TY - JOUR AB - Spontaneously arising channels that transport the phytohormone auxin provide positional cues for self-organizing aspects of plant development such as flexible vasculature regeneration or its patterning during leaf venation. The auxin canalization hypothesis proposes a feedback between auxin signaling and transport as the underlying mechanism, but molecular players await discovery. We identified part of the machinery that routes auxin transport. The auxin-regulated receptor CAMEL (Canalization-related Auxin-regulated Malectin-type RLK) together with CANAR (Canalization-related Receptor-like kinase) interact with and phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated PIN polarization, which macroscopically manifests as defects in leaf venation and vasculature regeneration after wounding. The CAMEL-CANAR receptor complex is part of the auxin feedback that coordinates polarization of individual cells during auxin canalization. AU - Hajny, Jakub AU - Prat, Tomas AU - Rydza, N AU - Rodriguez Solovey, Lesia AU - Tan, Shutang AU - Verstraeten, Inge AU - Domjan, David AU - Mazur, E AU - Smakowska-Luzan, E AU - Smet, W AU - Mor, E AU - Nolf, J AU - Yang, B AU - Grunewald, W AU - Molnar, Gergely AU - Belkhadir, Y AU - De Rybel, B AU - Friml, Jiří ID - 8721 IS - 6516 JF - Science SN - 0036-8075 TI - Receptor kinase module targets PIN-dependent auxin transport during canalization VL - 370 ER - TY - JOUR AB - Organic materials are known to feature long spin-diffusion times, originating in a generally small spin–orbit coupling observed in these systems. From that perspective, chiral molecules acting as efficient spin selectors pose a puzzle that attracted a lot of attention in recent years. Here, we revisit the physical origins of chiral-induced spin selectivity (CISS) and propose a simple analytic minimal model to describe it. The model treats a chiral molecule as an anisotropic wire with molecular dipole moments aligned arbitrarily with respect to the wire’s axes and is therefore quite general. Importantly, it shows that the helical structure of the molecule is not necessary to observe CISS and other chiral nonhelical molecules can also be considered as potential candidates for the CISS effect. We also show that the suggested simple model captures the main characteristics of CISS observed in the experiment, without the need for additional constraints employed in the previous studies. The results pave the way for understanding other related physical phenomena where the CISS effect plays an essential role. AU - Ghazaryan, Areg AU - Paltiel, Yossi AU - Lemeshko, Mikhail ID - 7968 IS - 21 JF - The Journal of Physical Chemistry C SN - 1932-7447 TI - Analytic model of chiral-induced spin selectivity VL - 124 ER - TY - JOUR AB - Recent discoveries have shown that, when two layers of van der Waals (vdW) materials are superimposed with a relative twist angle between them, the electronic properties of the coupled system can be dramatically altered. Here, we demonstrate that a similar concept can be extended to the optics realm, particularly to propagating phonon polaritons–hybrid light-matter interactions. To do this, we fabricate stacks composed of two twisted slabs of a vdW crystal (α-MoO3) supporting anisotropic phonon polaritons (PhPs), and image the propagation of the latter when launched by localized sources. Our images reveal that, under a critical angle, the PhPs isofrequency curve undergoes a topological transition, in which the propagation of PhPs is strongly guided (canalization regime) along predetermined directions without geometric spreading. These results demonstrate a new degree of freedom (twist angle) for controlling the propagation of polaritons at the nanoscale with potential for nanoimaging, (bio)-sensing, or heat management. AU - Duan, Jiahua AU - Capote-Robayna, Nathaniel AU - Taboada-Gutiérrez, Javier AU - Álvarez-Pérez, Gonzalo AU - Prieto Gonzalez, Ivan AU - Martín-Sánchez, Javier AU - Nikitin, Alexey Y. AU - Alonso-González, Pablo ID - 10866 IS - 7 JF - Nano Letters KW - Mechanical Engineering KW - Condensed Matter Physics KW - General Materials Science KW - General Chemistry KW - Bioengineering SN - 1530-6984 TI - Twisted nano-optics: Manipulating light at the nanoscale with twisted phonon polaritonic slabs VL - 20 ER - TY - JOUR AB - Dipolar (or spatially indirect) excitons (IXs) in semiconductor double quantum well (DQW) subjected to an electric field are neutral species with a dipole moment oriented perpendicular to the DQW plane. Here, we theoretically study interactions between IXs in stacked DQW bilayers, where the dipolar coupling can be either attractive or repulsive depending on the relative positions of the particles. By using microscopic band structure calculations to determine the electronic states forming the excitons, we show that the attractive dipolar interaction between stacked IXs deforms their electronic wave function, thereby increasing the inter-DQW interaction energy and making the IX even more electrically polarizable. Many-particle interaction effects are addressed by considering the coupling between a single IX in one of the DQWs to a cloud of IXs in the other DQW, which is modeled either as a closed-packed lattice or as a continuum IX fluid. We find that the lattice model yields IX interlayer binding energies decreasing with increasing lattice density. This behavior is due to the dominating role of the intra-DQW dipolar repulsion, which prevents more than one exciton from entering the attractive region of the inter-DQW coupling. Finally, both models shows that the single IX distorts the distribution of IXs in the adjacent DQW, thus inducing the formation of an IX dipolar polaron (dipolaron). While the interlayer binding energy reduces with IX density for lattice dipolarons, the continuous polaron model predicts a nonmonotonous dependence on density in semiquantitative agreement with a recent experimental study [cf. Hubert et al., Phys. Rev. X 9, 021026 (2019)]. AU - Hubert, C. AU - Cohen, K. AU - Ghazaryan, Areg AU - Lemeshko, Mikhail AU - Rapaport, R. AU - Santos, P. V. ID - 8588 IS - 4 JF - Physical Review B SN - 2469-9950 TI - Attractive interactions, molecular complexes, and polarons in coupled dipolar exciton fluids VL - 102 ER - TY - JOUR AB - One of the hallmarks of quantum statistics, tightly entwined with the concept of topological phases of matter, is the prediction of anyons. Although anyons are predicted to be realized in certain fractional quantum Hall systems, they have not yet been unambiguously detected in experiment. Here we introduce a simple quantum impurity model, where bosonic or fermionic impurities turn into anyons as a consequence of their interaction with the surrounding many-particle bath. A cloud of phonons dresses each impurity in such a way that it effectively attaches fluxes or vortices to it and thereby converts it into an Abelian anyon. The corresponding quantum impurity model, first, provides a different approach to the numerical solution of the many-anyon problem, along with a concrete perspective of anyons as emergent quasiparticles built from composite bosons or fermions. More importantly, the model paves the way toward realizing anyons using impurities in crystal lattices as well as ultracold gases. In particular, we consider two heavy electrons interacting with a two-dimensional lattice crystal in a magnetic field, and show that when the impurity-bath system is rotated at the cyclotron frequency, impurities behave as anyons as a consequence of the angular momentum exchange between the impurities and the bath. A possible experimental realization is proposed by identifying the statistics parameter in terms of the mean-square distance of the impurities and the magnetization of the impurity-bath system, both of which are accessible to experiment. Another proposed application is impurities immersed in a two-dimensional weakly interacting Bose gas. AU - Yakaboylu, Enderalp AU - Ghazaryan, Areg AU - Lundholm, D. AU - Rougerie, N. AU - Lemeshko, Mikhail AU - Seiringer, Robert ID - 8769 IS - 14 JF - Physical Review B SN - 2469-9950 TI - Quantum impurity model for anyons VL - 102 ER - TY - JOUR AB - Multilayer graphene lattices allow for an additional tunability of the band structure by the strong perpendicular electric field. In particular, the emergence of the new multiple Dirac points in ABA stacked trilayer graphene subject to strong transverse electric fields was proposed theoretically and confirmed experimentally. These new Dirac points dubbed “gullies” emerge from the interplay between strong electric field and trigonal warping. In this work, we first characterize the properties of new emergent Dirac points and show that the electric field can be used to tune the distance between gullies in the momentum space. We demonstrate that the band structure has multiple Lifshitz transitions and higher-order singularity of “monkey saddle” type. Following the characterization of the band structure, we consider the spectrum of Landau levels and structure of their wave functions. In the limit of strong electric fields when gullies are well separated in momentum space, they give rise to triply degenerate Landau levels. In the second part of this work, we investigate how degeneracy between three gully Landau levels is lifted in the presence of interactions. Within the Hartree-Fock approximation we show that the symmetry breaking state interpolates between the fully gully polarized state that breaks C3 symmetry at high displacement field and the gully symmetric state when the electric field is decreased. The discontinuous transition between these two states is driven by enhanced intergully tunneling and exchange. We conclude by outlining specific experimental predictions for the existence of such a symmetry-breaking state. AU - Rao, Peng AU - Serbyn, Maksym ID - 7971 IS - 24 JF - Physical Review B SN - 2469-9950 TI - Gully quantum Hall ferromagnetism in biased trilayer graphene VL - 101 ER - TY - JOUR AB - In laboratory studies and numerical simulations, we observe clear signatures of unstable time-periodic solutions in a moderately turbulent quasi-two-dimensional flow. We validate the dynamical relevance of such solutions by demonstrating that turbulent flows in both experiment and numerics transiently display time-periodic dynamics when they shadow unstable periodic orbits (UPOs). We show that UPOs we computed are also statistically significant, with turbulent flows spending a sizable fraction of the total time near these solutions. As a result, the average rates of energy input and dissipation for the turbulent flow and frequently visited UPOs differ only by a few percent. AU - Suri, Balachandra AU - Kageorge, Logan AU - Grigoriev, Roman O. AU - Schatz, Michael F. ID - 8634 IS - 6 JF - Physical Review Letters KW - General Physics and Astronomy SN - 0031-9007 TI - Capturing turbulent dynamics and statistics in experiments with unstable periodic orbits VL - 125 ER - TY - JOUR AB - Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-terminally encoded peptide 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance. AU - Smith, S AU - Zhu, S AU - Joos, L AU - Roberts, I AU - Nikonorova, N AU - Vu, LD AU - Stes, E AU - Cho, H AU - Larrieu, A AU - Xuan, W AU - Goodall, B AU - van de Cotte, B AU - Waite, JM AU - Rigal, A AU - R Harborough, SR AU - Persiau, G AU - Vanneste, S AU - Kirschner, GK AU - Vandermarliere, E AU - Martens, L AU - Stahl, Y AU - Audenaert, D AU - Friml, Jiří AU - Felix, G AU - Simon, R AU - Bennett, M AU - Bishopp, A AU - De Jaeger, G AU - Ljung, K AU - Kepinski, S AU - Robert, S AU - Nemhauser, J AU - Hwang, I AU - Gevaert, K AU - Beeckman, T AU - De Smet, I ID - 7949 IS - 8 JF - Molecular & Cellular Proteomics TI - The CEP5 peptide promotes abiotic stress tolerance, as revealed by quantitative proteomics, and attenuates the AUX/IAA equilibrium in Arabidopsis VL - 19 ER - TY - JOUR AB - Cell polarity is a fundamental feature of all multicellular organisms. In plants, prominent cell polarity markers are PIN auxin transporters crucial for plant development. To identify novel components involved in cell polarity establishment and maintenance, we carried out a forward genetic screening with PIN2:PIN1-HA;pin2 Arabidopsis plants, which ectopically express predominantly basally localized PIN1 in the root epidermal cells leading to agravitropic root growth. From the screen, we identified the regulator of PIN polarity 12 (repp12) mutation, which restored gravitropic root growth and caused PIN1-HA polarity switch from basal to apical side of root epidermal cells. Complementation experiments established the repp12 causative mutation as an amino acid substitution in Aminophospholipid ATPase3 (ALA3), a phospholipid flippase with predicted function in vesicle formation. ala3 T-DNA mutants show defects in many auxin-regulated processes, in asymmetric auxin distribution and in PIN trafficking. Analysis of quintuple and sextuple mutants confirmed a crucial role of ALA proteins in regulating plant development and in PIN trafficking and polarity. Genetic and physical interaction studies revealed that ALA3 functions together with GNOM and BIG3 ARF GEFs. Taken together, our results identified ALA3 flippase as an important interactor and regulator of ARF GEF functioning in PIN polarity, trafficking and auxin-mediated development. AU - Zhang, Xixi AU - Adamowski, Maciek AU - Marhavá, Petra AU - Tan, Shutang AU - Zhang, Yuzhou AU - Rodriguez Solovey, Lesia AU - Zwiewka, Marta AU - Pukyšová, Vendula AU - Sánchez, Adrià Sans AU - Raxwal, Vivek Kumar AU - Hardtke, Christian S. AU - Nodzynski, Tomasz AU - Friml, Jiří ID - 7619 IS - 5 JF - The Plant Cell SN - 1040-4651 TI - Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters VL - 32 ER - TY - JOUR AB - Clathrin-mediated endocytosis (CME) and its core endocytic machinery are evolutionarily conserved across all eukaryotes. In mammals, the heterotetrameric adaptor protein complex-2 (AP-2) sorts plasma membrane (PM) cargoes into vesicles through the recognition of motifs based on tyrosine or di-leucine in their cytoplasmic tails. However, in plants, very little is known on how PM proteins are sorted for CME and whether similar motifs are required. In Arabidopsis thaliana, the brassinosteroid (BR) receptor, BR INSENSITIVE1 (BRI1), undergoes endocytosis that depends on clathrin and AP-2. Here we demonstrate that BRI1 binds directly to the medium AP-2 subunit, AP2M. The cytoplasmic domain of BRI1 contains five putative canonical surface-exposed tyrosine-based endocytic motifs. The tyrosine-to-phenylalanine substitution in Y898KAI reduced BRI1 internalization without affecting its kinase activity. Consistently, plants carrying the BRI1Y898F mutation were hypersensitive to BRs. Our study demonstrates that AP-2-dependent internalization of PM proteins via the recognition of functional tyrosine motifs also operates in plants. AU - Liu, D AU - Kumar, R AU - LAN, Claus AU - Johnson, Alexander J AU - Siao, W AU - Vanhoutte, I AU - Wang, P AU - Bender, KW AU - Yperman, K AU - Martins, S AU - Zhao, X AU - Vert, G AU - Van Damme, D AU - Friml, Jiří AU - Russinova, E ID - 8607 IS - 11 JF - Plant Cell SN - 1040-4651 TI - Endocytosis of BRASSINOSTEROID INSENSITIVE1 is partly driven by a canonical tyrosine-based Motif VL - 32 ER - TY - JOUR AB - The TPLATE complex (TPC) is a key endocytic adaptor protein complex in plants. TPC in Arabidopsis (Arabidopsis thaliana) contains six evolutionarily conserved subunits and two plant-specific subunits, AtEH1/Pan1 and AtEH2/Pan1, although cytoplasmic proteins are not associated with the hexameric subcomplex in the cytoplasm. To investigate the dynamic assembly of the octameric TPC at the plasma membrane (PM), we performed state-of-the-art dual-color live cell imaging at physiological and lowered temperatures. Lowering the temperature slowed down endocytosis, thereby enhancing the temporal resolution of the differential recruitment of endocytic components. Under both normal and lowered temperature conditions, the core TPC subunit TPLATE and the AtEH/Pan1 proteins exhibited simultaneous recruitment at the PM. These results, together with co-localization analysis of different TPC subunits, allow us to conclude that TPC in plant cells is not recruited to the PM sequentially but as an octameric complex. AU - Wang, J AU - Mylle, E AU - Johnson, Alexander J AU - Besbrugge, N AU - De Jaeger, G AU - Friml, Jiří AU - Pleskot, R AU - van Damme, D ID - 7695 IS - 3 JF - Plant Physiology SN - 0032-0889 TI - High temporal resolution reveals simultaneous plasma membrane recruitment of TPLATE complex subunits VL - 183 ER - TY - JOUR AB - Cell production and differentiation for the acquisition of specific functions are key features of living systems. The dynamic network of cellular microtubules provides