@inproceedings{17170, abstract = {In this article we extend and strengthen the seminal work by Niyogi, Smale, and Weinberger on the learning of the homotopy type from a sample of an underlying space. In their work, Niyogi, Smale, and Weinberger studied samples of C² manifolds with positive reach embedded in ℝ^d. We extend their results in the following ways: - As the ambient space we consider both ℝ^d and Riemannian manifolds with lower bounded sectional curvature. - In both types of ambient spaces, we study sets of positive reach - a significantly more general setting than C² manifolds - as well as general manifolds of positive reach. - The sample P of a set (or a manifold) 𝒮 of positive reach may be noisy. We work with two one-sided Hausdorff distances - ε and δ - between P and 𝒮. We provide tight bounds in terms of ε and δ, that guarantee that there exists a parameter r such that the union of balls of radius r centred at the sample P deformation-retracts to 𝒮. We exhibit their tightness by an explicit construction. We carefully distinguish the roles of δ and ε. This is not only essential to achieve tight bounds, but also sensible in practical situations, since it allows one to adapt the bound according to sample density and the amount of noise present in the sample separately.}, author = {Attali, Dominique and Kourimska, Hana and Fillmore, Christopher D and Ghosh, Ishika and Lieutier, André and Stephenson, Elizabeth R and Wintraecken, Mathijs}, booktitle = {40th International Symposium on Computational Geometry}, isbn = {9783959773164}, issn = {1868-8969}, location = {Athens, Greece}, pages = {11:1--11:19}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Tight bounds for the learning of homotopy à la Niyogi, Smale, and Weinberger for subsets of euclidean spaces and of Riemannian manifolds}}, doi = {10.4230/LIPIcs.SoCG.2024.11}, volume = {293}, year = {2024}, } @article{17187, abstract = {The generation of diverse cell types during development is fundamental to brain functions. We outline a protocol to quantitatively assess the clonal output of individual neural progenitors using mosaic analysis with double markers (MADM) in mice. We first describe steps to acquire and reconstruct adult MADM clones in the superior colliculus. Then we detail analysis pipelines to determine clonal composition and architecture. This protocol enables the buildup of quantitative frameworks of lineage progression with precise spatial resolution in the brain. For complete details on the use and execution of this protocol, please refer to Cheung et al.1}, author = {Cheung, Giselle T and Streicher, Carmen and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, number = {3}, publisher = {Elsevier}, title = {{Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice}}, doi = {10.1016/j.xpro.2024.103157}, volume = {5}, year = {2024}, } @article{17188, abstract = {In a delegation problem, a principal P with commitment power tries to pick one out of 𝑛 options. Each option is drawn independently from a known distribution. Instead of inspecting the options herself, P delegates the information acquisition to a rational and self-interested agent A. After inspection, A proposes one of the options, and P can accept or reject. Delegation is a classic setting in economic information design with many prominent applications, but the computational problems are only poorly understood. In this paper, we study a natural online variant of delegation, in which the agent searches through the options in an online fashion. For each option, he has to irrevocably decide if he wants to propose the current option or discard it, before seeing information on the next option(s). How can we design algorithms for P that approximate the utility of her best option in hindsight? We show that in general P can obtain a Θ(1∕𝑛)-approximation and extend this result to ratios of Θ(𝑘∕𝑛) in case (1) A has a lookahead of 𝑘 rounds, or (2) A can propose up to 𝑘 different options. We provide fine-grained bounds independent of 𝑛 based on three parameters. If the ratio of maximum and minimum utility for A is bounded by a factor 𝛼, we obtain an Ω(loglog 𝛼∕ log 𝛼)- approximation algorithm, and we show that this is best possible. Additionally, if P cannot distinguish options with the same value for herself, we show that ratios polynomial in 1∕𝛼 cannot be avoided. If there are at most 𝛽 different utility values for A, we show a Θ(1∕𝛽)-approximation. If the utilities of P and A for each option are related by a factor 𝛾, we obtain an Ω(1∕ log 𝛾)- approximation, where 𝑂(log log 𝛾∕ log 𝛾) is best possible.