hard also in the supported LOCAL model
VL - 209
ER -
TY - JOUR
AB - We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors.
The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance.
It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.
AU - Avvakumov, Sergey
AU - Mabillard, Isaac
AU - Skopenkov, Arkadiy B.
AU - Wagner, Uli
ID - 10220
JF - Israel Journal of Mathematics
SN - 0021-2172
TI - Eliminating higher-multiplicity intersections. III. Codimension 2
VL - 245
ER -
TY - JOUR
AB - We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020).
AU - Cipolloni, Giorgio
AU - Erdös, László
AU - Schröder, Dominik J
ID - 10221
IS - 2
JF - Communications in Mathematical Physics
SN - 0010-3616
TI - Eigenstate thermalization hypothesis for Wigner matrices
VL - 388
ER -
TY - JOUR
AB - Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density.
AU - Akopyan, Arseniy
AU - Edelsbrunner, Herbert
AU - Nikitenko, Anton
ID - 10222
JF - Experimental Mathematics
SN - 10586458
TI - The beauty of random polytopes inscribed in the 2-sphere
ER -
TY - JOUR
AB - Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments.
AU - Li, Lanxin
AU - Verstraeten, Inge
AU - Roosjen, Mark
AU - Takahashi, Koji
AU - Rodriguez Solovey, Lesia
AU - Merrin, Jack
AU - Chen, Jian
AU - Shabala, Lana
AU - Smet, Wouter
AU - Ren, Hong
AU - Vanneste, Steffen
AU - Shabala, Sergey
AU - De Rybel, Bert
AU - Weijers, Dolf
AU - Kinoshita, Toshinori
AU - Gray, William M.
AU - Friml, Jiří
ID - 10223
IS - 7884
JF - Nature
KW - Multidisciplinary
SN - 00280836
TI - Cell surface and intracellular auxin signalling for H^{+} fluxes in root growth
VL - 599
ER -
TY - JOUR
AB - We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging.
AU - Feliciangeli, Dario
AU - Seiringer, Robert
ID - 10224
IS - 3
JF - Archive for Rational Mechanics and Analysis
SN - 0003-9527
TI - The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics
VL - 242
ER -
TY - CHAP
AB - Tropisms are among the most important growth responses for plant adaptation to the surrounding environment. One of the most common tropisms is root gravitropism. Root gravitropism enables the plant to anchor securely to the soil enabling the absorption of water and nutrients. Most of the knowledge related to the plant gravitropism has been acquired from the flowering plants, due to limited research in non-seed plants. Limited research on non-seed plants is due in large part to the lack of standard research methods. Here, we describe the experimental methods to evaluate gravitropism in representative non-seed plant species, including the non-vascular plant moss Physcomitrium patens, the early diverging extant vascular plant lycophyte Selaginella moellendorffii and fern Ceratopteris richardii. In addition, we introduce the methods used for statistical analysis of the root gravitropism in non-seed plant species.
AU - Zhang, Yuzhou
AU - Li, Lanxin
AU - Friml, Jiří
ID - 10267
SN - 978-1-0716-1676-5
T2 - Plant Gravitropism
TI - Evaluation of gravitropism in non-seed plants
VL - 2368
ER -
TY - CHAP
AB - The analysis of dynamic cellular processes such as plant cytokinesis stands and falls with live-cell time-lapse confocal imaging. Conventional approaches to time-lapse imaging of cell division in Arabidopsis root tips are tedious and have low throughput. Here, we describe a protocol for long-term time-lapse simultaneous imaging of multiple root tips on a vertical-stage confocal microscope with automated root tracking. We also provide modifications of the basic protocol to implement this imaging method in the analysis of genetic, pharmacological or laser ablation wounding-mediated experimental manipulations. Our method dramatically improves the efficiency of cell division time-lapse imaging by increasing the throughput, while reducing the person-hour requirements of such experiments.
AU - Hörmayer, Lukas
AU - Friml, Jiří
AU - Glanc, Matous
ID - 10268
SN - 1064-3745
T2 - Plant Cell Division
TI - Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy
VL - 2382
ER -
TY - JOUR
AB - Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions.
AU - Qi, Qin
AU - Angermayr, S. Andreas
AU - Bollenbach, Mark Tobias
ID - 10271
JF - Frontiers in Microbiology
KW - microbiology
TI - Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli
VL - 12
ER -
TY - JOUR
AB - Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials.
AU - Aubret, Antoine
AU - Martinet, Quentin
AU - Palacci, Jérémie A
ID - 10280
IS - 1
JF - Nature Communications
TI - Metamachines of pluripotent colloids
VL - 12
ER -
TY - JOUR
AB - Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development.