the necessary platform to accommodate processes associated with the transition of cells through the individual phases of cytogenesis. Here, we show that the plant hormone cytokinin fine‐tunes the activity of the microtubular cytoskeleton during cell differentiation and counteracts microtubular rearrangements driven by the hormone auxin. The endogenous upward gradient of cytokinin activity along the longitudinal growth axis in Arabidopsis thaliana roots correlates with robust rearrangements of the microtubule cytoskeleton in epidermal cells progressing from the proliferative to the differentiation stage. Controlled increases in cytokinin activity result in premature re‐organization of the microtubule network from transversal to an oblique disposition in cells prior to their differentiation, whereas attenuated hormone perception delays cytoskeleton conversion into a configuration typical for differentiated cells. Intriguingly, cytokinin can interfere with microtubules also in animal cells, such as leukocytes, suggesting that a cytokinin‐sensitive control pathway for the microtubular cytoskeleton may be at least partially conserved between plant and animal cells. AU - Montesinos López, Juan C AU - Abuzeineh, A AU - Kopf, Aglaja AU - Juanes Garcia, Alba AU - Ötvös, Krisztina AU - Petrášek, J AU - Sixt, Michael K AU - Benková, Eva ID - 8142 IS - 17 JF - The Embo Journal SN - 0261-4189 TI - Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage VL - 39 ER - TY - JOUR AB - Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation. AU - Lombardi, Fabrizio AU - Gómez-Extremera, Manuel AU - Bernaola-Galván, Pedro AU - Vetrivelan, Ramalingam AU - Saper, Clifford B. AU - Scammell, Thomas E. AU - Ivanov, Plamen Ch. ID - 8084 IS - 1 JF - Journal of Neuroscience SN - 0270-6474 TI - Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake VL - 40 ER - TY - JOUR AB - We consider a dilute, homogeneous Bose gas at positive temperature. The system is investigated in the Gross–Pitaevskii limit, where the scattering length a is so small that the interaction energy is of the same order of magnitude as the spectral gap of the Laplacian, and for temperatures that are comparable to the critical temperature of the ideal gas. We show that the difference between the specific free energy of the interacting system and the one of the ideal gas is to leading order given by 4πa(2ϱ2−ϱ20). Here ϱ denotes the density of the system and ϱ0 is the expected condensate density of the ideal gas. Additionally, we show that the one-particle density matrix of any approximate minimizer of the Gibbs free energy functional is to leading order given by the one of the ideal gas. This in particular proves Bose–Einstein condensation with critical temperature given by the one of the ideal gas to leading order. One key ingredient of our proof is a novel use of the Gibbs variational principle that goes hand in hand with the c-number substitution. AU - Deuchert, Andreas AU - Seiringer, Robert ID - 7650 IS - 6 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - Gross-Pitaevskii limit of a homogeneous Bose gas at positive temperature VL - 236 ER - TY - JOUR AB - We study the dynamics of a system of N interacting bosons in a disc-shaped trap, which is realised by an external potential that confines the bosons in one spatial dimension to an interval of length of order ε. The interaction is non-negative and scaled in such a way that its scattering length is of order ε/N, while its range is proportional to (ε/N)β with scaling parameter β∈(0,1]. We consider the simultaneous limit (N,ε)→(∞,0) and assume that the system initially exhibits Bose–Einstein condensation. We prove that condensation is preserved by the N-body dynamics, where the time-evolved condensate wave function is the solution of a two-dimensional non-linear equation. The strength of the non-linearity depends on the scaling parameter β. For β∈(0,1), we obtain a cubic defocusing non-linear Schrödinger equation, while the choice β=1 yields a Gross–Pitaevskii equation featuring the scattering length of the interaction. In both cases, the coupling parameter depends on the confining potential. AU - Bossmann, Lea ID - 8130 IS - 11 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - Derivation of the 2d Gross–Pitaevskii equation for strongly confined 3d Bosons VL - 238 ER - TY - JOUR AB - We consider the Fröhlich model of a polaron, and show that its effective mass diverges in thestrong coupling limit. AU - Lieb, Elliott H. AU - Seiringer, Robert ID - 7235 JF - Journal of Statistical Physics SN - 0022-4715 TI - Divergence of the effective mass of a polaron in the strong coupling limit VL - 180 ER - TY - CONF AB - For 1≤m≤n, we consider a natural m-out-of-n multi-instance scenario for a public-key encryption (PKE) scheme. An adversary, given n independent instances of PKE, wins if he breaks at least m out of the n instances. In this work, we are interested in the scaling factor of PKE schemes, SF, which measures how well the difficulty of breaking m out of the n instances scales in m. That is, a scaling factor SF=ℓ indicates that breaking m out of n instances is at least ℓ times more difficult than breaking one single instance. A PKE scheme with small scaling factor hence provides an ideal target for mass surveillance. In fact, the Logjam attack (CCS 2015) implicitly exploited, among other things, an almost constant scaling factor of ElGamal over finite fields (with shared group parameters). For Hashed ElGamal over elliptic curves, we use the generic group model to argue that the scaling factor depends on the scheme's granularity. In low granularity, meaning each public key contains its independent group parameter, the scheme has optimal scaling factor SF=m; In medium and high granularity, meaning all public keys share the same group parameter, the scheme still has a reasonable scaling factor SF=√m. Our findings underline that instantiating ElGamal over elliptic curves should be preferred to finite fields in a multi-instance scenario. As our main technical contribution, we derive new generic-group lower bounds of Ω(√(mp)) on the difficulty of solving both the m-out-of-n Gap Discrete Logarithm and the m-out-of-n Gap Computational Diffie-Hellman problem over groups of prime order p, extending a recent result by Yun (EUROCRYPT 2015). We establish the lower bound by studying the hardness of a related computational problem which we call the search-by-hypersurface problem. AU - Auerbach, Benedikt AU - Giacon, Federico AU - Kiltz, Eike ID - 7966 SN - 0302-9743 T2 - Advances in Cryptology – EUROCRYPT 2020 TI - Everybody’s a target: Scalability in public-key encryption VL - 12107 ER - TY - CONF AB - We introduce the monitoring of trace properties under assumptions. An assumption limits the space of possible traces that the monitor may encounter. An assumption may result from knowledge about the system that is being monitored, about the environment, or about another, connected monitor. We define monitorability under assumptions and study its theoretical properties. In particular, we show that for every assumption A, the boolean combinations of properties that are safe or co-safe relative to A are monitorable under A. We give several examples and constructions on how an assumption can make a non-monitorable property monitorable, and how an assumption can make a monitorable property monitorable with fewer resources, such as integer registers. AU - Henzinger, Thomas A AU - Sarac, Naci E ID - 8623 SN - 0302-9743 T2 - Runtime Verification TI - Monitorability under assumptions VL - 12399 ER - TY - CHAP AB - We introduce the notion of Witness Maps as a cryptographic notion of a proof system. A Unique Witness Map (UWM) deterministically maps all witnesses for an NP statement to a single representative witness, resulting in a computationally sound, deterministic-prover, non-interactive witness independent proof system. A relaxation of UWM, called Compact Witness Map (CWM), maps all the witnesses to a small number of witnesses, resulting in a “lossy” deterministic-prover, non-interactive proof-system. We also define a Dual Mode Witness Map (DMWM) which adds an “extractable” mode to a CWM. Our main construction is a DMWM for all NP relations, assuming sub-exponentially secure indistinguishability obfuscation ( iO ), along with standard cryptographic assumptions. The DMWM construction relies on a CWM and a new primitive called Cumulative All-Lossy-But-One Trapdoor Functions (C-ALBO-TDF), both of which are in turn instantiated based on iO and other primitives. Our instantiation of a CWM is in fact a UWM; in turn, we show that a UWM implies Witness Encryption. Along the way to constructing UWM and C-ALBO-TDF, we also construct, from standard assumptions, Puncturable Digital Signatures and a new primitive called Cumulative Lossy Trapdoor Functions (C-LTDF). The former improves up on a construction of Bellare et al. (Eurocrypt 2016), who relied on sub-exponentially secure iO and sub-exponentially secure OWF. As an application of our constructions, we show how to use a DMWM to construct the first leakage and tamper-resilient signatures with a deterministic signer, thereby solving a decade old open problem posed by Katz and Vaikunthanathan (Asiacrypt 2009), by Boyle, Segev and Wichs (Eurocrypt 2011), as well as by Faonio and Venturi (Asiacrypt 2016). Our construction achieves the optimal leakage rate of 1−o(1) . AU - Chakraborty, Suvradip AU - Prabhakaran, Manoj AU - Wichs, Daniel ED - Kiayias, A ID - 10865 SN - 0302-9743 T2 - Public-Key Cryptography TI - Witness maps and applications VL - 12110 ER - TY - JOUR AB - We consider a system of N bosons in the limit N→∞, interacting through singular potentials. For initial data exhibiting Bose–Einstein condensation, the many-body time evolution is well approximated through a quadratic fluctuation dynamics around a cubic nonlinear Schrödinger equation of the condensate wave function. We show that these fluctuations satisfy a (multi-variate) central limit theorem. AU - Rademacher, Simone Anna Elvira ID - 7611 JF - Letters in Mathematical Physics SN - 0377-9017 TI - Central limit theorem for Bose gases interacting through singular potentials VL - 110 ER - TY - JOUR AB - The biotic interactions hypothesis posits that biotic interactions are more important drivers of adaptation closer to the equator, evidenced by “stronger” contemporary interactions (e.g. greater interaction rates) and/or patterns of trait evolution consistent with a history of stronger interactions. Support for the hypothesis is mixed, but few studies span tropical and temperate regions while experimentally controlling for evolutionary history. Here, we integrate field observations and common garden experiments to quantify the relative importance of pollination and herbivory in a pair of tropical‐temperate congeneric perennial herbs. Phytolacca rivinoides and P. americana are pioneer species native to the Neotropics and the eastern USA, respectively. We compared plant‐pollinator and plant‐herbivore interactions between three tropical populations of P. rivinoides from Costa Rica and three temperate populations of P. americana from its northern range edge in Michigan and Ohio. For some metrics of interaction importance, we also included three subtropical populations of P. americana from its southern range edge in Florida. This approach confounds species and region but allows us, uniquely, to measure complementary proxies of interaction importance across a tropical‐temperate range in one system. To test the prediction that lower‐latitude plants are more reliant on insect pollinators, we quantified floral display and reward, insect visitation rates, and self‐pollination ability (autogamy). To test the prediction that lower‐latitude plants experience more herbivore pressure, we quantified herbivory rates, herbivore abundance, and leaf palatability. We found evidence supporting the biotic interactions hypothesis for most comparisons between P. rivinoides and north‐temperate P. americana (floral display, insect visitation, autogamy, herbivory, herbivore abundance, and young‐leaf palatability). Results for subtropical P. americana populations, however, were typically not intermediate between P. rivinoides and north‐temperate P. americana, as would be predicted by a linear latitudinal gradient in interaction importance. Subtropical young‐leaf palatability was intermediate, but subtropical mature leaves were the least palatable, and pollination‐related traits did not differ between temperate and subtropical regions. These nonlinear patterns of interaction importance suggest future work to relate interaction importance to climatic or biotic thresholds. In sum, we found that the biotic interactions hypothesis was more consistently supported at the larger spatial scale of our study. AU - Baskett, Carina AU - Schroeder, Lucy AU - Weber, Marjorie G. AU - Schemske, Douglas W. ID - 7236 IS - 1 JF - Ecological Monographs SN - 0012-9615 TI - Multiple metrics of latitudinal patterns in insect pollination and herbivory for a tropical‐temperate congener pair VL - 90 ER - TY - JOUR AB - * Morphogenesis and adaptive tropic growth in plants depend on gradients of the phytohormone auxin, mediated by the membrane‐based PIN‐FORMED (PIN) auxin transporters. PINs localize to a particular side of the plasma membrane (PM) or to the endoplasmic reticulum (ER) to directionally transport auxin and maintain intercellular and intracellular auxin homeostasis, respectively. However, the molecular cues that confer their diverse cellular localizations remain largely unknown. * In this study, we systematically swapped the domains between ER‐ and PM‐localized PIN proteins, as well as between apical and basal PM‐localized PINs from Arabidopsis thaliana , to shed light on why PIN family members with similar topological structures reside at different membrane compartments within cells. * Our results show that not only do the N‐ and C‐terminal transmembrane domains (TMDs) and central hydrophilic loop contribute to their differential subcellular localizations and cellular polarity, but that the pairwise‐matched N‐ and C‐terminal TMDs resulting from intramolecular domain–domain coevolution are also crucial for their divergent patterns of localization. * These findings illustrate the complexity of the evolutionary path of PIN proteins in acquiring their plethora of developmental functions and adaptive growth in plants. AU - Zhang, Yuzhou AU - Hartinger, Corinna AU - Wang, Xiaojuan AU - Friml, Jiří ID - 7697 IS - 5 JF - New Phytologist SN - 0028-646X TI - Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters VL - 227 ER - TY - JOUR AB - This paper introduces a simple method for simulating highly anisotropic elastoplastic material behaviors like the dissolution of fibrous phenomena (splintering wood, shredding bales of hay) and materials composed of large numbers of irregularly‐shaped bodies (piles of twigs, pencils, or cards). We introduce a simple transformation of the anisotropic problem into an equivalent isotropic one, and we solve this new “fictitious” isotropic problem using an existing simulator based on the material point method. Our approach results in minimal changes to existing simulators, and it allows us to re‐use popular isotropic plasticity models like the Drucker‐Prager yield criterion instead of inventing new anisotropic plasticity models for every phenomenon we wish to simulate. AU - Schreck, Camille AU - Wojtan, Christopher J ID - 8765 IS - 2 JF - Computer Graphics Forum KW - Computer Networks and Communications SN - 0167-7055 TI - A practical method for animating anisotropic elastoplastic materials VL - 39 ER - TY - JOUR AB - Water-in-salt electrolytes based on highly concentrated bis(trifluoromethyl)sulfonimide (TFSI) promise aqueous electrolytes with stabilities approaching 3 V. However, especially with an electrode approaching the cathodic (reductive) stability, cycling stability is insufficient. While stability critically relies on a solid electrolyte interphase (SEI), the mechanism behind the cathodic stability limit remains unclear. Here, we reveal two distinct reduction potentials for the chemical environments of ‘free’ and ‘bound’ water and that both contribute to SEI formation. Free-water is reduced ~1V above bound water in a hydrogen evolution reaction (HER) and responsible for SEI formation via reactive intermediates of the HER; concurrent LiTFSI precipitation/dissolution establishes a dynamic interface. The free-water population emerges, therefore, as the handle to extend the cathodic limit of aqueous electrolytes and the battery cycling stability. AU - Bouchal, Roza AU - Li, Zhujie AU - Bongu, Chandra AU - Le Vot, Steven AU - Berthelot, Romain AU - Rotenberg, Benjamin AU - Favier, Frederic AU - Freunberger, Stefan Alexander AU - Salanne, Mathieu AU - Fontaine, Olivier