}, author = {Braun, Pirmin and Hahn, Niklas and Hoefer, Martin and Schecker, Conrad}, issn = {0004-3702}, journal = {Artificial Intelligence}, publisher = {Elsevier}, title = {{Delegated online search}}, doi = {10.1016/j.artint.2024.104171}, volume = {334}, year = {2024}, } @article{17190, abstract = {For a locally finite set, 𝐴⊆ℝ𝑑 , the 𝑘 th Brillouin zone of 𝑎∈𝐴 is the region of points 𝑥∈ℝ𝑑 for which ‖𝑥−𝑎‖ is the 𝑘 th smallest among the Euclidean distances between 𝑥 and the points in 𝐴 . If 𝐴 is a lattice, the 𝑘 th Brillouin zones of the points in 𝐴 are translates of each other, and together they tile space. Depending on the value of 𝑘 , they express medium- or long-range order in the set. We study fundamental geometric and combinatorial properties of Brillouin zones, focusing on the integer lattice and its perturbations. Our results include the stability of a Brillouin zone under perturbations, a linear upper bound on the number of chambers in a zone for lattices in ℝ2 , and the convergence of the maximum volume of a chamber to zero for the integer lattice.}, author = {Edelsbrunner, Herbert and Garber, Alexey and Ghafaris, Mohadese and Heiss, Teresa and Saghafiant, Morteza and Wintraecken, Mathijs}, issn = {0895-4801}, journal = {SIAM Journal on Discrete Mathematics}, number = {2}, pages = {1784--1807}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Brillouin zones of integer lattices and their perturbations}}, doi = {10.1137/22M1489071}, volume = {38}, year = {2024}, } @misc{17196, abstract = {This .zip File contains the data for the figures presented in the main text and supplementary material of "A gate tunable transmon qubit in planar Ge" by O.Sagi et al. The measurements were done using Qcodes. The description of the files and the instructions on opening the data can be found in the Readme. An additional Jupyter Notebook is attached that walks through the data analysis.}, author = {Sagi, Oliver}, publisher = {Institute of Science and Technology Austria}, title = {{A gate-tunable transmon in planar Ge}}, doi = {10.15479/AT:ISTA:17196}, year = {2024}, } @article{18444, abstract = {Animals rely on compensatory actions to maintain stability and navigate their environment efficiently. These actions depend on global visual motion cues known as optic-flow. While the optomotor response has been the traditional focus for studying optic-flow compensation in insects, its simplicity has been insufficient to determine the role of the intricate optic-flow processing network involved in visual course control. Here, we reveal a series of course control behaviours in Drosophila and link them to specific neural circuits. We show that bilateral electrical coupling of optic-flow-sensitive neurons in the fly’s lobula plate are required for a proper course control. This electrical interaction works alongside chemical synapses within the HS-H2 network to control the dynamics and direction of turning behaviours. Our findings reveal how insects use bilateral motion cues for navigation, assigning a new functional significance to the HS-H2 network and suggesting a previously unknown role for gap junctions in non-linear operations.}, author = {Pokusaeva, Victoria and Satapathy, Roshan K and Symonova, Olga and Jösch, Maximilian A}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Bilateral interactions of optic-flow sensitive neurons coordinate course control in flies}}, doi = {10.1038/s41467-024-53173-w}, volume = {15}, year = {2024}, } @article{18451, abstract = {Inorganic nanoparticles can be assembled into superlattices with unique optical and magnetic properties arising from collective behavior. Protein cages can be utilized to guide this assembly by encapsulating nanoparticles and promoting their assembly into ordered structures. However, creating ordered multi-component structures with different protein cage types and sizes remains a challenge. Here, the co-crystallization of two different protein cages (cowpea chlorotic mottle virus and ferritin) characterized