@inproceedings{25, abstract = {Partially observable Markov decision processes (POMDPs) are the standard models for planning under uncertainty with both finite and infinite horizon. Besides the well-known discounted-sum objective, indefinite-horizon objective (aka Goal-POMDPs) is another classical objective for POMDPs. In this case, given a set of target states and a positive cost for each transition, the optimization objective is to minimize the expected total cost until a target state is reached. In the literature, RTDP-Bel or heuristic search value iteration (HSVI) have been used for solving Goal-POMDPs. Neither of these algorithms has theoretical convergence guarantees, and HSVI may even fail to terminate its trials. We give the following contributions: (1) We discuss the challenges introduced in Goal-POMDPs and illustrate how they prevent the original HSVI from converging. (2) We present a novel algorithm inspired by HSVI, termed Goal-HSVI, and show that our algorithm has convergence guarantees. (3) We show that Goal-HSVI outperforms RTDP-Bel on a set of well-known examples.}, author = {Horák, Karel and Bošanský, Branislav and Chatterjee, Krishnendu}, booktitle = {Proceedings of the Twenty-Seventh International Joint Conference on Artificial Intelligence}, location = {Stockholm, Sweden}, pages = {4764 -- 4770}, publisher = {IJCAI}, title = {{Goal-HSVI: Heuristic search value iteration for goal-POMDPs}}, doi = {10.24963/ijcai.2018/662}, volume = {2018-July}, year = {2018}, } @inproceedings{24, abstract = {Partially-observable Markov decision processes (POMDPs) with discounted-sum payoff are a standard framework to model a wide range of problems related to decision making under uncertainty. Traditionally, the goal has been to obtain policies that optimize the expectation of the discounted-sum payoff. A key drawback of the expectation measure is that even low probability events with extreme payoff can significantly affect the expectation, and thus the obtained policies are not necessarily risk-averse. An alternate approach is to optimize the probability that the payoff is above a certain threshold, which allows obtaining risk-averse policies, but ignores optimization of the expectation. We consider the expectation optimization with probabilistic guarantee (EOPG) problem, where the goal is to optimize the expectation ensuring that the payoff is above a given threshold with at least a specified probability. We present several results on the EOPG problem, including the first algorithm to solve it.}, author = {Chatterjee, Krishnendu and Elgyütt, Adrian and Novotny, Petr and Rouillé, Owen}, location = {Stockholm, Sweden}, pages = {4692 -- 4699}, publisher = {IJCAI}, title = {{Expectation optimization with probabilistic guarantees in POMDPs with discounted-sum objectives}}, doi = {10.24963/ijcai.2018/652}, volume = {2018}, year = {2018}, } @inproceedings{34, abstract = {Partially observable Markov decision processes (POMDPs) are widely used in probabilistic planning problems in which an agent interacts with an environment using noisy and imprecise sensors. We study a setting in which the sensors are only partially defined and the goal is to synthesize “weakest” additional sensors, such that in the resulting POMDP, there is a small-memory policy for the agent that almost-surely (with probability 1) satisfies a reachability objective. We show that the problem is NP-complete, and present a symbolic algorithm by encoding the problem into SAT instances. We illustrate trade-offs between the amount of memory of the policy and the number of additional sensors on a simple example. We have implemented our approach and consider three classical POMDP examples from the literature, and show that in all the examples the number of sensors can be significantly decreased (as compared to the existing solutions in the literature) without increasing the complexity of the policies.}, author = {Chatterjee, Krishnendu and Chemlík, Martin and Topcu, Ufuk}, location = {Delft, Netherlands}, pages = {47 -- 55}, publisher = {AAAI Press}, title = {{Sensor synthesis for POMDPs with reachability objectives}}, volume = {2018}, year = {2018}, } @article{18, abstract = {An N-superconcentrator is a directed, acyclic graph with N input nodes and N output nodes such that every subset of the inputs and every subset of the outputs of same cardinality can be connected by node-disjoint paths. It is known that linear-size and bounded-degree superconcentrators exist. We prove the existence of such superconcentrators with asymptotic density 25.3 (where the density is the number of edges divided by N). The previously best known densities were 28 [12] and 27.4136 [17].}, author = {Kolmogorov, Vladimir and Rolinek, Michal}, issn = {0381-7032}, journal = {Ars Combinatoria}, number = {10}, pages = {269 -- 304}, publisher = {Charles Babbage Research Centre}, title = {{Superconcentrators of density 25.3}}, volume = {141}, year = {2018}, } @article{6355, abstract = {We prove that any cyclic quadrilateral can be inscribed in any closed convex C1-curve. The smoothness condition is not required if the quadrilateral is a rectangle.}, author = {Akopyan, Arseniy and Avvakumov, Sergey}, issn = {2050-5094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Any cyclic quadrilateral can be inscribed in any closed convex smooth curve}}, doi = {10.1017/fms.2018.7}, volume = {6}, year = {2018}, } @inproceedings{6195, abstract = {In the context of robotic manipulation and grasping, the shift from a view that is static (force closure of a single posture) and contact-deprived (only contact for force closure is allowed, everything else is obstacle) towards a view that is dynamic and contact-rich (soft manipulation) has led to an increased interest in soft hands. These hands can easily exploit environmental constraints and object surfaces without risk, and safely interact with humans, but present also some challenges. Designing them is difficult, as well as predicting, modelling, and “programming” their interactions with the objects and the environment. This paper tackles the problem of simulating them in a fast and effective way, leveraging on novel and existing simulation technologies. We present a triple-layered simulation framework where dynamic properties such as stiffness are determined from slow but accurate FEM simulation data once, and then condensed into a lumped parameter model that can be used to fast simulate soft fingers and soft hands. We apply our approach to the simulation of soft pneumatic fingers.}, author = {Pozzi, Maria and Miguel Villalba, Eder and Deimel, Raphael and Malvezzi, Monica and Bickel, Bernd and Brock, Oliver and Prattichizzo, Domenico}, isbn = {9781538630815}, location = {Brisbane, Australia}, publisher = {IEEE}, title = {{Efficient FEM-based simulation of soft robots modeled as kinematic chains}}, doi = {10.1109/icra.2018.8461106}, year = {2018}, } @inproceedings{6941, abstract = {Bitcoin has become the most successful cryptocurrency ever deployed, and its most distinctive feature is that it is decentralized. Its underlying protocol (Nakamoto consensus) achieves this by using proof of work, which has the drawback that it causes the consumption of vast amounts of energy to maintain the ledger. Moreover, Bitcoin mining dynamics have become less distributed over time. Towards addressing these issues, we propose SpaceMint, a cryptocurrency based on proofs of space instead of proofs of work. Miners in SpaceMint dedicate disk space rather than computation. We argue that SpaceMint’s design solves or alleviates several of Bitcoin’s issues: most notably, its large energy consumption. SpaceMint also rewards smaller miners fairly according to their contribution to the network, thus incentivizing more distributed participation. This paper adapts proof of space to enable its use in cryptocurrency, studies the attacks that can arise against a Bitcoin-like blockchain that uses proof of space, and proposes a new blockchain format and transaction types to address these attacks. Our prototype shows that initializing 1 TB for mining takes about a day (a one-off setup cost), and miners spend on average just a fraction of a second per block mined. Finally, we provide a game-theoretic analysis modeling SpaceMint as an extensive game (the canonical game-theoretic notion for games that take place over time) and show that this stylized game satisfies a strong equilibrium notion, thereby arguing for SpaceMint ’s stability and consensus.}, author = {Park, Sunoo and Kwon, Albert and Fuchsbauer, Georg and Gazi, Peter and Alwen, Joel F and Pietrzak, Krzysztof Z}, booktitle = {22nd International Conference on Financial Cryptography and Data Security}, isbn = {9783662583869}, issn = {1611-3349}, location = {Nieuwpoort, Curacao}, pages = {480--499}, publisher = {Springer Nature}, title = {{SpaceMint: A cryptocurrency based on proofs of space}}, doi = {10.1007/978-3-662-58387-6_26}, volume = {10957}, year = {2018}, } @article{6497, abstract = {T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations.}, author = {Moalli, Federica and Ficht, Xenia and Germann, Philipp and Vladymyrov, Mykhailo and Stolp, Bettina and de Vries, Ingrid and Lyck, Ruth and Balmer, Jasmin and Fiocchi, Amleto and Kreutzfeldt, Mario and Merkler, Doron and Iannacone, Matteo and Ariga, Akitaka and Stoffel, Michael H. and Sharpe, James and Bähler, Martin and Sixt, Michael K and Diz-Muñoz, Alba and Stein, Jens V.}, issn = {1540-9538}, journal = {The Journal of Experimental Medicine}, number = {7}, pages = {1869–1890}, publisher = {Rockefeller University Press}, title = {{The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells}}, doi = {10.1084/jem.20170896}, volume = {2015}, year = {2018}, } @article{6499, abstract = {Expansion microscopy is a recently introduced imaging technique that achieves super‐resolution through physically expanding the specimen by ~4×, after embedding into a swellable gel. The resolution attained is, correspondingly, approximately fourfold better than the diffraction limit, or ~70 nm. This is a major improvement over conventional microscopy, but still lags behind modern STED or STORM setups, whose resolution can reach 20–30 nm. We addressed this issue here by introducing an improved gel recipe that enables an expansion factor of ~10× in each dimension, which corresponds to an expansion of the sample volume by more than 1,000‐fold. Our protocol, which we termed X10 microscopy, achieves a resolution of 25–30 nm on conventional epifluorescence microscopes. X10 provides multi‐color images similar or even superior to those produced with more challenging methods, such as STED, STORM, and iterative expansion microscopy (iExM). X10 is therefore the cheapest and easiest option for high‐quality super‐resolution imaging currently available. X10 should be usable in any laboratory, irrespective of the machinery owned or of the technical knowledge.}, author = {Truckenbrodt, Sven M and Maidorn, Manuel and Crzan, Dagmar and Wildhagen, Hanna and Kabatas, Selda and Rizzoli, Silvio O}, issn = {1469-3178}, journal = {EMBO reports}, number = {9}, publisher = {EMBO}, title = {{X10 expansion microscopy enables 25‐nm resolution on conventional microscopes}}, doi = {10.15252/embr.201845836}, volume = {19}, year = {2018}, } @inproceedings{7123, abstract = {Population protocols are a popular model of distributed computing, in which n agents with limited local state interact randomly, and cooperate to collectively compute global predicates. Inspired by recent developments in DNA programming, an extensive series of papers, across different communities, has examined the computability and complexity characteristics of this model. Majority, or consensus, is a central task in this model, in which agents need to collectively reach a decision as to which one of two states A or B had a higher initial count. Two metrics are important: the time that a protocol requires to stabilize to an output decision, and the state space size that each agent requires to do so. It is known that majority requires Ω(log log n) states per agent to allow for fast (poly-logarithmic time) stabilization, and that O(log2 n) states are sufficient. Thus, there is an exponential gap between the space upper and lower bounds for this problem. This paper addresses this question. On the negative side, we provide a new lower bound of Ω(log n) states for any protocol which stabilizes in O(n1–c) expected time, for any constant c > 0. This result is conditional on monotonicity and output assumptions, satisfied by all known protocols. Technically, it represents a departure from previous lower bounds, in that it does not rely on the existence of dense configurations. Instead, we introduce a new generalized surgery technique to prove the existence of incorrect executions for any algorithm which would contradict the lower bound. Subsequently, our lower bound also applies to general initial configurations, including ones with a leader. On the positive side, we give a new algorithm for majority which uses O(log n) states, and stabilizes in O(log2 n) expected time. Central to the algorithm is a new leaderless phase clock technique, which allows agents to synchronize in phases of Θ(n log n) consecutive interactions using O(log n) states per agent, exploiting a new connection between population protocols and power-of-two-choices load balancing mechanisms. We also employ our phase clock to build a leader election algorithm with a state space of size O(log n), which stabilizes in O(log2 n) expected time.