@article{12291,
  abstract     = {The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.},
  author       = {Friml, Jiří and Gallei, Michelle C and Gelová, Zuzana and Johnson, Alexander J and Mazur, Ewa and Monzer, Aline and Rodriguez Solovey, Lesia and Roosjen, Mark and Verstraeten, Inge and Živanović, Branka D. and Zou, Minxia and Fiedler, Lukas and Giannini, Caterina and Grones, Peter and Hrtyan, Mónika and Kaufmann, Walter and Kuhn, Andre and Narasimhan, Madhumitha and Randuch, Marek and Rýdza, Nikola and Takahashi, Koji and Tan, Shutang and Teplova, Anastasiia and Kinoshita, Toshinori and Weijers, Dolf and Rakusová, Hana},
  issn         = {1476-4687},
  journal      = {Nature},
  number       = {7927},
  pages        = {575--581},
  publisher    = {Springer Nature},
  title        = {{ABP1–TMK auxin perception for global phosphorylation and auxin canalization}},
  doi          = {10.1038/s41586-022-05187-x},
  volume       = {609},
  year         = {2022},
}

@phdthesis{11362,
  abstract     = {Deep learning has enabled breakthroughs in challenging computing problems and has emerged as the standard problem-solving tool for computer vision and natural language processing tasks.
One exception to this trend is safety-critical tasks where robustness and resilience requirements contradict the black-box nature of neural networks. 
To deploy deep learning methods for these tasks, it is vital to provide guarantees on neural network agents' safety and robustness criteria. 
This can be achieved by developing formal verification methods to verify the safety and robustness properties of neural networks.

Our goal is to design, develop and assess safety verification methods for neural networks to improve their reliability and trustworthiness in real-world applications.
This thesis establishes techniques for the verification of compressed and adversarially trained models as well as the design of novel neural networks for verifiably safe decision-making.

First, we establish the problem of verifying quantized neural networks. Quantization is a technique that trades numerical precision for the computational efficiency of running a neural network and is widely adopted in industry.
We show that neglecting the reduced precision when verifying a neural network can lead to wrong conclusions about the robustness and safety of the network, highlighting that novel techniques for quantized network verification are necessary. We introduce several bit-exact verification methods explicitly designed for quantized neural networks and experimentally confirm on realistic networks that the network's robustness and other formal properties are affected by the quantization.

Furthermore, we perform a case study providing evidence that adversarial training, a standard technique for making neural networks more robust, has detrimental effects on the network's performance. This robustness-accuracy tradeoff has been studied before regarding the accuracy obtained on classification datasets where each data point is independent of all other data points. On the other hand, we investigate the tradeoff empirically in robot learning settings where a both, a high accuracy and a high robustness, are desirable.
Our results suggest that the negative side-effects of adversarial training outweigh its robustness benefits in practice.

Finally, we consider the problem of verifying safety when running a Bayesian neural network policy in a feedback loop with systems over the infinite time horizon. Bayesian neural networks are probabilistic models for learning uncertainties in the data and are therefore often used on robotic and healthcare applications where data is inherently stochastic.
We introduce a method for recalibrating Bayesian neural networks so that they yield probability distributions over safe decisions only.
Our method learns a safety certificate that guarantees safety over the infinite time horizon to determine which decisions are safe in every possible state of the system.
We demonstrate the effectiveness of our approach on a series of reinforcement learning benchmarks.},
  author       = {Lechner, Mathias},
  isbn         = {978-3-99078-017-6},
  keywords     = {neural networks, verification, machine learning},
  pages        = {124},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Learning verifiable representations}},
  doi          = {10.15479/at:ista:11362},
  year         = {2022},
}

@inproceedings{11476,
  abstract     = {Messaging platforms like Signal are widely deployed and provide strong security in an asynchronous setting. It is a challenging problem to construct a protocol with similar security guarantees that can efficiently scale to large groups. A major bottleneck are the frequent key rotations users need to perform to achieve post compromise forward security.

In current proposals – most notably in TreeKEM (which is part of the IETF’s Messaging Layer Security (MLS) protocol draft) – for users in a group of size n to rotate their keys, they must each craft a message of size log(n) to be broadcast to the group using an (untrusted) delivery server.

In larger groups, having users sequentially rotate their keys requires too much bandwidth (or takes too long), so variants allowing any T≤n users to simultaneously rotate their keys in just 2 communication rounds have been suggested (e.g. “Propose and Commit” by MLS). Unfortunately, 2-round concurrent updates are either damaging or expensive (or both); i.e. they either result in future operations being more costly (e.g. via “blanking” or “tainting”) or are costly themselves requiring Ω(T) communication for each user [Bienstock et al., TCC’20].

