@inproceedings{13967,
  abstract     = {A classic solution technique for Markov decision processes (MDP) and stochastic games (SG) is value iteration (VI). Due to its good practical performance, this approximative approach is typically preferred over exact techniques, even though no practical bounds on the imprecision of the result could be given until recently. As a consequence, even the most used model checkers could return arbitrarily wrong results. Over the past decade, different works derived stopping criteria, indicating when the precision reaches the desired level, for various settings, in particular MDP with reachability, total reward, and mean payoff, and SG with reachability.In this paper, we provide the first stopping criteria for VI on SG with total reward and mean payoff, yielding the first anytime algorithms in these settings. To this end, we provide the solution in two flavours: First through a reduction to the MDP case and second directly on SG. The former is simpler and automatically utilizes any advances on MDP. The latter allows for more local computations, heading towards better practical efficiency.Our solution unifies the previously mentioned approaches for MDP and SG and their underlying ideas. To achieve this, we isolate objective-specific subroutines as well as identify objective-independent concepts. These structural concepts, while surprisingly simple, form the very essence of the unified solution.},
  author       = {Kretinsky, Jan and Meggendorfer, Tobias and Weininger, Maximilian},
  booktitle    = {38th Annual ACM/IEEE Symposium on Logic in Computer Science},
  isbn         = {9798350335873},
  issn         = {1043-6871},
  location     = {Boston, MA, United States},
  publisher    = {IEEE},
  title        = {{Stopping criteria for value iteration on stochastic games with quantitative objectives}},
  doi          = {10.1109/LICS56636.2023.10175771},
  volume       = {2023},
  year         = {2023},
}

@article{14751,
  abstract     = {We consider zero-error communication over a two-transmitter deterministic adversarial multiple access channel (MAC) governed by an adversary who has access to the transmissions of both senders (hence called omniscient ) and aims to maliciously corrupt the communication. None of the encoders, jammer and decoder is allowed to randomize using private or public randomness. This enforces a combinatorial nature of the problem. Our model covers a large family of channels studied in the literature, including all deterministic discrete memoryless noisy or noiseless MACs. In this work, given an arbitrary two-transmitter deterministic omniscient adversarial MAC, we characterize when the capacity region: 1) has nonempty interior (in particular, is two-dimensional); 2) consists of two line segments (in particular, has empty interior); 3) consists of one line segment (in particular, is one-dimensional); 4) or only contains (0,0) (in particular, is zero-dimensional). This extends a recent result by Wang et al. (201 9) from the point-to-point setting to the multiple access setting. Indeed, our converse arguments build upon their generalized Plotkin bound and involve delicate case analysis. One of the technical challenges is to take care of both “joint confusability” and “marginal confusability”. In particular, the treatment of marginal confusability does not follow from the point-to-point results by Wang et al. Our achievability results follow from random coding with expurgation.},
  author       = {Zhang, Yihan},
  issn         = {1557-9654},
  journal      = {IEEE Transactions on Information Theory},
  keywords     = {Computer Science Applications, Information Systems},
  number       = {7},
  pages        = {4093--4127},
  publisher    = {IEEE},
  title        = {{Zero-error communication over adversarial MACs}},
  doi          = {10.1109/tit.2023.3257239},
  volume       = {69},
  year         = {2023},
}

@article{13269,
  abstract     = {This paper is a collection of results on combinatorial properties of codes for the Z-channel . A Z-channel with error fraction τ takes as input a length- n binary codeword and injects in an adversarial manner up to n τ asymmetric errors, i.e., errors that only zero out bits but do not flip 0’s to 1’s. It is known that the largest ( L - 1)-list-decodable code for the Z-channel with error fraction τ has exponential size (in n ) if τ is less than a critical value that we call the ( L - 1)- list-decoding Plotkin point and has constant size if τ is larger than the threshold. The ( L -1)-list-decoding Plotkin point is known to be L -1/L-1 – L -L/ L-1 , which equals 1/4 for unique-decoding with L -1 = 1. In this paper, we derive various results for the size of the largest codes above and below the list-decoding Plotkin point. In particular, we show that the largest ( L -1)-list-decodable code ε-above the Plotkin point, for any given sufficiently small positive constant ε > 0, has size Θ L (ε -3/2 ) for any L - 1 ≥ 1. We also devise upper and lower bounds on the exponential size of codes below the list-decoding Plotkin point.},
  author       = {Polyanskii, Nikita and Zhang, Yihan},
  issn         = {1557-9654},
  journal      = {IEEE Transactions on Information Theory},
  number       = {10},
  pages        = {6340--6357},
  publisher    = {IEEE},
  title        = {{Codes for the Z-channel}},
  doi          = {10.1109/TIT.2023.3292219},
  volume       = {69},
  year         = {2023},
}

