@phdthesis{7680, abstract = {Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone. In optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability. Most optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry. This work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment. CBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo.}, author = {Kainrath, Stephanie}, issn = {2663-337X}, pages = {98}, publisher = {Institute of Science and Technology Austria}, title = {{Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals}}, doi = {10.15479/AT:ISTA:7680}, year = {2020}, } @article{7683, abstract = {For any free oriented Borel–Moore homology theory A, we construct an associative product on the A-theory of the stack of Higgs torsion sheaves over a projective curve C. We show that the resulting algebra AHa0C admits a natural shuffle presentation, and prove it is faithful when A is replaced with usual Borel–Moore homology groups. We also introduce moduli spaces of stable triples, heavily inspired by Nakajima quiver varieties, whose A-theory admits an AHa0C-action. These triples can be interpreted as certain sheaves on PC(ωC⊕OC). In particular, we obtain an action of AHa0C on the cohomology of Hilbert schemes of points on T∗C.}, author = {Minets, Sasha}, issn = {14209020}, journal = {Selecta Mathematica, New Series}, number = {2}, publisher = {Springer Nature}, title = {{Cohomological Hall algebras for Higgs torsion sheaves, moduli of triples and sheaves on surfaces}}, doi = {10.1007/s00029-020-00553-x}, volume = {26}, year = {2020}, } @article{7684, author = {Gridchyn, Igor and Schönenberger, Philipp and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {10974199}, journal = {Neuron}, number = {2}, pages = {291--300.e6}, publisher = {Elsevier}, title = {{Assembly-specific disruption of hippocampal replay leads to selective memory deficit}}, doi = {10.1016/j.neuron.2020.01.021}, volume = {106}, year = {2020}, } @article{7686, abstract = {The agricultural green revolution spectacularly enhanced crop yield and lodging resistance with modified DELLA-mediated gibberellin signaling. However, this was achieved at the expense of reduced nitrogen-use efficiency (NUE). Recently, Wu et al. revealed novel gibberellin signaling that provides a blueprint for improving tillering and NUE in Green Revolution varieties (GRVs). }, author = {Xue, Huidan and Zhang, Yuzhou and Xiao, Guanghui}, issn = {1360-1385}, journal = {Trends in Plant Science}, number = {6}, pages = {520--522}, publisher = {Elsevier}, title = {{Neo-gibberellin signaling: Guiding the next generation of the green revolution}}, doi = {10.1016/j.tplants.2020.04.001}, volume = {25}, year = {2020}, } @misc{7689, abstract = {These are the supplementary research data to the publication "Zero field splitting of heavy-hole states in quantum dots". All matrix files have the same format. Within each column the bias voltage is changed. Each column corresponds to either a different gate voltage or magnetic field. The voltage values are given in mV, the current values in pA. Find a specific description in the included Readme file. }, author = {Katsaros, Georgios}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for "Zero field splitting of heavy-hole states in quantum dots"}}, doi = {10.15479/AT:ISTA:7689}, year = {2020}, } @article{7695, abstract = {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.}, author = {Wang, J and Mylle, E and Johnson, Alexander J and Besbrugge, N and De Jaeger, G and Friml, Jiří and Pleskot, R and van Damme, D}, issn = {1532-2548}, journal = {Plant Physiology}, number = {3}, pages = {986--997}, publisher = {American Society of Plant Biologists}, title = {{High temporal resolution reveals simultaneous plasma membrane recruitment of TPLATE complex subunits}}, doi = {10.1104/pp.20.00178}, volume = {183}, year = {2020}, } @article{7697, abstract = {* 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.}, author = {Zhang, Yuzhou and Hartinger, Corinna and Wang, Xiaojuan and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {5}, pages = {1406--1416}, publisher = {Wiley}, title = {{Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters}}, doi = {10.1111/nph.16629}, volume = {227}, year = {2020}, } @article{5681, abstract = {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.}, author = {Hikaru, Ibayashi and Wojtan, Christopher J and Thuerey, Nils and Igarashi, Takeo and Ando, Ryoichi}, issn = {19410506}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {6}, pages = {2288--2302}, publisher = {IEEE}, title = {{Simulating liquids on dynamically warping grids}}, doi = {10.1109/TVCG.2018.2883628}, volume = {26}, year = {2020}, } @article{6184, abstract = {We prove edge universality for a general class of correlated real symmetric or complex Hermitian Wigner matrices with arbitrary expectation. Our theorem also applies to internal edges of the self-consistent density of states. In particular, we establish a strong form of band rigidity which excludes mismatches between location and label of eigenvalues close to internal edges in these general models.