@phdthesis{9920, abstract = {This work is concerned with two fascinating circuit quantum electrodynamics components, the Josephson junction and the geometric superinductor, and the interesting experiments that can be done by combining the two. The Josephson junction has revolutionized the field of superconducting circuits as a non-linear dissipation-less circuit element and is used in almost all superconducting qubit implementations since the 90s. On the other hand, the superinductor is a relatively new circuit element introduced as a key component of the fluxonium qubit in 2009. This is an inductor with characteristic impedance larger than the resistance quantum and self-resonance frequency in the GHz regime. The combination of these two elements can occur in two fundamental ways: in parallel and in series. When connected in parallel the two create the fluxonium qubit, a loop with large inductance and a rich energy spectrum reliant on quantum tunneling. On the other hand placing the two elements in series aids with the measurement of the IV curve of a single Josephson junction in a high impedance environment. In this limit theory predicts that the junction will behave as its dual element: the phase-slip junction. While the Josephson junction acts as a non-linear inductor the phase-slip junction has the behavior of a non-linear capacitance and can be used to measure new Josephson junction phenomena, namely Coulomb blockade of Cooper pairs and phase-locked Bloch oscillations. The latter experiment allows for a direct link between frequency and current which is an elusive connection in quantum metrology. This work introduces the geometric superinductor, a superconducting circuit element where the high inductance is due to the geometry rather than the material properties of the superconductor, realized from a highly miniaturized superconducting planar coil. These structures will be described and characterized as resonators and qubit inductors and progress towards the measurement of phase-locked Bloch oscillations will be presented.}, author = {Peruzzo, Matilda}, isbn = {978-3-99078-013-8}, issn = {2663-337X}, keywords = {quantum computing, superinductor, quantum metrology}, pages = {149}, publisher = {Institute of Science and Technology Austria}, title = {{Geometric superinductors and their applications in circuit quantum electrodynamics}}, doi = {10.15479/at:ista:9920}, year = {2021}, } @phdthesis{10422, abstract = {Those who aim to devise new materials with desirable properties usually examine present methods first. However, they will find out that some approaches can exist only conceptually without high chances to become practically useful. It seems that a numerical technique called automatic differentiation together with increasing supply of computational accelerators will soon shift many methods of the material design from the category ”unimaginable” to the category ”expensive but possible”. Approach we suggest is not an exception. Our overall goal is to have an efficient and generalizable approach allowing to solve inverse design problems. In this thesis we scratch its surface. We consider jammed systems of identical particles. And ask ourselves how the shape of those particles (or the parameters codifying it) may affect mechanical properties of the system. An indispensable part of reaching the answer is an appropriate particle parametrization. We come up with a simple, yet generalizable and purposeful scheme for it. Using our generalizable shape parameterization, we simulate the formation of a solid composed of pentagonal-like particles and measure anisotropy in the resulting elastic response. Through automatic differentiation techniques, we directly connect the shape parameters with the elastic response. Interestingly, for our system we find that less isotropic particles lead to a more isotropic elastic response. Together with other results known about our method it seems that it can be successfully generalized for different inverse design problems.}, author = {Piankov, Anton}, issn = {2791-4585}, publisher = {Institute of Science and Technology Austria}, title = {{Towards designer materials using customizable particle shape}}, doi = {10.15479/at:ista:10422}, year = {2021}, } @phdthesis{9418, abstract = {Deep learning is best known for its empirical success across a wide range of applications spanning computer vision, natural language processing and speech. Of equal significance, though perhaps less known, are its ramifications for learning theory: deep networks have been observed to perform surprisingly well in the high-capacity regime, aka the overfitting or underspecified regime. Classically, this regime on the far right of the bias-variance curve is associated with poor generalisation; however, recent experiments with deep networks challenge this view. This thesis is devoted to investigating various aspects of underspecification in deep learning. First, we argue that deep learning models are underspecified on two levels: a) any given training dataset can be fit by many different functions, and b) any given function can be expressed