@inproceedings{13221,
  abstract     = {The safety-liveness dichotomy is a fundamental concept in formal languages which plays a key role in verification. Recently, this dichotomy has been lifted to quantitative properties, which are arbitrary functions from infinite words to partially-ordered domains. We look into harnessing the dichotomy for the specific classes of quantitative properties expressed by quantitative automata. These automata contain finitely many states and rational-valued transition weights, and their common value functions Inf, Sup, LimInf, LimSup, LimInfAvg, LimSupAvg, and DSum map infinite words into the totallyordered domain of real numbers. In this automata-theoretic setting, we establish a connection between quantitative safety and topological continuity and provide an alternative characterization of quantitative safety and liveness in terms of their boolean counterparts. For all common value functions, we show how the safety closure of a quantitative automaton can be constructed in PTime, and we provide PSpace-complete checks of whether a given quantitative automaton is safe or live, with the exception of LimInfAvg and LimSupAvg automata, for which the safety check is in ExpSpace. Moreover, for deterministic Sup, LimInf, and LimSup automata, we give PTime decompositions into safe and live automata. These decompositions enable the separation of techniques for safety and liveness verification for quantitative specifications.},
  author       = {Boker, Udi and Henzinger, Thomas A and Mazzocchi, Nicolas Adrien and Sarac, Naci E},
  booktitle    = {34th International Conference on Concurrency Theory},
  isbn         = {9783959772990},
  issn         = {1868-8969},
  location     = {Antwerp, Belgium},
  publisher    = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
  title        = {{Safety and liveness of quantitative automata}},
  doi          = {10.4230/LIPIcs.CONCUR.2023.17},
  volume       = {279},
  year         = {2023},
}

@article{13965,
  abstract     = {Many modes and mechanisms of epigenetic inheritance have been elucidated in eukaryotes. Most of them are relatively short-term, generally not exceeding one or a few organismal generations. However, emerging evidence indicates that one mechanism, cytosine DNA methylation, can mediate epigenetic inheritance over much longer timescales, which are mostly or completely inaccessible in the laboratory. Here we discuss the evidence for, and mechanisms and implications of, such long-term epigenetic inheritance. We argue that compelling evidence supports the long-term epigenetic inheritance of gene body methylation, at least in the model angiosperm Arabidopsis thaliana, and that variation in such methylation can therefore serve as an epigenetic basis for phenotypic variation in natural populations.},
  author       = {Hollwey, Elizabeth and Briffa, Amy and Howard, Martin and Zilberman, Daniel},
  issn         = {1879-0380},
  journal      = {Current Opinion in Genetics & Development},
  number       = {8},
  publisher    = {Elsevier},
  title        = {{Concepts, mechanisms and implications of long-term epigenetic inheritance}},
  doi          = {10.1016/j.gde.2023.102087},
  volume       = {81},
  year         = {2023},
}

@article{14774,
  abstract     = {Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.},
  author       = {Harish, Rohit K and Gupta, Mansi and Zöller, Daniela and Hartmann, Hella and Gheisari, Ali and Machate, Anja and Hans, Stefan and Brand, Michael},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {19},
  publisher    = {Company of Biologists},
  title        = {{Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation}},
  doi          = {10.1242/dev.201559},
  volume       = {150},
  year         = {2023},
}

