@article{7103,
  abstract     = {Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.},
  author       = {Wang, Jilin W. J. L. and Lombardi, Fabrizio and Zhang, Xiyun and Anaclet, Christelle and Ivanov, Plamen Ch.},
  issn         = {1553-7358},
  journal      = {PLoS Computational Biology},
  number       = {11},
  publisher    = {Public Library of Science},
  title        = {{Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture}},
  doi          = {10.1371/journal.pcbi.1007268},
  volume       = {15},
  year         = {2019},
}

@article{7105,
  abstract     = {Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.},
  author       = {Yolland, Lawrence and Burki, Mubarik and Marcotti, Stefania and Luchici, Andrei and Kenny, Fiona N. and Davis, John Robert and Serna-Morales, Eduardo and Müller, Jan and Sixt, Michael K and Davidson, Andrew and Wood, Will and Schumacher, Linus J. and Endres, Robert G. and Miodownik, Mark and Stramer, Brian M.},
  issn         = {1476-4679},
  journal      = {Nature Cell Biology},
  number       = {11},
  pages        = {1370--1381},
  publisher    = {Springer Nature},
  title        = {{Persistent and polarized global actin flow is essential for directionality during cell migration}},
  doi          = {10.1038/s41556-019-0411-5},
  volume       = {21},
  year         = {2019},
}

@article{7106,
  abstract     = {PIN-FORMED (PIN) transporters mediate directional, intercellular movement of the phytohormone auxin in land plants. To elucidate the evolutionary origins of this developmentally crucial mechanism, we analysed the single PIN homologue of a simple green alga Klebsormidium flaccidum. KfPIN functions as a plasma membrane-localized auxin exporter in land plants and heterologous models. While its role in algae remains unclear, PIN-driven auxin export is probably an ancient and conserved trait within streptophytes.},
  author       = {Skokan, Roman and Medvecká, Eva and Viaene, Tom and Vosolsobě, Stanislav and Zwiewka, Marta and Müller, Karel and Skůpa, Petr and Karady, Michal and Zhang, Yuzhou and Janacek, Dorina P. and Hammes, Ulrich Z. and Ljung, Karin and Nodzyński, Tomasz and Petrášek, Jan and Friml, Jiří},
  issn         = {2055-0278},
  journal      = {Nature Plants},
  number       = {11},
  pages        = {1114--1119},
  publisher    = {Springer Nature},
  title        = {{PIN-driven auxin transport emerged early in streptophyte evolution}},
  doi          = {10.1038/s41477-019-0542-5},
  volume       = {5},
  year         = {2019},
}

@article{7108,
  abstract     = {We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes. Another simple corollary of our result is that it is NP-hard to decide whether a given poset is CL-shellable.},
  author       = {Goaoc, Xavier and Patak, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli},
  issn         = {0004-5411},
  journal      = {Journal of the ACM},
  number       = {3},
  publisher    = {ACM},
  title        = {{Shellability is NP-complete}},
  doi          = {10.1145/3314024},
  volume       = {66},
  year         = {2019},
}

@article{7109,
  abstract     = {We show how to construct temporal testers for the logic MITL, a prominent linear-time logic for real-time systems. A temporal tester is a transducer that inputs a signal holding the Boolean value of atomic propositions and outputs the truth value of a formula along time. Here we consider testers over continuous-time Boolean signals that use clock variables to enforce duration constraints, as in timed automata. We first rewrite the MITL formula into a “simple” formula using a limited set of temporal modalities. We then build testers for these specific modalities and show how to compose testers for simple formulae into complex ones. Temporal testers can be turned into acceptors, yielding a compositional translation from MITL to timed automata. This construction is much simpler than previously known and remains asymptotically optimal. It supports both past and future operators and can easily be extended.},
  author       = {Ferrere, Thomas and Maler, Oded and Ničković, Dejan and Pnueli, Amir},
  issn         = {0004-5411},
  journal      = {Journal of the ACM},
  number       = {3},
  publisher    = {ACM},
  title        = {{From real-time logic to timed automata}},
  doi          = {10.1145/3286976},
  volume       = {66},
  year         = {2019},
}