by opposing surface charges and unequal diameter is shown. Precise tuning of the electrostatic attraction between the cages enabled the preparation of binary crystals with dimensions up to several tens of micrometers. Additionally, binary metal nanoparticle superlattices are achieved by loading gold and iron oxide nanoparticles inside the cavities of the protein cages. The resulting structure adopts an AB2FCC configuration that also impacts the dipolar coupling between the particles and hence the optical properties of the crystals, providing key insight for the future preparation of plasmonic and magnetic nanoparticle metamaterials.}, author = {Zhou, Yu and Shaukat, Ahmed and Seitsonen, Jani and Rigoni, Carlo and Timonen, Jaakko V.I. and Kostiainen, Mauri A.}, issn = {2198-3844}, journal = {Advanced Science}, number = {45}, publisher = {Wiley}, title = {{Protein cage directed assembly of binary nanoparticle superlattices}}, doi = {10.1002/advs.202408416}, volume = {11}, year = {2024}, } @article{18465, abstract = {The phytohormone auxin is polarly transported in plants by PIN-FORMED (PIN) transporters and controls virtually all growth and developmental processes. Canonical PINs possess a long, largely disordered cytosolic loop. Auxin transport by canonical PINs is activated by loop phosphorylation by certain kinases. The structure of the PIN transmembrane domains was recently determined, their transport properties remained poorly characterized, and the role of the loop in the transport process was unclear. Here, we determined the quantitative kinetic parameters of auxin transport mediated by Arabidopsis PINs to mathematically model auxin distribution in roots and to test these predictions in vivo. Using chimeras between transmembrane and loop domains of different PINs, we demonstrate a strong correlation between transport parameters and physiological output, indicating that the loop domain is not only required to activate PIN-mediated auxin transport, but it has an additional role in the transport process by a currently unknown mechanism.}, author = {Janacek, DP and Kolb, M and Schulz, L and Mergner, J and Kuster, B and Glanc, Matous and Friml, Jiří and Ten Tusscher, K and Schwechheimer, C and Hammes, UZ}, issn = {1878-1551}, journal = {Developmental Cell}, number = {14}, pages = {S1534--5807(24)00569--0}, publisher = {Elsevier}, title = {{Transport properties of canonical PIN-FORMED proteins from Arabidopsis and the role of the loop domain in auxin transport}}, doi = {10.1016/j.devcel.2024.09.020}, volume = {59}, year = {2024}, } @article{18483, abstract = {In this paper we prove a perturbative version of a remarkable Bialy–Mironov (Ann. Math. 196(1):389–413, 2022) result. They prove non perturbative Birkhoff conjecture for centrally-symmetric convex domains, namely, a centrally-symmetric convex domain with integrable billiard is ellipse. We combine techniques from Bialy–Mironov (Ann. Math. 196(1):389–413, 2022) with a local result by Kaloshin–Sorrentino (Ann. Math. 188(1):315–380, 2018) and show that a domain close enough to a centrally symmetric one with integrable billiard is ellipse. To combine these results we derive a slight extension of Bialy–Mironov (Ann. Math. 196(1):389–413, 2022) by proving that a notion of rational integrability is equivalent to the C0-integrability condition used in their paper.}, author = {Kaloshin, Vadim and Koudjinan, Edmond and Zhang, Ke}, issn = {1420-8970}, journal = {Geometric and Functional Analysis}, pages = {1973--2007}, publisher = {Springer Nature}, title = {{Birkhoff conjecture for nearly centrally symmetric domains}}, doi = {10.1007/s00039-024-00695-6}, volume = {34}, year = {2024}, } @article{18488, abstract = {The advancement of quantum simulators motivates the development of a theoretical framework to assist with efficient state preparation in quantum many-body systems. Generally, preparing a target entangled state via unitary evolution with time-dependent couplings is a challenging task and very little is known about the existence of solutions and their properties. In this work we develop a constructive approach for preparing matrix product states (MPS) via continuous unitary evolution. We provide an explicit construction of the operator that exactly implements the evolution of