}, author = {Alistarh, Dan-Adrian and Aspnes, James and Gelashvili, Rati}, booktitle = {Proceedings of the 29th Annual ACM-SIAM Symposium on Discrete Algorithms}, isbn = {9781611975031}, location = {New Orleans, LA, United States}, pages = {2221--2239}, publisher = {ACM}, title = {{Space-optimal majority in population protocols}}, doi = {10.1137/1.9781611975031.144}, year = {2018}, } @article{9917, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, issn = {2056-3744}, journal = {Evolution Letters}, number = {4}, pages = {297--309}, publisher = {Wiley}, title = {{Clines on the seashore: The genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.1002/evl3.74}, volume = {2}, year = {2018}, } @article{9915, abstract = {The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favor reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence.}, author = {Hollander, Johan and Montaño-Rendón, Mauricio and Bianco, Giuseppe and Yang, Xi and Westram, Anja M and Duvaux, Ludovic and Reid, David G. and Butlin, Roger K.}, issn = {2056-3744}, journal = {Evolution Letters}, number = {6}, pages = {557--566}, publisher = {Wiley}, title = {{Are assortative mating and genital divergence driven by reinforcement?}}, doi = {10.1002/evl3.85}, volume = {2}, year = {2018}, } @article{8618, abstract = {The reversibly switchable fluorescent proteins (RSFPs) commonly used for RESOLFT nanoscopy have been developed from fluorescent proteins of the GFP superfamily. These proteins are bright, but exhibit several drawbacks such as relatively large size, oxygen-dependence, sensitivity to low pH, and limited switching speed. Therefore, RSFPs from other origins with improved properties need to be explored. Here, we report the development of two RSFPs based on the LOV domain of the photoreceptor protein YtvA from Bacillus subtilis. LOV domains obtain their fluorescence by association with the abundant cellular cofactor flavin mononucleotide (FMN). Under illumination with blue and ultraviolet light, they undergo a photocycle, making these proteins inherently photoswitchable. Our first improved variant, rsLOV1, can be used for RESOLFT imaging, whereas rsLOV2 proved useful for STED nanoscopy of living cells with a resolution of down to 50 nm. In addition to their smaller size compared to GFP-related proteins (17 kDa instead of 27 kDa) and their usability at low pH, rsLOV1 and rsLOV2 exhibit faster switching kinetics, switching on and off 3 times faster than rsEGFP2, the fastest-switching RSFP reported to date. Therefore, LOV-domain-based RSFPs have potential for applications where the switching speed of GFP-based proteins is limiting.}, author = {Gregor, Carola and Sidenstein, Sven C. and Andresen, Martin and Sahl, Steffen J. and Danzl, Johann G and Hell, Stefan W.}, issn = {2045-2322}, journal = {Scientific Reports}, keywords = {Multidisciplinary}, publisher = {Springer Nature}, title = {{Novel reversibly switchable fluorescent proteins for RESOLFT and STED nanoscopy engineered from the bacterial photoreceptor YtvA}}, doi = {10.1038/s41598-018-19947-1}, volume = {8}, year = {2018}, } @article{10881, abstract = {Strigolactones (SLs) are a relatively recent addition to the list of plant hormones that control different aspects of plant development. SL signalling is perceived by an α/β hydrolase, DWARF 14 (D14). A close homolog of D14, KARRIKIN INSENSTIVE2 (KAI2), is involved in perception of an uncharacterized molecule called karrikin (KAR). Recent studies in Arabidopsis identified the SUPPRESSOR OF MAX2 1 (SMAX1) and SMAX1-LIKE 7 (SMXL7) to be potential SCF–MAX2 complex-mediated proteasome targets of KAI2 and D14, respectively. Genetic studies on SMXL7 and SMAX1 demonstrated distinct developmental roles for each, but very little is known about these repressors in terms of their sequence features. In this study, we performed an extensive comparative analysis of SMXLs and determined their phylogenetic and evolutionary history in the plant lineage. Our results show that SMXL family members can be sub-divided into four distinct phylogenetic clades/classes, with an ancient SMAX1. Further, we identified the clade-specific motifs that have evolved and that might act as determinants of SL-KAR signalling specificity. These specificities resulted from functional diversities among the clades. Our results suggest that a gradual co-evolution of SMXL members with their upstream receptors D14/KAI2 provided an increased specificity to both the SL perception and response in land plants.}, author = {Moturu, Taraka Ramji and Thula, Sravankumar and Singh, Ravi Kumar and Nodzyński, Tomasz and Vařeková, Radka Svobodová and Friml, Jiří and Simon, Sibu}, issn = {1460-2431}, journal = {Journal of Experimental Botany}, keywords = {Plant Science, Physiology}, number = {9}, pages = {2367--2378}, publisher = {Oxford University Press}, title = {{Molecular evolution and diversification of the SMXL gene family}}, doi = {10.1093/jxb/ery097}, volume = {69}, year = {2018}, } @article{10880, abstract = {Acquisition of evolutionary novelties is a fundamental process for adapting to the external environment and invading new niches and results in the diversification of life, which we can see in the world today. How such novel phenotypic traits are acquired in the course of evolution and are built up in developing embryos has been a central question in biology. Whole-genome duplication (WGD) is a process of genome doubling that supplies raw genetic materials and increases genome complexity. Recently, it has been gradually revealed that WGD and subsequent fate changes of duplicated genes can facilitate phenotypic evolution. Here, we review the current understanding of the relationship between WGD and the acquisition of evolutionary novelties. We show some examples of this link and discuss how WGD and subsequent duplicated genes can facilitate phenotypic evolution as well as when such genomic doubling can be advantageous for adaptation.}, author = {Yuuta, Moriyama and Koshiba-Takeuchi, Kazuko}, issn = {2041-2657}, journal = {Briefings in Functional Genomics}, keywords = {Genetics, Molecular Biology, Biochemistry, General Medicine}, number = {5}, pages = {329--338}, publisher = {Oxford University Press}, title = {{Significance of whole-genome duplications on the emergence of evolutionary novelties}}, doi = {10.1093/bfgp/ely007}, volume = {17}, year = {2018}, } @misc{9930, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g. outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e. focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally-suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasises that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Clines on the seashore: the genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.5061/dryad.bp25b65}, year = {2018}, } @misc{9929, abstract = {The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favour reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence.}, author = {Hollander, Johan and Montaño-Rendón, Mauricio and Bianco, Giuseppe and Yang, Xi and Westram, Anja M and Duvaux, Ludovic and Reid, David G. and Butlin, Roger K.}, publisher = {Dryad}, title = {{Data from: Are assortative mating and genital divergence driven by reinforcement?}}, doi = {10.5061/dryad.51sd2p5}, year = {2018}, } @inproceedings{10882, abstract = {We introduce Intelligent Annotation Dialogs for bounding box annotation. We train an agent to automatically choose a sequence of actions for a human annotator to produce a bounding box in a minimal amount of time. Specifically, we consider two actions: box verification [34], where the annotator verifies a box generated by an object detector, and manual box drawing. We explore two kinds of agents, one based on predicting the probability that a box will be positively verified, and the other based on reinforcement learning. We demonstrate that (1) our agents are able to learn efficient annotation strategies in several scenarios, automatically adapting to the image difficulty, the desired quality of the boxes, and the detector strength; (2) in all scenarios the resulting annotation dialogs speed up annotation compared to manual box drawing alone and box verification alone, while also outperforming any fixed combination of verification and drawing in most scenarios; (3) in a realistic scenario where the detector is iteratively re-trained, our agents evolve a series of strategies that reflect the shifting trade-off between verification and drawing as the detector grows stronger.}, author = {Uijlings, Jasper and Konyushkova, Ksenia and Lampert, Christoph and Ferrari, Vittorio}, booktitle = {2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition}, isbn = {9781538664209}, issn = {2575-7075}, location = {Salt Lake City, UT, United States}, pages = {9175--9184}, publisher = {IEEE}, title = {{Learning intelligent dialogs for bounding box annotation}}, doi = {10.1109/cvpr.2018.00956}, year = {2018}, } @inproceedings{6558, abstract = {This paper studies the problem of distributed stochastic optimization in an adversarial setting where, out of m machines which allegedly compute stochastic gradients every iteration, an α-fraction are Byzantine, and may behave adversarially. Our main result is a variant of stochastic gradient descent (SGD) which finds ε-approximate minimizers of convex functions in T=O~(1/ε²m+α²/ε²) iterations. In contrast, traditional mini-batch SGD needs T=O(1/ε²m) iterations, but cannot tolerate Byzantine failures. Further, we provide a lower bound showing that, up to logarithmic factors, our algorithm is information-theoretically optimal both in terms of sample complexity and time complexity.}, author = {Alistarh, Dan-Adrian and Allen-Zhu, Zeyuan and Li, Jerry}, booktitle = {Advances in Neural Information Processing Systems}, location = {Montreal, Canada}, pages = {4613--4623}, publisher = {Neural Information Processing Systems Foundation}, title = {{Byzantine stochastic gradient descent}}, volume = {2018}, year = {2018}, } @article{6032, abstract = {The main result of this article is a generalization of the classical blossom algorithm for finding perfect matchings. Our algorithm can efficiently solve Boolean CSPs where each variable appears in exactly two constraints (we call it edge CSP) and all constraints are even Δ-matroid relations (represented by lists of tuples). As a consequence of this, we settle the complexity classification of planar Boolean CSPs started by Dvorak and Kupec. Using a reduction to even Δ-matroids, we then extend the tractability result to larger classes of Δ-matroids that we call efficiently coverable. It properly includes classes that were known to be tractable before, namely, co-independent, compact, local, linear, and binary, with the following caveat:We represent Δ-matroids by lists of tuples, while the last two use a representation by matrices. Since an n ×n matrix can represent exponentially many tuples, our tractability result is not strictly stronger than the known algorithm for linear and binary Δ-matroids.