@article{14657,
  abstract     = {Natural selection is usually studied between mutants that differ in reproductive rate, but are subject to the same population structure. Here we explore how natural selection acts on mutants that have the same reproductive rate, but different population structures. In our framework, population structure is given by a graph that specifies where offspring can disperse. The invading mutant disperses offspring on a different graph than the resident wild-type. We find that more densely connected dispersal graphs tend to increase the invader’s fixation probability, but the exact relationship between structure and fixation probability is subtle. We present three main results. First, we prove that if both invader and resident are on complete dispersal graphs, then removing a single edge in the invader’s dispersal graph reduces its fixation probability. Second, we show that for certain island models higher invader’s connectivity increases its fixation probability, but the magnitude of the effect depends on the exact layout of the connections. Third, we show that for lattices the effect of different connectivity is comparable to that of different fitness: for large population size, the invader’s fixation probability is either constant or exponentially small, depending on whether it is more or less connected than the resident.},
  author       = {Tkadlec, Josef and Kaveh, Kamran and Chatterjee, Krishnendu and Nowak, Martin A.},
  issn         = {1742-5662},
  journal      = {Journal of the Royal Society Interface},
  number       = {208},
  publisher    = {Royal Society},
  title        = {{Evolutionary dynamics of mutants that modify population structure}},
  doi          = {10.1098/rsif.2023.0355},
  volume       = {20},
  year         = {2023},
}

@inproceedings{14953,
  abstract     = {This paper provides statistical sample complexity bounds for score-matching and
its applications in causal discovery. We demonstrate that accurate estimation of the
score function is achievable by training a standard deep ReLU neural network using
stochastic gradient descent. We establish bounds on the error rate of recovering
causal relationships using the score-matching-based causal discovery method of
Rolland et al. [2022], assuming a sufficiently good estimation of the score function.
Finally, we analyze the upper bound of score-matching estimation within the scorebased generative modeling, which has been applied for causal discovery but is also
of independent interest within the domain of generative models.y},
  author       = {Zhu, Zhenyu and Locatello, Francesco and Cevher, Volkan},
  booktitle    = {37th Conference on Neural Information Processing Systems},
  isbn         = {9781713899921},
  issn         = {1049-5258},
  location     = {New Orleans, LO, United States},
  pages        = {3325--3337},
  publisher    = {Neural Information Processing Systems Foundation},
  title        = {{Sample complexity bounds for score-matching: Causal discovery and generative modeling}},
  doi          = {10.52202/075280-0147},
  volume       = {36},
  year         = {2023},
}

@inproceedings{14954,
  abstract     = {When domain knowledge is limited and experimentation is restricted by ethical,
financial, or time constraints, practitioners turn to observational causal discovery
methods to recover the causal structure, exploiting the statistical properties of their
data. Because causal discovery without further assumptions is an ill-posed problem,
each algorithm comes with its own set of usually untestable assumptions, some
of which are hard to meet in real datasets. Motivated by these considerations, this
paper extensively benchmarks the empirical performance of recent causal discovery
methods on observational iid data generated under different background conditions,
allowing for violations of the critical assumptions required by each selected approach. Our experimental findings show that score matching-based methods demonstrate surprising performance in the false positive and false negative rate of the
inferred graph in these challenging scenarios, and we provide theoretical insights
into their performance. This work is also the first effort to benchmark the stability of
causal discovery algorithms with respect to the values of their hyperparameters. Finally, we hope this paper will set a new standard for the evaluation of causal discovery methods and can serve as an accessible entry point for practitioners interested
in the field, highlighting the empirical implications of different algorithm choices.},
  author       = {Montagna, Francesco and Mastakouri, Atalanti A. and Eulig, Elias and Noceti, Nicoletta and Rosasco, Lorenzo and Janzing, Dominik and Aragam, Bryon and Locatello, Francesco},
  booktitle    = {37th Conference on Neural Information Processing Systems},
  issn         = {1049-5258},
  location     = {New Orleans, LO, United States},
  publisher    = {Neural Information Processing Systems Foundation},
  title        = {{Assumption violations in causal discovery and the robustness of score matching}},
  doi          = {10.52202/075280-2050},
  volume       = {36},
  year         = {2023},
}

@article{14036,
  abstract     = {Magic-angle spinning (MAS) nuclear magnetic resonance (NMR) is establishing itself as a powerful method for the characterization of protein dynamics at the atomic scale. We discuss here how R1ρ MAS relaxation dispersion NMR can explore microsecond-to-millisecond motions. Progress in instrumentation, isotope labeling, and pulse sequence design has paved the way for quantitative analyses of even rare structural fluctuations. In addition to isotropic chemical-shift fluctuations exploited in solution-state NMR relaxation dispersion experiments, MAS NMR has a wider arsenal of observables, allowing to see motions even if the exchanging states do not differ in their chemical shifts. We demonstrate the potential of the technique for probing motions in challenging large enzymes, membrane proteins, and protein assemblies.},
  author       = {Napoli, Federico and Becker, Lea Marie and Schanda, Paul},
  issn         = {1879-033X},
  journal      = {Current Opinion in Structural Biology},
  number       = {10},
  publisher    = {Elsevier},
  title        = {{Protein dynamics detected by magic-angle spinning relaxation dispersion NMR}},
  doi          = {10.1016/j.sbi.2023.102660},
  volume       = {82},
  year         = {2023},
}