by many different parameter configurations. We refer to the second kind of underspecification as parameterisation redundancy and we precisely characterise its extent. Second, we characterise the implicit criteria (the inductive bias) that guide learning in the underspecified regime. Specifically, we consider a nonlinear but tractable classification setting, and show that given the choice, neural networks learn classifiers with a large margin. Third, we consider learning scenarios where the inductive bias is not by itself sufficient to deal with underspecification. We then study different ways of ‘tightening the specification’: i) In the setting of representation learning with variational autoencoders, we propose a hand- crafted regulariser based on mutual information. ii) In the setting of binary classification, we consider soft-label (real-valued) supervision. We derive a generalisation bound for linear networks supervised in this way and verify that soft labels facilitate fast learning. Finally, we explore an application of soft-label supervision to the training of multi-exit models.}, author = {Bui Thi Mai, Phuong}, issn = {2663-337X}, pages = {125}, publisher = {Institute of Science and Technology Austria}, title = {{Underspecification in deep learning}}, doi = {10.15479/AT:ISTA:9418}, year = {2021}, } @phdthesis{10199, abstract = {The design and verification of concurrent systems remains an open challenge due to the non-determinism that arises from the inter-process communication. In particular, concurrent programs are notoriously difficult both to be written correctly and to be analyzed formally, as complex thread interaction has to be accounted for. The difficulties are further exacerbated when concurrent programs get executed on modern-day hardware, which contains various buffering and caching mechanisms for efficiency reasons. This causes further subtle non-determinism, which can often produce very unintuitive behavior of the concurrent programs. Model checking is at the forefront of tackling the verification problem, where the task is to decide, given as input a concurrent system and a desired property, whether the system satisfies the property. The inherent state-space explosion problem in model checking of concurrent systems causes naïve explicit methods not to scale, thus more inventive methods are required. One such method is stateless model checking (SMC), which explores in memory-efficient manner the program executions rather than the states of the program. State-of-the-art SMC is typically coupled with partial order reduction (POR) techniques, which argue that certain executions provably produce identical system behavior, thus limiting the amount of executions one needs to explore in order to cover all possible behaviors. Another method to tackle the state-space explosion is symbolic model checking, where the considered techniques operate on a succinct implicit representation of the input system rather than explicitly accessing the system. In this thesis we present new techniques for verification of concurrent systems. We present several novel POR methods for SMC of concurrent programs under various models of semantics, some of which account for write-buffering mechanisms. Additionally, we present novel algorithms for symbolic model checking of finite-state concurrent systems, where the desired property of the systems is to ensure a formally defined notion of fairness.}, author = {Toman, Viktor}, issn = {2663-337X}, keywords = {concurrency, verification, model checking}, pages = {166}, publisher = {Institute of Science and Technology Austria}, title = {{Improved verification techniques for concurrent systems}}, doi = {10.15479/at:ista:10199}, year = {2021}, } @phdthesis{10035, abstract = {Many security definitions come in two flavors: a stronger “adaptive” flavor, where the adversary can arbitrarily make various choices during the course of the attack, and a weaker “selective” flavor where the adversary must commit to some or all of their choices a-priori. For example, in the context of identity-based encryption, selective security requires the adversary to decide on the identity of the attacked party at the very beginning of the game whereas adaptive security allows the attacker to first see the master public key and some secret keys before making this choice. Often, it appears to be much easier to achieve selective security than it is to achieve adaptive security. A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption [Pan07][FJP15], constrained PRFs [FKPR14], and Yao’s garbled circuits [JW16]. Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework (published at Crypto ’17 [JKK+17a]) that connects all of these works and allows us to present them in a unified and simplified fashion. Having the framework in place, we show how to achieve adaptive security for proxy re-encryption schemes (published at PKC ’19 [FKKP19]) and provide the first adaptive security proofs for continuous group key agreement protocols (published at S&P ’21 [KPW+21]). Questioning optimality of our framework, we then show that currently used proof techniques cannot lead to significantly better security guarantees for "graph-building" games (published at TCC ’21 [KKPW21a]). These games cover generalized selective decryption, as well as the security of prominent constructions for constrained PRFs, continuous group key agreement, and proxy re-encryption. Finally, we revisit the adaptive security of Yao’s garbled circuits and extend the analysis of Jafargholi and Wichs in two directions: While they prove adaptive security only for a modified construction with increased online complexity, we provide the first positive results for the original construction by Yao (published at TCC ’21 [KKP21a]). On the negative side, we prove that the results of Jafargholi and Wichs are essentially optimal by showing that no black-box reduction can provide a significantly better security bound (published at Crypto ’21 [KKPW21c]).}, author = {Klein, Karen}, issn = {2663-337X}, pages = {276}, publisher = {Institute of Science and Technology Austria}, title = {{On the adaptive security of graph-based games}}, doi = {10.15479/at:ista:10035}, year = {2021}, } @phdthesis{10429, abstract = {The scalability of concurrent data structures and distributed algorithms strongly depends on reducing the contention for shared resources and the costs of synchronization and communication. We show how such cost reductions can be attained by relaxing the strict consistency conditions required by sequential implementations. In the first part of the thesis, we consider relaxation in the context of concurrent data structures. Specifically, in data structures such as priority queues, imposing strong semantics renders scalability impossible, since a correct implementation of the remove operation should return only the element with highest priority. Intuitively, attempting to invoke remove operations concurrently creates a race condition. This bottleneck can be circumvented by relaxing semantics of the affected data structure, thus allowing removal of the elements which are no longer required to have the highest priority. We prove that the randomized implementations of relaxed data structures provide provable guarantees on the priority of the removed elements even under concurrency. Additionally, we show that in some cases the relaxed data structures can be used to scale the classical algorithms which are usually implemented with the exact ones. In the second part, we study parallel variants of the stochastic gradient descent (SGD) algorithm, which distribute computation among the multiple processors, thus reducing the running time. Unfortunately, in order for standard parallel SGD to succeed, each processor has to maintain a local copy of the necessary model parameter, which is identical to the local copies of other processors; the overheads from this perfect consistency in terms of communication and synchronization can negate the speedup gained by distributing the computation. We show that the consistency conditions required by SGD can be relaxed, allowing the algorithm to be more flexible in terms of tolerating quantized communication, asynchrony, or even crash faults, while its convergence remains asymptotically the same.}, author = {Nadiradze, Giorgi}, issn = {2663-337X}, pages = {132}, publisher = {Institute of Science and Technology Austria}, title = {{On achieving scalability through relaxation}}, doi = {10.15479/at:ista:10429}, year = {2021}, } @phdthesis{9733, abstract = {This thesis is the result of the research carried out by the author during his PhD at IST Austria between 2017 and 2021. It mainly focuses on the Fröhlich polaron model, specifically to its regime of strong coupling. This model, which is rigorously introduced and discussed in the introduction, has been of great interest in condensed matter physics and field theory for more than eighty years. It is used to describe an electron interacting with the atoms of a solid material (the strength of this interaction is modeled by the presence of a coupling constant α in the Hamiltonian of the system). The particular regime examined here, which is mathematically described by considering the limit α →∞, displays many interesting features related to the emergence of classical behavior, which allows for a simplified effective description of the system under analysis. The properties, the range of validity and a quantitative analysis of the precision of such classical approximations are the main object of the present work. We specify our investigation to the study of the ground state energy of the system, its dynamics and its effective mass. For each of these problems, we provide in the introduction an overview of the previously known results and a detailed account of the original contributions by the author.