}, author = {Kazda, Alexandr and Kolmogorov, Vladimir and Rolinek, Michal}, journal = {ACM Transactions on Algorithms}, number = {2}, publisher = {ACM}, title = {{Even delta-matroids and the complexity of planar boolean CSPs}}, doi = {10.1145/3230649}, volume = {15}, year = {2018}, } @phdthesis{200, abstract = {This thesis is concerned with the inference of current population structure based on geo-referenced genetic data. The underlying idea is that population structure affects its spatial genetic structure. Therefore, genotype information can be utilized to estimate important demographic parameters such as migration rates. These indirect estimates of population structure have become very attractive, as genotype data is now widely available. However, there also has been much concern about these approaches. Importantly, genetic structure can be influenced by many complex patterns, which often cannot be disentangled. Moreover, many methods merely fit heuristic patterns of genetic structure, and do not build upon population genetics theory. Here, I describe two novel inference methods that address these shortcomings. In Chapter 2, I introduce an inference scheme based on a new type of signal, identity by descent (IBD) blocks. Recently, it has become feasible to detect such long blocks of genome shared between pairs of samples. These blocks are direct traces of recent coalescence events. As such, they contain ample signal for inferring recent demography. I examine sharing of IBD blocks in two-dimensional populations with local migration. Using a diffusion approximation, I derive formulas for an isolation by distance pattern of long IBD blocks and show that sharing of long IBD blocks approaches rapid exponential decay for growing sample distance. I describe an inference scheme based on these results. It can robustly estimate the dispersal rate and population density, which is demonstrated on simulated data. I also show an application to estimate mean migration and the rate of recent population growth within Eastern Europe. Chapter 3 is about a novel method to estimate barriers to gene flow in a two dimensional population. This inference scheme utilizes geographically localized allele frequency fluctuations - a classical isolation by distance signal. The strength of these local fluctuations increases on average next to a barrier, and there is less correlation across it. I again use a framework of diffusion of ancestral lineages to model this effect, and provide an efficient numerical implementation to fit the results to geo-referenced biallelic SNP data. This inference scheme is able to robustly estimate strong barriers to gene flow, as tests on simulated data confirm.}, author = {Ringbauer, Harald}, issn = {2663-337X}, pages = {146}, publisher = {Institute of Science and Technology Austria}, title = {{Inferring recent demography from spatial genetic structure}}, doi = {10.15479/AT:ISTA:th_963}, year = {2018}, } @article{1064, abstract = {In 1945, A.W. Goodman and R.E. Goodman proved the following conjecture by P. Erdős: Given a family of (round) disks of radii r1, … , rn in the plane, it is always possible to cover them by a disk of radius R= ∑ ri, provided they cannot be separated into two subfamilies by a straight line disjoint from the disks. In this note we show that essentially the same idea may work for different analogues and generalizations of their result. In particular, we prove the following: Given a family of positive homothetic copies of a fixed convex body K⊂ Rd with homothety coefficients τ1, … , τn> 0 , it is always possible to cover them by a translate of d+12(∑τi)K, provided they cannot be separated into two subfamilies by a hyperplane disjoint from the homothets.}, author = {Akopyan, Arseniy and Balitskiy, Alexey and Grigorev, Mikhail}, issn = {14320444}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {1001--1009}, publisher = {Springer}, title = {{On the circle covering theorem by A.W. Goodman and R.E. Goodman}}, doi = {10.1007/s00454-017-9883-x}, volume = {59}, year = {2018}, } @phdthesis{418, abstract = {The aim of this thesis was the development of new strategies for optical and optogenetic control of proliferative and pro-survival signaling, and characterizing them from the molecular mechanism up to cellular effects. These new light-based methods have unique features, such as red light as an activator, or the avoidance of gene delivery, which enable to overcome current limitations, such as light delivery to target tissues and feasibility as therapeutic approach. A special focus was placed on implementing these new light-based approaches in pancreatic β-cells, as β-cells are the key players in diabetes and especially their loss in number negatively affects disease progression. Currently no treatment options are available to compensate the lack of functional β-cells in diabetic patients. In a first approach, red-light-activated growth factor receptors, in particular receptor tyrosine kinases were engineered and characterized. Receptor activation with light allows spatio-temporal control compared to ligand-based activation, and especially red light exhibits deeper tissue penetration than other wavelengths of the visible spectrum. Red-light-activated receptor tyrosine kinases robustly activated major growth factor related signaling pathways with a high temporal resolution. Moreover, the remote activation of the proliferative MAPK/Erk pathway by red-light-activated receptor tyrosine kinases in a pancreatic β-cell line was also achieved, through one centimeter thick mouse tissue. Although red-light-activated receptor tyrosine kinases are particularly attractive for applications in animal models due to the deep tissue penetration of red light, a drawback, especially with regard to translation into humans, is the requirement of gene therapy. In a second approach an endogenous light-sensitive mechanism was identified and its potential to promote proliferative and pro-survival signals was explored, towards light-based tissue regeneration without the need for gene transfer. Blue-green light illumination was found to be sufficient for the activation of proliferation and survival promoting signaling pathways in primary pancreatic murine and human islets. Blue-green light also led to an increase in proliferation of primary islet cells, an effect which was shown to be mostly β-cell specific in human islets. Moreover, it was demonstrated that this approach of pancreatic β-cell expansion did not have any negative effect on the β-cell function, in particular on their insulin secretion capacity. In contrast, a trend for enhanced insulin secretion under high glucose conditions after illumination was detected. In order to unravel the detailed characteristics of this endogenous light-sensitive mechanism, the precise light requirements were determined. In addition, the expression of light sensing proteins, OPN3 and rhodopsin, was detected. The observed effects were found to be independent of handling effects such as temperature differences and cytochrome c oxidase dependent ATP increase, but they were found to be enhanced through the knockout of OPN3. The exact mechanism of how islets cells sense light and the identity of the photoreceptor remains unknown. Summarized two new light-based systems with unique features were established that enable the activation of proliferative and pro-survival signaling pathways. While red-light-activated receptor tyrosine kinases open a new avenue for optogenetics research, by allowing non-invasive control of signaling in vivo, the identified endogenous light-sensitive mechanism has the potential to be the basis of a gene therapy-free therapeutical approach for light-based β-cell expansion.}, author = {Gschaider-Reichhart, Eva}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Optical and optogenetic control of proliferation and survival }}, doi = {10.15479/AT:ISTA:th_913}, year = {2018}, } @article{1012, abstract = {We prove a new central limit theorem (CLT) for the difference of linear eigenvalue statistics of a Wigner random matrix H and its minor H and find that the fluctuation is much smaller than the fluctuations of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of H and H. In particular, our theorem identifies the fluctuation of Kerov's rectangular Young diagrams, defined by the interlacing eigenvalues ofH and H, around their asymptotic shape, the Vershik'Kerov'Logan'Shepp curve. Young diagrams equipped with the Plancherel measure follow the same limiting shape. For this, algebraically motivated, ensemble a CLT has been obtained in Ivanov and Olshanski [20] which is structurally similar to our result but the variance is different, indicating that the analogy between the two models has its limitations. Moreover, our theorem shows that Borodin's result [7] on the convergence of the spectral distribution of Wigner matrices to a Gaussian free field also holds in derivative sense.}, author = {Erdös, László and Schröder, Dominik J}, issn = {10737928}, journal = {International Mathematics Research Notices}, number = {10}, pages = {3255--3298}, publisher = {Oxford University Press}, title = {{Fluctuations of rectangular young diagrams of interlacing wigner eigenvalues}}, doi = {10.1093/imrn/rnw330}, volume = {2018}, year = {2018}, } @article{6006, abstract = {Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally-optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an over-approximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. We extend the abstraction-refinement methodology to labeled networks, where the objectives of the players are regular languages. Our experimental results demonstrate the effectiveness of the methodology. }, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {2073-4336}, journal = {Games}, number = {3}, publisher = {MDPI AG}, title = {{An abstraction-refinement methodology for reasoning about network games}}, doi = {10.3390/g9030039}, volume = {9}, year = {2018}, } @inproceedings{35, abstract = {We consider planning problems for graphs, Markov decision processes (MDPs), and games on graphs. While graphs represent the most basic planning model, MDPs represent interaction with nature and games on graphs represent interaction with an adversarial environment. We consider two planning problems where there are k different target sets, and the problems are as follows: (a) the coverage problem asks whether there is a plan for each individual target set; and (b) the sequential target reachability problem asks whether the targets can be reached in sequence. For the coverage problem, we present a linear-time algorithm for graphs, and quadratic conditional lower bound for MDPs and games on graphs. For the sequential target problem, we present a linear-time algorithm for graphs, a sub-quadratic algorithm for MDPs, and a quadratic conditional lower bound for games on graphs. Our results with conditional lower bounds establish (i) model-separation results showing that for the coverage problem MDPs and games on graphs are harder than graphs and for the sequential reachability problem games on graphs are harder than MDPs and graphs; and (ii) objective-separation results showing that for MDPs the coverage problem is harder than the sequential target problem.}, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {28th International Conference on Automated Planning and Scheduling }, location = {Delft, Netherlands}, publisher = {AAAI Press}, title = {{Algorithms and conditional lower bounds for planning problems}}, year = {2018}, } @article{738, abstract = {This paper is devoted to automatic competitive analysis of real-time scheduling algorithms for firm-deadline tasksets, where only completed tasks con- tribute some utility to the system. Given such a taskset T , the competitive ratio of an on-line scheduling algorithm A for T is the worst-case utility ratio of A over the utility achieved by a clairvoyant algorithm. We leverage the theory of quantitative graph games to address the competitive analysis and competitive synthesis problems. For the competitive analysis case, given any taskset T and any finite-memory on- line scheduling algorithm A , we show that the competitive ratio of A in T can be computed in polynomial time in the size of the state space of A . Our approach is flexible as it also provides ways to model meaningful constraints on the released task sequences that determine the competitive ratio. We provide an experimental study of many well-known on-line scheduling algorithms, which demonstrates the feasibility of our competitive analysis approach that effectively replaces human ingenuity (required Preliminary versions of this paper have appeared in Chatterjee et al. ( 2013 , 2014 ). B Andreas Pavlogiannis pavlogiannis@ist.ac.at Krishnendu Chatterjee krish.chat@ist.ac.at Alexander Kößler koe@ecs.tuwien.ac.at Ulrich Schmid s@ecs.tuwien.ac.at 1 IST Austria (Institute of Science and Technology Austria), Am Campus 1, 3400 Klosterneuburg, Austria 2 Embedded Computing Systems Group, Vienna University of Technology, Treitlstrasse 3, 1040 Vienna, Austria 123 Real-Time Syst for finding worst-case scenarios) by computing power. For the competitive synthesis case, we are just given a taskset T , and the goal is to automatically synthesize an opti- mal on-line scheduling algorithm A , i.e., one that guarantees the largest competitive ratio possible for T . We show how the competitive synthesis problem can be reduced to a two-player graph game with partial information, and establish that the compu- tational complexity of solving this game is Np -complete. The competitive synthesis problem is hence in Np in the size of the state space of the non-deterministic labeled transition system encoding the taskset. Overall, the proposed framework assists in the selection of suitable scheduling algorithms for a given taskset, which is in fact the most common situation in real-time systems design. }, author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Kößler, Alexander