@article{14042,
  abstract     = {Long-time and large-data existence of weak solutions for initial- and boundary-value problems concerning three-dimensional flows of incompressible fluids is nowadays available not only for Navier–Stokes fluids but also for various fluid models where the relation between the Cauchy stress tensor and the symmetric part of the velocity gradient is nonlinear. The majority of such studies however concerns models where such a dependence is explicit (the stress is a function of the velocity gradient), which makes the class of studied models unduly restrictive. The same concerns boundary conditions, or more precisely the slipping mechanisms on the boundary, where the no-slip is still the most preferred condition considered in the literature. Our main objective is to develop a robust mathematical theory for unsteady internal flows of implicitly constituted incompressible fluids with implicit relations between the tangential projections of the velocity and the normal traction on the boundary. The theory covers numerous rheological models used in chemistry, biorheology, polymer and food industry as well as in geomechanics. It also includes, as special cases, nonlinear slip as well as stick–slip boundary conditions. Unlike earlier studies, the conditions characterizing admissible classes of constitutive equations are expressed by means of tools of elementary calculus. In addition, a fully constructive proof (approximation scheme) is incorporated. Finally, we focus on the question of uniqueness of such weak solutions.},
  author       = {Bulíček, Miroslav and Málek, Josef and Maringová, Erika},
  issn         = {1422-6952},
  journal      = {Journal of Mathematical Fluid Mechanics},
  number       = {3},
  publisher    = {Springer Nature},
  title        = {{On unsteady internal flows of incompressible fluids characterized by implicit constitutive equations in the bulk and on the boundary}},
  doi          = {10.1007/s00021-023-00803-w},
  volume       = {25},
  year         = {2023},
}

@inproceedings{14691,
  abstract     = {Continuous Group-Key Agreement (CGKA) allows a group of users to maintain a shared key. It is the fundamental cryptographic primitive underlying group messaging schemes and related protocols, most notably TreeKEM, the underlying key agreement protocol of the Messaging Layer Security (MLS) protocol, a standard for group messaging by the IETF. CKGA works in an asynchronous setting where parties only occasionally must come online, and their messages are relayed by an untrusted server. The most expensive operation provided by CKGA is that which allows for a user to refresh their key material in order to achieve forward secrecy (old messages are secure when a user is compromised) and post-compromise security (users can heal from compromise). One caveat of early CGKA protocols is that these update operations had to be performed sequentially, with any user wanting to update their key material having had to receive and process all previous updates. Late versions of TreeKEM do allow for concurrent updates at the cost of a communication overhead per update message that is linear in the number of updating parties. This was shown to be indeed necessary when achieving PCS in just two rounds of communication by [Bienstock et al. TCC’20].
The recently proposed protocol CoCoA [Alwen et al. Eurocrypt’22], however, shows that this overhead can be reduced if PCS requirements are relaxed, and only a logarithmic number of rounds is required. The natural question, thus, is whether CoCoA is optimal in this setting.
In this work we answer this question, providing a lower bound on the cost (concretely, the amount of data to be uploaded to the server) for CGKA protocols that heal in an arbitrary k number of rounds, that shows that CoCoA is very close to optimal. Additionally, we extend CoCoA to heal in an arbitrary number of rounds, and propose a modification of it, with a reduced communication cost for certain k.
We prove our bound in a combinatorial setting where the state of the protocol progresses in rounds, and the state of the protocol in each round is captured by a set system, each set specifying a set of users who share a secret key. We show this combinatorial model is equivalent to a symbolic model capturing building blocks including PRFs and public-key encryption, related to the one used by Bienstock et al.
Our lower bound is of order k•n1+1/(k-1)/log(k), where 2≤k≤log(n) is the number of updates per user the protocol requires to heal. This generalizes the n2 bound for k=2 from Bienstock et al.. This bound almost matches the k⋅n1+2/(k-1) or k2⋅n1+1/(k-1) efficiency we get for the variants of the CoCoA protocol also introduced in this paper.},
  author       = {Auerbach, Benedikt and Cueto Noval, Miguel and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z},
  booktitle    = {21st International Conference on Theory of Cryptography},
  isbn         = {9783031486203},
  issn         = {1611-3349},
  location     = {Taipei, Taiwan},
  pages        = {271--300},
  publisher    = {Springer Nature},
  title        = {{On the cost of post-compromise security in concurrent Continuous Group-Key Agreement}},
  doi          = {10.1007/978-3-031-48621-0_10},
  volume       = {14371},
  year         = {2023},
}