In this paper we propose CoCoA; a new scheme that allows for T concurrent updates that are neither damaging nor costly. That is, they add no cost to future operations yet they only require Ω(log2(n)) communication per user. To circumvent the [Bienstock et al.] lower bound, CoCoA increases the number of rounds needed to complete all updates from 2 up to (at most) log(n); though typically fewer rounds are needed.

The key insight of our protocol is the following: in the (non-concurrent version of) TreeKEM, a delivery server which gets T concurrent update requests will approve one and reject the remaining T−1. In contrast, our server attempts to apply all of them. If more than one user requests to rotate the same key during a round, the server arbitrarily picks a winner. Surprisingly, we prove that regardless of how the server chooses the winners, all previously compromised users will recover after at most log(n) such update rounds.

To keep the communication complexity low, CoCoA is a server-aided CGKA. That is, the delivery server no longer blindly forwards packets, but instead actively computes individualized packets tailored to each user. As the server is untrusted, this change requires us to develop new mechanisms ensuring robustness of the protocol.},
  author       = {Alwen, Joël and Auerbach, Benedikt and Cueto Noval, Miguel and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael},
  booktitle    = {Advances in Cryptology – EUROCRYPT 2022},
  isbn         = {9783031070846},
  issn         = {1611-3349},
  location     = {Trondheim, Norway},
  pages        = {815–844},
  publisher    = {Springer Nature},
  title        = {{CoCoA: Concurrent continuous group key agreement}},
  doi          = {10.1007/978-3-031-07085-3_28},
  volume       = {13276},
  year         = {2022},
}

@phdthesis{11196,
  abstract     = {One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). 
	In addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.
},
  author       = {Kim, Olena},
  issn         = {2663-337X},
  pages        = {132},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses}},
  doi          = {10.15479/at:ista:11196},
  year         = {2022},
}

@phdthesis{11879,
  abstract     = {As the overall global mean surface temperature is increasing due to climate change, plant
adaptation to those stressful conditions is of utmost importance for their survival. Plants are
sessile organisms, thus to compensate for their lack of mobility, they evolved a variety of
mechanisms enabling them to flexibly adjust their physiological, growth and developmental
processes to fluctuating temperatures and to survive in harsh environments. While these unique
adaptation abilities provide an important evolutionary advantage, overall modulation of plant
growth and developmental program due to non-optimal temperature negatively affects biomass
production, crop productivity or sensitivity to pathogens. Thus, understanding molecular
processes underlying plant adaptation to increased temperature can provide important
resources for breeding strategies to ensure sufficient agricultural food production.
An increase in ambient temperature by a few degrees leads to profound changes in organ growth
including enhanced hypocotyl elongation, expansion of petioles, hyponastic growth of leaves and
cotyledons, collectively named thermomorphogenesis (Casal & Balasubramanian, 2019). Auxin,
one of the best-studied growth hormones, plays an essential role in this process by direct
activation of transcriptional and non-transcriptional processes resulting in elongation growth
(Majda & Robert, 2018).To modulate hypocotyl growth in response to high ambient temperature
(hAT), auxin needs to be redistributed accordingly. PINs, auxin efflux transporters, are key
components of the polar auxin transport (PAT) machinery, which controls the amount and
direction of auxin translocated in the plant tissues and organs(Adamowski & Friml, 2015). Hence,
PIN-mediated transport is tightly linked with thermo-morphogenesis, and interference with PAT
through either chemical or genetic means dramatically affecting the adaptive responses to hAT.
Intriguingly, despite the key role of PIN mediated transport in growth response to hAT, whether
and how PINs at the level of expression adapt to fluctuation in temperature is scarcely
understood.
With genetic, molecular and advanced bio-imaging approaches, we demonstrate the role of PIN
auxin transporters in the regulation of hypocotyl growth in response to hAT. We show that via
adjustment of PIN3, PIN4 and PIN7 expression in cotyledons and hypocotyls, auxin distribution is modulated thereby determining elongation pattern of epidermal cells at hAT. Furthermore, we
identified three Zinc-Finger (ZF) transcription factors as novel molecular components of the
thermo-regulatory network, which through negative regulation of PIN transcription adjust the
transport of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of the
negative feedback loop attenuating the activity of the thermo-sensing pathway to restrain
exaggerated growth and developmental responses to hAT.},
  author       = {Artner, Christina},
  isbn         = {978-3-99078-022-0},
  issn         = {2663-337X},
  keywords     = {high ambient temperature, auxin, PINs, Zinc-Finger proteins, thermomorphogenesis, stress},
  pages        = {128},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature}},
  doi          = {10.15479/at:ista:11879},
  year         = {2022},
}