ID - 8057 IS - 37 JF - Angewandte Chemie SN - 0044-8249 TI - Competitive salt precipitation/dissolution during free‐water reduction in water‐in‐salt electrolyte VL - 132 ER - TY - JOUR AB - Coinfections with multiple pathogens can result in complex within‐host dynamics affecting virulence and transmission. While multiple infections are intensively studied in solitary hosts, it is so far unresolved how social host interactions interfere with pathogen competition, and if this depends on coinfection diversity. We studied how the collective disease defences of ants – their social immunity – influence pathogen competition in coinfections of same or different fungal pathogen species. Social immunity reduced virulence for all pathogen combinations, but interfered with spore production only in different‐species coinfections. Here, it decreased overall pathogen sporulation success while increasing co‐sporulation on individual cadavers and maintaining a higher pathogen diversity at the community level. Mathematical modelling revealed that host sanitary care alone can modulate competitive outcomes between pathogens, giving advantage to fast‐germinating, thus less grooming‐sensitive ones. Host social interactions can hence modulate infection dynamics in coinfected group members, thereby altering pathogen communities at the host level and population level. AU - Milutinovic, Barbara AU - Stock, Miriam AU - Grasse, Anna V AU - Naderlinger, Elisabeth AU - Hilbe, Christian AU - Cremer, Sylvia ID - 7343 IS - 3 JF - Ecology Letters SN - 1461-023X TI - Social immunity modulates competition between coinfecting pathogens VL - 23 ER - TY - JOUR AB - Sewall Wright developed FST for describing population differentiation and it has since been extended to many novel applications, including the detection of homomorphic sex chromosomes. However, there has been confusion regarding the expected estimate of FST for a fixed difference between the X‐ and Y‐chromosome when comparing males and females. Here, we attempt to resolve this confusion by contrasting two common FST estimators and explain why they yield different estimates when applied to the case of sex chromosomes. We show that this difference is true for many allele frequencies, but the situation characterized by fixed differences between the X‐ and Y‐chromosome is among the most extreme. To avoid additional confusion, we recommend that all authors using FST clearly state which estimator of FST their work uses. AU - Gammerdinger, William J AU - Toups, Melissa A AU - Vicoso, Beatriz ID - 8099 IS - 6 JF - Molecular Ecology Resources SN - 1755-098X TI - Disagreement in FST estimators: A case study from sex chromosomes VL - 20 ER - TY - JOUR AB - Water-in-salt electrolytes based on highly concentrated bis(trifluoromethyl)sulfonimide (TFSI) promise aqueous electrolytes with stabilities nearing 3 V. However, especially with an electrode approaching the cathodic (reductive) stability, cycling stability is insufficient. While stability critically relies on a solid electrolyte interphase (SEI), the mechanism behind the cathodic stability limit remains unclear. Here, we reveal two distinct reduction potentials for the chemical environments of 'free' and 'bound' water and that both contribute to SEI formation. Free-water is reduced ~1V above bound water in a hydrogen evolution reaction (HER) and responsible for SEI formation via reactive intermediates of the HER; concurrent LiTFSI precipitation/dissolution establishes a dynamic interface. The free-water population emerges, therefore, as the handle to extend the cathodic limit of aqueous electrolytes and the battery cycling stability. AU - Bouchal, Roza AU - Li, Zhujie AU - Bongu, Chandra AU - Le Vot, Steven AU - Berthelot, Romain AU - Rotenberg, Benjamin AU - Favier, Fréderic AU - Freunberger, Stefan Alexander AU - Salanne, Mathieu AU - Fontaine, Olivier ID - 7847 IS - 37 JF - Angewandte Chemie International Edition SN - 1433-7851 TI - Competitive salt precipitation/dissolution during free‐water reduction in water‐in‐salt electrolyte VL - 59 ER - TY - JOUR AB - Habitat loss is one of the key drivers of the ongoing decline of biodiversity. However, ecologists still argue about how fragmentation of habitat (independent of habitat loss) affects species richness. The recently proposed habitat amount hypothesis posits that species richness only depends on the total amount of habitat in a local landscape. In contrast, empirical studies report contrasting patterns: some find positive and others negative effects of fragmentation per se on species richness. To explain this apparent disparity, we devise a stochastic, spatially explicit model of competitive species communities in heterogeneous habitats. The model shows that habitat loss and fragmentation have complex effects on species diversity in competitive communities. When the total amount of habitat is large, fragmentation per se tends to increase species diversity, but if the total amount of habitat is small, the situation is reversed: fragmentation per se decreases species diversity. AU - Rybicki, Joel AU - Abrego, Nerea AU - Ovaskainen, Otso ID - 7224 IS - 3 JF - Ecology Letters SN - 1461-023X TI - Habitat fragmentation and species diversity in competitive communities VL - 23 ER - TY - JOUR AB - We show the synthesis of a redox‐active quinone, 2‐methoxy‐1,4‐hydroquinone (MHQ), from a bio‐based feedstock and its suitability as electrolyte in aqueous redox flow batteries. We identified semiquinone intermediates at insufficiently low pH and quinoid radicals as responsible for decomposition of MHQ under electrochemical conditions. Both can be avoided and/or stabilized, respectively, using H 3 PO 4 electrolyte, allowing for reversible cycling in a redox flow battery for hundreds of cycles. AU - Schlemmer, Werner AU - Nothdurft, Philipp AU - Petzold, Alina AU - Frühwirt, Philipp AU - Schmallegger, Max AU - Gescheidt-Demner, Georg AU - Fischer, Roland AU - Freunberger, Stefan Alexander AU - Kern, Wolfgang AU - Spirk, Stefan ID - 8329 IS - 51 JF - Angewandte Chemie International Edition SN - 1433-7851 TI - 2‐methoxyhydroquinone from vanillin for aqueous redox‐flow batteries VL - 59 ER - TY - GEN AB - Coinfections with multiple pathogens can result in complex within-host dynamics affecting virulence and transmission. Whilst multiple infections are intensively studied in solitary hosts, it is so far unresolved how social host interactions interfere with pathogen competition, and if this depends on coinfection diversity. We studied how the collective disease defenses of ants – their social immunity ­– influence pathogen competition in coinfections of same or different fungal pathogen species. Social immunity reduced virulence for all pathogen combinations, but interfered with spore production only in different-species coinfections. Here, it decreased overall pathogen sporulation success, whilst simultaneously increasing co-sporulation on individual cadavers and maintaining a higher pathogen diversity at the community-level. Mathematical modeling revealed that host sanitary care alone can modulate competitive outcomes between pathogens, giving advantage to fast-germinating, thus less grooming-sensitive ones. Host social interactions can hence modulate infection dynamics in coinfected group members, thereby altering pathogen communities at the host- and population-level. AU - Milutinovic, Barbara AU - Stock, Miriam AU - Grasse, Anna V AU - Naderlinger, Elisabeth AU - Hilbe, Christian AU - Cremer, Sylvia ID - 13060 TI - Social immunity modulates competition between coinfecting pathogens ER - TY - GEN AB - PADREV : 4,4'-dimethoxy[1,1'-biphenyl]-2,2',5,5'-tetrol Space Group: C 2 (5), Cell: a 24.488(16)Å b 5.981(4)Å c 3.911(3)Å, α 90° β 91.47(3)° γ 90° AU - Schlemmer, Werner AU - Nothdurft, Philipp AU - Petzold, Alina AU - Riess, Gisbert AU - Frühwirt, Philipp AU - Schmallegger, Max AU - Gescheidt-Demner, Georg AU - Fischer, Roland AU - Freunberger, Stefan Alexander AU - Kern, Wolfgang AU - Spirk, Stefan ID - 9780 TI - CCDC 1991959: Experimental Crystal Structure Determination ER - TY - JOUR AB - The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD. AU - Martín-Belmonte, Alejandro AU - Aguado, Carolina AU - Alfaro-Ruíz, Rocío AU - Moreno-Martínez, Ana Esther AU - De La Ossa, Luis AU - Martínez-Hernández, José AU - Buisson, Alain AU - Früh, Simon AU - Bettler, Bernhard AU - Shigemoto, Ryuichi AU - Fukazawa, Yugo AU - Luján, Rafael ID - 7207 IS - 3 JF - Brain Pathology SN - 10156305 TI - Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer's disease VL - 30 ER - TY - JOUR AB - Genetic incompatibilities contribute to reproductive isolation between many diverging populations, but it is still unclear to what extent they play a role if divergence happens with gene flow. In contact zones between the "Crab" and "Wave" ecotypes of the snail Littorina saxatilis, divergent selection forms strong barriers to gene flow, while the role of post‐zygotic barriers due to selection against hybrids remains unclear. High embryo abortion rates in this species could indicate the presence of such barriers. Post‐zygotic barriers might include genetic incompatibilities (e.g. Dobzhansky–Muller incompatibilities) but also maladaptation, both expected to be most pronounced in contact zones. In addition, embryo abortion might reflect physiological stress on females and embryos independent of any genetic stress. We examined all embryos of >500 females sampled outside and inside contact zones of three populations in Sweden. Females' clutch size ranged from 0 to 1,011 embryos (mean 130 ± 123), and abortion rates varied between 0% and 100% (mean 12%). We described female genotypes by using a hybrid index based on hundreds of SNPs differentiated between ecotypes with which we characterized female genotypes. We also calculated female SNP heterozygosity and inversion karyotype. Clutch size did not vary with female hybrid index, and abortion rates were only weakly related to hybrid index in two sites but not at all in a third site. No additional variation in abortion rate was explained by female SNP heterozygosity, but increased female inversion heterozygosity added slightly to increased abortion. Our results show only weak and probably biologically insignificant post‐zygotic barriers contributing to ecotype divergence, and the high and variable abortion rates were marginally, if at all, explained by hybrid index of females. AU - Johannesson, Kerstin AU - Zagrodzka, Zuzanna AU - Faria, Rui AU - Westram, Anja M AU - Butlin, Roger K. ID - 7205 IS - 3 JF - Journal of Evolutionary Biology SN - 1010061X TI - Is embryo abortion a post-zygotic barrier to gene flow between Littorina ecotypes? VL - 33 ER - TY - JOUR AB - Previously, we reported that the allelic de-etiolated by zinc (dez) and trichome birefringence (tbr) mutants exhibit photomorphogenic development in the dark, which is enhanced by high Zn. TRICHOME BIREFRINGENCE-LIKE proteins had been implicated in transferring acetyl groups to various hemicelluloses. Pectin O-acetylation levels were lower in dark-grown dez seedlings than in the wild type. We observed Zn-enhanced photomorphogenesis in the dark also in the reduced wall acetylation 2 (rwa2-3) mutant, which exhibits lowered O-acetylation levels of cell wall macromolecules including pectins and xyloglucans, supporting a role for cell wall macromolecule O-acetylation in the photomorphogenic phenotypes of rwa2-3 and dez. Application of very short oligogalacturonides (vsOGs) restored skotomorphogenesis in dark-grown dez and rwa2-3. Here we demonstrate that in dez, O-acetylation of non-pectin cell wall components, notably of xyloglucan, is enhanced. Our results highlight the complexity of cell wall homeostasis and indicate against an influence of xyloglucan O-acetylation on light-dependent seedling development. AU - Sinclair, Scott A AU - Gille, S. AU - Pauly, M. AU - Krämer, U. ID - 7417 IS - 1 JF - Plant Signaling & Behavior SN - 1559-2324 TI - Regulation of acetylation of plant cell wall components is complex and responds to external stimuli VL - 15 ER - TY - JOUR AB - For complex Wigner-type matrices, i.e. Hermitian random matrices with independent, not necessarily identically distributed entries above the diagonal, we show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are universal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner–Dyson–Mehta universality conjecture for the last remaining universality type in the complex Hermitian class. Our analysis holds not only for exact cusps, but approximate cusps as well, where an extended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp for both symmetry classes. This result is also the key input in the companion paper (Cipolloni et al. in Pure Appl Anal, 2018. arXiv:1811.04055) where the cusp universality for real symmetric Wigner-type matrices is proven. The novel cusp fluctuation mechanism is also essential for the recent results on the spectral radius of non-Hermitian random matrices (Alt et al. in Spectral radius of random matrices with independent entries, 2019. arXiv:1907.13631), and the non-Hermitian edge universality (Cipolloni et al. in Edge universality for non-Hermitian random matrices, 2019. arXiv:1908.00969). AU - Erdös, László AU - Krüger, Torben H AU - Schröder, Dominik J ID - 6185 JF - Communications in Mathematical Physics SN - 0010-3616 TI - Cusp universality for random matrices I: Local law and the complex Hermitian case VL - 378 ER - TY - THES AB - This thesis is based on three main topics: In the first part, we study convergence of discrete gradient flow structures associated with regular finite-volume discretisations of Fokker-Planck equations. We show evolutionary I convergence of the discrete gradient flows to the L2-Wasserstein gradient flow corresponding to the solution of a Fokker-Planck equation in arbitrary dimension d >= 1. Along the argument, we prove Mosco- and I-convergence results for discrete energy functionals, which are of independent interest for convergence of equivalent gradient flow structures in Hilbert spaces. The second part investigates L2-Wasserstein flows on metric graph. The starting point is a Benamou-Brenier formula for the L2-Wasserstein distance, which is proved via a regularisation scheme for solutions of the continuity equation, adapted to the peculiar geometric structure of metric graphs. Based on those results, we show that the L2-Wasserstein space over a metric graph admits a gradient flow which may be identified as a solution of a Fokker-Planck equation. In the third part, we focus again on the discrete gradient flows, already encountered in the first part. We propose a variational structure which extends the gradient flow structure to Markov chains violating the detailed-balance conditions. Using this structure, we characterise contraction estimates for the discrete heat flow in terms of convexity of corresponding path-dependent energy functionals. In addition, we use this approach to derive several functional inequalities for said functionals. AU - Forkert, Dominik L ID - 7629 SN - 2663-337X TI - Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains ER - TY - THES AB - This thesis concerns itself with the interactions of evolutionary and ecological forces and the consequences on genetic diversity and the ultimate survival of populations. It is important to understand what signals processes leave on the genome and what we can infer from such data, which is usually abundant but noisy. Furthermore, understanding how and when populations adapt or go extinct is important for practical purposes, such as the genetic management of populations, as well as for theoretical questions, since local adaptation can be the first step toward speciation. In Chapter 2, we introduce the method of maximum entropy to approximate the demographic changes of a population in a simple setting, namely the logistic growth model with immigration. We show that this method is not only a powerful tool in physics but can be gainfully applied in an ecological framework. We investigate how well it approximates the real behavior of the system, and find that is does so, even in unexpected situations. Finally, we illustrate how it can model changing environments. In Chapter 3, we analyze the co-evolution of allele frequencies and population sizes in an infinite island model. We give conditions under which polygenic adaptation to a rare habitat is possible. The model we use is based on the diffusion approximation, considers eco-evolutionary feedback mechanisms (hard selection), and treats both drift and environmental fluctuations explicitly. We also look at limiting scenarios, for which we derive analytical expressions. In Chapter 4, we present a coalescent based simulation tool to obtain patterns of diversity in a spatially explicit subdivided population, in which