@article{12334,
  abstract     = {Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform–specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.</jats:p>},
  author       = {Fäßler, Florian and Javoor, Manjunath and Datler, Julia and Döring, Hermann and Hofer, Florian and Dimchev, Georgi A and Hodirnau, Victor-Valentin and Faix, Jan and Rottner, Klemens and Schur, Florian KM},
  issn         = {2375-2548},
  journal      = {Science Advances},
  keywords     = {Multidisciplinary},
  number       = {3},
  publisher    = {American Association for the Advancement of Science},
  title        = {{ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential Ena/VASP positioning}},
  doi          = {10.1126/sciadv.add6495},
  volume       = {9},
  year         = {2023},
}

@article{12421,
  abstract     = {The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions.},
  author       = {Fäßler, Florian and Javoor, Manjunath and Schur, Florian KM},
  issn         = {1470-8752},
  journal      = {Biochemical Society Transactions},
  keywords     = {Biochemistry},
  number       = {1},
  pages        = {87--99},
  publisher    = {Portland Press},
  title        = {{Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM}},
  doi          = {10.1042/bst20220221},
  volume       = {51},
  year         = {2023},
}

@phdthesis{12491,
  abstract     = {The extracellular matrix (ECM) is a hydrated and complex three-dimensional network consisting of proteins, polysaccharides, and water. It provides structural scaffolding for the cells embedded within it and is essential in regulating numerous physiological processes, including cell migration and proliferation, wound healing, and stem cell fate. 
Despite extensive study, detailed structural knowledge of ECM components in physiologically relevant conditions is still rudimentary. This is due to methodological limitations in specimen preparation protocols which are incompatible with keeping large samples, such as the ECM, in their native state for subsequent imaging. Conventional electron microscopy (EM) techniques rely on fixation, dehydration, contrasting, and sectioning. This results in the alteration of a highly hydrated environment and the potential introduction of artifacts. Other structural biology techniques, such as nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, allow high-resolution analysis of protein structures but only work on homogenous and purified samples, hence lacking contextual information. Currently, no approach exists for the ultrastructural and structural study of extracellular components under native conditions in a physiological, 3D environment. 
In this thesis, I have developed a workflow that allows for the ultrastructural analysis of the ECM in near-native conditions at molecular resolution. The developments I introduced include implementing a novel specimen preparation workflow for cell-derived matrices (CDMs) to render them compatible with ion-beam milling and subsequent high-resolution cryo-electron tomography (ET). 
To this end, I have established protocols to generate CDMs grown over several weeks on EM grids that are compatible with downstream cryo-EM sample preparation and imaging techniques. Characterization of these ECMs confirmed that they contain essential ECM components such as collagen I, collagen VI, and fibronectin I in high abundance and hence represent a bona fide biologically-relevant sample. I successfully optimized vitrification of these specimens by testing various vitrification techniques and cryoprotectants. 
In order to obtain high-resolution molecular insights into the ultrastructure and organization of CDMs, I established cryo-focused ion beam scanning electron microscopy (FIBSEM) on these challenging and complex specimens. I explored different approaches for the creation of thin cryo-lamellae by FIB milling and succeeded in optimizing the cryo-lift-out technique, resulting in high-quality lamellae of approximately 200 nm thickness. 
High-resolution Cryo-ET of these lamellae revealed for the first time the architecture of native CDM in the context of matrix-secreting cells. This allowed for the in situ visualization of fibrillar matrix proteins such as collagen, laying the foundation for future structural and ultrastructural characterization of these proteins in their near-native environment. 
In summary, in this thesis, I present a novel workflow that combines state-of-the-art cryo-EM specimen preparation and imaging technologies to permit characterization of the ECM, an important tissue component in higher organisms. This innovative and highly versatile workflow will enable addressing far-reaching questions on ECM architecture, composition, and reciprocal ECM-cell interactions.},
  author       = {Zens, Bettina},
  isbn         = {978-3-99078-027-5},
  issn         = {2663-337X},
  keywords     = {cryo-EM, cryo-ET, FIB milling, method development, FIBSEM, extracellular matrix, ECM, cell-derived matrices, CDMs, cell culture, high pressure freezing, HPF, structural biology, tomography, collagen},
  pages        = {187},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography}},
  doi          = {10.15479/at:ista:12491},
  year         = {2023},
}