@phdthesis{12364,
  abstract     = {Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by behavioral symptoms such as problems in social communication and interaction, as
well as repetitive, restricted behaviors and interests. These disorders show a high degree
of heritability and hundreds of risk genes have been identifed using high throughput
sequencing technologies. This genetic heterogeneity has hampered eforts in understanding
the pathogenesis of ASD but at the same time given rise to the concept of convergent
mechanisms. Previous studies have identifed that risk genes for ASD broadly converge
onto specifc functional categories with transcriptional regulation being one of the biggest
groups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory
consequences of some of them in the context of neurodevelopment.
First, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead
to perturbations of gene regulatory programs in early cell fate specifcation. In addition,
adult animals display abnormal learning behavior which is mirrored at the transcriptional
level by altered activity dependent regulation of postsynaptic gene expression. Lastly,
we link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR
complex.
Second, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral
organoids we demonstrate profound changes in the developmental trajectories of both
inhibitory and excitatory neurons using single cell RNA-sequencing. While the former
were generated earlier in CHD8+/- organoids, the generation of the latter was shifted to
later times in favor of a prolonged progenitor expansion phase and ultimately increased
organoid size.
Finally, by modeling heterozygous mutations for four ASD associated chromatin modifers,
ASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of
regulatory convergence across three of those genes. We observe a shift from dorsal cortical
excitatory neuron fates towards partially ventralized cell types resembling cells from the
lateral ganglionic eminence. As this project is still ongoing at the time of writing, future
experiments will aim at elucidating the regulatory mechanisms underlying this shift with
the aim of linking these three ASD risk genes through biological convergence.},
  author       = {Dotter, Christoph},
  issn         = {2663-337X},
  pages        = {152},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder}},
  doi          = {10.15479/at:ista:12094},
  year         = {2022},
}

@phdthesis{11393,
  abstract     = {AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is
implicated in complex processes such as learning and memory and various neurological
diseases. These receptors are composed of different subunits and the subunit composition can
affect channel properties, receptor trafficking and interaction with other associated proteins.
Using the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for
electron microscopy I investigated the number, density, and localization of AMPAR subunits,
GluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse
hippocampus. I have found that the immunogold labeling for all of these subunits in the
postsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual
increase from the pyramidal cell soma towards the distal part of stratum radiatum. The densities
of extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities,
while the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those
for other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their
densities were higher in the periphery than center of synapses. In contrast, the GluA3-
containing receptors were more centrally localized compared to the GluA1- and GluA2-
containing receptors.
The hippocampus plays a central role in learning and memory. Contextual learning has been
shown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus.
However, proximodistal heterogeneity of this plasticity and particular contribution of different
AMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a
hippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an
increase in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.
The intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred
pattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but
not stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings
further contribute to our understanding of how specific hippocampal subregions and AMPA
receptor subunits are involved in physiological learning.
Although the immunolabeling results above shed light on subunit-specific plasticity in
AMPAR distribution, no tools to visualize and study the subunit composition at the single
channel level in situ have been available. Electron microscopy with conventional immunogold
labeling approaches has limitations in the single channel analysis because of the large size of
antibodies and steric hindrance hampering multiple subunit labeling of single channels. I
managed to develop a new chemical labeling system using a short peptide tag and small
synthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to
proteins of interest (reactive tag system). I additionally made substantial progress into adapting
this system for AMPA receptor subunits.},
  author       = {Jevtic, Marijo},
  issn         = {2663-337X},
  pages        = {108},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus}},
  doi          = {10.15479/at:ista:11393},
  year         = {2022},
}