}, author = {Feliciangeli, Dario}, issn = {2663-337X}, pages = {180}, publisher = {Institute of Science and Technology Austria}, title = {{The polaron at strong coupling}}, doi = {10.15479/at:ista:9733}, year = {2021}, } @phdthesis{9992, abstract = {Blood – this is what animals use to heal wounds fast and efficient. Plants do not have blood circulation and their cells cannot move. However, plants have evolved remarkable capacities to regenerate tissues and organs preventing further damage. In my PhD research, I studied the wound healing in the Arabidopsis root. I used a UV laser to ablate single cells in the root tip and observed the consequent wound healing. Interestingly, the inner adjacent cells induced a division plane switch and subsequently adopted the cell type of the killed cell to replace it. We termed this form of wound healing “restorative divisions”. This initial observation triggered the questions of my PhD studies: How and why do cells orient their division planes, how do they feel the wound and why does this happen only in inner adjacent cells. For answering these questions, I used a quite simple experimental setup: 5 day - old seedlings were stained with propidium iodide to visualize cell walls and dead cells; ablation was carried out using a special laser cutter and a confocal microscope. Adaptation of the novel vertical microscope system made it possible to observe wounds in real time. This revealed that restorative divisions occur at increased frequency compared to normal divisions. Additionally, the major plant hormone auxin accumulates in wound adjacent cells and drives the expression of the wound-stress responsive transcription factor ERF115. Using this as a marker gene for wound responses, we found that an important part of wound signalling is the sensing of the collapse of the ablated cell. The collapse causes a radical pressure drop, which results in strong tissue deformations. These deformations manifest in an invasion of the now free spot specifically by the inner adjacent cells within seconds, probably because of higher pressure of the inner tissues. Long-term imaging revealed that those deformed cells continuously expand towards the wound hole and that this is crucial for the restorative division. These wound-expanding cells exhibit an abnormal, biphasic polarity of microtubule arrays before the division. Experiments inhibiting cell expansion suggest that it is the biphasic stretching that induces those MT arrays. Adapting the micromanipulator aspiration system from animal scientists at our institute confirmed the hypothesis that stretching influences microtubule stability. In conclusion, this shows that microtubules react to tissue deformation and this facilitates the observed division plane switch. This puts mechanical cues and tensions at the most prominent position for explaining the growth and wound healing properties of plants. Hence, it shines light onto the importance of understanding mechanical signal transduction. }, author = {Hörmayer, Lukas}, issn = {2663-337X}, pages = {168}, publisher = {Institute of Science and Technology Austria}, title = {{Wound healing in the Arabidopsis root meristem}}, doi = {10.15479/at:ista:9992}, year = {2021}, } @phdthesis{9623, abstract = {Cytoplasmic reorganizations are essential for morphogenesis. In large cells like oocytes, these reorganizations become crucial in patterning the oocyte for later stages of embryonic development. Ascidians oocytes reorganize their cytoplasm (ooplasm) in a spectacular manner. Ooplasmic reorganization is initiated at fertilization with the contraction of the actomyosin cortex along the animal-vegetal axis of the oocyte, driving the accumulation of cortical endoplasmic reticulum (cER), maternal mRNAs associated to it and a mitochondria-rich subcortical layer – the myoplasm – in a region of the vegetal pole termed contraction pole (CP). Here we have used the species Phallusia mammillata to investigate the changes in cell shape that accompany these reorganizations and the mechanochemical mechanisms underlining CP formation. We report that the length of the animal-vegetal (AV) axis oscillates upon fertilization: it first undergoes a cycle of fast elongation-lengthening followed by a slow expansion of mainly the vegetal pole (VP) of the cell. We show that the fast oscillation corresponds to a dynamic polarization of the actin cortex as a result of a fertilization-induced increase in cortical tension in the oocyte that triggers a rupture of the cortex at the animal pole and the establishment of vegetal-directed cortical flows. These flows are responsible for the vegetal accumulation of actin causing the VP to flatten. We find that the slow expansion of the VP, leading to CP formation, correlates with a relaxation of the vegetal cortex and that the myoplasm plays a role in the expansion. We show that the myoplasm is a solid-like layer that buckles under compression forces arising from the contracting actin cortex at the VP. Straightening of the myoplasm when actin flows stops, facilitates the expansion of the VP and the CP. Altogether, our results present a previously unrecognized role for the myoplasm in ascidian ooplasmic segregation. }, author = {Caballero Mancebo, Silvia}, isbn = {978-3-99078-012-1}, issn = {2663-337X}, pages = {111}, publisher = {Institute of Science and Technology Austria}, title = {{Fertilization-induced deformations are controlled by the actin cortex and a mitochondria-rich subcortical