@phdthesis{13984,
  abstract     = {Social insects fight disease using their individual immune systems and the cooperative
sanitary behaviors of colony members. These social defenses are well explored against
externally-infecting pathogens, but little is known about defense strategies against
internally-infecting pathogens, such as viruses. Viruses are ubiquitous and in the last decades
it has become evident that also many ant species harbor viruses. We present one of the first
studies addressing transmission dynamics and collective disease defenses against viruses in
ants on a mechanistic level. I successfully established an experimental ant host – viral
pathogen system as a model for the defense strategies used by social insects against internal
pathogen infections, as outlined in the third chapter. In particular, we studied how garden ants
(Lasius neglectus) defend themselves and their colonies against the generalist insect virus
CrPV (cricket paralysis virus). We chose microinjections of virus directly into the ants’
hemolymph because it allowed us to use a defined exposure dose. Here we show that this is a
good model system, as the virus is replicating and thus infecting the host. The ants mount a
clear individual immune response against the viral infection, which is characterized by a
specific siRNA pattern, namely siRNAs mapping against the viral genome with a peak of 21
and 22 bp long fragments. The onset of this immune response is consistent with the timeline
of viral replication that starts already within two days post injection. The disease manifests in
decreased survival over a course of two to three weeks.
Regarding group living, we find that infected ants show a strong individual immune response,
but that their course of disease is little affected by nestmate presence, as described in chapter
four. Hence, we do not find social immunity in the context of viral infections in ants.
Nestmates, however, can contract the virus. Using Drosophila S2R+ cells in culture, we
showed that 94 % of the nestmates contract active virus within four days of social contact to
an infected individual. Virus is transmitted in low doses, thus not causing disease
transmission within the colony. While virus can be transmitted during short direct contacts,
we also assume transmission from deceased ants and show that the nestmates’ immune
system gets activated after contracting a low viral dose. We find considerable potential for
indirect transmission via the nest space. Virus is shed to the nest, where it stays viable for one
week and is also picked up by other ants. Apart from that, we want to underline the potential
of ant poison as antiviral agent. We determined that ant poison successfully inactivates CrPV
in vitro. However, we found no evidence for effective poison use to sanitize the nest space.
On the other hand, local application of ant poison by oral poison uptake, which is part of the
ants prophylactic behavioral repertoire, probably contributes to keeping the gut of each
individual sanitized. We hypothesize that oral poison uptake might be the reason why we did
not find viable virus in the trophallactic fluid.
The fifth chapter encompasses preliminary data on potential social immunization. However,
our experiments do not confirm an actual survival benefit for the nestmates upon pathogen
challenge under the given experimental settings. Nevertheless, we do not want to rule out the
possibility for nestmate immunization, but rather emphasize that considering different
experimental timelines and viral doses would provide a multitude of options for follow-up
experiments.
In conclusion, we find that prophylactic individual behaviors, such as oral poison uptake,
might play a role in preventing viral disease transmission. Compared to colony defense
against external pathogens, internal pathogen infections require a stronger component of
individual physiological immunity than behavioral social immunity, yet could still lead to
collective protection.},
  author       = {Franschitz, Anna},
  isbn         = {978-3-99078-034-3},
  issn         = {2663-337X},
  pages        = {89},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Individual and social immunity against viral infections in ants}},
  doi          = {10.15479/at:ista:13984},
  year         = {2023},
}