and Schmid, Ulrich}, journal = {Real-Time Systems}, number = {1}, pages = {166 -- 207}, publisher = {Springer}, title = {{Automated competitive analysis of real time scheduling with graph games}}, doi = {10.1007/s11241-017-9293-4}, volume = {54}, year = {2018}, } @phdthesis{52, abstract = {In this thesis we will discuss systems of point interacting fermions, their stability and other spectral properties. Whereas for bosons a point interacting system is always unstable this ques- tion is more subtle for a gas of two species of fermions. In particular the answer depends on the mass ratio between these two species. Most of this work will be focused on the N + M model which consists of two species of fermions with N, M particles respectively which interact via point interactions. We will introduce this model using a formal limit and discuss the N + 1 system in more detail. In particular, we will show that for mass ratios above a critical one, which does not depend on the particle number, the N + 1 system is stable. In the context of this model we will prove rigorous versions of Tan relations which relate various quantities of the point-interacting model. By restricting the N + 1 system to a box we define a finite density model with point in- teractions. In the context of this system we will discuss the energy change when introducing a point-interacting impurity into a system of non-interacting fermions. We will see that this change in energy is bounded independently of the particle number and in particular the bound only depends on the density and the scattering length. As another special case of the N + M model we will show stability of the 2 + 2 model for mass ratios in an interval around one. Further we will investigate a different model of point interactions which was discussed before in the literature and which is, contrary to the N + M model, not given by a limiting procedure but is based on a Dirichlet form. We will show that this system behaves trivially in the thermodynamic limit, i.e. the free energy per particle is the same as the one of the non-interacting system.}, author = {Moser, Thomas}, issn = {2663-337X}, pages = {115}, publisher = {Institute of Science and Technology Austria}, title = {{Point interactions in systems of fermions}}, doi = {10.15479/AT:ISTA:th_1043}, year = {2018}, } @article{913, abstract = {Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We performed a microarray-based approach to find regulators of the auxin-induced PIN relocation in the Arabidopsis thaliana root. We identified a subset of a family of phosphatidylinositol transfer proteins (PITP), the PATELLINs (PATL). Here, we show that PATLs are expressed in partially overlapping cells types in different tissues going through mitosis or initiating differentiation programs. PATLs are plasma membrane-associated proteins accumulated in Arabidopsis embryos, primary roots, lateral root primordia, and developing stomata. Higher order patl mutants display reduced PIN1 repolarization in response to auxin, shorter root apical meristem, and drastic defects in embryo and seedling development. This suggests PATLs redundantly play a crucial role in polarity and patterning in Arabidopsis.}, author = {Tejos, Ricardo and Rodríguez Furlán, Cecilia and Adamowski, Maciek and Sauer, Michael and Norambuena, Lorena and Friml, Jirí}, issn = {00219533}, journal = {Journal of Cell Science}, number = {2}, publisher = {Company of Biologists}, title = {{PATELLINS are regulators of auxin mediated PIN1 relocation and plant development in Arabidopsis thaliana}}, doi = {10.1242/jcs.204198}, volume = {131}, year = {2018}, } @phdthesis{69, abstract = {A qubit, a unit of quantum information, is essentially any quantum mechanical two-level system which can be coherently controlled. Still, to be used for computation, it has to fulfill criteria. Qubits, regardless of the system in which they are realized, suffer from decoherence. This leads to loss of the information stored in the qubit. The upper bound of the time scale on which decoherence happens is set by the spin relaxation time. In this thesis I studied a two-level system consisting of a Zeeman-split hole spin confined in a quantum dot formed in a Ge hut wire. Such Ge hut wires have emerged as a promising material system for the realization of spin qubits, due to the combination of two significant properties: long spin coherence time as expected for group IV semiconductors due to the low hyperfine interaction and a strong valence band spin-orbit coupling. Here, I present how to fabricate quantum dot devices suitable for electrical transport measurements. Coupled quantum dot devices allowed the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot. By integrating the charge sensor into a radio-frequency reflectometry setup, I performed for the first time single-shot readout measurements of hole spins and extracted the hole spin relaxation times in Ge hut wires.}, author = {Vukušić, Lada}, issn = {2663-337X}, pages = {103}, publisher = {Institute of Science and Technology Austria}, title = {{Charge sensing and spin relaxation times of holes in Ge hut wires}}, doi = {10.15479/AT:ISTA:TH_1047}, year = {2018}, } @phdthesis{324, abstract = {Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ~10% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed Syt2 triggered release with shorter latency and higher temporal precision, and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity.}, author = {Chen, Chong}, issn = {2663-337X}, pages = {110}, publisher = {Institute of Science and Technology Austria}, title = {{Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release}}, doi = {10.15479/AT:ISTA:th_997}, year = {2018}, } @article{742, abstract = {We give a detailed and easily accessible proof of Gromov’s Topological Overlap Theorem. Let X be a finite simplicial complex or, more generally, a finite polyhedral cell complex of dimension d. Informally, the theorem states that if X has sufficiently strong higher-dimensional expansion properties (which generalize edge expansion of graphs and are defined in terms of cellular cochains of X) then X has the following topological overlap property: for every continuous map (Formula presented.) there exists a point (Formula presented.) that is contained in the images of a positive fraction (Formula presented.) of the d-cells of X. More generally, the conclusion holds if (Formula presented.) is replaced by any d-dimensional piecewise-linear manifold M, with a constant (Formula presented.) that depends only on d and on the expansion properties of X, but not on M.}, author = {Dotterrer, Dominic and Kaufman, Tali and Wagner, Uli}, journal = {Geometriae Dedicata}, number = {1}, pages = {307–317}, publisher = {Springer}, title = {{On expansion and topological overlap}}, doi = {10.1007/s10711-017-0291-4}, volume = {195}, year = {2018}, } @article{70, abstract = {We consider the totally asymmetric simple exclusion process in a critical scaling parametrized by a≥0, which creates a shock in the particle density of order aT−1/3, T the observation time. When starting from step initial data, we provide bounds on the limiting law which in particular imply that in the double limit lima→∞limT→∞ one recovers the product limit law and the degeneration of the correlation length observed at shocks of order 1. This result is shown to apply to a general last-passage percolation model. We also obtain bounds on the two-point functions of several airy processes.}, author = {Nejjar, Peter}, issn = {1980-0436}, journal = {Latin American Journal of Probability and Mathematical Statistics}, number = {2}, pages = {1311--1334}, publisher = {Instituto Nacional de Matematica Pura e Aplicada}, title = {{Transition to shocks in TASEP and decoupling of last passage times}}, doi = {10.30757/ALEA.v15-49}, volume = {15}, year = {2018}, } @article{44, abstract = {Recent realization of a kinetically constrained chain of Rydberg atoms by Bernien et al., [Nature (London) 551, 579 (2017)] resulted in the observation of unusual revivals in the many-body quantum dynamics. In our previous work [C. J. Turner et al., Nat. Phys. 14, 745 (2018)], such dynamics was attributed to the existence of “quantum scarred” eigenstates in the many-body spectrum of the experimentally realized model. Here, we present a detailed study of the eigenstate properties of the same model. We find that the majority of the eigenstates exhibit anomalous thermalization: the observable expectation values converge to their Gibbs ensemble values, but parametrically slower compared to the predictions of the eigenstate thermalization hypothesis (ETH). Amidst the thermalizing spectrum, we identify nonergodic eigenstates that strongly violate the ETH, whose number grows polynomially with system size. Previously, the same eigenstates were identified via large overlaps with certain product states, and were used to explain the revivals observed in experiment. Here, we find that these eigenstates, in addition to highly atypical expectation values of local observables, also exhibit subthermal entanglement entropy that scales logarithmically with the system size. Moreover, we identify an additional class of quantum scarred eigenstates, and discuss their manifestations in the dynamics starting from initial product states. We use forward scattering approximation to describe the structure and physical properties of quantum scarred eigenstates. Finally, we discuss the stability of quantum scars to various perturbations. We observe that quantum scars remain robust when the introduced perturbation is compatible with the forward scattering approximation. In contrast, the perturbations which most efficiently destroy quantum scars also lead to the restoration of “canonical” thermalization.}, author = {Turner, C J and Michailidis, Alexios and Abanin, D A and Serbyn, Maksym and Papić, Z}, journal = {Physical Review B}, number = {15}, publisher = {American Physical Society}, title = {{Quantum scarred eigenstates in a Rydberg atom chain: Entanglement, breakdown of thermalization, and stability to perturbations}}, doi = {10.1103/PhysRevB.98.155134}, volume = {98}, year = {2018}, } @article{328, abstract = {The drag of turbulent flows can be drastically decreased by adding small amounts of high molecular weight polymers. While drag reduction initially increases with polymer concentration, it eventually saturates to what is known as the maximum drag reduction (MDR) asymptote; this asymptote is generally attributed to the dynamics being reduced to a marginal yet persistent state of subdued turbulent motion. Contrary to this accepted view, we show that, for an appropriate choice of parameters, polymers can reduce the drag beyond the suggested asymptotic limit, eliminating turbulence and giving way to laminar flow. At higher polymer concentrations, however, the laminar state becomes unstable, resulting in a fluctuating flow with the characteristic drag of the MDR asymptote. Our findings indicate that the asymptotic state is hence dynamically disconnected from ordinary turbulence. © 2018 American Physical Society.}, author = {Choueiri, George H and Lopez Alonso, Jose M and Hof, Björn}, journal = {Physical Review Letters}, number = {12}, publisher = {American Physical Society}, title = {{Exceeding the asymptotic limit of polymer drag reduction}}, doi = {10.1103/PhysRevLett.120.124501}, volume = {120}, year = {2018}, } @article{136, abstract = {Recent studies suggest that unstable, nonchaotic solutions of the Navier-Stokes equation may provide deep insights into fluid turbulence. In this article, we present a combined experimental and numerical study exploring the dynamical role of unstable equilibrium solutions and their invariant manifolds in a weakly turbulent, electromagnetically driven, shallow fluid layer. Identifying instants when turbulent evolution slows down, we compute 31 unstable equilibria of a realistic two-dimensional model of the flow. We establish the dynamical relevance of these unstable equilibria by showing that they are closely visited by the turbulent flow. We also establish the dynamical relevance of unstable manifolds by verifying that they are shadowed by turbulent trajectories departing from the neighborhoods of unstable equilibria over large distances in state space.}, author = {Suri, Balachandra and Tithof, Jeffrey and Grigoriev, Roman and Schatz, Michael}, journal = {Physical Review E}, number = {2}, publisher = {American Physical Society}, title = {{Unstable equilibria and invariant manifolds in quasi-two-dimensional Kolmogorov-like flow}}, doi = {10.1103/PhysRevE.98.023105}, volume = {98}, year = {2018}, } @article{691, abstract = {Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain. Objective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families. Methods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease. Results: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold. Conclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function.