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {0091-1798}, journal = {Annals of Probability}, number = {2}, pages = {963--1001}, publisher = {Institute of Mathematical Statistics}, title = {{Correlated random matrices: Band rigidity and edge universality}}, doi = {10.1214/19-AOP1379}, volume = {48}, year = {2020}, } @article{6185, abstract = {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).}, author = {Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, pages = {1203--1278}, publisher = {Springer Nature}, title = {{Cusp universality for random matrices I: Local law and the complex Hermitian case}}, doi = {10.1007/s00220-019-03657-4}, volume = {378}, year = {2020}, } @article{6358, abstract = {We study dynamical optimal transport metrics between density matricesassociated to symmetric Dirichlet forms on finite-dimensional C∗-algebras. Our settingcovers arbitrary skew-derivations and it provides a unified framework that simultaneously generalizes recently constructed transport metrics for Markov chains, Lindblad equations, and the Fermi Ornstein–Uhlenbeck semigroup. We develop a non-nommutative differential calculus that allows us to obtain non-commutative Ricci curvature bounds, logarithmic Sobolev inequalities, transport-entropy inequalities, andspectral gap estimates.}, author = {Carlen, Eric A. and Maas, Jan}, issn = {15729613}, journal = {Journal of Statistical Physics}, number = {2}, pages = {319--378}, publisher = {Springer Nature}, title = {{Non-commutative calculus, optimal transport and functional inequalities in dissipative quantum systems}}, doi = {10.1007/s10955-019-02434-w}, volume = {178}, year = {2020}, } @article{6359, abstract = {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.}, author = {Dareiotis, Konstantinos and Gerencser, Mate}, issn = {1083-6489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{On the regularisation of the noise for the Euler-Maruyama scheme with irregular drift}}, doi = {10.1214/20-EJP479}, volume = {25}, year = {2020}, } @article{6488, abstract = {We prove a central limit theorem for the difference of linear eigenvalue statistics of a sample covariance matrix W˜ and its minor W. We find that the fluctuation of this difference is much smaller than those of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of W˜ and W. Our result identifies the fluctuation of the spatial derivative of the approximate Gaussian field in the recent paper by Dumitru and Paquette. Unlike in a similar result for Wigner matrices, for sample covariance matrices, the fluctuation may entirely vanish.}, author = {Cipolloni, Giorgio and Erdös, László}, issn = {20103271}, journal = {Random Matrices: Theory and Application}, number = {3}, publisher = {World Scientific Publishing}, title = {{Fluctuations for differences of linear eigenvalue statistics for sample covariance matrices}}, doi = {10.1142/S2010326320500069}, volume = {9}, year = {2020}, } @article{6563, abstract = {This paper presents two algorithms. The first decides the existence of a pointed homotopy between given simplicial maps 𝑓,𝑔:𝑋→𝑌, and the second computes the group [𝛴𝑋,𝑌]∗ of pointed homotopy classes of maps from a suspension; in both cases, the target Y is assumed simply connected. More generally, these algorithms work relative to 𝐴⊆𝑋.}, author = {Filakovský, Marek and Vokřínek, Lukas}, issn = {16153383}, journal = {Foundations of Computational Mathematics}, pages = {311--330}, publisher = {Springer Nature}, title = {{Are two given maps homotopic? An algorithmic viewpoint}}, doi = {10.1007/s10208-019-09419-x}, volume = {20}, year = {2020}, } @article{6593, abstract = {We consider the monotone variational inequality problem in a Hilbert space and describe a projection-type method with inertial terms under the following properties: (a) The method generates a strongly convergent iteration sequence; (b) The method requires, at each iteration, only one projection onto the feasible set and two evaluations of the operator; (c) The method is designed for variational inequality for which the underline operator is monotone and uniformly continuous; (d) The method includes an inertial term. The latter is also shown to speed up the convergence in our numerical results. A comparison with some related methods is given and indicates that the new method is promising.