a given MPS along a specified direction in its tangent space. This operator can be written as a sum of local terms of finite range, yet it is in general non-Hermitian. Relying on the explicit construction of the non-Hermitian generator of the dynamics, we demonstrate the existence of a Hermitian sequence of operators that implements the desired MPS evolution with an error that decreases exponentially with the operator range. The construction is benchmarked on an explicit periodic trajectory in a translationally invariant MPS manifold. We demonstrate that the Floquet unitary generating the dynamics over one period of the trajectory features an approximate MPS-like eigenstate embedded among a sea of thermalizing eigenstates. These results show that our construction is not only useful for state preparation and control of many-body systems, but also provides a generic route towards Floquet scars—periodically driven models with quasilocal generators of dynamics that have exact MPS eigenstates in their spectrum.}, author = {Ljubotina, Marko and Petrova, Elena and Schuch, Norbert and Serbyn, Maksym}, issn = {2691-3399}, journal = {PRX Quantum}, number = {4}, publisher = {American Physical Society}, title = {{Tangent space generators of matrix product states and exact floquet quantum scars}}, doi = {10.1103/prxquantum.5.040311}, volume = {5}, year = {2024}, } @article{18490, abstract = {For large classes of even-dimensional Riemannian manifolds (Formula presented.), we construct and analyze conformally invariant random fields. These centered Gaussian fields (Formula presented.), called co-polyharmonic Gaussian fields, are characterized by their covariance kernels k which exhibit a precise logarithmic divergence: (Formula presented.). They share a fundamental quasi-invariance property under conformal transformations. In terms of the co-polyharmonic Gaussian field (Formula presented.), we define the Liouville Quantum Gravity measure, a random measure on (Formula presented.), heuristically given as (Formula presented.) and rigorously obtained as almost sure weak limit of the right-hand side with (Formula presented.) replaced by suitable regular approximations (Formula presented.). In terms on the Liouville Quantum Gravity measure, we define the Liouville Brownian motion on (Formula presented.) and the random GJMS operators. Finally, we present an approach to a conformal field theory in arbitrary even dimension with an ansatz based on Branson's (Formula presented.) -curvature: we give a rigorous meaning to the Polyakov–Liouville measure (Formula presented.) and we derive the corresponding conformal anomaly. The set of admissible manifolds is conformally invariant. It includes all compact 2-dimensional Riemannian manifolds, all compact non-negatively curved Einstein manifolds of even dimension, and large classes of compact hyperbolic manifolds of even dimension. However, not every compact even-dimensional Riemannian manifold is admissible. Our results concerning the logarithmic divergence of the kernel (Formula presented.) rely on new sharp estimates for heat kernels and higher order Green kernels on arbitrary closed manifolds. }, author = {Dello Schiavo, Lorenzo and Herry, Ronan and Kopfer, Eva and Sturm, Karl Theodor}, issn = {1469-7750}, journal = {Journal of the London Mathematical Society}, number = {5}, publisher = {London Mathematical Society}, title = {{Conformally invariant random fields, Liouville quantum gravity measures, and random Paneitz operators on Riemannian manifolds of even dimension}}, doi = {10.1112/jlms.70003}, volume = {110}, year = {2024}, } @article{18494, abstract = {We expect luminous (M 1450 ≲ −26.5) high-redshift quasars to trace the highest-density peaks in the early Universe. Here, we present observations of four z ≳ 6 quasar fields using JWST/NIRCam in the imaging and wide-field slitless spectroscopy mode and report a wide range in the number of detected [O iii]-emitting galaxies in the quasars’ environments, ranging between a density enhancement of δ ≈ 65 within a 2 cMpc radius—one of the largest protoclusters during the Epoch of Reionization discovered to date—to a density contrast consistent with zero, indicating the presence of a UV-luminous quasar in a region comparable to the average density of the Universe. By