}, author = {Marin Valencia, Isaac and Novarino, Gaia and Johansen, Anide and Rosti, Başak and Issa, Mahmoud and Musaev, Damir and Bhat, Gifty and Scott, Eric and Silhavy, Jennifer and Stanley, Valentina and Rosti, Rasim and Gleeson, Jeremy and Imam, Farhad and Zaki, Maha and Gleeson, Joseph}, issn = {0022-2593}, journal = {Journal of Medical Genetics}, number = {1}, pages = {48 -- 54}, publisher = {BMJ Publishing Group}, title = {{A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features}}, doi = {10.1136/jmedgenet-2017-104627}, volume = {55}, year = {2018}, } @article{284, abstract = {Borel probability measures living on metric spaces are fundamental mathematical objects. There are several meaningful distance functions that make the collection of the probability measures living on a certain space a metric space. We are interested in the description of the structure of the isometries of such metric spaces. We overview some of the recent results of the topic and we also provide some new ones concerning the Wasserstein distance. More specifically, we consider the space of all Borel probability measures on the unit sphere of a Euclidean space endowed with the Wasserstein metric W_p for arbitrary p >= 1, and we show that the action of a Wasserstein isometry on the set of Dirac measures is induced by an isometry of the underlying unit sphere.}, author = {Virosztek, Daniel}, issn = {2064-8316}, journal = {Acta Scientiarum Mathematicarum}, number = {1-2}, pages = {65 -- 80}, publisher = {Springer Nature}, title = {{Maps on probability measures preserving certain distances - a survey and some new results}}, doi = {10.14232/actasm-018-753-y}, volume = {84}, year = {2018}, } @article{180, abstract = {In this paper we define and study the classical Uniform Electron Gas (UEG), a system of infinitely many electrons whose density is constant everywhere in space. The UEG is defined differently from Jellium, which has a positive constant background but no constraint on the density. We prove that the UEG arises in Density Functional Theory in the limit of a slowly varying density, minimizing the indirect Coulomb energy. We also construct the quantum UEG and compare it to the classical UEG at low density.}, author = {Lewi, Mathieu and Lieb, Élliott and Seiringer, Robert}, issn = {2270-518X}, journal = {Journal de l'Ecole Polytechnique - Mathematiques}, pages = {79 -- 116}, publisher = {Ecole Polytechnique}, title = {{Statistical mechanics of the uniform electron gas}}, doi = {10.5802/jep.64}, volume = {5}, year = {2018}, } @article{163, abstract = {For ultrafast fixation of biological samples to avoid artifacts, high-pressure freezing (HPF) followed by freeze substitution (FS) is preferred over chemical fixation at room temperature. After HPF, samples are maintained at low temperature during dehydration and fixation, while avoiding damaging recrystallization. This is a notoriously slow process. McDonald and Webb demonstrated, in 2011, that sample agitation during FS dramatically reduces the necessary time. Then, in 2015, we (H.G. and S.R.) introduced an agitation module into the cryochamber of an automated FS unit and demonstrated that the preparation of algae could be shortened from days to a couple of hours. We argued that variability in the processing, reproducibility, and safety issues are better addressed using automated FS units. For dissemination, we started low-cost manufacturing of agitation modules for two of the most widely used FS units, the Automatic Freeze Substitution Systems, AFS(1) and AFS2, from Leica Microsystems, using three dimensional (3D)-printing of the major components. To test them, several labs independently used the modules on a wide variety of specimens that had previously been processed by manual agitation, or without agitation. We demonstrate that automated processing with sample agitation saves time, increases flexibility with respect to sample requirements and protocols, and produces data of at least as good quality as other approaches.}, author = {Reipert, Siegfried and Goldammer, Helmuth and Richardson, Christine and Goldberg, Martin and Hawkins, Timothy and Hollergschwandtner, Elena and Kaufmann, Walter and Antreich, Sebastian and Stierhof, York}, issn = {0022-1554}, journal = {Journal of Histochemistry and Cytochemistry}, number = {12}, pages = {903--921}, publisher = {SAGE Publications}, title = {{Agitation modules: Flexible means to accelerate automated freeze substitution}}, doi = {10.1369/0022155418786698}, volume = {66}, year = {2018}, } @inproceedings{6012, abstract = {We present an approach to identify concise equations from data using a shallow neural network approach. In contrast to ordinary black-box regression, this approach allows understanding functional relations and generalizing them from observed data to unseen parts of the parameter space. We show how to extend the class of learnable equations for a recently proposed equation learning network to include divisions, and we improve the learning and model selection strategy to be useful for challenging real-world data. For systems governed by analytical expressions, our method can in many cases identify the true underlying equation and extrapolate to unseen domains. We demonstrate its effectiveness by experiments on a cart-pendulum system, where only 2 random rollouts are required to learn the forward dynamics and successfully achieve the swing-up task.}, author = {Sahoo, Subham and Lampert, Christoph and Martius, Georg S}, booktitle = {Proceedings of the 35th International Conference on Machine Learning}, location = {Stockholm, Sweden}, pages = {4442--4450}, publisher = {ML Research Press}, title = {{Learning equations for extrapolation and control}}, volume = {80}, year = {2018}, } @inproceedings{6011, abstract = {We establish a data-dependent notion of algorithmic stability for Stochastic Gradient Descent (SGD), and employ it to develop novel generalization bounds. This is in contrast to previous distribution-free algorithmic stability results for SGD which depend on the worst-case constants. By virtue of the data-dependent argument, our bounds provide new insights into learning with SGD on convex and non-convex problems. In the convex case, we show that the bound on the generalization error depends on the risk at the initialization point. In the non-convex case, we prove that the expected curvature of the objective function around the initialization point has crucial influence on the generalization error. In both cases, our results suggest a simple data-driven strategy to stabilize SGD by pre-screening its initialization. As a corollary, our results allow us to show optimistic generalization bounds that exhibit fast convergence rates for SGD subject to a vanishing empirical risk and low noise of stochastic gradient. }, author = {Kuzborskij, Ilja and Lampert, Christoph}, booktitle = {Proceedings of the 35 th International Conference on Machine Learning}, location = {Stockholm, Sweden}, pages = {2815--2824}, publisher = {ML Research Press}, title = {{Data-dependent stability of stochastic gradient descent}}, volume = {80}, year = {2018}, } @inproceedings{6589, abstract = {Distributed training of massive machine learning models, in particular deep neural networks, via Stochastic Gradient Descent (SGD) is becoming commonplace. Several families of communication-reduction methods, such as quantization, large-batch methods, and gradient sparsification, have been proposed. To date, gradient sparsification methods--where each node sorts gradients by magnitude, and only communicates a subset of the components, accumulating the rest locally--are known to yield some of the largest practical gains. Such methods can reduce the amount of communication per step by up to \emph{three orders of magnitude}, while preserving model accuracy. Yet, this family of methods currently has no theoretical justification. This is the question we address in this paper. We prove that, under analytic assumptions, sparsifying gradients by magnitude with local error correction provides convergence guarantees, for both convex and non-convex smooth objectives, for data-parallel SGD. The main insight is that sparsification methods implicitly maintain bounds on the maximum impact of stale updates, thanks to selection by magnitude. Our analysis and empirical validation also reveal that these methods do require analytical conditions to converge well, justifying existing heuristics.}, author = {Alistarh, Dan-Adrian and Hoefler, Torsten and Johansson, Mikael and Konstantinov, Nikola H and Khirirat, Sarit and Renggli, Cedric}, booktitle = {Advances in Neural Information Processing Systems 31}, location = {Montreal, Canada}, pages = {5973--5983}, publisher = {Neural Information Processing Systems Foundation}, title = {{The convergence of sparsified gradient methods}}, volume = {Volume 2018}, year = {2018}, } @article{7, abstract = {Animal social networks are shaped by multiple selection pressures, including the need to ensure efficient communication and functioning while simultaneously limiting disease transmission. Social animals could potentially further reduce epidemic risk by altering their social networks in the presence of pathogens, yet there is currently no evidence for such pathogen-triggered responses. We tested this hypothesis experimentally in the ant Lasius niger using a combination of automated tracking, controlled pathogen exposure, transmission quantification, and temporally explicit simulations. Pathogen exposure induced behavioral changes in both exposed ants and their nestmates, which helped contain the disease by reinforcing key transmission-inhibitory properties of the colony's contact network. This suggests that social network plasticity in response to pathogens is an effective strategy for mitigating the effects of disease in social groups.}, author = {Stroeymeyt, Nathalie and Grasse, Anna V and Crespi, Alessandro and Mersch, Danielle and Cremer, Sylvia and Keller, Laurent}, issn = {1095-9203}, journal = {Science}, number = {6417}, pages = {941 -- 945}, publisher = {AAAS}, title = {{Social network plasticity decreases disease transmission in a eusocial insect}}, doi = {10.1126/science.aat4793}, volume = {362}, year = {2018}, } @article{19, abstract = {Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses.}, author = {Palmer, Adam and Chait, Remy P and Kishony, Roy}, issn = {0737-4038}, journal = {Molecular Biology and Evolution}, number = {11}, pages = {2669 -- 2684}, publisher = {Oxford University Press}, title = {{Nonoptimal gene expression creates latent potential for antibiotic resistance}}, doi = {10.1093/molbev/msy163}, volume = {35}, year = {2018}, } @article{6, abstract = {Lesion and electrode location verification are traditionally done via histological examination of stained brain slices, a time-consuming procedure that requires manual estimation. Here, we describe a simple, straightforward method for quantifying lesions and locating electrodes in the brain that is less laborious and yields more detailed results. Whole brains are stained with osmium tetroxide, embedded in resin, and imaged with a micro-CT scanner. The scans result in 3D digital volumes of the brains with resolutions and virtual section thicknesses dependent on the sample size (12-15 and 5-6 µm per voxel for rat and zebra finch brains, respectively). Surface and deep lesions can be characterized, and single tetrodes, tetrode arrays, electrolytic lesions, and silicon probes can also be localized. Free and proprietary software allows experimenters to examine the sample volume from any plane and segment the volume manually or automatically. Because this method generates whole brain volume, lesions and electrodes can be quantified to a much higher degree than in current methods, which will help standardize comparisons within and across studies.