}, author = {Shehu, Yekini and Li, Xiao-Huan and Dong, Qiao-Li}, issn = {1572-9265}, journal = {Numerical Algorithms}, pages = {365--388}, publisher = {Springer Nature}, title = {{An efficient projection-type method for monotone variational inequalities in Hilbert spaces}}, doi = {10.1007/s11075-019-00758-y}, volume = {84}, year = {2020}, } @inproceedings{14326, abstract = {Learning object-centric representations of complex scenes is a promising step towards enabling efficient abstract reasoning from low-level perceptual features. Yet, most deep learning approaches learn distributed representations that do not capture the compositional properties of natural scenes. In this paper, we present the Slot Attention module, an architectural component that interfaces with perceptual representations such as the output of a convolutional neural network and produces a set of task-dependent abstract representations which we call slots. These slots are exchangeable and can bind to any object in the input by specializing through a competitive procedure over multiple rounds of attention. We empirically demonstrate that Slot Attention can extract object-centric representations that enable generalization to unseen compositions when trained on unsupervised object discovery and supervised property prediction tasks. }, author = {Locatello, Francesco and Weissenborn, Dirk and Unterthiner, Thomas and Mahendran, Aravindh and Heigold, Georg and Uszkoreit, Jakob and Dosovitskiy, Alexey and Kipf, Thomas}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781713829546}, location = {Virtual}, pages = {11525--11538}, publisher = {Curran Associates}, title = {{Object-centric learning with slot attention}}, volume = {33}, year = {2020}, } @misc{14592, abstract = {Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights into biological processes and structures within a native context. However, a major challenge still lies in the efficient and reproducible preparation of adherent cells for subsequent cryo-EM analysis. This is due to the sensitivity of many cellular specimens to the varying seeding and culturing conditions required for EM experiments, the often limited amount of cellular material and also the fragility of EM grids and their substrate. Here, we present low-cost and reusable 3D printed grid holders, designed to improve specimen preparation when culturing challenging cellular samples directly on grids. The described grid holders increase cell culture reproducibility and throughput, and reduce the resources required for cell culturing. We show that grid holders can be integrated into various cryo-EM workflows, including micro-patterning approaches to control cell seeding on grids, and for generating samples for cryo-focused ion beam milling and cryo-electron tomography experiments. Their adaptable design allows for the generation of specialized grid holders customized to a large variety of applications.}, author = {Schur, Florian KM}, publisher = {Institute of Science and Technology Austria}, title = {{STL-files for 3D-printed grid holders described in Fäßler F, Zens B, et al.; 3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy}}, doi = {10.15479/AT:ISTA:14592}, year = {2020}, } @article{14694, abstract = {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.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, issn = {1431-0643}, journal = {Documenta Mathematica}, keywords = {General Mathematics}, pages = {1421--1539}, publisher = {EMS Press}, title = {{The Dyson equation with linear self-energy: Spectral bands, edges and cusps}}, doi = {10.4171/dm/780}, volume = {25}, year = {2020}, } @article{14891, abstract = {We give the first mathematically rigorous justification of the local density approximation in density functional theory. We provide a quantitative estimate on the difference between the grand-canonical Levy–Lieb energy of a given density (the lowest possible energy of all quantum states having this density) and the integral over the uniform electron gas energy of this density. The error involves gradient terms and justifies the use of the local density approximation in the situation where the density is very flat on sufficiently large regions in space.}, author = {Lewin, Mathieu and Lieb, Elliott H. and Seiringer, Robert}, issn = {2578-5885}, journal = {Pure and Applied Analysis}, number = {1}, pages = {35--73}, publisher = {Mathematical Sciences Publishers}, title = {{ The local density approximation in density functional theory}}, doi = {10.2140/paa.2020.2.35}, volume = {2}, year = {2020}, } @article{15036, abstract = {The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.}, author = {Rosa, Higor Vinícius Dias and Leonardo, Diego Antonio and Brognara, Gabriel and Brandão-Neto, José and D'Muniz Pereira, Humberto and Araújo, Ana Paula Ulian and Garratt, Richard Charles}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology, Structural Biology}, number = {21}, pages = {5784--5801}, publisher = {Elsevier}, title = {{Molecular recognition at septin interfaces: The switches hold the key}}, doi = {10.1016/j.jmb.2020.09.001}, volume = {432}, year = {2020}, }