@phdthesis{12964,
  abstract     = {Pattern formation is of great importance for its contribution across different biological behaviours. During developmental processes for example, patterns of chemical gradients are
established to determine cell fate and complex tissue patterns emerge to define structures such
as limbs and vascular networks. Patterns are also seen in collectively migrating groups, for
instance traveling waves of density emerging in moving animal flocks as well as collectively migrating cells and tissues. To what extent these biological patterns arise spontaneously through
the local interaction of individual constituents or are dictated by higher level instructions is
still an open question however there is evidence for the involvement of both types of process.
Where patterns arise spontaneously there is a long standing interest in how far the interplay
of mechanics, e.g. force generation and deformation, and chemistry, e.g. gene regulation
and signaling, contributes to the behaviour. This is because many systems are able to both
chemically regulate mechanical force production and chemically sense mechanical deformation,
forming mechano-chemical feedback loops which can potentially become unstable towards
spatio and/or temporal patterning.
We work with experimental collaborators to investigate the possibility that this type of
interaction drives pattern formation in biological systems at different scales. We focus first on
tissue-level ERK-density waves observed during the wound healing response across different
systems where many previous studies have proposed that patterns depend on polarized cell
migration and arise from a mechanical flocking-like mechanism. By combining theory with
mechanical and optogenetic perturbation experiments on in vitro monolayers we instead find
evidence for mechanochemical pattern formation involving only scalar bilateral feedbacks
between ERK signaling and cell contraction. We perform further modeling and experiment
to study how this instability couples with polar cell migration in order to produce a robust
and efficient wound healing response. In a following chapter we implement ERK-density
coupling and cell migration in a 2D active vertex model to investigate the interaction of
ERK-density patterning with different tissue rheologies and find that the spatio-temporal
dynamics are able to both locally and globally fluidize a tissue across the solid-fluid glass
transition. In a last chapter we move towards lower spatial scales in the context of subcellular
patterning of the cell cytoskeleton where we investigate the transition between phases of
spatially homogeneous temporal oscillations and chaotic spatio-temporal patterning in the
dynamics of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton
and its activator). Experimental evidence supports an intrinsic chemical oscillator which we
encode in a reaction model and couple to a contractile active gel description of the cell cortex.
The model exhibits phases of chemical oscillations and contractile spatial patterning which
reproduce many features of the dynamics seen in Drosophila oocyte epithelia in vivo. However,
additional pharmacological perturbations to inhibit myosin contractility leaves the role of
contractile instability unclear. We discuss alternative hypotheses and investigate the possibility
of reaction-diffusion instability.},
  author       = {Boocock, Daniel R},
  isbn         = {978-3-99078-032-9},
  issn         = {2663-337X},
  pages        = {146},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Mechanochemical pattern formation across biological scales}},
  doi          = {10.15479/at:ista:12964},
  year         = {2023},
}

@phdthesis{12897,
  abstract     = {Inverse design problems in fabrication-aware shape optimization are typically solved on discrete representations such as polygonal meshes. This thesis argues that there are benefits to treating these problems in the same domain as human designers, namely, the parametric one. One reason is that discretizing a parametric model usually removes the capability of making further manual changes to the design, because the human intent is captured by the shape parameters. Beyond this, knowledge about a design problem can sometimes reveal a structure that is present in a smooth representation, but is fundamentally altered by discretizing. In this case, working in the parametric domain may even simplify the optimization task. We present two lines of research that explore both of these aspects of fabrication-aware shape optimization on parametric representations.

The first project studies the design of plane elastic curves and Kirchhoff rods, which are common mathematical models for describing the deformation of thin elastic rods such as beams, ribbons, cables, and hair. Our main contribution is a characterization of all curved shapes that can be attained by bending and twisting elastic rods having a stiffness that is allowed to vary across the length. Elements like these can be manufactured using digital fabrication devices such as 3d printers and digital cutters, and have applications in free-form architecture and soft robotics.

We show that the family of curved shapes that can be produced this way admits geometric description that is concise and computationally convenient. In the case of plane curves, the geometric description is intuitive enough to allow a designer to determine whether a curved shape is physically achievable by visual inspection alone. We also present shape optimization algorithms that convert a user-defined curve in the plane or in three dimensions into the geometry of an elastic rod that will naturally deform to follow this curve when its endpoints are attached to a support structure. Implemented in an interactive software design tool, the rod geometry is generated in real time as the user edits a curve and enables fast prototyping. 