@phdthesis{12366,
  abstract     = {Recent substantial advances in the feld of superconducting circuits have shown its
potential as a leading platform for future quantum computing. In contrast to classical
computers based on bits that are represented by a single binary value, 0 or 1, quantum
bits (or qubits) can be in a superposition of both. Thus, quantum computers can store
and handle more information at the same time and a quantum advantage has already
been demonstrated for two types of computational tasks. Rapid progress in academic
and industry labs accelerates the development of superconducting processors which may
soon fnd applications in complex computations, chemical simulations, cryptography, and
optimization. Now that these machines are scaled up to tackle such problems the questions
of qubit interconnects and networks becomes very relevant. How to route signals on-chip
between diferent processor components? What is the most efcient way to entangle
qubits? And how to then send and process entangled signals between distant cryostats
hosting superconducting processors?
In this thesis, we are looking for solutions to these problems by studying the collective
behavior of superconducting qubit ensembles. We frst demonstrate on-demand tunable
directional scattering of microwave photons from a pair of qubits in a waveguide. Such a
device can route microwave photons on-chip with a high diode efciency. Then we focus
on studying ultra-strong coupling regimes between light (microwave photons) and matter
(superconducting qubits), a regime that could be promising for extremely fast multi-qubit
entanglement generation. Finally, we show coherent pulse storage and periodic revivals
in a fve qubit ensemble strongly coupled to a resonator. Such a reconfgurable storage
device could be used as part of a quantum repeater that is needed for longer-distance
quantum communication.
The achieved high degree of control over multi-qubit ensembles highlights not only the
beautiful physics of circuit quantum electrodynamics, it also represents the frst step
toward new quantum simulation and communication methods, and certain techniques
may also fnd applications in future superconducting quantum computing hardware.
},
  author       = {Redchenko, Elena},
  isbn         = {978-3-99078-024-4},
  issn         = {2663-337X},
  pages        = {168},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Controllable states of superconducting Qubit ensembles}},
  doi          = {10.15479/at:ista:12132},
  year         = {2022},
}

@misc{10934,
  abstract     = {FtsA is crucial for assembly of the E. coli divisome, as it dynamically links cytoplasmic FtsZ filaments with transmembrane cell division proteins. FtsA allegedly initiates cell division by switching from an inactive polymeric to an active monomeric confirmation, which recruits downstream proteins and stabilizes FtsZ filaments. Here, we use biochemical reconstitution experiments combined with quantitative fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing FtsZ filaments and recruiting FtsN. We attribute these differences to a faster membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments.  Using FRET microscopy, we find that FtsN binding does not compete with, but promotes FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic polymers on the membrane, which re-organize during assembly and activation of the divisome. },
  author       = {Radler, Philipp},
  keywords     = {Bacterial cell division, in vitro reconstitution, FtsZ, FtsN, FtsA},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{In vitro reconstitution of Escherichia coli divisome activation}},
  doi          = {10.15479/AT:ISTA:10934},
  year         = {2022},
}

@phdthesis{11193,
  abstract     = {The infiltration of immune cells into tissues underlies the establishment of tissue-resident
macrophages and responses to infections and tumors. However, the mechanisms immune
cells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.
In this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to
overcome the tissue barrier of the germband in the embryo. One strategy is the strengthening
of the actin cortex through developmentally controlled transcriptional regulation induced by
the Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces
expression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the
activated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical
strength allows hemocytes to overcome the physical resistance of the surrounding tissue and
translocate their nucleus to move forward. This mechanism affects the speed of migration
when hemocytes face a confined environment in vivo.
Another aspect of the invasion process is the initial step of the leading hemocytes entering
the tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel
subpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads
penetration into the germband. Hemocytes that are deficient in BMP signaling activation
show impaired persistence at the tissue entry, while their migration speed remains
unaffected.
This suggests that there might be different mechanisms controlling immune cell migration
within the confined environment in vivo, one of these being the general ability to overcome
the resistance of the surrounding tissue and another affecting the order of hemocytes that
collectively invade the tissue in a stream of individual cells.
Together, my findings provide deeper insights into transcriptional changes in immune
cells that enable efficient tissue invasion and pave the way for future studies investigating the
early colonization of tissues by macrophages in higher organisms. Moreover, they extend the
current view of Drosophila immune cell heterogeneity and point toward a potentially
conserved role for canonical BMP signaling in specifying immune cells that lead the migration
of tissue resident macrophages during embryogenesis.},
  author       = {Wachner, Stephanie},
  issn         = {2663-337X},
  pages        = {170},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells}},
  doi          = {10.15479/at:ista:11193},
  year         = {2022},
}

@phdthesis{12378,
  abstract     = {Environmental cues influence the highly dynamic morphology of microglia. Strategies to 
characterize these changes usually involve user-selected morphometric features, which 
preclude the identification of a spectrum of context-dependent morphological phenotypes. 
Here, we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,
overcomes feature-selection bias and minimizes biological variability. 
First, with MorphOMICs we derive the morphological spectrum of microglia across seven 
brain regions during postnatal development and in two distinct Alzheimer’s disease 
degeneration mouse models. We uncover region-specific and sexually dimorphic
morphological trajectories, with females showing an earlier morphological shift than males in 
the degenerating brain. Overall, we demonstrate that both long primary- and short terminal 
processes provide distinct insights to morphological phenotypes. Moreover, using machine 
learning to map novel condition on the spectrum, we observe that microglia morphologies 
reflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control 
morphologies.
Next, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of 
microglial morphological spectrum in the retina, covering postnatal development and rd10 
degeneration. Here, following photoreceptor death, microglia assume an early developmentlike morphology. Finally, we map microglial morphology following optic nerve crush on the 
retinal spectrum and observe a layer- and sex-dependent response. 
Overall, MorphOMICs opens a new perspective to analyze microglial morphology across 
multiple conditions, and provides a novel tool to characterize microglial morphology beyond 
the traditionally dichotomized view of microglia.},
  author       = {Colombo, Gloria},
  issn         = {2663-337X},
  pages        = {142},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes}},
  doi          = {10.15479/at:ista:12378},
  year         = {2022},
}