layer in ascidian oocytes}}, doi = {10.15479/at:ista:9623}, year = {2021}, } @phdthesis{10058, abstract = {Quantum information and computation has become a vast field paved with opportunities for researchers and investors. As large multinational companies and international funds are heavily investing in quantum technologies it is still a question which platform is best suited for the task of realizing a scalable quantum processor. In this work we investigate hole spins in Ge quantum wells. These hold great promise as they possess several favorable properties: a small effective mass, a strong spin-orbit coupling, long relaxation time and an inherent immunity to hyperfine noise. All these characteristics helped Ge hole spin qubits to evolve from a single qubit to a fully entangled four qubit processor in only 3 years. Here, we investigated a qubit approach leveraging the large out-of-plane g-factors of heavy hole states in Ge quantum dots. We found this qubit to be reproducibly operable at extremely low magnetic field and at large speeds while maintaining coherence. This was possible because large differences of g-factors in adjacent dots can be achieved in the out-of-plane direction. In the in-plane direction the small g-factors, on the other hand, can be altered very effectively by the confinement potentials. Here, we found that this can even lead to a sign change of the g-factors. The resulting g-factor difference alters the dynamics of the system drastically and produces effects typically attributed to a spin-orbit induced spin-flip term. The investigations carried out in this thesis give further insights into the possibilities of holes in Ge and reveal new physical properties that need to be considered when designing future spin qubit experiments.}, author = {Jirovec, Daniel}, issn = {2663-337X}, keywords = {qubits, quantum computing, holes}, pages = {151}, publisher = {Institute of Science and Technology Austria}, title = {{Singlet-Triplet qubits and spin-orbit interaction in 2-dimensional Ge hole gases}}, doi = {10.15479/at:ista:10058}, year = {2021}, } @phdthesis{9397, abstract = {Accumulation of interstitial fluid (IF) between embryonic cells is a common phenomenon in vertebrate embryogenesis. Unlike other model systems, where these accumulations coalesce into a large central cavity – the blastocoel, in zebrafish, IF is more uniformly distributed between the deep cells (DC) before the onset of gastrulation. This is likely due to the presence of a large extraembryonic structure – the yolk cell (YC) at the position where the blastocoel typically forms in other model organisms. IF has long been speculated to play a role in tissue morphogenesis during embryogenesis, but direct evidence supporting such function is still sparse. Here we show that the relocalization of IF to the interface between the YC and DC/epiblast is critical for axial mesendoderm (ME) cell protrusion formation and migration along this interface, a key process in embryonic axis formation. We further demonstrate that axial ME cell migration and IF relocalization engage in a positive feedback loop, where axial ME migration triggers IF accumulation ahead of the advancing axial ME tissue by mechanically compressing the overlying epiblast cell layer. Upon compression, locally induced flow relocalizes the IF through the porous epiblast tissue resulting in an IF accumulation ahead of the leading axial ME. This IF accumulation, in turn, promotes cell protrusion formation and migration of the leading axial ME cells, thereby facilitating axial ME extension. Our findings reveal a central role of dynamic IF relocalization in orchestrating germ layer morphogenesis during gastrulation.}, author = {Huljev, Karla}, issn = {2663-337X}, pages = {101}, publisher = {Institute of Science and Technology Austria}, title = {{Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation}}, doi = {10.15479/at:ista:9397}, year = {2021}, } @phdthesis{9562, abstract = {Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry.}, author = {Kleindienst, David}, issn = {2663-337X}, pages = {124}, publisher = {Institute of Science and Technology Austria}, title = {{2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning}}, doi = {10.15479/at:ista:9562}, year = {2021}, } @phdthesis{8934, abstract = {In this thesis, we consider several of the most classical and fundamental problems in static analysis and formal verification, including invariant generation, reachability analysis, termination analysis of probabilistic programs, data-flow analysis, quantitative analysis of Markov chains and Markov decision processes, and the problem of data packing in cache management. We use techniques from parameterized complexity theory, polyhedral geometry, and real algebraic geometry to significantly improve the state-of-the-art, in terms of both scalability and completeness guarantees, for the mentioned problems. In some cases, our results are the first theoretical improvements for the respective problems in two or three decades.