measuring the two-point cross-correlation function of quasars and their surrounding galaxies, as well as the galaxy autocorrelation function, we infer a correlation length of quasars at 〈z〉 = 6.25 of r 0 QQ = 22.0 − 2.9 + 3.0 cMpc h − 1 , while we obtain a correlation length of the [O iii]-emitting galaxies of r 0 GG = 4.1 ± 0.3 cMpc h − 1 . By comparing the correlation functions to dark-matter-only simulations we estimate the minimum mass of the quasars’ host dark matter halos to be log 10 ( M halo , min / M ⊙ ) = 12.43 − 0.15 + 0.13 (and log 10 ( M halo , min [ OIII ] / M ⊙ ) = 10.56 − 0.03 + 0.05 for the [O iii] emitters), indicating that (a) luminous quasars do not necessarily reside within the most overdense regions in the early Universe, and that (b) the UV-luminous duty cycle of quasar activity at these redshifts is f duty ≪ 1. Such short quasar activity timescales challenge our understanding of early supermassive black hole growth and provide evidence for highly dust-obscured growth phases or episodic, radiatively inefficient accretion rates.}, author = {Eilers, Anna Christina and Mackenzie, Ruari and Pizzati, Elia and Matthee, Jorryt J and Hennawi, Joseph F. and Zhang, Haowen and Bordoloi, Rongmon and Kashino, Daichi and Lilly, Simon J. and Naidu, Rohan P. and Simcoe, Robert A. and Yue, Minghao and Frenk, Carlos S. and Helly, John C. and Schaller, Matthieu and Schaye, Joop}, issn = {1538-4357}, journal = {Astrophysical Journal}, number = {2}, publisher = {IOP Publishing}, title = {{EIGER. VI. The correlation function, host halo mass, and duty cycle of luminous quasars at z ≳ 6}}, doi = {10.3847/1538-4357/ad778b}, volume = {974}, year = {2024}, } @misc{18498, abstract = {Scripts and data used in the research study Predicting rapid adaptation in time from adaptation in space: a 30-year field experiment in marine snails. https://doi.org/10.1101/2023.09.27.559715}, author = {Garcia Castillo, Diego Fernando and Barton, Nicholas H and Faria, Rui and Larsson, Jenny and Stankowski, Sean and Butlin, Roger and Johannesson, Kerstin and Westram, Anja M}, publisher = {Zenodo}, title = {{Data and code for: Predicting rapid adaptation in time from adaptation in space: a 30-year field experiment in marine snails}}, doi = {10.5281/ZENODO.12159343}, year = {2024}, } @inproceedings{18503, abstract = {In 1996, Karger [Kar96] gave a startling randomized algorithm that finds a minimum-cut in a (weighted) graph in time O(m log3 n) which he termed near-linear time meaning linear (in the size of the input) times a polylogarthmic factor. In this paper, we give the first deterministic algorithm which runs in near-linear time for weighted graphs. Previously, the breakthrough results of Kawarabayashi and Thorup [KT19] gave a near-linear time algorithm for simple graphs (which was improved to have running time O(m log2 n log log n) in [HRW20].) The main technique here is a clustering procedure that perfectly preserves minimum cuts. Recently, Li [Li21] gave an m1+o(1) deterministic minimum-cut algorithm for weighted graphs; this form of running time has been termed “almost-linear”. Li uses almost-linear time deterministic expander decompositions which do not perfectly preserve minimum cuts, but he can use these clusterings to, in a sense, “derandomize” the methods of Karger. In terms of techniques, we provide a structural theorem that says there exists a sparse clustering that preserves minimum cuts in a weighted graph with o(1) error. In addition, we construct it deterministically in near linear time. This was done exactly for simple graphs in [KT19, HRW20] and with polylogarithmic error for weighted graphs in [Li21]. Extending the techniques in [KT19, HRW20] to weighted graphs presents significant challenges, and moreover, the algorithm can only polylogarithmically approximately preserve minimum cuts. A remaining challenge is to reduce the polylogarithmic-approximate clusterings to 1 + o(1/ log n)-approximate so that they can be applied recursively as in [Li21] over O(log n) many levels. This is an additional challenge that requires building on properties of tree-packings in the presence of a wide range of edge weights to, for example, find sources for local flow computations which identify minimum cuts that cross clusters.