@article{7117,
  abstract     = {We propose a novel generic shape optimization method for CAD models based on the eXtended Finite Element Method (XFEM). Our method works directly on the intersection between the model and a regular simulation grid, without the need to mesh or remesh, thus removing a bottleneck of classical shape optimization strategies. This is made possible by a novel hierarchical integration scheme that accurately integrates finite element quantities with sub-element precision. For optimization, we efficiently compute analytical shape derivatives of the entire framework, from model intersection to integration rule generation and XFEM simulation. Moreover, we describe a differentiable projection of shape parameters onto a constraint manifold spanned by user-specified shape preservation, consistency, and manufacturability constraints. We demonstrate the utility of our approach by optimizing mass distribution, strength-to-weight ratio, and inverse elastic shape design objectives directly on parameterized 3D CAD models.},
  author       = {Hafner, Christian and Schumacher, Christian and Knoop, Espen and Auzinger, Thomas and Bickel, Bernd and Bächer, Moritz},
  issn         = {0730-0301},
  journal      = {ACM Transactions on Graphics},
  number       = {6},
  publisher    = {ACM},
  title        = {{X-CAD: Optimizing CAD Models with Extended Finite Elements}},
  doi          = {10.1145/3355089.3356576},
  volume       = {38},
  year         = {2019},
}

@inproceedings{7122,
  abstract     = {Data-rich applications in machine-learning and control have motivated an intense research on large-scale optimization. Novel algorithms have been proposed and shown to have optimal convergence rates in terms of iteration counts. However, their practical performance is severely degraded by the cost of exchanging high-dimensional gradient vectors between computing nodes. Several gradient compression heuristics have recently been proposed to reduce communications, but few theoretical results exist that quantify how they impact algorithm convergence. This paper establishes and strengthens the convergence guarantees for gradient descent under a family of gradient compression techniques. For convex optimization problems, we derive admissible step sizes and quantify both the number of iterations and the number of bits that need to be exchanged to reach a target accuracy. Finally, we validate the performance of different gradient compression techniques in simulations. The numerical results highlight the properties of different gradient compression algorithms and confirm that fast convergence with limited information exchange is possible.},
  author       = {Khirirat, Sarit and Johansson, Mikael and Alistarh, Dan-Adrian},
  booktitle    = {2018 IEEE Conference on Decision and Control},
  isbn         = {9781538613955},
  issn         = {0743-1546},
  location     = {Miami Beach, FL, United States},
  publisher    = {IEEE},
  title        = {{Gradient compression for communication-limited convex optimization}},
  doi          = {10.1109/cdc.2018.8619625},
  year         = {2019},
}

@phdthesis{7132,
  abstract     = {A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta.
Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing.},
  author       = {Mckenzie, Catherine},
  issn         = {2663-337X},
  pages        = {95},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Design and characterization of methods and biological components to realize synthetic neurotransmission}},
  doi          = {10.15479/at:ista:7132},
  year         = {2019},
}

@inproceedings{7136,
  abstract     = {It is well established that the notion of min-entropy fails to satisfy the \emph{chain rule} of the form H(X,Y)=H(X|Y)+H(Y), known for Shannon Entropy. Such a property would help to analyze how min-entropy is split among smaller blocks. Problems of this kind arise for example when constructing extractors and dispersers.
We show that any sequence of variables exhibits a very strong strong block-source structure (conditional distributions of blocks are nearly flat) when we \emph{spoil few correlated bits}. This implies, conditioned on the spoiled bits, that \emph{splitting-recombination properties} hold. In particular, we have many nice properties that min-entropy doesn't obey in general, for example strong chain rules, "information can't hurt" inequalities, equivalences of average and worst-case conditional entropy definitions and others. Quantitatively, for any sequence X1,…,Xt of random variables over an alphabet X we prove that, when conditioned on m=t⋅O(loglog|X|+loglog(1/ϵ)+logt) bits of auxiliary information, all conditional distributions of the form Xi|X<i are ϵ-close to be nearly flat (only a constant factor away). The argument is combinatorial (based on simplex coverings).
This result may be used as a generic tool for \emph{exhibiting block-source structures}. We demonstrate this by reproving the fundamental converter due to Nisan and Zuckermann (\emph{J. Computer and System Sciences, 1996}), which shows that sampling blocks from a min-entropy source roughly preserves the entropy rate. Our bound implies, only by straightforward chain rules, an additive loss of o(1) (for sufficiently many samples), which qualitatively meets the first tighter analysis of this problem due to Vadhan (\emph{CRYPTO'03}), obtained by large deviation techniques. },
  author       = {Skórski, Maciej},
  booktitle    = {2019 IEEE International Symposium on Information Theory},
  isbn         = {9781538692912},
  location     = {Paris, France},
  publisher    = {IEEE},
  title        = {{Strong chain rules for min-entropy under few bits spoiled}},
  doi          = {10.1109/isit.2019.8849240},
  year         = {2019},
}

@article{7143,
  abstract     = {Roots grow downwards parallel to the gravity vector, to anchor a plant in soil and acquire water and nutrients, using a gravitropic mechanism dependent on the asymmetric distribution of the phytohormone auxin. Recently, Chang et al. demonstrate that asymmetric distribution of another phytohormone, cytokinin, directs root growth towards higher water content.},
  author       = {Sinclair, Scott A and Friml, Jiří},
  issn         = {1748-7838},
  journal      = {Cell Research},
  pages        = {965--966},
  publisher    = {Springer Nature},
  title        = {{Defying gravity: a plant's quest for moisture}},
  doi          = {10.1038/s41422-019-0254-4},
  volume       = {29},
  year         = {2019},
}