@phdthesis{11388,
  abstract     = {In evolve and resequence experiments, a population is sequenced, subjected to selection and
then sequenced again, so that genetic changes before and after selection can be observed at
the genetic level. Here, I use these studies to better understand the genetic basis of complex
traits - traits which depend on more than a few genes.
In the first chapter, I discuss the first evolve and resequence experiment, in which a population
of mice, the so-called "Longshanks" mice, were selected for tibia length while their body mass
was kept constant. The full pedigree is known. We observed a selection response on all
chromosomes and used the infinitesimal model with linkage, a model which assumes an infinite
number of genes with infinitesimally small effect sizes, as a null model. Results implied a very
polygenic basis with a few loci of major effect standing out and changing in parallel. There
was large variability between the different chromosomes in this study, probably due to LD.
In chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency
based summary statistic, giving an equation based on the initial allele frequencies, average
pairwise LD, and the first four moments of the haplotype block copy number distribution. I
describe this distribution by referring back to the founder generation. I then demonstrate
how to infer selection via a maximum likelihood scheme on the example of a single locus and
discuss how to extend this to more realistic scenarios.
In chapter three, I discuss the second evolve and resequence experiment, in which a small
population of Drosophila melanogaster was selected for increased pupal case size over 6
generations. The experiment was highly replicated with 27 lines selected within family and a
known pedigree. We observed a phenotypic selection response of over one standard deviation.
I describe the patterns in allele frequency data, including allele frequency changes and patterns
of heterozygosity, and give ideas for future work.},
  author       = {Belohlavy, Stefanie},
  isbn         = {978-3-99078-018-3},
  pages        = {98},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{The genetic basis of complex traits studied via analysis of evolve and resequence experiments}},
  doi          = {10.15479/at:ista:11388},
  year         = {2022},
}

@phdthesis{12401,
  abstract     = {Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which
is the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.
Recent studies indicate a crucial role of the tumor microenvironment in malignant
transformation and metastasis. Studying cancer cell invasion and detachments quantitatively in
the context of its physiological microenvironment is technically challenging. Especially, precise
control of microenvironmental properties in vivo is currently not possible. Here, I studied the
role of microenvironment geometry in the invasion and detachment of cancer cells from the
bulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic
devices to mimic a pseudo 3D extracellular matrix environment, where I was able to
quantitatively tune the geometrical configuration of the microenvironment and follow tumor
cells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable
software application to automatically analyze and visualize particle tracking data.
Quantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments
showed that heterogeneity in the microenvironment promotes faster invasion and more
frequent detachment of cells. These observations correlated with overall higher speed of cells at
the edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially
passed through larger pores, thus invading areas of least resistance and generating finger-like
invasive structures. The detachments occurred mostly at the tips of these structures.
To investigate the potential mechanism, we established a two dimensional model to simulate
active Brownian particles representing the cell nuclei dynamics. These simulations backed our in
vitro observations without the need of precise fitting the simulation parameters. Our model
suggests the importance of the pore heterogeneity in the direction perpendicular to the
orientation of bias field (lateral heterogeneity), which causes the interface roughening.},
  author       = {Tasciyan, Saren},
  issn         = {2663-337X},
  pages        = {105},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Role of microenvironment heterogeneity in cancer cell invasion}},
  doi          = {10.15479/at:ista:12401},
  year         = {2022},
}

