@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{18553, abstract = {Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4CSA ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4CSA serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment. However, the precise regulatory mechanisms of CRL4CSA activity and TFIIH recruitment remain elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a TC-NER factor, which is essential for correct DNA damage removal and subsequent transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA, UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability and CRL4CSA activity, resulting in efficient RNA Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core TC-NER component.}, author = {Ramadhin, Anisha R. and Lee, Shun-Hsiao and Zhou, Di and Testa Salmazo, Anita P and Gonzalo-Hansen, Camila and van Sluis, Marjolein and Blom, Cindy M.A. and Janssens, Roel C. and Raams, Anja and Dekkers, Dick and Bezstarosti, Karel and Slade, Dea and Vermeulen, Wim and Pines, Alex and Demmers, Jeroen A.A. and Bernecky, Carrie A and Sixma, Titia K. and Marteijn, Jurgen A.}, issn = {1097-2765}, journal = {Molecular Cell}, number = {24}, pages = {4740--4757.e12}, publisher = {Elsevier}, title = {{STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment}}, doi = {10.1016/j.molcel.2024.10.030}, volume = {84}, 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}, } @inproceedings{18556, abstract = {Given a finite set, A ⊆ ℝ², and a subset, B ⊆ A, the MST-ratio is the combined length of the minimum spanning trees of B and A⧵B divided by the length of the minimum spanning tree of A. The question of the supremum, over all sets A, of the maximum, over all subsets B, is related to the Steiner ratio, and we prove this sup-max is between 2.154 and 2.427. Restricting ourselves to 2-dimensional lattices, we prove that the sup-max is 2, while the inf-max is 1.25. By some margin the most difficult of these results is the upper bound for the inf-max, which we prove by showing that the hexagonal lattice cannot have MST-ratio larger than 1.25.}, author = {Cultrera di Montesano, Sebastiano and Draganov, Ondrej and Edelsbrunner, Herbert and Saghafian, Morteza}, booktitle = {32nd International Symposium on Graph Drawing and Network Visualization}, isbn = {9783959773430}, issn = {1868-8969}, location = {Vienna, Austria}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The Euclidean MST-ratio for bi-colored lattices}}, doi = {10.4230/LIPIcs.GD.2024.3}, volume = {320}, year = {2024}, } @article{18559, abstract = {We prove a 1973 conjecture due to Erdős on the existence of Steiner triple systems with arbitrarily high girth.}, author = {Kwan, Matthew Alan and Sah, Ashwin and Sawhney, Mehtaab and Simkin, Michael}, issn = {1939-8980}, journal = {Annals of Mathematics}, number = {3}, pages = {1059--1156}, publisher = {Princeton University}, title = {{High-girth Steiner triple systems}}, doi = {10.4007/annals.2024.200.3.4}, volume = {200}, year = {2024}, } @inbook{18563, abstract = {I give a personal account about the wave of new research activities that rose in the 1990s on the specification, verification, and control of real-time systems.}, author = {Henzinger, Thomas A}, booktitle = {Real Time and Such}, editor = {Graf, Susanne and Pettersson, Paul and Steffen, Bernhard}, isbn = {9783031737503}, issn = {1611-3349}, pages = {154--164}, publisher = {Springer Nature}, title = {{Reminiscences of a Real-Time Researcher}}, doi = {10.1007/978-3-031-73751-0_12}, volume = {15230}, year = {2024}, } @phdthesis{18568, abstract = {Locomotion is ubiquitous in the animal kingdom because an animal's survival depends on its ability to navigate its environment to find food, avoid predators and locate potential mates. These behaviours require control mechanisms that can extract information from the environment, particularly visual cues. Selective evolutionary pressures have thus refined such visuomotor transformations in a species-specific manner to meet the specific ecological and ethological challenges of each organism. However, a common challenge across organisms as visual information processing becomes increasingly detailed is the mechanisms required to synthesise disparate pieces of information into a coherent percept or unified picture of the world. In this thesis, I investigate how disparate visual information is combined in the brain of Drosophila melanogaster to effectively guide locomotion. For this, I first designed and built a behavioural setup to record locomotion and present visual stimuli to freely-walking fruit flies in a closed-loop manner. This setup allowed the investigation of innate visually-guided behaviours, including the optomotor reflex and courtship. Second, taking advantage of my system I investigated the optomotor response, a reflexive visual stabilisation behaviour in which flies turn in the direction of global motion to minimise retinal slip. This behaviour is thought to be mediated by Lobula plate tangential cells (LPTCs); a complex network of optic-flow-sensitive neurons essential for self-motion estimation. Using a novel genetic mutant, I demonstrate that electrical coupling between two LPTC subtypes, contralateral HS and H2 neurons, regulates the balance between smooth optomotor turning and saccadic anti-optomotor