}, author = {Masís, Javier and Mankus, David and Wolff, Steffen and Guitchounts, Grigori and Jösch, Maximilian A and Cox, David}, journal = {Journal of visualized experiments}, publisher = {MyJove Corporation}, title = {{A micro-CT-based method for characterising lesions and locating electrodes in small animal brains}}, doi = {10.3791/58585}, volume = {141}, year = {2018}, } @misc{13055, abstract = {Dataset for manuscript 'Social network plasticity decreases disease transmission in a eusocial insect' Compared to previous versions: - raw image files added - correction of URLs within README.txt file }, author = {Stroeymeyt, Nathalie and Grasse, Anna V and Crespi, Alessandro and Mersch, Danielle and Cremer, Sylvia and Keller, Laurent}, publisher = {Zenodo}, title = {{Social network plasticity decreases disease transmission in a eusocial insect}}, doi = {10.5281/ZENODO.1322669}, year = {2018}, } @article{22, abstract = {Conventional ultra-high sensitivity detectors in the millimeter-wave range are usually cooled as their own thermal noise at room temperature would mask the weak received radiation. The need for cryogenic systems increases the cost and complexity of the instruments, hindering the development of, among others, airborne and space applications. In this work, the nonlinear parametric upconversion of millimeter-wave radiation to the optical domain inside high-quality (Q) lithium niobate whispering-gallery mode (WGM) resonators is proposed for ultra-low noise detection. We experimentally demonstrate coherent upconversion of millimeter-wave signals to a 1550 nm telecom carrier, with a photon conversion efficiency surpassing the state-of-the-art by 2 orders of magnitude. Moreover, a theoretical model shows that the thermal equilibrium of counterpropagating WGMs is broken by overcoupling the millimeter-wave WGM, effectively cooling the upconverted mode and allowing ultra-low noise detection. By theoretically estimating the sensitivity of a correlation radiometer based on the presented scheme, it is found that room-temperature radiometers with better sensitivity than state-of-the-art high-electron-mobility transistor (HEMT)-based radiometers can be designed. This detection paradigm can be used to develop room-temperature instrumentation for radio astronomy, earth observation, planetary missions, and imaging systems.}, author = {Botello, Gabriel and Sedlmeir, Florian and Rueda Sanchez, Alfredo R and Abdalmalak, Kerlos and Brown, Elliott and Leuchs, Gerd and Preu, Sascha and Segovia Vargas, Daniel and Strekalov, Dmitry and Munoz, Luis and Schwefel, Harald}, issn = {23342536}, journal = {Optica}, number = {10}, pages = {1210 -- 1219}, title = {{Sensitivity limits of millimeter-wave photonic radiometers based on efficient electro-optic upconverters}}, doi = {10.1364/OPTICA.5.001210}, volume = {5}, year = {2018}, } @article{5677, abstract = {Recently, contract-based design has been proposed as an “orthogonal” approach that complements system design methodologies proposed so far to cope with the complexity of system design. Contract-based design provides a rigorous scaffolding for verification, analysis, abstraction/refinement, and even synthesis. A number of results have been obtained in this domain but a unified treatment of the topic that can help put contract-based design in perspective was missing. This monograph intends to provide such a treatment where contracts are precisely defined and characterized so that they can be used in design methodologies with no ambiguity. In particular, this monograph identifies the essence of complex system design using contracts through a mathematical “meta-theory”, where all the properties of the methodology are derived from a very abstract and generic notion of contract. We show that the meta-theory provides deep and illuminating links with existing contract and interface theories, as well as guidelines for designing new theories. Our study encompasses contracts for both software and systems, with emphasis on the latter. We illustrate the use of contracts with two examples: requirement engineering for a parking garage management, and the development of contracts for timing and scheduling in the context of the Autosar methodology in use in the automotive sector.}, author = {Benveniste, Albert and Nickovic, Dejan and Caillaud, Benoît and Passerone, Roberto and Raclet, Jean Baptiste and Reinkemeier, Philipp and Sangiovanni-Vincentelli, Alberto and Damm, Werner and Henzinger, Thomas A and Larsen, Kim G.}, issn = {1551-3939}, journal = {Foundations and Trends in Electronic Design Automation}, number = {2-3}, pages = {124--400}, publisher = {Now Publishers}, title = {{Contracts for system design}}, doi = {10.1561/1000000053}, volume = {12}, year = {2018}, } @article{435, abstract = {It is shown that two fundamentally different phenomena, the bound states in continuum and the spectral singularity (or time-reversed spectral singularity), can occur simultaneously. This can be achieved in a rectangular core dielectric waveguide with an embedded active (or absorbing) layer. In such a system a two-dimensional bound state in a continuum is created in the plane of a waveguide cross section, and it is emitted or absorbed along the waveguide core. The idea can be used for experimental implementation of a laser or a coherent-perfect-absorber for a photonic bound state that resides in a continuous spectrum.}, author = {Midya, Bikashkali and Konotop, Vladimir}, journal = {Optics Letters}, number = {3}, pages = {607 -- 610}, publisher = {Optica Publishing Group}, title = {{Coherent-perfect-absorber and laser for bound states in a continuum}}, doi = {10.1364/OL.43.000607}, volume = {43}, year = {2018}, } @article{139, abstract = {Genome-scale diversity data are increasingly available in a variety of biological systems, and can be used to reconstruct the past evolutionary history of species divergence. However, extracting the full demographic information from these data is not trivial, and requires inferential methods that account for the diversity of coalescent histories throughout the genome. Here, we evaluate the potential and limitations of one such approach. We reexamine a well-known system of mussel sister species, using the joint site frequency spectrum (jSFS) of synonymousmutations computed either fromexome capture or RNA-seq, in an Approximate Bayesian Computation (ABC) framework. We first assess the best sampling strategy (number of: individuals, loci, and bins in the jSFS), and show that model selection is robust to variation in the number of individuals and loci. In contrast, different binning choices when summarizing the jSFS, strongly affect the results: including classes of low and high frequency shared polymorphisms can more effectively reveal recent migration events. We then take advantage of the flexibility of ABC to compare more realistic models of speciation, including variation in migration rates through time (i.e., periodic connectivity) and across genes (i.e., genome-wide heterogeneity in migration rates). We show that these models were consistently selected as the most probable, suggesting that mussels have experienced a complex history of gene flow during divergence and that the species boundary is semi-permeable. Our work provides a comprehensive evaluation of ABC demographic inference in mussels based on the coding jSFS, and supplies guidelines for employing different sequencing techniques and sampling strategies. We emphasize, perhaps surprisingly, that inferences are less limited by the volume of data, than by the way in which they are analyzed.}, author = {Fraisse, Christelle and Roux, Camille and Gagnaire, Pierre and Romiguier, Jonathan and Faivre, Nicolas and Welch, John and Bierne, Nicolas}, journal = {PeerJ}, number = {7}, publisher = {PeerJ}, title = {{The divergence history of European blue mussel species reconstructed from Approximate Bayesian Computation: The effects of sequencing techniques and sampling strategies}}, doi = {10.7717/peerj.5198}, volume = {2018}, year = {2018}, } @article{33, abstract = {Secondary contact is the reestablishment of gene flow between sister populations that have diverged. For instance, at the end of the Quaternary glaciations in Europe, secondary contact occurred during the northward expansion of the populations which had found refugia in the southern peninsulas. With the advent of multi-locus markers, secondary contact can be investigated using various molecular signatures including gradients of allele frequency, admixture clines, and local increase of genetic differentiation. We use coalescent simulations to investigate if molecular data provide enough information to distinguish between secondary contact following range expansion and an alternative evolutionary scenario consisting of a barrier to gene flow in an isolation-by-distance model. We find that an excess of linkage disequilibrium and of genetic diversity at the suture zone is a unique signature of secondary contact. We also find that the directionality index ψ, which was proposed to study range expansion, is informative to distinguish between the two hypotheses. However, although evidence for secondary contact is usually conveyed by statistics related to admixture coefficients, we find that they can be confounded by isolation-by-distance. We recommend to account for the spatial repartition of individuals when investigating secondary contact in order to better reflect the complex spatio-temporal evolution of populations and species.}, author = {Bertl, Johanna and Ringbauer, Harald and Blum, Michaël}, journal = {PeerJ}, number = {10}, publisher = {PeerJ}, title = {{Can secondary contact following range expansion be distinguished from barriers to gene flow?}}, doi = {10.7717/peerj.5325}, volume = {2018}, year = {2018}, } @article{5673, abstract = {Cell polarity, manifested by the localization of proteins to distinct polar plasma membrane domains, is a key prerequisite of multicellular life. In plants, PIN auxin transporters are prominent polarity markers crucial for a plethora of developmental processes. Cell polarity mechanisms in plants are distinct from other eukaryotes and still largely elusive. In particular, how the cell polarities are propagated and maintained following cell division remains unknown. Plant cytokinesis is orchestrated by the cell plate—a transient centrifugally growing endomembrane compartment ultimately forming the cross wall1. Trafficking of polar membrane proteins is typically redirected to the cell plate, and these will consequently have opposite polarity in at least one of the daughter cells2–5. Here, we provide mechanistic insights into post-cytokinetic re-establishment of cell polarity as manifested by the apical, polar localization of PIN2. We show that the apical domain is defined in a cell-intrinsic manner and that re-establishment of PIN2 localization to this domain requires de novo protein secretion and endocytosis, but not basal-to-apical transcytosis. Furthermore, we identify a PINOID-related kinase WAG1, which phosphorylates PIN2 in vitro6 and is transcriptionally upregulated specifically in dividing cells, as a crucial regulator of post-cytokinetic PIN2 polarity re-establishment.}, author = {Glanc, Matous and Fendrych, Matyas and Friml, Jirí}, issn = {2055-0278}, journal = {Nature Plants}, number = {12}, pages = {1082--1088}, publisher = {Nature Research}, title = {{Mechanistic framework for cell-intrinsic re-establishment of PIN2 polarity after cell division}}, doi = {10.1038/s41477-018-0318-3}, volume = {4}, year = {2018}, } @article{198, abstract = {We consider a class of students learning a language from a teacher. The situation can be interpreted as a group of child learners receiving input from the linguistic environment. The teacher provides sample sentences. The students try to learn the grammar from the teacher. In addition to just listening to the teacher, the students can also communicate with each other. The students hold hypotheses about the grammar and change them if they receive counter evidence. The process stops when all students have converged to the correct grammar. We study how the time to convergence depends on the structure of the classroom by introducing and evaluating various complexity measures. We find that structured communication between students, although potentially introducing confusion, can greatly reduce some of the complexity measures. Our theory can also be interpreted as applying to the scientific process, where nature is the teacher and the scientists are the students.}, author = {Ibsen-Jensen, Rasmus and Tkadlec, Josef and Chatterjee, Krishnendu and Nowak, Martin}, issn = {1742-5662}, journal = {Journal of the Royal Society Interface}, number = {140}, publisher = {The Royal Society}, title = {{Language acquisition with communication between learners}}, doi = {10.1098/rsif.2018.0073}, volume = {15}, year = {2018}, } @article{5859, abstract = {The emergence of syntax during childhood is a remarkable example of how complex correlations unfold in nonlinear ways through development. In particular, rapid transitions seem to occur as children reach the age of two, which seems to separate a two-word, tree-like network of syntactic relations among words from the scale-free graphs associated with the adult, complex grammar. Here, we explore the evolution of syntax networks through language acquisition using the chromatic number, which captures the transition and provides a natural link to standard theories on syntactic structures. The data analysis is compared to a null model of network growth dynamics which is shown to display non-trivial and sensible differences. At a more general level, we observe that the chromatic classes define independent regions of the graph, and thus, can be interpreted as the footprints of incompatibility relations, somewhat as opposed to modularity considerations.