The second project tackles the problem of general-purpose shape optimization on CAD models using a novel variant of the extended finite element method (XFEM). Our goal is the decoupling between the simulation mesh and the CAD model, so no geometry-dependent meshing or remeshing needs to be performed when the CAD parameters change during optimization. This is achieved by discretizing the embedding space of the CAD model, and using a new high-accuracy numerical integration method to enable XFEM on free-form elements bounded by the parametric surface patches of the model. Our simulation is differentiable from the CAD parameters to the simulation output, which enables us to use off-the-shelf gradient-based optimization procedures. The result is a method that fits seamlessly into the CAD workflow because it works on the same representation as the designer, enabling the alternation of manual editing and fabrication-aware optimization at will.},
  author       = {Hafner, Christian},
  isbn         = {978-3-99078-031-2},
  issn         = {2663-337X},
  pages        = {180},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Inverse shape design with parametric representations: Kirchhoff Rods and parametric surface models}},
  doi          = {10.15479/at:ista:12897},
  year         = {2023},
}

@article{13188,
  abstract     = {The Kirchhoff rod model describes the bending and twisting of slender elastic rods in three dimensions, and has been widely studied to enable the prediction of how a rod will deform, given its geometry and boundary conditions. In this work, we study a number of inverse problems with the goal of computing the geometry of a straight rod that will automatically deform to match a curved target shape after attaching its endpoints to a support structure. Our solution lets us finely control the static equilibrium state of a rod by varying the cross-sectional profiles along its length.
We also show that the set of physically realizable equilibrium states admits a concise geometric description in terms of linear line complexes, which leads to very efficient computational design algorithms. Implemented in an interactive software tool, they allow us to convert three-dimensional hand-drawn spline curves to elastic rods, and give feedback about the feasibility and practicality of a design in real time. We demonstrate the efficacy of our method by designing and manufacturing several physical prototypes with applications to interior design and soft robotics.},
  author       = {Hafner, Christian and Bickel, Bernd},
  issn         = {1557-7368},
  journal      = {ACM Transactions on Graphics},
  keywords     = {Computer Graphics, Computational Design, Computational Geometry, Shape Modeling},
  number       = {5},
  publisher    = {Association for Computing Machinery},
  title        = {{The design space of Kirchhoff rods}},
  doi          = {10.1145/3606033},
  volume       = {42},
  year         = {2023},
}

@phdthesis{12809,
  abstract     = {Understanding the mechanisms of learning and memory formation has always been one of
the main goals in neuroscience. Already Pavlov (1927) in his early days has used his classic
conditioning experiments to study the neural mechanisms governing behavioral adaptation.
What was not known back then was that the part of the brain that is largely responsible for
this type of associative learning is the cerebellum.
Since then, plenty of theories on cerebellar learning have emerged. Despite their differences,
one thing they all have in common is that learning relies on synaptic and intrinsic plasticity.
The goal of my PhD project was to unravel the molecular mechanisms underlying synaptic
plasticity in two synapses that have been shown to be implicated in motor learning, in an
effort to understand how learning and memory formation are processed in the cerebellum.
One of the earliest and most well-known cerebellar theories postulates that motor learning
largely depends on long-term depression at the parallel fiber-Purkinje cell (PC-PC) synapse.
However, the discovery of other types of plasticity in the cerebellar circuitry, like long-term
potentiation (LTP) at the PC-PC synapse, potentiation of molecular layer interneurons (MLIs),
and plasticity transfer from the cortex to the cerebellar/ vestibular nuclei has increased the
popularity of the idea that multiple sites of plasticity might be involved in learning.
Still a lot remains unknown about the molecular mechanisms responsible for these types of
plasticity and whether they occur during physiological learning.
In the first part of this thesis we have analyzed the variation and nanodistribution of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
type glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell synapse after vestibuloocular reflex phase reversal adaptation, a behavior that has been suggested to rely on PF-PC
LTP. We have found that on the last day of adaptation there is no learning trace in form of
VGCCs nor AMPARs variation at the PF-PC synapse, but instead a decrease in the number of
PF-PC synapses. These data seem to support the view that learning is only stored in the
cerebellar cortex in an initial learning phase, being transferred later to the vestibular nuclei.
Next, we have studied the role of MLIs in motor learning using a relatively simple and well characterized behavioral paradigm – horizontal optokinetic reflex (HOKR) adaptation. We
have found behavior-induced MLI potentiation in form of release probability increase that
could be explained by the increase of VGCCs at the presynaptic side. Our results strengthen
the idea of distributed cerebellar plasticity contributing to learning and provide a novel
mechanism for release probability increase. },
  author       = {Alcarva, Catarina},
  issn         = {2663-337X},
  pages        = {115},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning}},
  doi          = {10.15479/at:ista:12809},
  year         = {2023},
}