@misc{11653,
  abstract     = {Eurasian brine shrimp (genus Artemia) have closely related sexual and asexual lineages of parthenogenetic females, which produce rare males at low frequencies. Although they are known to have ZW chromosomes, these are not well characterized, and it is unclear whether they are shared across the clade. Furthermore, the underlying genetic architecture of the transmission of asexuality, which can occur when rare males mate with closely related sexual females, is not well understood. We produced a chromosome-level assembly for the sexual Eurasian species A. sinica and characterized in detail the pair of sex chromosomes of this species. We combined this new assembly with short-read genomic data for the sexual species A. sp. Kazakhstan and several asexual lineages of A. parthenogenetica, allowing us to perform an in-depth characterization of sex-chromosome evolution across the genus. We identified a small differentiated region of the ZW pair that is shared by all sexual and asexual lineages, supporting the shared ancestry of the sex chromosomes. We also inferred that recombination suppression has spread to larger sections of the chromosome independently in the American and Eurasian lineages. Finally, we took advantage of a rare male, which we backcrossed to sexual females, to explore the genetic basis of asexuality. Our results suggest that parthenogenesis is likely partly controlled by a locus on the Z chromosome, highlighting the interplay between sex determination and asexuality.},
  author       = {Elkrewi, Marwan N},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Data from Elkrewi, Khauratovich, Toups et al. 2022, "ZW sex-chromosome evolution and contagious parthenogenesis in Artemia brine shrimp"}},
  doi          = {10.15479/AT:ISTA:11653},
  year         = {2022},
}

@phdthesis{11932,
  abstract     = {The ability to form and retrieve memories is central to survival. In mammals, the hippocampus
is a brain region essential to the acquisition and consolidation of new memories. It is also
involved in keeping track of one’s position in space and aids navigation. Although this
space-memory has been a source of contradiction, evidence supports the view that the role of
the hippocampus in navigation is memory, thanks to the formation of cognitive maps. First
introduced by Tolman in 1948, cognitive maps are generally used to organize experiences in
memory; however, the detailed mechanisms by which these maps are formed and stored are not
yet agreed upon. Some influential theories describe this process as involving three fundamental
steps: initial encoding by the hippocampus, interactions between the hippocampus and other
cortical areas, and long-term extra-hippocampal consolidation. In this thesis, I will show how
the investigation of cognitive maps of space helped to shed light on each of these three memory
processes.
The first study included in this thesis deals with the initial encoding of spatial memories in
the hippocampus. Much is known about encoding at the level of single cells, but less about
their co-activity or joint contribution to the encoding of novel spatial information. I will
describe the structure of an interaction network that allows for efficient encoding of noisy
spatial information during the first exploration of a novel environment.
The second study describes the interactions between the hippocampus and the prefrontal
cortex (PFC), two areas directly and indirectly connected. It is known that the PFC, in concert
with the hippocampus, is involved in various processes, including memory storage and spatial
navigation. Nonetheless, the detailed mechanisms by which PFC receives information from the
hippocampus are not clear. I will show how a transient improvement in theta phase locking of
PFC cells enables interactions of cell pairs across the two regions.
The third study describes the learning of behaviorally-relevant spatial locations in the hippocampus and the medial entorhinal cortex. I will show how the accumulation of firing around
goal locations, a correlate of learning, can shed light on the transition from short- to long-term
spatial memories and the speed of consolidation in different brain areas.
The studies included in this thesis represent the main scientific contributions of my Ph.D. They
involve statistical analyses and models of neural responses of cells in different brain areas of
rats executing spatial tasks. I will conclude the thesis by discussing the impact of the findings
on principles of memory formation and retention, including the mechanisms, the speed, and
the duration of these processes.},
  author       = {Nardin, Michele},
  issn         = {2663-337X},
  pages        = {136},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{On the encoding, transfer, and consolidation of spatial memories}},
  doi          = {10.15479/at:ista:11932},
  year         = {2022},
}