}, author = {Goharshady, Amir Kafshdar}, issn = {2663-337X}, pages = {278}, publisher = {Institute of Science and Technology Austria}, title = {{Parameterized and algebro-geometric advances in static program analysis}}, doi = {10.15479/AT:ISTA:8934}, year = {2021}, } @phdthesis{10307, abstract = {Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.}, author = {Tomasek, Kathrin}, issn = {2663-337X}, pages = {73}, publisher = {Institute of Science and Technology Austria}, title = {{Pathogenic Escherichia coli hijack the host immune response}}, doi = {10.15479/at:ista:10307}, year = {2021}, } @phdthesis{10303, abstract = {Nitrogen is an essential macronutrient determining plant growth, development and affecting agricultural productivity. Root, as a hub that perceives and integrates local and systemic signals on the plant’s external and endogenous nitrogen resources, communicates with other plant organs to consolidate their physiology and development in accordance with actual nitrogen balance. Over the last years, numerous studies demonstrated that these comprehensive developmental adaptations rely on the interaction between pathways controlling nitrogen homeostasis and hormonal networks acting globally in the plant body. However, molecular insights into how the information about the nitrogen status is translated through hormonal pathways into specific developmental output are lacking. In my work, I addressed so far poorly understood mechanisms underlying root-to-shoot communication that lead to a rapid re-adjustment of shoot growth and development after nitrate provision. Applying a combination of molecular, cell, and developmental biology approaches, genetics and grafting experiments as well as hormonal analytics, I identified and characterized an unknown molecular framework orchestrating shoot development with a root nitrate sensory system. }, author = {Abualia, Rashed}, issn = {2663-337X}, pages = {139}, publisher = {Institute of Science and Technology Austria}, title = {{Role of hormones in nitrate regulated growth}}, doi = {10.15479/at:ista:10303}, year = {2021}, } @phdthesis{9962, abstract = {The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration.}, author = {Hansen, Andi H}, issn = {2663-337X}, keywords = {Neuronal migration, Non-cell-autonomous, Cell-autonomous, Neurodevelopmental disease}, pages = {182}, publisher = {Institute of Science and Technology Austria}, title = {{Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration}}, doi = {10.15479/at:ista:9962}, year = {2021}, } @phdthesis{10083, abstract = {Plant motions occur across a wide spectrum of timescales, ranging from seed dispersal through bursting (milliseconds) and stomatal opening (minutes) to long-term adaptation of gross architecture. Relatively fast motions include water-driven growth as exemplified by root cell expansion under abiotic/biotic stresses or during gravitropism. A showcase is a root growth inhibition in 30 seconds triggered by the phytohormone auxin. However, the cellular and molecular mechanisms are still largely unknown. This thesis covers the studies about this topic as follows. By taking advantage of microfluidics combined with live imaging, pharmaceutical tools, and transgenic lines, we examined the kinetics of and causal relationship among various auxininduced rapid cellular changes in root growth, apoplastic pH, cytosolic Ca2+, cortical microtubule (CMT) orientation, and vacuolar morphology. We revealed that CMT reorientation and vacuolar constriction are the consequence of growth itself instead of responding directly to auxin. In contrast, auxin induces apoplast alkalinization to rapidly inhibit root growth in 30 seconds. This auxin-triggered apoplast alkalinization results from rapid H+- influx that is contributed by Ca2+ inward channel CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14)-dependent Ca2+ signaling. To dissect which auxin signaling mediates the rapid apoplast alkalinization, we combined microfluidics and genetic engineering to verify that TIR1/AFB receptors conduct a non-transcriptional regulation on Ca2+ and H+ -influx. This non-canonical pathway is mostly mediated by the cytosolic portion of TIR1/AFB. On the other hand, we uncovered, using biochemical and phospho-proteomic analysis, that auxin cell surface signaling component TRANSMEMBRANE KINASE 1 (TMK1) plays a negative role during auxin-trigger apoplast alkalinization and root growth inhibition through directly activating PM H+ -ATPases. Therefore, we discovered that PM H+ -ATPases counteract instead of mediate the auxintriggered rapid H+ -influx, and that TIR1/AFB and TMK1 regulate root growth antagonistically. This opposite effect of TIR1/AFB and TMK1 is consistent during auxin-induced hypocotyl elongation, leading us to explore the relation of two signaling pathways. Assisted with biochemistry and fluorescent imaging, we verified for the first time that TIR1/AFB and TMK1 can interact with each other. The ability of TIR1/AFB binding to membrane lipid provides a basis for the interaction of plasma membrane- and cytosol-localized proteins. Besides, transgenic analysis combined with genetic engineering and biochemistry showed that vi they do function in