}, author = {Henzinger, Monika H and Li, Jason and Rao, Satish and Wang, Di}, booktitle = {35th Annual ACM-SIAM Symposium on Discrete Algorithms}, location = {Alexandria, VA, United States}, pages = {3089--3139}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Deterministic near-linear time minimum cut in weighted graphs}}, doi = {10.1137/1.9781611977912.111}, year = {2024}, } @phdthesis{18515, abstract = {Understanding the role of evolutionary processes in shaping genetic variation has been a primary goal in evolutionary genetics. In this regard, a key question is how genetically distinct populations evolve in the face of gene flow, thereby generating genetic and phenotypic divergence and reproductive isolation (RI). This requires quantifying the role and relative contributions of prezygotic and postzygotic isolating mechanisms on the reduction of gene exchange between populations, and identifying regions in the genome that mediate RI, which is often polygenic. Further, this needs distinguishing neutral and selected regions in the genome, and discerning how selection influences patterns of neutral divergence. Population structure, defined as any deviation from panmixia, such as geographic distribution, movement and mating patterns of individuals, influences how genetic variation is structured in space and shapes the neutral null model. Availability of large scale spatial genomic datasets now enables us to detect signatures of population structure in genetic data and infer population genetic parameters. Such inferences are crucial and have wide applications in biodiversity, conservation genetics, population management and medical genetics. However, inferences are based on assumptions that do not always match the complex reality, thus leading to erroneous conclusions. Moreover, the role and interaction of heterogeneous population density and dispersal, which are ubiquitous in nature, has been challenging to study owing to their mathematical complexity. In such scenarios, feedback between theory, data and simulations can prove to be useful. In this thesis, I examine the effect of population structure on neutral genetic variation and barriers to gene exchange in hybridising populations, thereby bridging together the fields of spatial population genetics and speciation. Despite being a key concept in speciation, reproductive isolation (RI) lacks a quantitative definition and has been used and measured differently across different fields. Chapter 2 gives a quantitative definition of RI, in terms of the effect of genetic differences on gene flow. We give analytical predictions for RI in a range of scenarios, in terms of effective migration rates for discrete populations and barrier strength for continuous populations. In addition to this, we discuss current measures of RI and their limitations, and propose the need for new measures that combine organismal and genetic perspectives of RI. In chapter 3, I examine the combined effect of assortative mating, sexual selection and viability selection on RI. For this, we consider a polygenic ‘magic’ trait under a mainland-island model. We obtain novel theoretical predictions for molecular divergence in terms of effective migration rates, which bears a simple relationship to measurable fitness components of migrants and various early generation hybrids. We explore the conditions under which local adaptation can be maintained despite maladaptive gene flow and quantify the relative contributions of viability and sexual selection to genome-wide barriers to gene flow. The next two chapters of the thesis focus on a hybrid zone of Antirrhinum majus that consist of two subspecies- the magenta flowered A. m. pseudomajus and the yellow flowered A.m. striatum. Previous studies have suggested that flower colour is target of pollinator mediated selection and is influenced only by few genes. While these regions show high genetic differentiation between the subspecies, the rest of the genome is seen to be well mixed. Chapter 4 examines the effects of heterogeneous population density and leptokurtic dispersal on isolation by distance and the distribution of heterozygosity by focusing on non-flower colour markers. Chapter 5 analyses cline shapes and associations among 6 focal flower colour markers to understand how selection and dispersal maintain