AU - Kashkan, Ivan
AU - Hrtyan, Mónika
AU - Retzer, Katarzyna
AU - Humpolíčková, Jana
AU - Jayasree, Aswathy
AU - Filepová, Roberta
AU - Vondráková, Zuzana
AU - Simon, Sibu
AU - Rombaut, Debbie
AU - Jacobs, Thomas B.
AU - Frilander, Mikko J.
AU - Hejátko, Jan
AU - Friml, Jiří
AU - Petrášek, Jan
AU - Růžička, Kamil
ID - 10282
JF - New Phytologist
SN - 0028-646X
TI - Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana
ER -
TY - JOUR
AB - We study the overlaps between right and left eigenvectors for random matrices of the spherical ensemble, as well as truncated unitary ensembles in the regime where half of the matrix at least is truncated. These two integrable models exhibit a form of duality, and the essential steps of our investigation can therefore be performed in parallel. In every case, conditionally on all eigenvalues, diagonal overlaps are shown to be distributed as a product of independent random variables with explicit distributions. This enables us to prove that the scaled diagonal overlaps, conditionally on one eigenvalue, converge in distribution to a heavy-tail limit, namely, the inverse of a γ2 distribution. We also provide formulae for the conditional expectation of diagonal and off-diagonal overlaps, either with respect to one eigenvalue, or with respect to the whole spectrum. These results, analogous to what is known for the complex Ginibre ensemble, can be obtained in these cases thanks to integration techniques inspired from a previous work by Forrester & Krishnapur.
AU - Dubach, Guillaume
ID - 10285
JF - Electronic Journal of Probability
TI - On eigenvector statistics in the spherical and truncated unitary ensembles
VL - 26
ER -
TY - JOUR
AB - A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized filamentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner.
AU - Dimchev, Georgi A
AU - Amiri, Behnam
AU - Fäßler, Florian
AU - Falcke, Martin
AU - Schur, Florian KM
ID - 10290
IS - 4
JF - Journal of Structural Biology
KW - Structural Biology
SN - 1047-8477
TI - Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data
VL - 213
ER -
TY - THES
AB - Indirect reciprocity in evolutionary game theory is a prominent mechanism for explaining the evolution of cooperation among unrelated individuals. In contrast to direct reciprocity, which is based on individuals meeting repeatedly, and conditionally cooperating by using their own experiences, indirect reciprocity is based on individuals’ reputations. If a player helps another, this increases the helper’s public standing, benefitting them in the future. This lets cooperation in the population emerge without individuals having to meet more than once. While the two modes of reciprocity are intertwined, they are difficult to compare. Thus, they are usually studied in isolation. Direct reciprocity can maintain cooperation with simple strategies, and is robust against noise even when players do not remember more
than their partner’s last action. Meanwhile, indirect reciprocity requires its successful strategies, or social norms, to be more complex. Exhaustive search previously identified eight such norms, called the “leading eight”, which excel at maintaining cooperation. However, as the first result of this thesis, we show that the leading eight break down once we remove the fundamental assumption that information is synchronized and public, such that everyone agrees on reputations. Once we consider a more realistic scenario of imperfect information, where reputations are private, and individuals occasionally misinterpret or miss observations, the leading eight do not promote cooperation anymore. Instead, minor initial disagreements can proliferate, fragmenting populations into subgroups. In a next step, we consider ways to mitigate this issue. We first explore whether introducing “generosity” can stabilize cooperation when players use the leading eight strategies in noisy environments. This approach of modifying strategies to include probabilistic elements for coping with errors is known to work well in direct reciprocity. However, as we show here, it fails for the more complex norms of indirect reciprocity. Imperfect information still prevents cooperation from evolving. On the other hand, we succeeded to show in this thesis that modifying the leading eight to use “quantitative assessment”, i.e. tracking reputation scores on a scale beyond good and bad, and making overall judgments of others based on a threshold, is highly successful, even when noise increases in the environment. Cooperation can flourish when reputations
are more nuanced, and players have a broader understanding what it means to be “good.” Finally, we present a single theoretical framework that unites the two modes of reciprocity despite their differences. Within this framework, we identify a novel simple and successful strategy for indirect reciprocity, which can cope with noisy environments and has an analogue in direct reciprocity. We can also analyze decision making when different sources of information are available. Our results help highlight that for sustaining cooperation, already the most simple rules of reciprocity can be sufficient.