the demographic history of each subpopulation can be specified. We compare the results to existing predictions, and explore the relative importance of time and space under a variety of spatial arrangements and demographic histories, such as expansion and extinction. In the last chapter, we give a brief outlook to further research. AU - Szep, Eniko ID - 8574 TI - Local adaptation in metapopulations ER - TY - THES AB - We study the interacting homogeneous Bose gas in two spatial dimensions in the thermodynamic limit at fixed density. We shall be concerned with some mathematical aspects of this complicated problem in many-body quantum mechanics. More specifically, we consider the dilute limit where the scattering length of the interaction potential, which is a measure for the effective range of the potential, is small compared to the average distance between the particles. We are interested in a setting with positive (i.e., non-zero) temperature. After giving a survey of the relevant literature in the field, we provide some facts and examples to set expectations for the two-dimensional system. The crucial difference to the three-dimensional system is that there is no Bose–Einstein condensate at positive temperature due to the Hohenberg–Mermin–Wagner theorem. However, it turns out that an asymptotic formula for the free energy holds similarly to the three-dimensional case. We motivate this formula by considering a toy model with δ interaction potential. By restricting this model Hamiltonian to certain trial states with a quasi-condensate we obtain an upper bound for the free energy that still has the quasi-condensate fraction as a free parameter. When minimizing over the quasi-condensate fraction, we obtain the Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity, which plays an important role in our rigorous contribution. The mathematically rigorous result that we prove concerns the specific free energy in the dilute limit. We give upper and lower bounds on the free energy in terms of the free energy of the non-interacting system and a correction term coming from the interaction. Both bounds match and thus we obtain the leading term of an asymptotic approximation in the dilute limit, provided the thermal wavelength of the particles is of the same order (or larger) than the average distance between the particles. The remarkable feature of this result is its generality: the correction term depends on the interaction potential only through its scattering length and it holds for all nonnegative interaction potentials with finite scattering length that are measurable. In particular, this allows to model an interaction of hard disks. AU - Mayer, Simon ID - 7514 SN - 2663-337X TI - The free energy of a dilute two-dimensional Bose gas ER - TY - THES AB - Mrp (Multi resistance and pH adaptation) are broadly distributed secondary active antiporters that catalyze the transport of monovalent ions such as sodium and potassium outside of the cell coupled to the inward translocation of protons. Mrp antiporters are unique in a way that they are composed of seven subunits (MrpABCDEFG) encoded in a single operon, whereas other antiporters catalyzing the same reaction are mostly encoded by a single gene. Mrp exchangers are crucial for intracellular pH homeostasis and Na+ efflux, essential mechanisms for H+ uptake under alkaline environments and for reduction of the intracellular concentration of toxic cations. Mrp displays no homology to any other monovalent Na+(K+)/H+ antiporters but Mrp subunits have primary sequence similarity to essential redox-driven proton pumps, such as respiratory complex I and membrane-bound hydrogenases. This similarity reinforces the hypothesis that these present day redox-driven proton pumps are descended from the Mrp antiporter. The Mrp structure serves as a model to understand the yet obscure coupling mechanism between ion or electron transfer and proton translocation in this large group of proteins. In the thesis, I am presenting the purification, biochemical analysis, cryo-EM analysis and molecular structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. Numerous conditions were screened to purify Mrp to high homogeneity and to obtain an appropriate distribution of single particles on cryo-EM grids covered with a continuous layer of ultrathin carbon. A preferred particle orientation problem was solved by performing a tilted data collection. The activity assays showed the specific pH-dependent profile of secondary active antiporters. The molecular structure shows that Mrp is a dimer of seven-subunit protomers with 50 trans-membrane helices each. The dimer interface is built by many short and tilted transmembrane helices, probably causing a thinning of the bacterial membrane. The surface charge distribution shows an extraordinary asymmetry within each monomer, revealing presumable proton and sodium translocation pathways. The two largest and homologous Mrp subunits MrpA and MrpD probably translocate one proton each into the cell. The sodium ion is likely being translocated in the opposite direction within the small subunits along a ladder of charged and conserved residues. Based on the structure, we propose a mechanism were the antiport activity is accomplished via electrostatic interactions between the charged cations and key charged residues. The flexible key TM helices coordinate these electrostatic interactions, while the membrane thinning between the monomers enables the translocation of sodium across the charged membrane. The entire family of redox-driven proton pumps is likely to perform their mechanism in a likewise manner. AU - Steiner, Julia ID - 8353 SN - 2663-337X TI - Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I ER - TY - THES AB - The plant hormone auxin plays indispensable roles in plant growth and development. An essential level of regulation in auxin action is the directional auxin transport within cells. The establishment of auxin gradient in plant tissue has been attributed to local auxin biosynthesis and directional intercellular auxin transport, which both are controlled by various environmental and developmental signals. It is well established that asymmetric auxin distribution in cells is achieved by polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the initial insights into cellular mechanisms of PIN polarization obtained from the last decades, the molecular mechanism and specific regulators mediating PIN polarization remains elusive. In this thesis, we aim to find novel players in PIN subcellular polarity regulation during Arabidopsis development. We first characterize the physiological effect of piperonylic acid (PA) on Arabidopsis hypocotyl gravitropic bending and PIN polarization. Secondly, we reveal the importance of SCFTIR1/AFB auxin signaling pathway in shoot gravitropism bending termination. In addition, we also explore the role of myosin XI complex, and actin cytoskeleton in auxin feedback regulation on PIN polarity. In Chapter 1, we give an overview of the current knowledge about PIN-mediated auxin fluxes in various plant tropic responses. In Chapter 2, we study the physiological effect of PA on shoot gravitropic bending. Our results show that PA treatment inhibits auxin-mediated PIN3 repolarization by interfering with PINOID and PIN3 phosphorylation status, ultimately leading to hyperbending hypocotyls. In Chapter 3, we provide evidence to show that the SCFTIR1/AFB nuclear auxin signaling pathway is crucial and required for auxin-mediated PIN3 repolarization and shoot gravitropic bending termination. In Chapter 4, we perform a phosphoproteomics approach and identify the motor protein Myosin XI and its binding protein, the MadB2 family, as an essential regulator of PIN polarity for auxin-canalization related developmental processes. In Chapter 5, we demonstrate the vital role of actin cytoskeleton in auxin feedback on PIN polarity by regulating PIN subcellular trafficking. Overall, the data presented in this PhD thesis brings novel insights into the PIN polar localization regulation that resulted in the (re)establishment of the polar auxin flow and gradient in response to environmental stimuli during plant development. AU - Han, Huibin ID - 8589 SN - 2663-337X TI - Novel insights into PIN polarity regulation during Arabidopsis development ER - TY - JOUR AB - Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements. AU - Steiner, Julia AU - Sazanov, Leonid A ID - 8284 JF - eLife TI - Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter VL - 9 ER - TY - THES AB - In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as transcriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal non-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters. In the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are hard to evolve or maintain. AU - Grah, Rok ID - 8155 SN - 2663-337X TI - Gene regulation across scales – how biophysical constraints shape evolution ER - TY - JOUR AU - Han, Huibin AU - Rakusova, Hana AU - Verstraeten, Inge AU - Zhang, Yuzhou AU - Friml, Jiří ID - 7643 IS - 5 JF - Plant Physiology SN - 0032-0889 TI - SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism VL - 183 ER - TY - GEN AB - In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology. AU - Grah, Rok AU - Zoller, Benjamin AU - Tkačik, Gašper ID - 7675 T2 - bioRxiv TI - Normative models of enhancer function ER - TY - THES AB - Many methods for the reconstruction of shapes from sets of points produce ordered simplicial complexes, which are collections of vertices, edges, triangles, and their higher-dimensional analogues, called simplices, in which every simplex gets assigned a real value measuring its size. This thesis studies ordered simplicial complexes, with a focus on their topology, which reflects the connectedness of the represented shapes and the presence of holes. We are interested both in understanding better the structure of these complexes, as well as in developing algorithms for applications. For the Delaunay triangulation, the most popular measure for a simplex is the radius of the smallest empty circumsphere. Based on it, we revisit Alpha and Wrap complexes and experimentally determine their probabilistic properties for random data. Also, we prove the existence of tri-partitions, propose algorithms to open and close holes, and extend the concepts from Euclidean to Bregman geometries. AU - Ölsböck, Katharina ID - 7460 KW - shape reconstruction KW - hole manipulation KW - ordered complexes KW - Alpha complex KW - Wrap complex KW - computational topology KW - Bregman geometry SN - 2663-337X TI - The hole system of triangulated shapes ER - TY - THES AB - A search problem lies in the complexity class FNP if a solution to the given instance of the problem can be verified efficiently. The complexity class TFNP consists of all search problems in FNP that are total in the sense that a solution is guaranteed to exist. TFNP contains a host of interesting problems from fields such as algorithmic game theory, computational topology, number theory and combinatorics. Since TFNP is a semantic class, it is unlikely to have a complete problem. Instead, one studies its syntactic subclasses which are defined based on the combinatorial principle used to argue totality. Of particular interest is the subclass PPAD, which contains important problems like computing Nash equilibrium for bimatrix games and computational counterparts of several fixed-point theorems as complete. In the thesis, we undertake the study of averagecase hardness of TFNP, and in particular its subclass PPAD. Almost nothing was known about average-case hardness of PPAD before a series of recent results showed how to achieve it using a cryptographic primitive called program obfuscation. However, it is currently not known how to construct program obfuscation from standard cryptographic assumptions. Therefore, it is desirable to relax the assumption under which average-case hardness of PPAD can be shown. In the thesis we take a step in this direction. First, we show that assuming the (average-case) hardness of a numbertheoretic problem related to factoring of integers, which we call Iterated-Squaring, PPAD is hard-on-average in the random-oracle model. Then we strengthen this result to show that the average-case hardness of PPAD reduces to the (adaptive) soundness of the Fiat-Shamir Transform, a well-known technique used to compile a public-coin interactive protocol into a non-interactive one. As a corollary, we obtain average-case hardness for PPAD in the random-oracle model assuming the worst-case hardness of #SAT. Moreover, the above results can all be strengthened to obtain average-case hardness for the class CLS ⊆ PPAD. Our main technical contribution is constructing incrementally-verifiable procedures for computing Iterated-Squaring and #SAT. By incrementally-verifiable, we mean that every intermediate state of the computation includes a proof of its correctness, and the proof can be updated and verified in polynomial time. Previous constructions of such procedures relied on strong, non-standard assumptions. Instead, we introduce a technique called recursive proof-merging to obtain the same from weaker assumptions. AU - Kamath Hosdurg, Chethan ID - 7896 SN - 2663-337X TI - On the average-case hardness of total search problems ER - TY - CONF AB - State-of-the-art detection systems are generally evaluated on their ability to exhaustively retrieve objects densely distributed in the image, across a wide variety of appearances and semantic categories. Orthogonal to this, many real-life object detection applications, for example in remote sensing, instead require dealing with large images that contain only a few small objects of a single class, scattered heterogeneously across the space. In addition, they are often subject to strict computational constraints, such as limited battery capacity and computing power.To tackle these more practical scenarios, we propose a novel flexible detection scheme that efficiently adapts to variable object sizes and densities: We rely on a sequence of detection stages, each of which has the ability to predict groups of objects as well as individuals. Similar to a detection cascade, this multi-stage architecture spares computational effort by discarding large irrelevant regions of the image early during the detection process. The ability to group objects provides further computational and memory savings, as it allows working with lower image resolutions in early stages, where groups are more easily detected than individuals, as they are more salient. We report experimental results on two aerial image datasets, and show that the proposed method is as accurate yet computationally more efficient than standard single-shot detectors, consistently across three different backbone architectures. AU - Royer, Amélie AU - Lampert, Christoph ID - 7936 SN - 9781728165530 T2 - IEEE Winter Conference on Applications of Computer Vision TI - Localizing grouped instances for efficient detection in low-resource scenarios ER - TY - CONF AB - Fine-tuning is a popular way of exploiting knowledge contained in a pre-trained convolutional network for a new visual recognition task. However, the orthogonal setting of transferring knowledge from a pretrained network to a visually different yet semantically close source is rarely considered: This commonly happens with real-life data, which is not necessarily as clean as the training source (noise, geometric transformations, different modalities, etc.).To tackle such scenarios, we introduce a new, generalized form of fine-tuning, called flex-tuning, in which any individual unit (e.g. layer) of a network can be tuned, and the most promising one is chosen automatically. In order to make the method appealing for practical use, we propose two lightweight and faster selection procedures that prove to be good approximations in practice. We study these selection criteria empirically across a variety of domain shifts and data scarcity scenarios, and show that fine-tuning individual units, despite its simplicity, yields very good results as an adaptation technique. As it turns out, in contrast to common practice, rather than the last fully-connected unit it is best to tune an intermediate or early one in many domain- shift scenarios, which is accurately detected by flex-tuning. AU - Royer, Amélie AU - Lampert, Christoph ID - 7937 SN - 9781728165530 T2 - 2020 IEEE Winter Conference on Applications of Computer Vision TI - A flexible selection scheme for minimum-effort transfer learning ER - TY - CHAP AB - Image translation refers to the task of mapping images from a visual domain to another. Given two unpaired collections of images, we aim to learn a mapping between the corpus-level style of each collection, while preserving semantic content shared across the two domains. We introduce