this hybrid zone. We see sharp coincident stepped clines at all loci and positive associations throughout the hybrid zone, contrary to the expected patterns from diffusive gene flow. With a novel scheme of inferring dispersal combined with multilocus simulations, we show that stepped clines do not reflect genetic barriers to gene flow, but are rather a result of long-distance migration. This framework allows us to get realistic estimates gene flow and selection and shows how traditional cline analysis may lead to inaccurate conclusions when assumptions of the theory are not met. Overall, this thesis investigates how different features of population structure leave detectable signatures in genetic variation, namely in patterns of isolation by distance, linkage disequilibrium and genetic divergence. It also highlights how effective migration rates provide useful way of analysing polygenic architectures and shed new light into hybrid zones. In doing so, I identify scenarios when simple models become insufficient and suggest possibe directions by combining genetic data with simulations.}, author = {Surendranadh, Parvathy}, issn = {2663-337X}, pages = {219}, publisher = {Institute of Science and Technology Austria}, title = {{Effect of population structure on neutral genetic variation and barriers to gene exchange}}, doi = {10.15479/at:ista:18515}, year = {2024}, } @inproceedings{18521, abstract = {In distributed systems with processes that do not share a global clock, partial synchrony is achieved by clock synchronization that guarantees bounded clock skew among all applications. Existing solutions for distributed runtime verification under partial synchrony against temporal logic specifications are exact but suffer from significant computational overhead. In this paper, we propose an approximate distributed monitoring algorithm for Signal Temporal Logic (STL) that mitigates this issue by abstracting away potential interleaving behaviors. This conservative abstraction enables a significant speedup of the distributed monitors, albeit with a tradeoff in accuracy. We address this tradeoff with a methodology that combines our approximate monitor with its exact counterpart, resulting in enhanced efficiency without sacrificing precision. We evaluate our approach with multiple experiments, showcasing its efficacy in both real-world applications and synthetic examples.}, author = {Bonakdarpour, Borzoo and Momtaz, Anik and Nickovic, Dejan and Sarac, Naci E}, booktitle = {24th International Conference on Runtime Verification}, isbn = {9783031742330}, issn = {1611-3349}, location = {Istanbul, Turkey}, pages = {282--301}, publisher = {Springer Nature}, title = {{Approximate distributed monitoring under partial synchrony: Balancing speed & accuracy}}, doi = {10.1007/978-3-031-74234-7_18}, volume = {15191}, year = {2024}, } @article{18522, abstract = {The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be extracted by Cdc48 for endosome and Golgi associated proteasomal degradation (EGAD), while others will undergo ESCRT dependent vacuolar degradation. Some substrates are degraded by both, EGAD- or ESCRT pathways. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thereby preserves cellular membrane protein and lipid composition.}, author = {Weyer, Yannick and Schwabl, Sinead I. and Tang, Xuechen and Purwar, Astha and Siegmann, Konstantin and Ruepp, Angela and Dunzendorfer-Matt, Theresia and Widerin, Michael A. and Niedrist, Veronika and Mutsters, Noa J.M. and Tettamanti, Maria G. and Weys, Sabine and Sarg, Bettina and Kremser, Leopold and Liedl, Klaus R. and Schmidt, Oliver and Teis, David}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi}}, doi = {10.1038/s41467-024-53676-6}, volume = {15}, year = {2024}, } @article{18523, abstract = {Recent observations from the EIGER JWST program have measured for the first time the quasar–galaxy cross-correlation function at z ≈ 6. The autocorrelation function of faint z ≈ 6 quasars was also recently estimated. These measurements provide key insights into the properties of quasars and galaxies at high redshift and their relation with the host dark matter haloes. In this work, we interpret these data building upon an empirical quasar population model that has been applied successfully to quasar clustering and