AU - Schmid, Laura
ID - 10293
SN - 2663-337X
TI - Evolution of cooperation via (in)direct reciprocity under imperfect information
ER -
TY - JOUR
AB - Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number.
AU - Choueiri, George H
AU - Lopez Alonso, Jose M
AU - Varshney, Atul
AU - Sankar, Sarath
AU - Hof, Björn
ID - 10299
IS - 45
JF - Proceedings of the National Academy of Sciences
KW - multidisciplinary
KW - elastoinertial turbulence
KW - viscoelastic flows
KW - elastic instability
KW - drag reduction
SN - 0027-8424
TI - Experimental observation of the origin and structure of elastoinertial turbulence
VL - 118
ER -
TY - JOUR
AB - De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.
AU - Conde-Dusman, María J
AU - Dey, Partha N
AU - Elía-Zudaire, Óscar
AU - Garcia Rabaneda, Luis E
AU - García-Lira, Carmen
AU - Grand, Teddy
AU - Briz, Victor
AU - Velasco, Eric R
AU - Andero Galí, Raül
AU - Niñerola, Sergio
AU - Barco, Angel
AU - Paoletti, Pierre
AU - Wesseling, John F
AU - Gardoni, Fabrizio
AU - Tavalin, Steven J
AU - Perez-Otaño, Isabel
ID - 10301
JF - eLife
KW - general immunology and microbiology
KW - general biochemistry
KW - genetics and molecular biology
KW - general medicine
KW - general neuroscience
SN - 2050-084X
TI - Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly
VL - 10
ER -
TY - THES
AB - Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.
AU - Tomasek, Kathrin
ID - 10307
SN - 2663-337X
TI - Pathogenic Escherichia coli hijack the host immune response
ER -
TY - JOUR
AB - A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.
AU - Çoruh, Mehmet Orkun
AU - Frank, Anna
AU - Tanaka, Hideaki
AU - Kawamoto, Akihiro
AU - El-Mohsnawy, Eithar
AU - Kato, Takayuki
AU - Namba, Keiichi
AU - Gerle, Christoph
AU - Nowaczyk, Marc M.
AU - Kurisu, Genji
ID - 10310
IS - 1
JF - Communications Biology
KW - general agricultural and biological Sciences
KW - general biochemistry
KW - genetics and molecular biology
KW - medicine (miscellaneous)
SN - 2399-3642
TI - Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster
VL - 4
ER -
TY - GEN
AB - A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.
AU - Tomasek, Kathrin
AU - Leithner, Alexander F
AU - Glatzová, Ivana
AU - Lukesch, Michael S.
AU - Guet, Calin C
AU - Sixt, Michael K
ID - 10316
T2 - bioRxiv
TI - Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
ER -
TY - JOUR
AB - Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).
AU - Amberg, Nicole
AU - Hippenmeyer, Simon
ID - 10321
IS - 4
JF - STAR Protocols
TI - Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers
VL - 2
ER -
TY - JOUR
AB - To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.
AU - Chauve, Laetitia
AU - Hodge, Francesca
AU - Murdoch, Sharlene
AU - Masoudzadeh, Fatemah
AU - Mann, Harry Jack
AU - Lopez-Clavijo, Andrea
AU - Okkenhaug, Hanneke
AU - West, Greg
AU - Sousa, Bebiana C.
AU - Segonds-Pichon, Anne
AU - Li, Cheryl
AU - Wingett, Steven
AU - Kienberger, Hermine
AU - Kleigrewe, Karin
AU - De Bono, Mario
AU - Wakelam, Michael
AU - Casanueva, Olivia
ID - 10322
IS - 11
JF - PLoS Biology
SN - 1544-9173
TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans
VL - 19
ER -
TY - CONF
AB - Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.
AU - Avarikioti, Zeta
AU - Kokoris Kogias, Eleftherios
AU - Wattenhofer, Roger
AU - Zindros, Dionysis
ID - 10324
SN - 0302-9743
T2 - 25th International Conference on Financial Cryptography and Data Security
TI - Brick: Asynchronous incentive-compatible payment channels
VL - 12675
ER -
TY - CONF
AB - Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains.
AU - Zamyatin, Alexei
AU - Al-Bassam, Mustafa
AU - Zindros, Dionysis
AU - Kokoris Kogias, Eleftherios
AU - Moreno-Sanchez, Pedro
AU - Kiayias, Aggelos
AU - Knottenbelt, William J.
ID - 10325
SN - 0302-9743
T2 - 25th International Conference on Financial Cryptography and Data Security
TI - SoK: Communication across distributed ledgers
VL - 12675
ER -
TY - JOUR
AB - Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.