xgan, a dual adversarial auto-encoder, which captures a shared representation of the common domain semantic content in an unsupervised way, while jointly learning the domain-to-domain image translations in both directions. We exploit ideas from the domain adaptation literature and define a semantic consistency loss which encourages the learned embedding to preserve semantics shared across domains. We report promising qualitative results for the task of face-to-cartoon translation. The cartoon dataset we collected for this purpose, “CartoonSet”, is also publicly available as a new benchmark for semantic style transfer at https://google.github.io/cartoonset/index.html. AU - Royer, Amélie AU - Bousmalis, Konstantinos AU - Gouws, Stephan AU - Bertsch, Fred AU - Mosseri, Inbar AU - Cole, Forrester AU - Murphy, Kevin ED - Singh, Richa ED - Vatsa, Mayank ED - Patel, Vishal M. ED - Ratha, Nalini ID - 8092 SN - 9783030306717 T2 - Domain Adaptation for Visual Understanding TI - XGAN: Unsupervised image-to-image translation for many-to-many mappings ER - TY - THES AB - This thesis considers two examples of reconfiguration problems: flipping edges in edge-labelled triangulations of planar point sets and swapping labelled tokens placed on vertices of a graph. In both cases the studied structures – all the triangulations of a given point set or all token placements on a given graph – can be thought of as vertices of the so-called reconfiguration graph, in which two vertices are adjacent if the corresponding structures differ by a single elementary operation – by a flip of a diagonal in a triangulation or by a swap of tokens on adjacent vertices, respectively. We study the reconfiguration of one instance of a structure into another via (shortest) paths in the reconfiguration graph. For triangulations of point sets in which each edge has a unique label and a flip transfers the label from the removed edge to the new edge, we prove a polynomial-time testable condition, called the Orbit Theorem, that characterizes when two triangulations of the same point set lie in the same connected component of the reconfiguration graph. The condition was first conjectured by Bose, Lubiw, Pathak and Verdonschot. We additionally provide a polynomial time algorithm that computes a reconfiguring flip sequence, if it exists. Our proof of the Orbit Theorem uses topological properties of a certain high-dimensional cell complex that has the usual reconfiguration graph as its 1-skeleton. In the context of token swapping on a tree graph, we make partial progress on the problem of finding shortest reconfiguration sequences. We disprove the so-called Happy Leaf Conjecture and demonstrate the importance of swapping tokens that are already placed at the correct vertices. We also prove that a generalization of the problem to weighted coloured token swapping is NP-hard on trees but solvable in polynomial time on paths and stars. AU - Masárová, Zuzana ID - 7944 KW - reconfiguration KW - reconfiguration graph KW - triangulations KW - flip KW - constrained triangulations KW - shellability KW - piecewise-linear balls KW - token swapping KW - trees KW - coloured weighted token swapping SN - 2663-337X TI - Reconfiguration problems ER - TY - JOUR AB - Inspired by the possibility to experimentally manipulate and enhance chemical reactivity in helium nanodroplets, we investigate the effective interaction and the resulting correlations between two diatomic molecules immersed in a bath of bosons. By analogy with the bipolaron, we introduce the biangulon quasiparticle describing two rotating molecules that align with respect to each other due to the effective attractive interaction mediated by the excitations of the bath. We study this system in different parameter regimes and apply several theoretical approaches to describe its properties. Using a Born–Oppenheimer approximation, we investigate the dependence of the effective intermolecular interaction on the rotational state of the two molecules. In the strong-coupling regime, a product-state ansatz shows that the molecules tend to have a strong alignment in the ground state. To investigate the system in the weak-coupling regime, we apply a one-phonon excitation variational ansatz, which allows us to access the energy spectrum. In comparison to the angulon quasiparticle, the biangulon shows shifted angulon instabilities and an additional spectral instability, where resonant angular momentum transfer between the molecules and the bath takes place. These features are proposed as an experimentally observable signature for the formation of the biangulon quasiparticle. Finally, by using products of single angulon and bare impurity wave functions as basis states, we introduce a diagonalization scheme that allows us to describe the transition from two separated angulons to a biangulon as a function of the distance between the two molecules. AU - Li, Xiang AU - Yakaboylu, Enderalp AU - Bighin, Giacomo AU - Schmidt, Richard AU - Lemeshko, Mikhail AU - Deuchert, Andreas ID - 8587 IS - 16 JF - The Journal of Chemical Physics KW - Physical and Theoretical Chemistry KW - General Physics and Astronomy SN - 0021-9606 TI - Intermolecular forces and correlations mediated by a phonon bath VL - 152 ER - TY - THES AB - One of the most striking hallmarks of the eukaryotic cell is the presence of intracellular vesicles and organelles. Each of these membrane-enclosed compartments has a distinct composition of lipids and proteins, which is essential for accurate membrane traffic and homeostasis. Interestingly, their biochemical identities are achieved with the help of small GTPases of the Rab family, which cycle between GDP- and GTP-bound forms on the selected membrane surface. While this activity switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate decisive signal propagation in space and time is unclear. In my PhD thesis, I present in vitro reconstitution experiments with theoretical modeling to systematically study a minimal Rab5 activation network from bottom-up. We find that positive feedback based on known molecular interactions gives rise to bistable GTPase activity switching on system’s scale. Furthermore, we determine that collective transition near the critical point is intrinsically stochastic and provide evidence that the inactive Rab5 abundance on the membrane can shape the network response. Finally, we demonstrate that collective switching can spread on the lipid bilayer as a traveling activation wave, representing a possible emergent activity pattern in endosomal maturation. Together, our findings reveal new insights into the self-organization properties of signaling networks away from chemical equilibrium. Our work highlights the importance of systematic characterization of biochemical systems in well-defined physiological conditions. This way, we were able to answer long-standing open questions in the field and close the gap between regulatory processes on a molecular scale and emergent responses on system’s level. AU - Bezeljak, Urban ID - 8341 SN - 2663-337X TI - In vitro reconstitution of a Rab activation switch ER - TY - JOUR AB - The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell. AU - Bezeljak, Urban AU - Loya, Hrushikesh AU - Kaczmarek, Beata M AU - Saunders, Timothy E. AU - Loose, Martin ID - 7580 IS - 12 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Stochastic activation and bistability in a Rab GTPase regulatory network VL - 117 ER - TY - THES AB - Algorithms in computational 3-manifold topology typically take a triangulation as an input and return topological information about the underlying 3-manifold. However, extracting the desired information from a triangulation (e.g., evaluating an invariant) is often computationally very expensive. In recent years this complexity barrier has been successfully tackled in some cases by importing ideas from the theory of parameterized algorithms into the realm of 3-manifolds. Various computationally hard problems were shown to be efficiently solvable for input triangulations that are sufficiently “tree-like.” In this thesis we focus on the key combinatorial parameter in the above context: we consider the treewidth of a compact, orientable 3-manifold, i.e., the smallest treewidth of the dual graph of any triangulation thereof. By building on the work of Scharlemann–Thompson and Scharlemann–Schultens–Saito on generalized Heegaard splittings, and on the work of Jaco–Rubinstein on layered triangulations, we establish quantitative relations between the treewidth and classical topological invariants of a 3-manifold. In particular, among other results, we show that the treewidth of a closed, orientable, irreducible, non-Haken 3-manifold is always within a constant factor of its Heegaard genus. AU - Huszár, Kristóf ID - 8032 SN - 2663-337X TI - Combinatorial width parameters for 3-dimensional manifolds ER - TY - CONF AB - This paper presents a foundation for refining concurrent programs with structured control flow. The verification problem is decomposed into subproblems that aid interactive program development, proof reuse, and automation. The formalization in this paper is the basis of a new design and implementation of the Civl verifier. AU - Kragl, Bernhard AU - Qadeer, Shaz AU - Henzinger, Thomas A ID - 8195 SN - 0302-9743 T2 - Computer Aided Verification TI - Refinement for structured concurrent programs VL - 12224 ER - TY - CONF AB - Asynchronous programs are notoriously difficult to reason about because they spawn computation tasks which take effect asynchronously in a nondeterministic way. Devising inductive invariants for such programs requires understanding and stating complex relationships between an unbounded number of computation tasks in arbitrarily long executions. In this paper, we introduce inductive sequentialization, a new proof rule that sidesteps this complexity via a sequential reduction, a sequential program that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed. We have implemented and integrated our proof rule in the CIVL verifier, allowing us to provably derive fine-grained implementations of asynchronous programs. We have successfully applied our proof rule to a diverse set of message-passing protocols, including leader election protocols, two-phase commit, and Paxos. AU - Kragl, Bernhard AU - Enea, Constantin AU - Henzinger, Thomas A AU - Mutluergil, Suha Orhun AU - Qadeer, Shaz ID - 8012 SN - 9781450376136 T2 - Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation TI - Inductive sequentialization of asynchronous programs ER - TY - THES AB - During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This so-called Z-ring acts as a scaffold recruiting several division-related proteins to mid-cell and plays a key role in distributing proteins at the division site, a feature driven by the treadmilling motion of FtsZ filaments around the septum. What regulates the architecture, dynamics and stability of the Z-ring is still poorly understood, but FtsZ-associated proteins (Zaps) are known to play an important role. Advances in fluorescence microscopy and in vitro reconstitution experiments have helped to shed light into some of the dynamic properties of these complex systems, but methods that allow to collect and analyze large quantitative data sets of the underlying polymer dynamics are still missing. Here, using an in vitro reconstitution approach, we studied how different Zaps affect FtsZ filament dynamics and organization into large-scale patterns, giving special emphasis to the role of the well-conserved protein ZapA. For this purpose, we use high-resolution fluorescence microscopy combined with novel image analysis workfows to study pattern organization and polymerization dynamics of active filaments. We quantified the influence of Zaps on FtsZ on three diferent spatial scales: the large-scale organization of the membrane-bound filament network, the underlying polymerization dynamics and the behavior of single molecules. We found that ZapA cooperatively increases the spatial order of the filament network, binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner, without compromising filament dynamics. Furthermore, we believe that our automated quantitative methods can be used to analyze a large variety of dynamic cytoskeletal systems, using standard time-lapse movies of homogeneously labeled proteins obtained from experiments in vitro or even inside the living cell. AU - Dos Santos Caldas, Paulo R ID - 8358 SN - 2663-337X TI - Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers ER - TY - CONF AB - Even though Delaunay originally introduced his famous triangulations in the case of infinite point sets with translational periodicity, a software that computes such triangulations in the general case is not yet available, to the best of our knowledge. Combining and generalizing previous work, we present a practical algorithm for computing such triangulations. The algorithm has been implemented and experiments show that its performance is as good as the one of the CGAL package, which is restricted to cubic periodicity. AU - Osang, Georg F AU - Rouxel-Labbé, Mael AU - Teillaud, Monique ID - 8703 SN - 18688969 T2 - 28th Annual European Symposium on Algorithms TI - Generalizing CGAL periodic Delaunay triangulations VL - 173 ER - TY - CONF AB - We address the following question: How redundant is the parameterisation of ReLU networks? Specifically, we consider transformations of the weight space which leave the function implemented by the network intact. Two such transformations are known for feed-forward architectures: permutation of neurons within a layer, and positive scaling of all incoming weights of a neuron coupled with inverse scaling of its outgoing weights. In this work, we show for architectures with non-increasing widths that permutation and scaling are in fact the only function-preserving weight transformations. For any eligible architecture we give an explicit construction of a neural network such that any other network that implements the same function can be obtained from the original one by the application of permutations and rescaling. The proof relies on a geometric understanding of boundaries between linear regions of ReLU networks, and we hope the developed mathematical tools are of independent interest. AU - Bui Thi Mai, Phuong AU - Lampert, Christoph ID - 7481 T2 - 8th International Conference on Learning Representations TI - Functional vs. parametric equivalence of ReLU networks ER - TY - JOUR AB - We consider the Pekar functional on a ball in ℝ3. We prove uniqueness of minimizers, and a quadratic lower bound in terms of the distance to the minimizer. The latter follows from nondegeneracy of the Hessian at the minimum. AU - Feliciangeli, Dario AU - Seiringer, Robert ID - 9781 IS - 1 JF - SIAM Journal on Mathematical Analysis KW - Applied Mathematics KW - Computational Mathematics KW - Analysis SN - 0036-1410 TI - Uniqueness and nondegeneracy of minimizers of the Pekar functional on a ball VL - 52 ER - TY - JOUR AB - In the present work, we consider the evolution of two fluids separated by a sharp interface in the presence of surface tension—like, for example, the evolution of oil bubbles in water. Our main result is a weak–strong uniqueness principle for the corresponding free boundary problem for the incompressible Navier–Stokes equation: as long as a strong solution exists, any varifold solution must coincide with it. In particular, in the absence of physical singularities, the concept of varifold solutions—whose global in time existence has been shown by Abels (Interfaces Free Bound 9(1):31–65, 2007) for general initial data—does not introduce a mechanism for non-uniqueness. The key ingredient of our approach is the construction of a relative entropy functional capable of controlling the interface error. If the viscosities of the two fluids do not coincide, even for classical (strong) solutions the gradient of the velocity field becomes discontinuous at the interface, introducing the need for a careful additional adaption of the relative entropy. AU - Fischer, Julian L AU - Hensel, Sebastian ID - 7489 JF - Archive for Rational Mechanics and Analysis SN - 00039527 TI - Weak–strong uniqueness for the Navier–Stokes equation for two fluids with surface tension VL - 236 ER - TY - GEN AB - We prove that in the absence of topological changes, the notion of BV solutions to planar multiphase mean curvature flow does not allow for a mechanism for (unphysical) non-uniqueness. Our approach is based on the local structure of the energy landscape near a classical evolution by mean curvature. Mean curvature flow being the gradient flow of the surface energy functional, we develop a gradient-flow analogue of the notion of calibrations. Just like the existence of a calibration guarantees that one has reached a global minimum in