demographic measurements at z ≈ 2–4. We use a new, large-volume N-body simulation with more than a trillion particles, FLAMINGO-10k, to model quasars and galaxies simultaneously. We successfully reproduce observations of z ≈ 6 quasars and galaxies (i.e. their clustering properties and luminosity functions), and infer key quantities such as their luminosity–halo mass relation, the mass function of their host haloes, and their duty cycle/occupation fraction. Our key findings are (i) quasars reside on average in ≈ 1012.5 M haloes (corresponding to ≈ 5σ fluctuations in the initial conditions of the linear density field), but the distribution of host halo masses is quite broad; (ii) the duty cycle of (UV-bright) quasar activity is relatively low (≈ 1 per cent); (iii) galaxies (that are bright in [O III]) live in much smaller haloes (≈ 1010.9 M) and have a larger duty cycle (occupation fraction) of ≈ 13 per cent. Finally, we focus on the inferred properties of quasars and present a homogeneous analysis of their evolution with redshift. The picture that emerges reveals a strong evolution of the host halo mass and duty cycle of quasars at z ≈ 2–6, and calls for new investigations of the role of quasar activity across cosmic time.}, author = {Pizzati, Elia and Hennawi, Joseph F. and Schaye, Joop and Schaller, Matthieu and Eilers, Anna Christina and Wang, Feige and Frenk, Carlos S. and Elbers, Willem and Helly, John C. and Mackenzie, Ruari and Matthee, Jorryt J and Bordoloi, Rongmon and Kashino, Daichi and Naidu, Rohan P. and Yue, Minghao}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {4}, pages = {3155--3175}, publisher = {Oxford University Press}, title = {{A unified model for the clustering of quasars and galaxies at z ≈ 6}}, doi = {10.1093/mnras/stae2307}, volume = {534}, year = {2024}, } @article{18545, abstract = {Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues. Here, we sought to redesign PsCas9 for in vivo editing using lipid nanoparticles. We solve the PsCas9 ribonucleoprotein structure with cryo-EM and characterize it biochemically, providing a basis for its rational engineering. Screening over numerous guide RNA and protein variants lead us to develop engineered PsCas9 (ePsCas9) with up to 20-fold increased activity across various targets and preserved safety advantages. We apply the same design principles to boost the activity of FnCas9, an enzyme phylogenetically relevant to PsCas9. Remarkably, a single administration of mRNA encoding ePsCas9 and its guide formulated with lipid nanoparticles results in high levels of editing in the Pcsk9 gene in mouse liver, a clinically relevant target for hypercholesterolemia treatment. Collectively, our findings introduce ePsCas9 as a highly efficient, and precise tool for therapeutic genome editing, in addition to the engineering strategy applicable to other Cas9 orthologues.}, author = {Degtev, Dmitrii and Bravo, Jack Peter Kelly and Emmanouilidi, Aikaterini and Zdravković, Aleksandar and Choong, Oi Kuan and Liz Touza, Julia and Selfjord, Niklas and Weisheit, Isabel and Francescatto, Margherita and Akcakaya, Pinar and Porritt, Michelle and Maresca, Marcello and Taylor, David and Sienski, Grzegorz}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles}}, doi = {10.1038/s41467-024-53418-8}, volume = {15}, year = {2024}, } @article{18554, abstract = {We prove the Eigenstate Thermalization Hypothesis for general Wigner-type matrices in the bulk of the self-consistent spectrum, with optimal control on the fluctuations for obs ervables of arbitrary rank. As the main technical ingredient, we prove rank-uniform optimal local laws for one and two resolvents of a Wigner-type matrix with regular observables. Our results hold under very general conditions on the variance profile, even allowing many vanishing entries, demonstrating that Eigenstate Thermalization occurs robustly across a diverse class of random matrix ensembles, for which the underlying quantum system has a non-trivial spatial structure.}, author = {Erdös, László and Riabov, Volodymyr}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, number = {12}, publisher = {Springer Nature}, title = {{Eigenstate Thermalization Hypothesis for Wigner-type matrices}}, doi = {10.1007/s00220-024-05143-y}, volume = {405}, year = {2024}, }