@article{7145,
  abstract     = {End-to-end correlated bound states are investigated in superconductor-semiconductor hybrid nanowires at zero magnetic field. Peaks in subgap conductance are independently identified from each wire end, and a cross-correlation function is computed that counts end-to-end coincidences, averaging over thousands of subgap features. Strong correlations in a short, 300-nm device are reduced by a factor of 4 in a long, 900-nm device. In addition, subgap conductance distributions are investigated, and correlations between the left and right distributions are identified based on their mutual information.},
  author       = {Anselmetti, G. L. R. and Martinez, E. A. and Ménard, G. C. and Puglia, D. and Malinowski, F. K. and Lee, J. S. and Choi, S. and Pendharkar, M. and Palmstrøm, C. J. and Marcus, C. M. and Casparis, L. and Higginbotham, Andrew P},
  issn         = {2469-9969},
  journal      = {Physical Review B},
  number       = {20},
  publisher    = {American Physical Society},
  title        = {{End-to-end correlated subgap states in hybrid nanowires}},
  doi          = {10.1103/physrevb.100.205412},
  volume       = {100},
  year         = {2019},
}

@article{7146,
  abstract     = {Prevailing models of sex-chromosome evolution were largely inspired by the stable and highly differentiated XY pairs of model organisms, such as those of mammals and flies. Recent work has uncovered an incredible diversity of sex-determining systems, bringing some of the assumptions of these traditional models into question. One particular question that has arisen is what drives some sex chromosomes to be maintained over millions of years and differentiate fully, while others are replaced by new sex-determining chromosomes before differentiation has occurred. Here, I review recent data on the variability of sex-determining genes and sex chromosomes in different non-model vertebrates and invertebrates, and discuss some theoretical models that have been put forward to account for this diversity.},
  author       = {Vicoso, Beatriz},
  issn         = {2397-334X},
  journal      = {Nature Ecology & Evolution},
  number       = {12},
  pages        = {1632--1641},
  publisher    = {Springer Nature},
  title        = {{Molecular and evolutionary dynamics of animal sex-chromosome turnover}},
  doi          = {10.1038/s41559-019-1050-8},
  volume       = {3},
  year         = {2019},
}

@inproceedings{7147,
  abstract     = {The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.

In this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.

The behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions.},
  author       = {Guet, Calin C and Henzinger, Thomas A and Igler, Claudia and Petrov, Tatjana and Sezgin, Ali},
  booktitle    = {17th International Conference on Computational Methods in Systems Biology},
  isbn         = {9783030313036},
  issn         = {1611-3349},
  location     = {Trieste, Italy},
  pages        = {155--187},
  publisher    = {Springer Nature},
  title        = {{Transient memory in gene regulation}},
  doi          = {10.1007/978-3-030-31304-3_9},
  volume       = {11773},
  year         = {2019},
}

@misc{7154,
  author       = {Guseinov, Ruslan},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Supplementary data for "Programming temporal morphing of self-actuated shells"}},
  doi          = {10.15479/AT:ISTA:7154},
  year         = {2019},
}

@article{7156,
  abstract     = {We propose an efficient microwave-photonic modulator as a resource for stationary entangled microwave-optical fields and develop the theory for deterministic entanglement generation and quantum state transfer in multi-resonant electro-optic systems. The device is based on a single crystal whispering gallery mode resonator integrated into a 3D-microwave cavity. The specific design relies on a new combination of thin-film technology and conventional machining that is optimized for the lowest dissipation rates in the microwave, optical, and mechanical domains. We extract important device properties from finite-element simulations and predict continuous variable entanglement generation rates on the order of a Mebit/s for optical pump powers of only a few tens of microwatts. We compare the quantum state transfer fidelities of coherent, squeezed, and non-Gaussian cat states for both teleportation and direct conversion protocols under realistic conditions. Combining the unique capabilities of circuit quantum electrodynamics with the resilience of fiber optic communication could facilitate long-distance solid-state qubit networks, new methods for quantum signal synthesis, quantum key distribution, and quantum enhanced detection, as well as more power-efficient classical sensing and modulation.},
  author       = {Rueda Sanchez, Alfredo R and Hease, William J and Barzanjeh, Shabir and Fink, Johannes M},
  issn         = {2056-6387},
  journal      = {npj Quantum Information},
  publisher    = {Springer Nature},
  title        = {{Electro-optic entanglement source for microwave to telecom quantum state transfer}},
  doi          = {10.1038/s41534-019-0220-5},
  volume       = {5},
  year         = {2019},
}

@article{7158,
  abstract     = {Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth.