the energy landscape, the existence of a "gradient flow calibration" ensures that the route of steepest descent in the energy landscape is unique and stable. AU - Fischer, Julian L AU - Hensel, Sebastian AU - Laux, Tim AU - Simon, Thilo ID - 10012 T2 - arXiv TI - The local structure of the energy landscape in multiphase mean curvature flow: weak-strong uniqueness and stability of evolutions ER - TY - JOUR AB - The superconducting circuit community has recently discovered the promising potential of superinductors. These circuit elements have a characteristic impedance exceeding the resistance quantum RQ ≈ 6.45 kΩ which leads to a suppression of ground state charge fluctuations. Applications include the realization of hardware protected qubits for fault tolerant quantum computing, improved coupling to small dipole moment objects and defining a new quantum metrology standard for the ampere. In this work we refute the widespread notion that superinductors can only be implemented based on kinetic inductance, i.e. using disordered superconductors or Josephson junction arrays. We present modeling, fabrication and characterization of 104 planar aluminum coil resonators with a characteristic impedance up to 30.9 kΩ at 5.6 GHz and a capacitance down to ≤ 1 fF, with lowloss and a power handling reaching 108 intra-cavity photons. Geometric superinductors are free of uncontrolled tunneling events and offer high reproducibility, linearity and the ability to couple magnetically - properties that significantly broaden the scope of future quantum circuits. AU - Peruzzo, Matilda AU - Trioni, Andrea AU - Hassani, Farid AU - Zemlicka, Martin AU - Fink, Johannes M ID - 8755 IS - 4 JF - Physical Review Applied TI - Surpassing the resistance quantum with a geometric superinductor VL - 14 ER - TY - JOUR AB - This paper deals with dynamical optimal transport metrics defined by spatial discretisation of the Benamou–Benamou formula for the Kantorovich metric . Such metrics appear naturally in discretisations of -gradient flow formulations for dissipative PDE. However, it has recently been shown that these metrics do not in general converge to , unless strong geometric constraints are imposed on the discrete mesh. In this paper we prove that, in a 1-dimensional periodic setting, discrete transport metrics converge to a limiting transport metric with a non-trivial effective mobility. This mobility depends sensitively on the geometry of the mesh and on the non-local mobility at the discrete level. Our result quantifies to what extent discrete transport can make use of microstructure in the mesh to reduce the cost of transport. AU - Gladbach, Peter AU - Kopfer, Eva AU - Maas, Jan AU - Portinale, Lorenzo ID - 7573 IS - 7 JF - Journal de Mathematiques Pures et Appliquees SN - 00217824 TI - Homogenisation of one-dimensional discrete optimal transport VL - 139 ER - TY - GEN AB - We consider finite-volume approximations of Fokker-Planck equations on bounded convex domains in R^d and study the corresponding gradient flow structures. We reprove the convergence of the discrete to continuous Fokker-Planck equation via the method of Evolutionary Γ-convergence, i.e., we pass to the limit at the level of the gradient flow structures, generalising the one-dimensional result obtained by Disser and Liero. The proof is of variational nature and relies on a Mosco convergence result for functionals in the discrete-to-continuum limit that is of independent interest. Our results apply to arbitrary regular meshes, even though the associated discrete transport distances may fail to converge to the Wasserstein distance in this generality. AU - Forkert, Dominik L AU - Maas, Jan AU - Portinale, Lorenzo ID - 10022 T2 - arXiv TI - Evolutionary Γ-convergence of entropic gradient flow structures for Fokker-Planck equations in multiple dimensions ER - TY - CONF AB - We study the problem of learning from multiple untrusted data sources, a scenario of increasing practical relevance given the recent emergence of crowdsourcing and collaborative learning paradigms. Specifically, we analyze the situation in which a learning system obtains datasets from multiple sources, some of which might be biased or even adversarially perturbed. It is known that in the single-source case, an adversary with the power to corrupt a fixed fraction of the training data can prevent PAC-learnability, that is, even in the limit of infinitely much training data, no learning system can approach the optimal test error. In this work we show that, surprisingly, the same is not true in the multi-source setting, where the adversary can arbitrarily corrupt a fixed fraction of the data sources. Our main results are a generalization bound that provides finite-sample guarantees for this learning setting, as well as corresponding lower bounds. Besides establishing PAC-learnability our results also show that in a cooperative learning setting sharing data with other parties has provable benefits, even if some participants are malicious. AU - Konstantinov, Nikola H AU - Frantar, Elias AU - Alistarh, Dan-Adrian AU - Lampert, Christoph ID - 8724 SN - 2640-3498 T2 - Proceedings of the 37th International Conference on Machine Learning TI - On the sample complexity of adversarial multi-source PAC learning VL - 119 ER - TY - JOUR AB - Determining the phase diagram of systems consisting of smaller subsystems 'connected' via a tunable coupling is a challenging task relevant for a variety of physical settings. A general question is whether new phases, not present in the uncoupled limit, may arise. We use machine learning and a suitable quasidistance between different points of the phase diagram to study layered spin models, in which the spin variables constituting each of the uncoupled systems (to which we refer as layers) are coupled to each other via an interlayer coupling. In such systems, in general, composite order parameters involving spins of different layers may emerge as a consequence of the interlayer coupling. We focus on the layered Ising and Ashkin–Teller models as a paradigmatic case study, determining their phase diagram via the application of a machine learning algorithm to the Monte Carlo data. Remarkably our technique is able to correctly characterize all the system phases also in the case of hidden order parameters, i.e. order parameters whose expression in terms of the microscopic configurations would require additional preprocessing of the data fed to the algorithm. We correctly retrieve the three known phases of the Ashkin–Teller model with ferromagnetic couplings, including the phase described by a composite order parameter. For the bilayer and trilayer Ising models the phases we find are only the ferromagnetic and the paramagnetic ones. Within the approach we introduce, owing to the construction of convolutional neural networks, naturally suitable for layered image-like data with arbitrary number of layers, no preprocessing of the Monte Carlo data is needed, also with regard to its spatial structure. The physical meaning of our results is discussed and compared with analytical data, where available. Yet, the method can be used without any a priori knowledge of the phases one seeks to find and can be applied to other models and structures. AU - Rzadkowski, Wojciech AU - Defenu, N AU - Chiacchiera, S AU - Trombettoni, A AU - Bighin, Giacomo ID - 8644 IS - 9 JF - New Journal of Physics SN - 13672630 TI - Detecting composite orders in layered models via machine learning VL - 22 ER - TY - JOUR AB - We consider the quantum mechanical many-body problem of a single impurity particle immersed in a weakly interacting Bose gas. The impurity interacts with the bosons via a two-body potential. We study the Hamiltonian of this system in the mean-field limit and rigorously show that, at low energies, the problem is well described by the Fröhlich polaron model. AU - Mysliwy, Krzysztof AU - Seiringer, Robert ID - 8705 IS - 12 JF - Annales Henri Poincare SN - 1424-0637 TI - Microscopic derivation of the Fröhlich Hamiltonian for the Bose polaron in the mean-field limit VL - 21 ER - TY - JOUR AB - Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models. AU - Grah, Rok AU - Friedlander, Tamar ID - 7569 IS - 2 JF - PLOS Computational Biology SN - 1553-7358 TI - The relation between crosstalk and gene regulation form revisited VL - 16 ER - TY - GEN AB - In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation. AU - Santini, Laura AU - Halbritter, Florian AU - Titz-Teixeira, Fabian AU - Suzuki, Toru AU - Asami, Maki AU - Ramesmayer, Julia AU - Ma, Xiaoyan AU - Lackner, Andreas AU - Warr, Nick AU - Pauler, Florian AU - Hippenmeyer, Simon AU - Laue, Ernest AU - Farlik, Matthias AU - Bock, Christoph AU - Beyer, Andreas AU - Perry, Anthony C. F. AU - Leeb, Martin ID - 8813 T2 - bioRxiv TI - Novel imprints in mouse blastocysts are predominantly DNA methylation independent ER - TY - GEN AU - Grah, Rok AU - Friedlander, Tamar ID - 9777 TI - Maximizing crosstalk ER - TY - THES AB - Designing and verifying concurrent programs is a notoriously challenging, time consuming, and error prone task, even for experts. This is due to the sheer number of possible interleavings of a concurrent program, all of which have to be tracked and accounted for in a formal proof. Inventing an inductive invariant that captures all interleavings of a low-level implementation is theoretically possible, but practically intractable. We develop a refinement-based verification framework that provides mechanisms to simplify proof construction by decomposing the verification task into smaller subtasks. In a first line of work, we present a foundation for refinement reasoning over structured concurrent programs. We introduce layered concurrent programs as a compact notation to represent multi-layer refinement proofs. A layered concurrent program specifies a sequence of connected concurrent programs, from most concrete to most abstract, such that common parts of different programs are written exactly once. Each program in this sequence is expressed as structured concurrent program, i.e., a program over (potentially recursive) procedures, imperative control flow, gated atomic actions, structured parallelism, and asynchronous concurrency. This is in contrast to existing refinement-based verifiers, which represent concurrent systems as flat transition relations. We present a powerful refinement proof rule that decomposes refinement checking over structured programs into modular verification conditions. Refinement checking is supported by a new form of modular, parameterized invariants, called yield invariants, and a linear permission system to enhance local reasoning. In a second line of work, we present two new reduction-based program transformations that target asynchronous programs. These transformations reduce the number of interleavings that need to be considered, thus reducing the complexity of invariants. Synchronization simplifies the verification of asynchronous programs by introducing the fiction, for proof purposes, that asynchronous operations complete synchronously. Synchronization summarizes an asynchronous computation as immediate atomic effect. Inductive sequentialization establishes sequential reductions that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed. Our approach is implemented the CIVL verifier, which has been successfully used for the verification of several complex concurrent programs. In our methodology, the overall correctness of a program is established piecemeal by focusing on the invariant required for each refinement step separately. While the programmer does the creative work of specifying the chain of programs and the inductive invariant justifying each link in the chain, the tool automatically constructs the verification conditions underlying each refinement step. AU - Kragl, Bernhard ID - 8332 SN - 2663-337X TI - Verifying concurrent programs: Refinement, synchronization, sequentialization ER - TY - JOUR AB - We consider dynamical transport metrics for probability measures on discretisations of a bounded convex domain in ℝd. These metrics are natural discrete counterparts to the Kantorovich metric 𝕎2, defined using a Benamou-Brenier type formula. Under mild assumptions we prove an asymptotic upper bound for the discrete transport metric Wt in terms of 𝕎2, as the size of the mesh T tends to 0. However, we show that the corresponding lower bound may fail in general, even on certain one-dimensional and symmetric two-dimensional meshes. In addition, we show that the asymptotic lower bound holds under an isotropy assumption on the mesh, which turns out to be essentially necessary. This assumption is satisfied, e.g., for tilings by convex regular polygons, and it implies Gromov-Hausdorff convergence of the transport metric. AU - Gladbach, Peter AU - Kopfer, Eva AU - Maas, Jan ID - 71 IS - 3 JF - SIAM Journal on Mathematical Analysis SN - 00361410 TI - Scaling limits of discrete optimal transport VL - 52 ER - TY - JOUR AB - We introduce dynamically warping grids for adaptive liquid simulation. Our primary contributions are a strategy for dynamically deforming regular grids over the course of a simulation and a method for efficiently utilizing these deforming grids for liquid simulation. Prior work has shown that unstructured grids are very effective for adaptive fluid simulations. However, unstructured grids often lead to complicated implementations and a poor cache hit rate due to inconsistent memory access. Regular grids, on the other hand, provide a fast, fixed memory access pattern and straightforward implementation. Our method combines the advantages of both: we leverage the simplicity of regular grids while still achieving practical and controllable spatial adaptivity. We demonstrate that our method enables adaptive simulations that are fast, flexible, and robust to null-space issues. At the same time, our method is simple to implement and takes advantage of existing highly-tuned algorithms. AU - Hikaru, Ibayashi AU - Wojtan, Christopher J AU - Thuerey, Nils AU - Igarashi, Takeo AU - Ando, Ryoichi ID - 5681 IS - 6 JF - IEEE Transactions on Visualization and Computer Graphics SN - 10772626 TI - Simulating liquids on dynamically warping grids VL - 26 ER - TY - THES AB - The oft-quoted dictum by Arthur Schawlow: ``A diatomic molecule has one atom too many'' has been disavowed. Inspired by the possibility to experimentally manipulate and enhance chemical reactivity in helium nanodroplets, we investigate the rotation of coupled cold molecules in the presence of a many-body environment. In this thesis, we introduce new variational approaches to quantum impurities and apply them to the Fröhlich polaron - a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon - a quasiparticle formed out of a rotating molecule in a bosonic bath. With this theoretical toolbox, we reveal the self-localization transition for the angulon quasiparticle. We show that, unlike for polarons, self-localization of angulons occurs at finite impurity-bath coupling already at the mean-field level. The transition is accompanied by the spherical-symmetry breaking of the angulon ground state and a discontinuity in the first derivative of the ground-state energy. Moreover, the type of symmetry breaking is dictated by the symmetry of the microscopic impurity-bath interaction, which leads to a number of distinct self-localized states. For the system containing multiple impurities, by analogy with the bipolaron, we introduce the biangulon quasiparticle describing two rotating molecules that align with respect to each other due to the effective attractive interaction mediated by the excitations of the bath. We study this system from the strong-coupling regime to the weak molecule-bath interaction regime. We show that the molecules tend to have a strong alignment in the ground state, the biangulon shows shifted angulon instabilities and an additional spectral instability, where resonant angular momentum transfer between the molecules and the bath takes place. Finally, we introduce a diagonalization scheme that allows us to describe the transition from two separated angulons to a biangulon as a function of the distance between the two molecules. AU - Li, Xiang ID - 8958 SN - 2663-337X TI - Rotation of coupled cold molecules in the presence of a many-body environment ER - TY - THES AB - Form versus function is a long-standing debate in various design-related fields, such as architecture as well as graphic and industrial design. A good design that balances form and function often requires considerable human effort and collaboration among experts from different professional fields. Computational design tools provide a new paradigm for designing functional objects. In computational design, form and function are represented as mathematical quantities, with the help of numerical and