the same pathway. Particularly, auxin-induced TMK1 increase is TIR1/AFB dependent, suggesting TIR1/AFB regulation on TMK1. Conversely, TMK1 also regulates TIR1/AFB protein levels and thus auxin canonical signaling. To follow the study of rapid growth regulation, we analyzed another rapid growth regulator, signaling peptide RALF1. We showed that RALF1 also triggers a rapid and reversible growth inhibition caused by H + influx, highly resembling but not dependent on auxin. Besides, RALF1 promotes auxin biosynthesis by increasing expression of auxin biosynthesis enzyme YUCCAs and thus induces auxin signaling in ca. 1 hour, contributing to the sustained RALF1-triggered growth inhibition. These studies collectively contribute to understanding rapid regulation on plant cell growth, novel auxin signaling pathway as well as auxin-peptide crosstalk. }, author = {Li, Lanxin}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Rapid cell growth regulation in Arabidopsis}}, doi = {10.15479/at:ista:10083}, year = {2021}, } @phdthesis{10293, abstract = {Indirect reciprocity in evolutionary game theory is a prominent mechanism for explaining the evolution of cooperation among unrelated individuals. In contrast to direct reciprocity, which is based on individuals meeting repeatedly, and conditionally cooperating by using their own experiences, indirect reciprocity is based on individuals’ reputations. If a player helps another, this increases the helper’s public standing, benefitting them in the future. This lets cooperation in the population emerge without individuals having to meet more than once. While the two modes of reciprocity are intertwined, they are difficult to compare. Thus, they are usually studied in isolation. Direct reciprocity can maintain cooperation with simple strategies, and is robust against noise even when players do not remember more than their partner’s last action. Meanwhile, indirect reciprocity requires its successful strategies, or social norms, to be more complex. Exhaustive search previously identified eight such norms, called the “leading eight”, which excel at maintaining cooperation. However, as the first result of this thesis, we show that the leading eight break down once we remove the fundamental assumption that information is synchronized and public, such that everyone agrees on reputations. Once we consider a more realistic scenario of imperfect information, where reputations are private, and individuals occasionally misinterpret or miss observations, the leading eight do not promote cooperation anymore. Instead, minor initial disagreements can proliferate, fragmenting populations into subgroups. In a next step, we consider ways to mitigate this issue. We first explore whether introducing “generosity” can stabilize cooperation when players use the leading eight strategies in noisy environments. This approach of modifying strategies to include probabilistic elements for coping with errors is known to work well in direct reciprocity. However, as we show here, it fails for the more complex norms of indirect reciprocity. Imperfect information still prevents cooperation from evolving. On the other hand, we succeeded to show in this thesis that modifying the leading eight to use “quantitative assessment”, i.e. tracking reputation scores on a scale beyond good and bad, and making overall judgments of others based on a threshold, is highly successful, even when noise increases in the environment. Cooperation can flourish when reputations are more nuanced, and players have a broader understanding what it means to be “good.” Finally, we present a single theoretical framework that unites the two modes of reciprocity despite their differences. Within this framework, we identify a novel simple and successful strategy for indirect reciprocity, which can cope with noisy environments and has an analogue in direct reciprocity. We can also analyze decision making when different sources of information are available. Our results help highlight that for sustaining cooperation, already the most simple rules of reciprocity can be sufficient.}, author = {Schmid, Laura}, issn = {2663-337X}, pages = {171}, publisher = {Institute of Science and Technology Austria}, title = {{Evolution of cooperation via (in)direct reciprocity under imperfect information}}, doi = {10.15479/at:ista:10293}, year = {2021}, } @phdthesis{10135, abstract = {Plants maintain the capacity to develop new organs e.g. lateral roots post-embryonically throughout their whole life and thereby flexibly adapt to ever-changing environmental conditions. Plant hormones auxin and cytokinin are the main regulators of the lateral root organogenesis. Additionally to their solo activities, the interaction between auxin and cytokinin plays crucial role in fine-tuning of lateral root development and growth. In particular, cytokinin modulates auxin distribution within the developing lateral root by affecting the endomembrane trafficking of auxin transporter PIN1 and promoting its vacuolar degradation (Marhavý et al., 2011, 2014). This effect is independent of transcription and translation. Therefore, it suggests novel, non-canonical cytokinin activity occuring possibly on the posttranslational level. Impact of cytokinin and other plant hormones on auxin transporters (including PIN1) on the posttranslational level is described in detail in the introduction part of this thesis in a form of a review (Semeradova et al., 2020). To gain insights into the molecular machinery underlying cytokinin effect on the endomembrane trafficking in the plant cell, in particular on the PIN1 degradation, we conducted two large proteomic screens: 1) Identification of cytokinin binding proteins using chemical proteomics. 