@phdthesis{10727,
  abstract     = {Social insects are a common model to study disease dynamics in social animals. Even though pathogens should thrive in social insect colonies as the hosts engage in frequent social interactions, are closely related and live in a pathogen-rich environment, disease outbreaks are rare. This is because social insects have evolved mechanisms to keep pathogens at bay – and fight disease as a collective. Social insect colonies are often viewed as “superorganisms” with division of labor between reproductive “germ-like” queens and males and “somatic” workers, which together form an interdependent reproductive unit that parallels a multicellular body. Superorganisms possess a “social immune system” that comprises of collective disease defenses performed by the workers - summarized as “social immunity”. In social groups immunization (reduced susceptibility to a parasite upon secondary exposure to the same parasite) can e.g. be triggered by social interactions (“social immunization”). Social immunization can be caused by (i) asymptomatic low-level infections that are acquired during caregiving to a contagious individual that can give an immune boost, which can induce protection upon later encounter with the same pathogen (active immunization) or (ii) by transfer of immune effectors between individuals (passive immunization).
In the second chapter, I built up on a study that I co-authored that found that low-level infections can not only be protective, but also be costly and make the host more susceptible to detrimental superinfections after contact to a very dissimilar pathogen. I here now tested different degrees of phylogenetically-distant fungal strains of M. brunneum and M. robertsii in L. neglectus and can describe the occurrence of cross-protection of social immunization if the first and second pathogen are from the same level. Interestingly, low-level infections only provided protection when the first strain was less virulent than the second strain and elicited higher immune gene expression.
In the third and fourth chapters, I expanded on the role of social immunity in sexual selection, a so far unstudied field. I used the fungus Metarhizium robertsii and the ant Cardiocondyla obscurior as a model, as in this species mating occurs in the presence of workers and can be studied under laboratory conditions. Before males mate with virgin queens in the nest they engage in fierce combat over the access to their mating partners.
First, I focused on male-male competition in the third chapter and found that fighting with a contagious male is costly as it can lead to contamination of the rival, but that workers can decrease the risk of disease contraction by performing sanitary care.
In the fourth chapter, I studied the effect of fungal infection on survival and mating success of sexuals (freshly emerged queens and males) and found that worker-performed sanitary care can buffer the negative effect that a pathogenic contagion would have on sexuals by spore removal from the exposed individuals. When social immunity was prevented and queens could contract spores from their mating partner, very low dosages led to negative consequences: their lifespan was reduced and they produced fewer offspring with poor immunocompetence compared to healthy queens. Interestingly, cohabitation with a late-stage infected male where no spore transfer was possible had a positive effect on offspring immunity – male offspring of mothers that apparently perceived an infected partner in their vicinity reacted more sensitively to fungal challenge than male offspring without paternal pathogen history.},
  author       = {Metzler, Sina},
  issn         = {2663-337X},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Pathogen-mediated sexual selection and immunization in ant colonies}},
  doi          = {10.15479/AT:ISTA:10727},
  year         = {2022},
}

@inproceedings{11458,
  abstract     = {The increasing computational requirements of deep neural networks (DNNs) have led to significant interest in obtaining DNN models that are sparse, yet accurate. Recent work has investigated the even harder case of sparse training, where the DNN weights are, for as much as possible, already sparse to reduce computational costs during training. Existing sparse training methods are often empirical and can have lower accuracy relative to the dense baseline. In this paper, we present a general approach called Alternating Compressed/DeCompressed (AC/DC) training of DNNs, demonstrate convergence for a variant of the algorithm, and show that AC/DC outperforms existing sparse training methods in accuracy at similar computational budgets; at high sparsity levels, AC/DC even outperforms existing methods that rely on accurate pre-trained dense models. An important property of AC/DC is that it allows co-training of dense and sparse models, yielding accurate sparse–dense model pairs at the end of the training process. This is useful in practice, where compressed variants may be desirable for deployment in resource-constrained settings without re-doing the entire training flow, and also provides us with insights into the accuracy gap between dense and compressed models. The code is available at: https://github.com/IST-DASLab/ACDC.},
  author       = {Peste, Elena-Alexandra and Iofinova, Eugenia B and Vladu, Adrian and Alistarh, Dan-Adrian},
  booktitle    = {35th Conference on Neural Information Processing Systems},
  isbn         = {9781713845393},
  issn         = {1049-5258},
  location     = {Virtual, Online},
  pages        = {8557--8570},
  publisher    = {Neural Information Processing Systems Foundation},
  title        = {{AC/DC: Alternating Compressed/DeCompressed training of deep neural networks}},
  volume       = {34},
  year         = {2021},
}

@phdthesis{10007,
  abstract     = {The present thesis is concerned with the derivation of weak-strong uniqueness principles for curvature driven interface evolution problems not satisfying a comparison principle. The specific examples being treated are two-phase Navier-Stokes flow with surface tension, modeling the evolution of two incompressible, viscous and immiscible fluids separated by a sharp interface, and multiphase mean curvature flow, which serves as an idealized model for the motion of grain boundaries in an annealing polycrystalline material. Our main results - obtained in joint works with Julian Fischer, Tim Laux and Theresa M. Simon - state that prior to the formation of geometric singularities due to topology changes, the weak solution concept of Abels (Interfaces Free Bound. 9, 2007) to two-phase Navier-Stokes flow with surface tension and the weak solution concept of Laux and Otto (Calc. Var. Partial Differential Equations 55, 2016) to multiphase mean curvature flow (for networks in R^2 or double bubbles in R^3) represents the unique solution to these interface evolution problems within the class of classical solutions, respectively. To the best of the author's knowledge, for interface evolution problems not admitting a geometric comparison principle the derivation of a weak-strong uniqueness principle represented an open problem, so that the works contained in the present thesis constitute the first positive results in this direction. The key ingredient of our approach consists of the introduction of a novel concept of relative entropies for a class of curvature driven interface evolution problems, for which the associated energy contains an interfacial contribution being proportional to the surface area of the evolving (network of) interface(s). The interfacial part of the relative entropy gives sufficient control on the interface error between a weak and a classical solution, and its time evolution can be computed, at least in principle, for any energy dissipating weak solution concept. A resulting stability estimate for the relative entropy essentially entails the above mentioned weak-strong uniqueness principles. The present thesis contains a detailed introduction to our relative entropy approach, which in particular highlights potential applications to other problems in curvature driven interface evolution not treated in this thesis.},
  author       = {Hensel, Sebastian},
  issn         = {2663-337X},
  pages        = {300},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Curvature driven interface evolution: Uniqueness properties of weak solution concepts}},
  doi          = {10.15479/at:ista:10007},
  year         = {2021},
}