combinatorial algorithms, they can assist even novice users in designing versatile models that exhibit their desired functionality. This thesis presents three disparate research studies on the computational design of functional objects: The appearance of 3d print—we optimize the volumetric material distribution for faithfully replicating colored surface texture in 3d printing; the dynamic motion of mechanical structures— our design system helps the novice user to retarget various mechanical templates with different functionality to complex 3d shapes; and a more abstract functionality, multistability—our algorithm automatically generates models that exhibit multiple stable target poses. For each of these cases, our computational design tools not only ensure the functionality of the results but also permit the user aesthetic freedom over the form. Moreover, fabrication constraints were taken into account, which allow for the immediate creation of physical realization via 3D printing or laser cutting. AU - Zhang, Ran ID - 8386 SN - 2663-337X TI - Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability ER - TY - THES AB - Quantum computation enables the execution of algorithms that have exponential complexity. This might open the path towards the synthesis of new materials or medical drugs, optimization of transport or financial strategies etc., intractable on even the fastest classical computers. A quantum computer consists of interconnected two level quantum systems, called qubits, that satisfy DiVincezo’s criteria. Worldwide, there are ongoing efforts to find the qubit architecture which will unite quantum error correction compatible single and two qubit fidelities, long distance qubit to qubit coupling and calability. Superconducting qubits have gone the furthest in this race, demonstrating an algorithm running on 53 coupled qubits, but still the fidelities are not even close to those required for realizing a single logical qubit. emiconductor qubits offer extremely good characteristics, but they are currently investigated across different platforms. Uniting those good characteristics into a single platform might be a big step towards the quantum computer realization. Here we describe the implementation of a hole spin qubit hosted in a Ge hut wire double quantum dot. The high and tunable spin-orbit coupling together with a heavy hole state character is expected to allow fast spin manipulation and long coherence times. Furthermore large lever arms, for hut wire devices, should allow good coupling to superconducting resonators enabling efficient long distance spin to spin coupling and a sensitive gate reflectometry spin readout. The developed cryogenic setup (printed circuit board sample holders, filtering, high-frequency wiring) enabled us to perform low temperature spin dynamics experiments. Indeed, we measured the fastest single spin qubit Rabi frequencies reported so far, reaching 140 MHz, while the dephasing times of 130 ns oppose the long decoherence predictions. In order to further investigate this, a double quantum dot gate was connected directly to a lumped element resonator which enabled gate reflectometry readout. The vanishing inter-dot transition signal, for increasing external magnetic field, revealed the spin nature of the measured quantity. AU - Kukucka, Josip ID - 7996 SN - 2663-337X TI - Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing ER - TY - CONF AB - We study turn-based stochastic zero-sum games with lexicographic preferences over reachability and safety objectives. Stochastic games are standard models in control, verification, and synthesis of stochastic reactive systems that exhibit both randomness as well as angelic and demonic non-determinism. Lexicographic order allows to consider multiple objectives with a strict preference order over the satisfaction of the objectives. To the best of our knowledge, stochastic games with lexicographic objectives have not been studied before. We establish determinacy of such games and present strategy and computational complexity results. For strategy complexity, we show that lexicographically optimal strategies exist that are deterministic and memory is only required to remember the already satisfied and violated objectives. For a constant number of objectives, we show that the relevant decision problem is in NP∩coNP , matching the current known bound for single objectives; and in general the decision problem is PSPACE -hard and can be solved in NEXPTIME∩coNEXPTIME . We present an algorithm that computes the lexicographically optimal strategies via a reduction to computation of optimal strategies in a sequence of single-objectives games. We have implemented our algorithm and report experimental results on various case studies. AU - Chatterjee, Krishnendu AU - Katoen, Joost P AU - Weininger, Maximilian AU - Winkler, Tobias ID - 8272 SN - 03029743 T2 - International Conference on Computer Aided Verification TI - Stochastic games with lexicographic reachability-safety objectives VL - 12225 ER - TY - CHAP AB - The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a nonbiased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material. AU - Dos Santos Caldas, Paulo R AU - Radler, Philipp AU - Sommer, Christoph M AU - Loose, Martin ED - Tran, Phong ID - 7572 SN - 0091679X T2 - Methods in Cell Biology TI - Computational analysis of filament polymerization dynamics in cytoskeletal networks VL - 158 ER - TY - JOUR AB - Most bacteria accomplish cell division with the help of a dynamic protein complex called the divisome, which spans the cell envelope in the plane of division. Assembly and activation of this machinery are coordinated by the tubulin-related GTPase FtsZ, which was found to form treadmilling filaments on supported bilayers in vitro1, as well as in live cells, in which filaments circle around the cell division site2,3. Treadmilling of FtsZ is thought to actively move proteins around the division septum, thereby distributing peptidoglycan synthesis and coordinating the inward growth of the septum to form the new poles of the daughter cells4. However, the molecular mechanisms underlying this function are largely unknown. Here, to study how FtsZ polymerization dynamics are coupled to downstream proteins, we reconstituted part of the bacterial cell division machinery using its purified components FtsZ, FtsA and truncated transmembrane proteins essential for cell division. We found that the membrane-bound cytosolic peptides of FtsN and FtsQ co-migrated with treadmilling FtsZ–FtsA filaments, but despite their directed collective behaviour, individual peptides showed random motion and transient confinement. Our work suggests that divisome proteins follow treadmilling FtsZ filaments by a diffusion-and-capture mechanism, which can give rise to a moving zone of signalling activity at the division site. AU - Baranova, Natalia S. AU - Radler, Philipp AU - Hernández-Rocamora, Víctor M. AU - Alfonso, Carlos AU - Lopez Pelegrin, Maria D AU - Rivas, Germán AU - Vollmer, Waldemar AU - Loose, Martin ID - 7387 JF - Nature Microbiology SN - 2058-5276 TI - Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments and cell division proteins VL - 5 ER - TY - JOUR AB - Fejes Tóth [3] studied approximations of smooth surfaces in three-space by piecewise flat triangular meshes with a given number of vertices on the surface that are optimal with respect to Hausdorff distance. He proves that this Hausdorff distance decreases inversely proportional with the number of vertices of the approximating mesh if the surface is convex. He also claims that this Hausdorff distance is inversely proportional to the square of the number of vertices for a specific non-convex surface, namely a one-sheeted hyperboloid of revolution bounded by two congruent circles. We refute this claim, and show that the asymptotic behavior of the Hausdorff distance is linear, that is the same as for convex surfaces. AU - Vegter, Gert AU - Wintraecken, Mathijs ID - 8163 IS - 2 JF - Studia Scientiarum Mathematicarum Hungarica SN - 0081-6906 TI - Refutation of a claim made by Fejes Tóth on the accuracy of surface meshes VL - 57 ER - TY - JOUR AB - We study relations between evidence theory and S-approximation spaces. Both theories have their roots in the analysis of Dempsterchr('39')s multivalued mappings and lower and upper probabilities, and have close relations to rough sets. We show that an S-approximation space, satisfying a monotonicity condition, can induce a natural belief structure which is a fundamental block in evidence theory. We also demonstrate that one can induce a natural belief structure on one set, given a belief structure on another set, if the two sets are related by a partial monotone S-approximation space. AU - Shakiba, A. AU - Goharshady, Amir Kafshdar AU - Hooshmandasl, M.R. AU - Alambardar Meybodi, M. ID - 8671 IS - 2 JF - Iranian Journal of Mathematical Sciences and Informatics SN - 1735-4463 TI - A note on belief structures and s-approximation spaces VL - 15 ER - TY - JOUR AB - The strong rate of convergence of the Euler-Maruyama scheme for nondegenerate SDEs with irregular drift coefficients is considered. In the case of α-Hölder drift in the recent literature the rate α/2 was proved in many related situations. By exploiting the regularising effect of the noise more efficiently, we show that the rate is in fact arbitrarily close to 1/2 for all α>0. The result extends to Dini continuous coefficients, while in d=1 also to all bounded measurable coefficients. AU - Dareiotis, Konstantinos AU - Gerencser, Mate ID - 6359 JF - Electronic Journal of Probability TI - On the regularisation of the noise for the Euler-Maruyama scheme with irregular drift VL - 25 ER - TY - THES AB - Deep neural networks have established a new standard for data-dependent feature extraction pipelines in the Computer Vision literature. Despite their remarkable performance in the standard supervised learning scenario, i.e. when models are trained with labeled data and tested on samples that follow a similar distribution, neural networks have been shown to struggle with more advanced generalization abilities, such as transferring knowledge across visually different domains, or generalizing to new unseen combinations of known concepts. In this thesis we argue that, in contrast to the usual black-box behavior of neural networks, leveraging more structured internal representations is a promising direction for tackling such problems. In particular, we focus on two forms of structure. First, we tackle modularity: We show that (i) compositional architectures are a natural tool for modeling reasoning tasks, in that they efficiently capture their combinatorial nature, which is key for generalizing beyond the compositions seen during training. We investigate how to to learn such models, both formally and experimentally, for the task of abstract visual reasoning. Then, we show that (ii) in some settings, modularity allows us to efficiently break down complex tasks into smaller, easier, modules, thereby improving computational efficiency; We study this behavior in the context of generative models for colorization, as well as for small objects detection. Secondly, we investigate the inherently layered structure of representations learned by neural networks, and analyze its role in the context of transfer learning and domain adaptation across visually dissimilar domains. AU - Royer, Amélie ID - 8390 SN - 2663-337X TI - Leveraging structure in Computer Vision tasks for flexible Deep Learning models ER - TY - CONF AB - Numerous methods have been proposed for probabilistic generative modelling of 3D objects. However, none of these is able to produce textured objects, which renders them of limited use for practical tasks. In this work, we present the first generative model of textured 3D meshes. Training such a model would traditionally require a large dataset of textured meshes, but unfortunately, existing datasets of meshes lack detailed textures. We instead propose a new training methodology that allows learning from collections of 2D images without any 3D information. To do so, we train our model to explain a distribution of images by modelling each image as a 3D foreground object placed in front of a 2D background. Thus, it learns to generate meshes that when rendered, produce images similar to those in its training set. A well-known problem when generating meshes with deep networks is the emergence of self-intersections, which are problematic for many use-cases. As a second contribution we therefore introduce a new generation process for 3D meshes that guarantees no self-intersections arise, based on the physical intuition that faces should push one another out of the way as they move. We conduct extensive experiments on our approach, reporting quantitative and qualitative results on both synthetic data and natural images. These show our method successfully learns to generate plausible and diverse textured 3D samples for five challenging object classes. AU - Henderson, Paul M AU - Tsiminaki, Vagia AU - Lampert, Christoph ID - 8186 T2 - Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition TI - Leveraging 2D data to learn textured 3D mesh generation ER - TY - JOUR AB - Earlier, we demonstrated that transcript levels of METAL TOLERANCE PROTEIN2 (MTP2) and of HEAVY METAL ATPase2 (HMA2) increase strongly in roots of Arabidopsis upon prolonged zinc (Zn) deficiency and respond to shoot physiological Zn status, and not to the local Zn status in roots. This provided evidence for shoot-to-root communication in the acclimation of plants to Zn deficiency. Zn-deficient soils limit both the yield and quality of agricultural crops and can result in clinically relevant nutritional Zn deficiency in human populations. Implementing Zn deficiency during cultivation of the model plant Arabidopsis thaliana on agar-solidified media is difficult because trace element contaminations are present in almost all commercially available agars. Here, we demonstrate root morphological acclimations to Zn deficiency on agar-solidified medium following the effective removal of contaminants. These advancements allow reproducible phenotyping toward understanding fundamental plant responses to deficiencies of Zn and other essential trace elements. AU - Sinclair, Scott A AU - Krämer, U. ID - 7416 IS - 1 JF - Plant Signaling & Behavior SN - 1559-2324 TI - Generation of effective zinc-deficient agar-solidified media allows identification of root morphology changes in response to zinc limitation VL - 15 ER - TY - JOUR AB - Retrovirus assembly is driven by the multidomain structural protein Gag. Interactions between the capsid domains (CA) of Gag result in Gag multimerization, leading to an immature virus particle that is formed by a protein lattice based on dimeric, trimeric, and hexameric protein contacts. Among retroviruses the inter- and intra-hexamer contacts differ, especially in the N-terminal sub-domain of CA (CANTD). For HIV-1 the cellular molecule inositol hexakisphosphate (IP6) interacts with and stabilizes the immature hexamer, and is required for production of infectious virus particles. We have used in vitro assembly, cryo-electron tomography and subtomogram averaging, atomistic molecular dynamics simulations and mutational analyses to study the HIV-related lentivirus equine infectious anemia virus (EIAV). In particular, we sought to understand the structural conservation of the immature lentivirus lattice and the role of IP6 in EIAV assembly. Similar to HIV-1, IP6 strongly promoted in vitro assembly of EIAV Gag proteins into virus-like particles (VLPs), which took three morphologically highly distinct forms: narrow tubes, wide tubes, and spheres. Structural characterization of these VLPs to sub-4Å resolution unexpectedly showed that all three morphologies are based on an immature lattice with preserved key structural components, highlighting the structural versatility of CA to form immature assemblies. A direct comparison between EIAV and HIV revealed that both lentiviruses maintain similar immature interfaces, which are established by both conserved and non-conserved residues. In both EIAV and HIV-1, IP6 regulates immature assembly via conserved lysine residues within the CACTD and SP. Lastly, we demonstrate that IP6 stimulates in vitro assembly of immature particles of several other retroviruses in the lentivirus genus, suggesting a conserved role for IP6 in lentiviral assembly. AU - Dick, Robert A. AU - Xu, Chaoyi AU - Morado, Dustin R. AU - Kravchuk, Vladyslav AU - Ricana, Clifton L. AU - Lyddon, Terri D. AU - Broad, Arianna M. AU - Feathers, J. Ryan AU - Johnson, Marc C. AU - Vogt, Volker M. AU - Perilla, Juan R. AU - Briggs, John A. G. AU - Schur, Florian KM ID - 7464 IS - 1 JF - PLOS Pathogens SN - 1553-7374 TI - Structures of immature EIAV Gag