AU - Xu, Enjun
AU - Chai, Liang
AU - Zhang, Shiqi
AU - Yu, Ruixue
AU - Zhang, Xixi
AU - Xu, Chongyi
AU - Hu, Yuxin
ID - 10326
JF - Nature Plants
TI - Catabolism of strigolactones by a carboxylesterase
VL - 7
ER -
TY - JOUR
AB - Composite materials offer numerous advantages in a wide range of applications, including thermoelectrics. Here, semiconductor–metal composites are produced by just blending nanoparticles of a sulfide semiconductor obtained in aqueous solution and at room temperature with a metallic Cu powder. The obtained blend is annealed in a reducing atmosphere and afterward consolidated into dense polycrystalline pellets through spark plasma sintering (SPS). We observe that, during the annealing process, the presence of metallic copper activates a partial reduction of the PbS, resulting in the formation of PbS–Pb–CuxS composites. The presence of metallic lead during the SPS process habilitates the liquid-phase sintering of the composite. Besides, by comparing the transport properties of PbS, the PbS–Pb–CuxS composites, and PbS–CuxS composites obtained by blending PbS and CuxS nanoparticles, we demonstrate that the presence of metallic lead decisively contributes to a strong increase of the charge carrier concentration through spillover of charge carriers enabled by the low work function of lead. The increase in charge carrier concentration translates into much higher electrical conductivities and moderately lower Seebeck coefficients. These properties translate into power factors up to 2.1 mW m–1 K–2 at ambient temperature, well above those of PbS and PbS + CuxS. Additionally, the presence of multiple phases in the final composite results in a notable decrease in the lattice thermal conductivity. Overall, the introduction of metallic copper in the initial blend results in a significant improvement of the thermoelectric performance of PbS, reaching a dimensionless thermoelectric figure of merit ZT = 1.1 at 750 K, which represents about a 400% increase over bare PbS. Besides, an average ZTave = 0.72 in the temperature range 320–773 K is demonstrated.
AU - Li, Mengyao
AU - Liu, Yu
AU - Zhang, Yu
AU - Han, Xu
AU - Xiao, Ke
AU - Nabahat, Mehran
AU - Arbiol, Jordi
AU - Llorca, Jordi
AU - Ibáñez, Maria
AU - Cabot, Andreu
ID - 10327
IS - 43
JF - ACS Applied Materials and Interfaces
KW - CuxS
KW - PbS
KW - energy conversion
KW - nanocomposite
KW - nanoparticle
KW - solution synthesis
KW - thermoelectric
SN - 1944-8244
TI - PbS–Pb–CuxS composites for thermoelectric application
VL - 13
ER -
TY - JOUR
AB - Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.
AU - Lee, Jungmin
AU - Vernet, Andyna
AU - Gruber, Nathalie
AU - Kready, Kasia M.
AU - Burrill, Devin R.
AU - Way, Jeffrey C.
AU - Silver, Pamela A.
ID - 10363
JF - Protein Engineering, Design and Selection
SN - 1741-0126
TI - Rational engineering of an erythropoietin fusion protein to treat hypoxia
VL - 34
ER -
TY - JOUR
AB - This paper characterizes the latency of the simplified successive-cancellation (SSC) decoding scheme for polar codes under hardware resource constraints. In particular, when the number of processing elements P that can perform SSC decoding operations in parallel is limited, as is the case in practice, the latency of SSC decoding is O(N1-1/μ + N/P log2 log2 N/P), where N is the block length of the code and μ is the scaling exponent of the channel. Three direct consequences of this bound are presented. First, in a fully-parallel implementation where P = N/2, the latency of SSC decoding is O(N1-1/μ), which is sublinear in the block length. This recovers a result from our earlier work. Second, in a fully-serial implementation where P = 1, the latency of SSC decoding scales as O(N log2 log2 N). The multiplicative constant is also calculated: we show that the latency of SSC decoding when P = 1 is given by (2 + o(1))N log2 log2 N. Third, in a semi-parallel implementation, the smallest P that gives the same latency as that of the fully-parallel implementation is P = N1/μ. The tightness of our bound on SSC decoding latency and the applicability of the foregoing results is validated through extensive simulations.
AU - Hashemi, Seyyed Ali
AU - Mondelli, Marco
AU - Fazeli, Arman
AU - Vardy, Alexander
AU - Cioffi, John
AU - Goldsmith, Andrea
ID - 10364
JF - IEEE Transactions on Wireless Communications
SN - 1536-1276
TI - Parallelism versus latency in simplified successive-cancellation decoding of polar codes
ER -