responses. These findings underscore the critical role of binocular motion cue integration in guiding course control. Finally, I developed a novel behavioural paradigm in which a sexually aroused male fruit fly is presented with an optomotor distractor. This setup creates competition between two visual behaviours, courtship tracking and the optomotor response, enabling me to explore how the visual system resolves this conflict. In this setting, males engaged in courtship selectively suppress their optomotor response based on the female's location. Furthermore, when this experiment is replicated with an “artificial female”, optogenetically aroused males alternate between tracking and optomotor responses. The probability and dynamics of this switching are determined by the relative strengths of the two competing stimuli. In summary, the results presented in this thesis explore two mechanisms – integration and competition - through which visual information is combined in the brain of the fruit fly to drive locomotion.}, author = {Satapathy, Roshan K}, isbn = {978-3-99078-047-3}, issn = {2663-337X}, pages = {114}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanisms of visual integration and competition in innate behaviours in Drosophila melanogaster}}, doi = {10.15479/at:ista:18568}, year = {2024}, } @misc{18579, abstract = {Electrophysiological, calcium two-photon recordings and behavioral data for Vega-Zuniga et al. Relevant information can be found in the 'README.txt' files. }, author = {Vega Zuniga, Tomas A and Sumser, Anton L and Symonova, Olga and Koppensteiner, Peter and Schmidt, Florian and Jösch, Maximilian A}, publisher = {Institute of Science and Technology Austria}, title = {{A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics}}, doi = {10.15479/AT:ISTA:18579}, year = {2024}, } @article{18581, abstract = {Background: Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM. Methods: MSCs were isolated from 13 donors (age 20–90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity. Results: Primary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development. Conclusions: Our data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies.}, author = {Marolt Presen, Darja and Goeschl, Vanessa and Hanetseder, Dominik and Ogrin, Laura and Stetco, Alexandra Larissa and Tansek, Anja and Pozenel, Laura and Bruszel, Bella and Mitulovic, Goran and Oesterreicher, Johannes and Zipperle, Johannes and Schaedl, Barbara and Holnthoner, Wolfgang and Grillari, Johannes and Redl, Heinz}, issn = {1757-6512}, journal = {Stem Cell Research and Therapy}, publisher = {Springer Nature}, title = {{Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium}}, doi = {10.1186/s13287-024-03960-5}, volume = {15}, year = {2024}, } @article{18582, abstract = {Identification of PIN exporters for auxin, the major coordinative signal in plants, some 25 years ago, signifies a landmark in our understanding of plant-specific mechanisms underlying development and adaptation. Auxin is directionally transported throughout the plant body; a unique feature already envisioned by Darwin and solidified by PINs’ discovery and characterization. The PIN-based auxin distribution network with its complex regulations of PIN expression, localization and activity turned out to underlie a remarkable multitude of developmental processes and represents means to integrate endogenous and environmental signals. Given the recent anniversary, we here summarize past and current developments in this exciting field.}, author = {Luschnig, Christian and Friml, Jiří}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Over 25 years of decrypting PIN-mediated plant development}}, doi = {10.1038/s41467-024-54240-y}, volume = {15}, year = {2024}, } @article{18583, abstract = {There are a number of well-known problems and conjectures about partitioning graphs to satisfy local constraints. For example, the majority colouring conjecture of Kreutzer, Oum, Seymour, van der Zypen and Wood states that every directed graph has a 3-colouring such that for every vertex v, at most half of the out-neighbours of v have the same colour as . As another example, the internal partition conjecture, due to DeVos and to Ban and Linial, states that for every d, all but finitely many d-regular graphs have a partition into two non-empty parts such that for every vertex v, at least half of the neighbours of v lie in the same part as v. We prove several results in this spirit: in particular, two of our results are that the majority colouring conjecture holds for Erdős–Rényi random directed graphs (of any density), and that the internal partition conjecture holds if we permit a tiny number of ‘exceptional vertices’. Our proofs involve a variety of techniques, including several different methods to analyse random recolouring processes. One highlight is a personality-changing scheme: we ‘forget’ certain information based on the state of a Markov chain, giving us more independence to work with.}, author = {Anastos, Michael and Cooley, Oliver and Kang, Mihyun and Kwan, Matthew Alan}, issn = {1469-7750}, journal = {Journal of the London Mathematical Society}, number = {6}, publisher = {Wiley}, title = {{Partitioning problems via random processes}}, doi = {10.1112/jlms.70010}, volume = {110}, year = {2024}, }