lattices reveal a conserved role for IP6 in lentivirus assembly VL - 16 ER - TY - JOUR AB - The fixation probability of a single mutant invading a population of residents is among the most widely-studied quantities in evolutionary dynamics. Amplifiers of natural selection are population structures that increase the fixation probability of advantageous mutants, compared to well-mixed populations. Extensive studies have shown that many amplifiers exist for the Birth-death Moran process, some of them substantially increasing the fixation probability or even guaranteeing fixation in the limit of large population size. On the other hand, no amplifiers are known for the death-Birth Moran process, and computer-assisted exhaustive searches have failed to discover amplification. In this work we resolve this disparity, by showing that any amplification under death-Birth updating is necessarily bounded and transient. Our boundedness result states that even if a population structure does amplify selection, the resulting fixation probability is close to that of the well-mixed population. Our transience result states that for any population structure there exists a threshold r⋆ such that the population structure ceases to amplify selection if the mutant fitness advantage r is larger than r⋆. Finally, we also extend the above results to δ-death-Birth updating, which is a combination of Birth-death and death-Birth updating. On the positive side, we identify population structures that maintain amplification for a wide range of values r and δ. These results demonstrate that amplification of natural selection depends on the specific mechanisms of the evolutionary process. AU - Tkadlec, Josef AU - Pavlogiannis, Andreas AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 7212 JF - PLoS computational biology TI - Limits on amplifiers of natural selection under death-Birth updating VL - 16 ER - TY - THES AB - In this thesis we study certain mathematical aspects of evolution. The two primary forces that drive an evolutionary process are mutation and selection. Mutation generates new variants in a population. Selection chooses among the variants depending on the reproductive rates of individuals. Evolutionary processes are intrinsically random – a new mutation that is initially present in the population at low frequency can go extinct, even if it confers a reproductive advantage. The overall rate of evolution is largely determined by two quantities: the probability that an invading advantageous mutation spreads through the population (called fixation probability) and the time until it does so (called fixation time). Both those quantities crucially depend not only on the strength of the invading mutation but also on the population structure. In this thesis, we aim to understand how the underlying population structure affects the overall rate of evolution. Specifically, we study population structures that increase the fixation probability of advantageous mutants (called amplifiers of selection). Broadly speaking, our results are of three different types: We present various strong amplifiers, we identify regimes under which only limited amplification is feasible, and we propose population structures that provide different tradeoffs between high fixation probability and short fixation time. AU - Tkadlec, Josef ID - 7196 TI - A role of graphs in evolutionary processes ER - TY - CONF AB - The optimization of multilayer neural networks typically leads to a solution with zero training error, yet the landscape can exhibit spurious local minima and the minima can be disconnected. In this paper, we shed light on this phenomenon: we show that the combination of stochastic gradient descent (SGD) and over-parameterization makes the landscape of multilayer neural networks approximately connected and thus more favorable to optimization. More specifically, we prove that SGD solutions are connected via a piecewise linear path, and the increase in loss along this path vanishes as the number of neurons grows large. This result is a consequence of the fact that the parameters found by SGD are increasingly dropout stable as the network becomes wider. We show that, if we remove part of the neurons (and suitably rescale the remaining ones), the change in loss is independent of the total number of neurons, and it depends only on how many neurons are left. Our results exhibit a mild dependence on the input dimension: they are dimension-free for two-layer networks and depend linearly on the dimension for multilayer networks. We validate our theoretical findings with numerical experiments for different architectures and classification tasks. AU - Shevchenko, Alexander AU - Mondelli, Marco ID - 9198 T2 - Proceedings of the 37th International Conference on Machine Learning TI - Landscape connectivity and dropout stability of SGD solutions for over-parameterized neural networks VL - 119 ER - TY - JOUR AB - Representing an atom by a solid sphere in 3-dimensional Euclidean space, we get the space-filling diagram of a molecule by taking the union. Molecular dynamics simulates its motion subject to bonds and other forces, including the solvation free energy. The morphometric approach [12, 17] writes the latter as a linear combination of weighted versions of the volume, area, mean curvature, and Gaussian curvature of the space-filling diagram. We give a formula for the derivative of the weighted mean curvature. Together with the derivatives of the weighted volume in [7], the weighted area in [3], and the weighted Gaussian curvature [1], this yields the derivative of the morphometric expression of the solvation free energy. AU - Akopyan, Arseniy AU - Edelsbrunner, Herbert ID - 9157 IS - 1 JF - Computational and Mathematical Biophysics SN - 2544-7297 TI - The weighted mean curvature derivative of a space-filling diagram VL - 8 ER - TY - JOUR AB - The morphometric approach [11, 14] writes the solvation free energy as a linear combination of weighted versions of the volume, area, mean curvature, and Gaussian curvature of the space-filling diagram. We give a formula for the derivative of the weighted Gaussian curvature. Together with the derivatives of the weighted volume in [7], the weighted area in [4], and the weighted mean curvature in [1], this yields the derivative of the morphometric expression of solvation free energy. AU - Akopyan, Arseniy AU - Edelsbrunner, Herbert ID - 9156 IS - 1 JF - Computational and Mathematical Biophysics SN - 2544-7297 TI - The weighted Gaussian curvature derivative of a space-filling diagram VL - 8 ER - TY - JOUR AB - We consider the symmetric simple exclusion process in Zd with quenched bounded dynamic random conductances and prove its hydrodynamic limit in path space. The main tool is the connection, due to the self-duality of the process, between the invariance principle for single particles starting from all points and the macroscopic behavior of the density field. While the hydrodynamic limit at fixed macroscopic times is obtained via a generalization to the time-inhomogeneous context of the strategy introduced in [41], in order to prove tightness for the sequence of empirical density fields we develop a new criterion based on the notion of uniform conditional stochastic continuity, following [50]. In conclusion, we show that uniform elliptic dynamic conductances provide an example of environments in which the so-called arbitrary starting point invariance principle may be derived from the invariance principle of a single particle starting from the origin. Therefore, our hydrodynamics result applies to the examples of quenched environments considered in, e.g., [1], [3], [6] in combination with the hypothesis of uniform ellipticity. AU - Redig, Frank AU - Saada, Ellen AU - Sau, Federico ID - 8973 JF - Electronic Journal of Probability TI - Symmetric simple exclusion process in dynamic environment: Hydrodynamics VL - 25 ER - TY - JOUR AB - An asymptotic formula is established for the number of rational points of bounded anticanonical height which lie on a certain Zariski dense subset of the biprojective hypersurface x1y21+⋯+x4y24=0 in ℙ3×ℙ3. This confirms the modified Manin conjecture for this variety, in which the removal of a thin set of rational points is allowed. AU - Browning, Timothy D AU - Heath Brown, Roger ID - 179 IS - 16 JF - Duke Mathematical Journal SN - 0012-7094 TI - Density of rational points on a quadric bundle in ℙ3×ℙ3 VL - 169 ER - TY - GEN AB - Data and mathematica notebooks for plotting figures from Language learning with communication between learners AU - Ibsen-Jensen, Rasmus AU - Tkadlec, Josef AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 9814 TI - Data and mathematica notebooks for plotting figures from language learning with communication between learners from language acquisition with communication between learners ER - TY - JOUR AB - We demonstrate the utility of optical cavity generated spin-squeezed states in free space atomic fountain clocks in ensembles of 390 000 87Rb atoms. Fluorescence imaging, correlated to an initial quantum nondemolition measurement, is used for population spectroscopy after the atoms are released from a confining lattice. For a free fall time of 4 milliseconds, we resolve a single-shot phase sensitivity of 814(61) microradians, which is 5.8(0.6) decibels (dB) below the quantum projection limit. We observe that this squeezing is preserved as the cloud expands to a roughly 200  μm radius and falls roughly 300  μm in free space. Ramsey spectroscopy with 240 000 atoms at a 3.6 ms Ramsey time results in a single-shot fractional frequency stability of 8.4(0.2)×10−12, 3.8(0.2) dB below the quantum projection limit. The sensitivity and stability are limited by the technical noise in the fluorescence detection protocol and the microwave system, respectively. AU - Malia, Benjamin K. AU - Martínez-Rincón, Julián AU - Wu, Yunfan AU - Hosten, Onur AU - Kasevich, Mark A. ID - 8285 IS - 4 JF - Physical Review Letters SN - 0031-9007 TI - Free space Ramsey spectroscopy in rubidium with noise below the quantum projection limit VL - 125 ER - TY - CONF AB - The search for biologically faithful synaptic plasticity rules has resulted in a large body of models. They are usually inspired by – and fitted to – experimental data, but they rarely produce neural dynamics that serve complex functions. These failures suggest that current plasticity models are still under-constrained by existing data. Here, we present an alternative approach that uses meta-learning to discover plausible synaptic plasticity rules. Instead of experimental data, the rules are constrained by the functions they implement and the structure they are meant to produce. Briefly, we parameterize synaptic plasticity rules by a Volterra expansion and then use supervised learning methods (gradient descent or evolutionary strategies) to minimize a problem-dependent loss function that quantifies how effectively a candidate plasticity rule transforms an initially random network into one with the desired function. We first validate our approach by re-discovering previously described plasticity rules, starting at the single-neuron level and “Oja’s rule”, a simple Hebbian plasticity rule that captures the direction of most variability of inputs to a neuron (i.e., the first principal component). We expand the problem to the network level and ask the framework to find Oja’s rule together with an anti-Hebbian rule such that an initially random two-layer firing-rate network will recover several principal components of the input space after learning. Next, we move to networks of integrate-and-fire neurons with plastic inhibitory afferents. We train for rules that achieve a target firing rate by countering tuned excitation. Our algorithm discovers a specific subset of the manifold of rules that can solve this task. Our work is a proof of principle of an automated and unbiased approach to unveil synaptic plasticity rules that obey biological constraints and can solve complex functions. AU - Confavreux, Basile J AU - Zenke, Friedemann AU - Agnes, Everton J. AU - Lillicrap, Timothy AU - Vogels, Tim P ID - 9633 SN - 1049-5258 T2 - Advances in Neural Information Processing Systems TI - A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network VL - 33 ER - TY - JOUR AB - The widely used non-steroidal anti-inflammatory drugs (NSAIDs) are derivatives of the phytohormone salicylic acid (SA). SA is well known to regulate plant immunity and development, whereas there have been few reports focusing on the effects of NSAIDs in plants. Our studies here reveal that NSAIDs exhibit largely overlapping physiological activities to SA in the model plant Arabidopsis. NSAID treatments lead to shorter and agravitropic primary roots and inhibited lateral root organogenesis. Notably, in addition to the SA-like action, which in roots involves binding to the protein phosphatase 2A (PP2A), NSAIDs also exhibit PP2A-independent effects. Cell biological and biochemical analyses reveal that many NSAIDs bind directly to and inhibit the chaperone activity of TWISTED DWARF1, thereby regulating actin cytoskeleton dynamics and subsequent endosomal trafficking. Our findings uncover an unexpected bioactivity of human pharmaceuticals in plants and provide insights into the molecular mechanism underlying the cellular action of this class of anti-inflammatory compounds. AU - Tan, Shutang AU - Di Donato, Martin AU - Glanc, Matous AU - Zhang, Xixi AU - Klíma, Petr AU - Liu, Jie AU - Bailly, Aurélien AU - Ferro, Noel AU - Petrášek, Jan AU - Geisler, Markus AU - Friml, Jiří ID - 8943 IS - 9 JF - Cell Reports TI - Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development VL - 33 ER - TY - JOUR AB - Pulsating flows through tubular geometries are laminar provided that velocities are moderate. This in particular is also believed to apply to cardiovascular flows where inertial forces are typically too low to sustain turbulence. On the other hand, flow instabilities and fluctuating shear stresses are held responsible for a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates. Geometrical distortions of small, yet finite, amplitude are found to excite a state consisting of helical vortices during flow deceleration. The resulting flow pattern grows rapidly in magnitude, breaks down into turbulence, and eventually returns to laminar when the flow accelerates. This scenario causes shear stress fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions can adversely affect blood vessels and have been shown to promote inflammation and dysfunction of the shear stress-sensitive endothelial cell layer. AU - Xu, Duo AU - Varshney, Atul AU - Ma, Xingyu AU - Song, Baofang AU - Riedl, Michael AU - Avila, Marc AU - Hof, Björn ID - 7932 IS - 21 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Nonlinear hydrodynamic instability and turbulence in pulsatile flow VL - 117 ER - TY - JOUR AB - We study the unique solution m of the Dyson equation \( -m(z)^{-1} = z\1 - a + S[m(z)] \) on a von Neumann algebra A with the constraint Imm≥0. Here, z lies in the complex upper half-plane, a is a self-adjoint element of A and S is a positivity-preserving linear operator on A. We show that m is the Stieltjes transform of a compactly supported A-valued measure on R. Under suitable assumptions, we establish that this measure has a uniformly 1/3-Hölder continuous density with respect to the Lebesgue measure, which is supported on finitely many intervals, called bands. In fact, the density is analytic inside the bands with a square-root growth at the edges and internal cubic root cusps whenever the gap between two bands vanishes. The shape of these singularities is universal and no other singularity may occur. We give a precise asymptotic description of m near the singular points. These asymptotics generalize the analysis at the regular edges given in the companion paper on the Tracy-Widom universality for the edge eigenvalue statistics for correlated random matrices [the first author et al., Ann. Probab. 48, No. 2, 963--1001 (2020; Zbl 1434.60017)] and they play a key role in the proof of the Pearcey universality at the cusp for Wigner-type matrices [G. Cipolloni et al., Pure Appl. Anal. 1, No. 4, 615--707 (2019; Zbl 07142203); the second author et al., Commun. Math. Phys. 378, No. 2, 1203--1278 (2020; Zbl 07236118)]. We also extend the finite dimensional band mass formula from [the first author et al., loc. cit.] to the von Neumann algebra setting by showing that the spectral mass of the bands is topologically rigid under deformations and we conclude that these masses are quantized in some important cases. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H ID - 14694 JF - Documenta Mathematica KW - General Mathematics SN - 1431-0635 TI - The Dyson equation with linear self-energy: Spectral bands, edges and cusps VL - 25 ER -