Our main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches.
},
  author       = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goyal, Prateesh and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas},
  issn         = {0164-0925},
  journal      = {ACM Transactions on Programming Languages and Systems},
  number       = {4},
  publisher    = {ACM},
  title        = {{Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth}},
  doi          = {10.1145/3363525},
  volume       = {41},
  year         = {2019},
}

@inproceedings{7159,
  abstract     = {Cyber-physical systems (CPS) and the Internet-of-Things (IoT) result in a tremendous amount of generated, measured and recorded time-series data. Extracting temporal segments that encode patterns with useful information out of these huge amounts of data is an extremely difficult problem. We propose shape expressions as a declarative formalism for specifying, querying and extracting sophisticated temporal patterns from possibly noisy data. Shape expressions are regular expressions with arbitrary (linear, exponential, sinusoidal, etc.) shapes with parameters as atomic predicates and additional constraints on these parameters. We equip shape expressions with a novel noisy semantics that combines regular expression matching semantics with statistical regression. We characterize essential properties of the formalism and propose an efficient approximate shape expression matching procedure. We demonstrate the wide applicability of this technique on two case studies. },
  author       = {Ničković, Dejan and Qin, Xin and Ferrere, Thomas and Mateis, Cristinel and Deshmukh, Jyotirmoy},
  booktitle    = {19th International Conference on Runtime Verification},
  isbn         = {9783030320782},
  issn         = {0302-9743},
  location     = {Porto, Portugal},
  pages        = {292--309},
  publisher    = {Springer Nature},
  title        = {{Shape expressions for specifying and extracting signal features}},
  doi          = {10.1007/978-3-030-32079-9_17},
  volume       = {11757},
  year         = {2019},
}

@article{7165,
  abstract     = {Cell division, movement and differentiation contribute to pattern formation in developing tissues. This is the case in the vertebrate neural tube, in which neurons differentiate in a characteristic pattern from a highly dynamic proliferating pseudostratified epithelium. To investigate how progenitor proliferation and differentiation affect cell arrangement and growth of the neural tube, we used experimental measurements to develop a mechanical model of the apical surface of the neuroepithelium that incorporates the effect of interkinetic nuclear movement and spatially varying rates of neuronal differentiation. Simulations predict that tissue growth and the shape of lineage-related clones of cells differ with the rate of differentiation. Growth is isotropic in regions of high differentiation, but dorsoventrally biased in regions of low differentiation. This is consistent with experimental observations. The absence of directional signalling in the simulations indicates that global mechanical constraints are sufficient to explain the observed differences in anisotropy. This provides insight into how the tissue growth rate affects cell dynamics and growth anisotropy and opens up possibilities to study the coupling between mechanics, pattern formation and growth in the neural tube.},
  author       = {Guerrero, Pilar and Perez-Carrasco, Ruben and Zagórski, Marcin P and Page, David and Kicheva, Anna and Briscoe, James and Page, Karen M.},
  issn         = {1477-9129},
  journal      = {Development},
  number       = {23},
  publisher    = {The Company of Biologists},
  title        = {{Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium}},
  doi          = {10.1242/dev.176297},
  volume       = {146},
  year         = {2019},
}

@book{7171,
  abstract     = {Wissen Sie, was sich hinter künstlicher Intelligenz und maschinellem Lernen verbirgt? 
Dieses Sachbuch erklärt Ihnen leicht verständlich und ohne komplizierte Formeln die grundlegenden Methoden und Vorgehensweisen des maschinellen Lernens. Mathematisches Vorwissen ist dafür nicht nötig. Kurzweilig und informativ illustriert Lisa, die Protagonistin des Buches, diese anhand von Alltagssituationen. 
Ein Buch für alle, die in Diskussionen über Chancen und Risiken der aktuellen Entwicklung der künstlichen Intelligenz und des maschinellen Lernens mit Faktenwissen punkten möchten. Auch für Schülerinnen und Schüler geeignet!},
  editor       = {Kersting, Kristian and Lampert, Christoph and Rothkopf, Constantin},
  isbn         = {978-3-658-26762-9},
  pages        = {XIV, 245},
  publisher    = {Springer Nature},
  title        = {{Wie Maschinen Lernen: Künstliche Intelligenz Verständlich Erklärt}},
  doi          = {10.1007/978-3-658-26763-6},
  year         = {2019},
}

@phdthesis{7172,
  abstract     = {The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers.
The first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone.
The second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition.
The third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24.
In the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis.
In the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results.
In the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes.},
  author       = {Vasileva, Mina K},
  issn         = {2663-337X},
  pages        = {192},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana}},
  doi          = {10.15479/AT:ISTA:7172},
  year         = {2019},
}