2) Monitoring of proteomic and phosphoproteomic changes upon cytokinin treatment. In the first screen, we identified DYNAMIN RELATED PROTEIN 2A (DRP2A). We found that DRP2A plays a role in cytokinin regulated processes during the plant growth and that cytokinin treatment promotes destabilization of DRP2A protein. However, the role of DRP2A in the PIN1 degradation remains to be elucidated. In the second screen, we found VACUOLAR PROTEIN SORTING 9A (VPS9A). VPS9a plays crucial role in plant’s response to cytokin and in cytokinin mediated PIN1 degradation. Altogether, we identified proteins, which bind to cytokinin and proteins that in response to cytokinin exhibit significantly changed abundance or phosphorylation pattern. By combining information from these two screens, we can pave our way towards understanding of noncanonical cytokinin effects.}, author = {Semerádová, Hana}, isbn = {978-3-99078-014-5}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis}}, doi = {10.15479/at:ista:10135}, year = {2021}, } @phdthesis{9728, abstract = {Most real-world flows are multiphase, yet we know little about them compared to their single-phase counterparts. Multiphase flows are more difficult to investigate as their dynamics occur in large parameter space and involve complex phenomena such as preferential concentration, turbulence modulation, non-Newtonian rheology, etc. Over the last few decades, experiments in particle-laden flows have taken a back seat in favour of ever-improving computational resources. However, computers are still not powerful enough to simulate a real-world fluid with millions of finite-size particles. Experiments are essential not only because they offer a reliable way to investigate real-world multiphase flows but also because they serve to validate numerical studies and steer the research in a relevant direction. In this work, we have experimentally investigated particle-laden flows in pipes, and in particular, examined the effect of particles on the laminar-turbulent transition and the drag scaling in turbulent flows. For particle-laden pipe flows, an earlier study [Matas et al., 2003] reported how the sub-critical (i.e., hysteretic) transition that occurs via localised turbulent structures called puffs is affected by the addition of particles. In this study, in addition to this known transition, we found a super-critical transition to a globally fluctuating state with increasing particle concentration. At the same time, the Newtonian-type transition via puffs is delayed to larger Reynolds numbers. At an even higher concentration, only the globally fluctuating state is found. The dynamics of particle-laden flows are hence determined by two competing instabilities that give rise to three flow regimes: Newtonian-type turbulence at low, a particle-induced globally fluctuating state at high, and a coexistence state at intermediate concentrations. The effect of particles on turbulent drag is ambiguous, with studies reporting drag reduction, no net change, and even drag increase. The ambiguity arises because, in addition to particle concentration, particle shape, size, and density also affect the net drag. Even similar particles might affect the flow dissimilarly in different Reynolds number and concentration ranges. In the present study, we explored a wide range of both Reynolds number and concentration, using spherical as well as cylindrical particles. We found that the spherical particles do not reduce drag while the cylindrical particles are drag-reducing within a specific Reynolds number interval. The interval strongly depends on the particle concentration and the relative size of the pipe and particles. Within this interval, the magnitude of drag reduction reaches a maximum. These drag reduction maxima appear to fall onto a distinct power-law curve irrespective of the pipe diameter and particle concentration, and this curve can be considered as the maximum drag reduction asymptote for a given fibre shape. Such an asymptote is well known for polymeric flows but had not been identified for particle-laden flows prior to this work.}, author = {Agrawal, Nishchal}, issn = {2663-337X}, keywords = {Drag Reduction, Transition to Turbulence, Multiphase Flows, particle Laden Flows, Complex Flows, Experiments, Fluid Dynamics}, pages = {118}, publisher = {Institute of Science and Technology Austria}, title = {{Transition to turbulence and drag reduction in particle-laden pipe flows}}, doi = {10.15479/at:ista:9728}, year = {2021}, }