@phdthesis{10030,
  abstract     = {This PhD thesis is primarily focused on the study of discrete transport problems, introduced for the first time in the seminal works of Maas [Maa11] and Mielke [Mie11] on finite state Markov chains and reaction-diffusion equations, respectively. More in detail, my research focuses on the study of transport costs on graphs, in particular the convergence and the stability of such problems in the discrete-to-continuum limit. This thesis also includes some results concerning
non-commutative optimal transport. The first chapter of this thesis consists of a general introduction to the optimal transport problems, both in the discrete, the continuous, and the non-commutative setting. Chapters 2 and 3 present the content of two works, obtained in collaboration with Peter Gladbach, Eva Kopfer, and Jan Maas, where we have been able to show the convergence of discrete transport costs on periodic graphs to suitable continuous ones, which can be described by means of a homogenisation result. We first focus on the particular case of quadratic costs on the real line and then extending the result to more general costs in arbitrary dimension. Our results are the first complete characterisation of limits of transport costs on periodic graphs in arbitrary dimension which do not rely on any additional symmetry. In Chapter 4 we turn our attention to one of the intriguing connection between evolution equations and optimal transport, represented by the theory of gradient flows. We show that discrete gradient flow structures associated to a finite volume approximation of a certain class of diffusive equations (Fokker–Planck) is stable in the limit of vanishing meshes, reproving the convergence of the scheme via the method of evolutionary Γ-convergence and exploiting a more variational point of view on the problem. This is based on a collaboration with Dominik Forkert and Jan Maas. Chapter 5 represents a change of perspective, moving away from the discrete world and reaching the non-commutative one. As in the discrete case, we discuss how classical tools coming from the commutative optimal transport can be translated into the setting of density matrices. In particular, in this final chapter we present a non-commutative version of the Schrödinger problem (or entropic regularised optimal transport problem) and discuss existence and characterisation of minimisers, a duality result, and present a non-commutative version of the well-known Sinkhorn algorithm to compute the above mentioned optimisers. This is based on a joint work with Dario Feliciangeli and Augusto Gerolin. Finally, Appendix A and B contain some additional material and discussions, with particular attention to Harnack inequalities and the regularity of flows on discrete spaces.},
  author       = {Portinale, Lorenzo},
  issn         = {2663-337X},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Discrete-to-continuum limits of transport problems and gradient flows in the space of measures}},
  doi          = {10.15479/at:ista:10030},
  year         = {2021},
}

@article{10191,
  abstract     = {In this work we solve the algorithmic problem of consistency verification for the TSO and PSO memory models given a reads-from map, denoted VTSO-rf and VPSO-rf, respectively. For an execution of n events over k threads and d variables, we establish novel bounds that scale as nk+1 for TSO and as nk+1· min(nk2, 2k· d) for PSO. Moreover, based on our solution to these problems, we develop an SMC algorithm under TSO and PSO that uses the RF equivalence. The algorithm is exploration-optimal, in the sense that it is guaranteed to explore each class of the RF partitioning exactly once, and spends polynomial time per class when k is bounded. Finally, we implement all our algorithms in the SMC tool Nidhugg, and perform a large number of experiments over benchmarks from existing literature. Our experimental results show that our algorithms for VTSO-rf and VPSO-rf provide significant scalability improvements over standard alternatives. Moreover, when used for SMC, the RF partitioning is often much coarser than the standard Shasha-Snir partitioning for TSO/PSO, which yields a significant speedup in the model checking task.

},
  author       = {Bui, Truc Lam and Chatterjee, Krishnendu and Gautam, Tushar and Pavlogiannis, Andreas and Toman, Viktor},
  issn         = {2475-1421},
  journal      = {Proceedings of the ACM on Programming Languages},
  keywords     = {safety, risk, reliability and quality, software},
  number       = {OOPSLA},
  publisher    = {Association for Computing Machinery},
  title        = {{The reads-from equivalence for the TSO and PSO memory models}},
  doi          = {10.1145/3485541},
  volume       = {5},
  year         = {2021},
}