}, author = {Corominas-Murtra, Bernat and Fibla, Martí Sànchez and Valverde, Sergi and Solé, Ricard}, issn = {2054-5703}, journal = {Royal Society Open Science}, number = {12}, publisher = {The Royal Society}, title = {{Chromatic transitions in the emergence of syntax networks}}, doi = {10.1098/rsos.181286}, volume = {5}, year = {2018}, } @unpublished{6183, abstract = {We study the unique solution $m$ of the Dyson equation \[ -m(z)^{-1} = z - a + S[m(z)] \] on a von Neumann algebra $\mathcal{A}$ with the constraint $\mathrm{Im}\,m\geq 0$. Here, $z$ lies in the complex upper half-plane, $a$ is a self-adjoint element of $\mathcal{A}$ and $S$ is a positivity-preserving linear operator on $\mathcal{A}$. We show that $m$ is the Stieltjes transform of a compactly supported $\mathcal{A}$-valued measure on $\mathbb{R}$. Under suitable assumptions, we establish that this measure has a uniformly $1/3$-H\"{o}lder continuous density with respect to the Lebesgue measure, which is supported on finitely many intervals, called bands. In fact, the density is analytic inside the bands with a square-root growth at the edges and internal cubic root cusps whenever the gap between two bands vanishes. The shape of these singularities is universal and no other singularity may occur. We give a precise asymptotic description of $m$ near the singular points. These asymptotics generalize the analysis at the regular edges given in the companion paper on the Tracy-Widom universality for the edge eigenvalue statistics for correlated random matrices [arXiv:1804.07744] and they play a key role in the proof of the Pearcey universality at the cusp for Wigner-type matrices [arXiv:1809.03971,arXiv:1811.04055]. We also extend the finite dimensional band mass formula from [arXiv:1804.07744] to the von Neumann algebra setting by showing that the spectral mass of the bands is topologically rigid under deformations and we conclude that these masses are quantized in some important cases.}, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, booktitle = {arXiv}, title = {{The Dyson equation with linear self-energy: Spectral bands, edges and cusps}}, year = {2018}, } @unpublished{75, abstract = {We prove that any convex body in the plane can be partitioned into m convex parts of equal areas and perimeters for any integer m≥2; this result was previously known for prime powers m=pk. We also give a higher-dimensional generalization.}, author = {Akopyan, Arseniy and Avvakumov, Sergey and Karasev, Roman}, publisher = {arXiv}, title = {{Convex fair partitions into arbitrary number of pieces}}, doi = {10.48550/arXiv.1804.03057}, year = {2018}, } @article{556, abstract = {We investigate the free boundary Schur process, a variant of the Schur process introduced by Okounkov and Reshetikhin, where we allow the first and the last partitions to be arbitrary (instead of empty in the original setting). The pfaffian Schur process, previously studied by several authors, is recovered when just one of the boundary partitions is left free. We compute the correlation functions of the process in all generality via the free fermion formalism, which we extend with the thorough treatment of “free boundary states.” For the case of one free boundary, our approach yields a new proof that the process is pfaffian. For the case of two free boundaries, we find that the process is not pfaffian, but a closely related process is. We also study three different applications of the Schur process with one free boundary: fluctuations of symmetrized last passage percolation models, limit shapes and processes for symmetric plane partitions and for plane overpartitions.}, author = {Betea, Dan and Bouttier, Jeremie and Nejjar, Peter and Vuletic, Mirjana}, issn = {1424-0637}, journal = {Annales Henri Poincare}, number = {12}, pages = {3663--3742}, publisher = {Springer Nature}, title = {{The free boundary Schur process and applications I}}, doi = {10.1007/s00023-018-0723-1}, volume = {19}, year = {2018}, } @misc{5573, abstract = {Graph matching problems for large displacement optical flow of RGB-D images.}, author = {Alhaija, Hassan and Sellent, Anita and Kondermann, Daniel and Rother, Carsten}, keywords = {graph matching, quadratic assignment problem<}, publisher = {Institute of Science and Technology Austria}, title = {{Graph matching problems for GraphFlow – 6D Large Displacement Scene Flow}}, doi = {10.15479/AT:ISTA:82}, year = {2018}, } @article{292, abstract = {Retina is a paradigmatic system for studying sensory encoding: the transformation of light into spiking activity of ganglion cells. The inverse problem, where stimulus is reconstructed from spikes, has received less attention, especially for complex stimuli that should be reconstructed “pixel-by-pixel”. We recorded around a hundred neurons from a dense patch in a rat retina and decoded movies of multiple small randomly-moving discs. We constructed nonlinear (kernelized and neural network) decoders that improved significantly over linear results. An important contribution to this was the ability of nonlinear decoders to reliably separate between neural responses driven by locally fluctuating light signals, and responses at locally constant light driven by spontaneous-like activity. This improvement crucially depended on the precise, non-Poisson temporal structure of individual spike trains, which originated in the spike-history dependence of neural responses. We propose a general principle by which downstream circuitry could discriminate between spontaneous and stimulus-driven activity based solely on higher-order statistical structure in the incoming spike trains.}, author = {Botella Soler, Vicent and Deny, Stephane and Martius, Georg S and Marre, Olivier and Tkacik, Gasper}, journal = {PLoS Computational Biology}, number = {5}, publisher = {Public Library of Science}, title = {{Nonlinear decoding of a complex movie from the mammalian retina}}, doi = {10.1371/journal.pcbi.1006057}, volume = {14}, year = {2018}, } @article{438, abstract = {The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin–antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress.}, author = {Nikolic, Nela and Bergmiller, Tobias and Vandervelde, Alexandra and Albanese, Tanino and Gelens, Lendert and Moll, Isabella}, journal = {Nucleic Acids Research}, number = {6}, pages = {2918--2931}, publisher = {Oxford University Press}, title = {{Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations}}, doi = {10.1093/nar/gky079}, volume = {46}, year = {2018}, } @article{131, abstract = {XY systems usually show chromosome-wide compensation of X-linked genes, while in many ZW systems, compensation is restricted to a minority of dosage-sensitive genes. Why such differences arose is still unclear. Here, we combine comparative genomics, transcriptomics and proteomics to obtain a complete overview of the evolution of gene dosage on the Z-chromosome of Schistosoma parasites. We compare the Z-chromosome gene content of African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes and describe lineage-specific evolutionary strata. We use these to assess gene expression evolution following sex-linkage. The resulting patterns suggest a reduction in expression of Z-linked genes in females, combined with upregulation of the Z in both sexes, in line with the first step of Ohno’s classic model of dosage compensation evolution. Quantitative proteomics suggest that post-transcriptional mechanisms do not play a major role in balancing the expression of Z-linked genes. }, author = {Picard, Marion A and Cosseau, Celine and Ferré, Sabrina and Quack, Thomas and Grevelding, Christoph and Couté, Yohann and Vicoso, Beatriz}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Evolution of gene dosage on the Z-chromosome of schistosome parasites}}, doi = {10.7554/eLife.35684}, volume = {7}, year = {2018}, } @misc{5584, abstract = {This package contains data for the publication "Nonlinear decoding of a complex movie from the mammalian retina" by Deny S. et al, PLOS Comput Biol (2018). The data consists of (i) 91 spike sorted, isolated rat retinal ganglion cells that pass stability and quality criteria, recorded on the multi-electrode array, in response to the presentation of the complex movie with many randomly moving dark discs. The responses are represented as 648000 x 91 binary matrix, where the first index indicates the timebin of duration 12.5 ms, and the second index the neural identity. The matrix entry is 0/1 if the neuron didn't/did spike in the particular time bin. (ii) README file and a graphical illustration of the structure of the experiment, specifying how the 648000 timebins are split into epochs where 1, 2, 4, or 10 discs were displayed, and which stimulus segments are exact repeats or unique ball trajectories. (iii) a 648000 x 400 matrix of luminance traces for each of the 20 x 20 positions ("sites") in the movie frame, with time that is locked to the recorded raster. The luminance traces are produced as described in the manuscript by filtering the raw disc movie with a small gaussian spatial kernel. }, author = {Deny, Stephane and Marre, Olivier and Botella-Soler, Vicente and Martius, Georg S and Tkacik, Gasper}, keywords = {retina, decoding, regression, neural networks, complex stimulus}, publisher = {Institute of Science and Technology Austria}, title = {{Nonlinear decoding of a complex movie from the mammalian retina}}, doi = {10.15479/AT:ISTA:98}, year = {2018}, } @article{286, abstract = {Pedigree and sibship reconstruction are important methods in quantifying relationships and fitness of individuals in natural populations. Current methods employ a Markov chain-based algorithm to explore plausible possible pedigrees iteratively. This provides accurate results, but is time-consuming. Here, we develop a method to infer sibship and paternity relationships from half-sibling arrays of known maternity using hierarchical clustering. Given 50 or more unlinked SNP markers and empirically derived error rates, the method performs as well as the widely used package Colony, but is faster by two orders of magnitude. Using simulations, we show that the method performs well across contrasting mating scenarios, even when samples are large. We then apply the method to open-pollinated arrays of the snapdragon Antirrhinum majus and find evidence for a high degree of multiple mating. Although we focus on diploid SNP data, the method does not depend on marker type and as such has broad applications in nonmodel systems. }, author = {Ellis, Thomas and Field, David and Barton, Nicholas H}, journal = {Molecular Ecology Resources}, number = {5}, pages = {988 -- 999}, publisher = {Wiley}, title = {{Efficient inference of paternity and sibship inference given known maternity via hierarchical clustering}}, doi = {10.1111/1755-0998.12782}, volume = {18}, year = {2018}, } @misc{5586, abstract = {Input files and scripts from "Evolution of gene dosage on the Z-chromosome of schistosome parasites" by Picard M.A.L., et al (2018).}, author = {Vicoso, Beatriz}, keywords = {schistosoma, Z-chromosome, gene expression}, publisher = {Institute of Science and Technology Austria}, title = {{Input files and scripts from "Evolution of gene dosage on the Z-chromosome of schistosome parasites" by Picard M.A.L., et al (2018)}}, doi = {10.15479/AT:ISTA:109}, year = {2018}, } @misc{5583, abstract = {Data and scripts are provided in support of the manuscript "Efficient inference of paternity and sibship inference given known maternity via hierarchical clustering", and the associated Python package FAPS, available from www.github.com/ellisztamas/faps. Simulation scripts cover: 1. Performance under different mating scenarios. 2. Comparison with Colony2. 3. Effect of changing the number of Monte Carlo draws The final script covers the analysis of half-sib arrays from wild-pollinated seed in an Antirrhinum majus hybrid zone.}, author = {Ellis, Thomas}, publisher = {Institute of Science and Technology Austria}, title = {{Data and Python scripts supporting Python package FAPS}}, doi = {10.15479/AT:ISTA:95}, year = {2018}, } @misc{5569, abstract = {Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese, Lendert Gelens, and Isabella Moll (2018) “Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations” Nucleic Acids Research, doi: 10.15479/AT:ISTA:74; microscopy experiments by Tobias Bergmiller; image and data analysis by Nela Nikolic.}, author = {Bergmiller, Tobias and Nikolic, Nela}, keywords = {microscopy, microfluidics}, publisher = {Institute of Science and Technology Austria}, title = {{Time-lapse microscopy data}}, doi = {10.15479/AT:ISTA:74}, year = {2018}, } @article{161, abstract = {Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells.}, author = {De Martino, Daniele and Mc, Andersson Anna and Bergmiller, Tobias and Guet, Calin C and Tkacik, Gasper}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Statistical mechanics for metabolic networks during steady state growth}}, doi = {10.1038/s41467-018-05417-9}, volume = {9}, year = {2018}, } @misc{5587, abstract = {Supporting material to the article STATISTICAL MECHANICS FOR METABOLIC NETWORKS IN STEADY-STATE GROWTH boundscoli.dat Flux Bounds of the E. coli catabolic core model iAF1260 in a glucose limited minimal medium. polcoli.dat Matrix enconding the polytope of the E. coli catabolic core model iAF1260 in a glucose limited minimal medium, obtained from the soichiometric matrix by standard linear algebra (reduced row echelon form). ellis.dat Approximate Lowner-John ellipsoid rounding the polytope of the E. coli catabolic core model iAF1260 in a glucose limited minimal medium obtained with the Lovasz method. point0.dat Center of the approximate Lowner-John ellipsoid rounding the polytope of the E. coli catabolic core model iAF1260 in a glucose limited minimal medium obtained with the Lovasz method. lovasz.cpp This c++ code file receives in input the polytope of the feasible steady states of a metabolic network, (matrix and bounds), and it gives in output an approximate Lowner-John ellipsoid rounding the polytope with the Lovasz method NB inputs are referred by defaults to the catabolic core of the E.Coli network iAF1260. For further details we refer to PLoS ONE 10.4 e0122670 (2015). sampleHRnew.cpp This c++ code file receives in input the polytope of the feasible steady states of a metabolic network, (matrix and bounds), the ellipsoid rounding the polytope, a point inside and it gives in output a max entropy sampling at fixed average growth rate of the steady states by performing an Hit-and-Run Monte Carlo Markov chain. NB inputs are referred by defaults to the catabolic core of the E.Coli network iAF1260. For further details we refer to PLoS ONE 10.4 e0122670 (2015).}, author = {De Martino, Daniele and Tkacik, Gasper}, keywords = {metabolic networks, e.coli core, maximum entropy, monte carlo markov chain sampling, ellipsoidal rounding}, publisher = {Institute of Science and Technology Austria}, title = {{Supporting materials "STATISTICAL MECHANICS FOR METABOLIC NETWORKS IN STEADY-STATE GROWTH"}}, doi = {10.15479/AT:ISTA:62}, year = {2018}, } @article{542, abstract = {The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history. As expected for a long genomic segment of very low recombination, the t-haplotype carries an excess of fixed nonsynonymous mutations compared to the standard chromosome. This excess is stronger for regions that have not undergone recent recombination, suggesting that occasional gene flow between the t and the standard chromosome may provide a mechanism to regenerate coding sequences that have accumulated deleterious mutations. Finally, we find that t-complex genes with altered expression largely overlap with deleted or amplified regions, and that carrying a t-haplotype alters the testis expression of genes outside of the t-complex, providing new leads into the pathways involved in the biology of this segregation distorter.}, author = {Kelemen, Réka K and Vicoso, Beatriz}, journal = {Genetics}, number = {1}, pages = {365 -- 375}, publisher = {Genetics Society of America}, title = {{Complex history and differentiation patterns of the t-haplotype, a mouse meiotic driver}}, doi = {10.1534/genetics.117.300513}, volume = {208}, year = {2018}, } @article{5751, abstract = {Because of the intrinsic randomness of the evolutionary process, a mutant with a fitness advantage has some chance to be selected but no certainty. Any experiment that searches for advantageous mutants will lose many of them due to random drift. It is therefore of great interest to find population structures that improve the odds of advantageous mutants. Such structures are called amplifiers of natural selection: they increase the probability that advantageous mutants are selected. Arbitrarily strong amplifiers guarantee the selection of advantageous mutants, even for very small fitness advantage. Despite intensive research over the past decade, arbitrarily strong amplifiers have remained rare. Here we show how to construct a large variety of them. Our amplifiers are so simple that they could be useful in biotechnology, when optimizing biological molecules, or as a diagnostic tool, when searching for faster dividing cells or viruses. They could also occur in natural population structures.}, author = {Pavlogiannis, Andreas and Tkadlec, Josef and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {2399-3642}, journal = {Communications Biology}, number = {1}, publisher = {Springer Nature}, title = {{Construction of arbitrarily strong amplifiers of natural selection using evolutionary graph theory}}, doi = {10.1038/s42003-018-0078-7}, volume = {1}, year = {2018}, } @misc{5757, abstract = {File S1. Variant Calling Format file of the ingroup: 197 haploid sequences of D. melanogaster from Zambia (Africa) aligned to the D. melanogaster 5.57 reference genome. File S2. Variant Calling Format file of the outgroup: 1 haploid sequence of D. simulans aligned to the D. melanogaster 5.57 reference genome. File S3. Annotations of each transcript in coding regions with SNPeff: Ps (# of synonymous polymorphic sites); Pn (# of non-synonymous polymorphic sites); Ds (# of synonymous divergent sites); Dn (# of non-synonymous divergent sites); DoS; ⍺ MK . All variants were included. File S4. Annotations of each transcript in non-coding regions with SNPeff: Ps (# of synonymous polymorphic sites); Pu (# of UTR polymorphic sites); Ds (# of synonymous divergent sites); Du (# of UTR divergent sites); DoS; ⍺ MK . All variants were included. File S5. Annotations of each transcript in coding regions with SNPGenie: Ps (# of synonymous polymorphic sites); πs (synonymous diversity); Ss_p (total # of synonymous sites in the polymorphism data); Pn (# of non-synonymous polymorphic sites); πn (non-synonymous diversity); Sn_p (total # of non-synonymous sites in the polymorphism data); Ds (# of synonymous divergent sites); ks (synonymous evolutionary rate); Ss_d (total # of synonymous sites in the divergence data); Dn (# of non-synonymous divergent sites); kn (non-synonymous evolutionary rate); Sn_d (total # of non- synonymous sites in the divergence data); DoS; ⍺ MK . All variants were included. File S6. Gene expression values (RPKM summed over all transcripts) for each sample. Values were quantile-normalized across all samples. File S7. Final dataset with all covariates, ⍺ MK , ωA MK and DoS for coding sites, excluding variants below 5% frequency. File S8. Final dataset with all covariates, ⍺ MK , ωA MK and DoS for non-coding sites, excluding variants below 5% frequency. File S9. Final dataset with all covariates, ⍺ EWK , ωA EWK and deleterious SFS for coding sites obtained with the Eyre-Walker and Keightley method on binned data and using all variants.}, author = {Fraisse, Christelle}, keywords = {(mal)adaptation, pleiotropy, selective constraint, evo-devo, gene expression, Drosophila melanogaster}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary Files for "Pleiotropy modulates the efficacy of selection in Drosophila melanogaster"}}, doi = {10.15479/at:ista:/5757}, year = {2018}, } @phdthesis{149, abstract = {The eigenvalue density of many large random matrices is well approximated by a deterministic measure, the self-consistent density of states. In the present work, we show this behaviour for several classes of random matrices. In fact, we establish that, in each of these classes, the self-consistent density of states approximates the eigenvalue density of the random matrix on all scales slightly above the typical eigenvalue spacing. For large classes of random matrices, the self-consistent density of states exhibits several universal features. We prove that, under suitable assumptions, random Gram matrices and Hermitian random matrices with decaying correlations have a 1/3-Hölder continuous self-consistent density of states ρ on R, which is analytic, where it is positive, and has either a square root edge or a cubic root cusp, where it vanishes. We, thus, extend the validity of the corresponding result for Wigner-type matrices from [4, 5, 7]. We show that ρ is determined as the inverse Stieltjes transform of the normalized trace of the unique solution m(z) to the Dyson equation −m(z) −1 = z − a + S[m(z)] on C N×N with the constraint Im m(z) ≥ 0. Here, z lies in the complex upper half-plane, a is a self-adjoint element of C N×N and S is a positivity-preserving operator on C N×N encoding the first two moments of the random matrix. In order to analyze a possible limit of ρ for N → ∞ and address some applications in free probability theory, we also consider the Dyson equation on infinite dimensional von Neumann algebras. We present two applications to random matrices. We first establish that, under certain assumptions, large random matrices with independent entries have a rotationally symmetric self-consistent density of states which is supported on a centered disk in C. Moreover, it is infinitely often differentiable apart from a jump on the boundary of this disk. Second, we show edge universality at all regular (not necessarily extreme) spectral edges for Hermitian random matrices with decaying correlations.}, author = {Alt, Johannes}, issn = {2663-337X}, pages = {456}, publisher = {Institute of Science and Technology Austria}, title = {{Dyson equation and eigenvalue statistics of random matrices}}, doi = {10.15479/AT:ISTA:TH_1040}, year = {2018}, } @article{415, abstract = {Recently it was shown that a molecule rotating in a quantum solvent can be described in terms of the “angulon” quasiparticle [M. Lemeshko, Phys. Rev. Lett. 118, 095301 (2017)]. Here we extend the angulon theory to the case of molecules possessing an additional spin-1/2 degree of freedom and study the behavior of the system in the presence of a static magnetic field. We show that exchange of angular momentum between the molecule and the solvent can be altered by the field, even though the solvent itself is non-magnetic. In particular, we demonstrate a possibility to control resonant emission of phonons with a given angular momentum using a magnetic field.}, author = {Rzadkowski, Wojciech and Lemeshko, Mikhail}, journal = {The Journal of Chemical Physics}, number = {10}, publisher = {AIP Publishing}, title = {{Effect of a magnetic field on molecule–solvent angular momentum transfer}}, doi = {10.1063/1.5017591}, volume = {148}, year = {2018}, } @article{134, abstract = {The current state of the art in real-time two-dimensional water wave simulation requires developers to choose between efficient Fourier-based methods, which lack interactions with moving obstacles, and finite-difference or finite element methods, which handle environmental interactions but are significantly more expensive. This paper attempts to bridge this long-standing gap between complexity and performance, by proposing a new wave simulation method that can faithfully simulate wave interactions with moving obstacles in real time while simultaneously preserving minute details and accommodating very large simulation domains. Previous methods for simulating 2D water waves directly compute the change in height of the water surface, a strategy which imposes limitations based on the CFL condition (fast moving waves require small time steps) and Nyquist's limit (small wave details require closely-spaced simulation variables). This paper proposes a novel wavelet transformation that discretizes the liquid motion in terms of amplitude-like functions that vary over space, frequency, and direction, effectively generalizing Fourier-based methods to handle local interactions. Because these new variables change much more slowly over space than the original water height function, our change of variables drastically reduces the limitations of the CFL condition and Nyquist limit, allowing us to simulate highly detailed water waves at very large visual resolutions. Our discretization is amenable to fast summation and easy to parallelize. We also present basic extensions like pre-computed wave paths and two-way solid fluid coupling. Finally, we argue that our discretization provides a convenient set of variables for artistic manipulation, which we illustrate with a novel wave-painting interface.}, author = {Jeschke, Stefan and Skrivan, Tomas and Mueller Fischer, Matthias and Chentanez, Nuttapong and Macklin, Miles and Wojtan, Christopher J}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Water surface wavelets}}, doi = {10.1145/3197517.3201336}, volume = {37}, year = {2018}, } @article{6339, abstract = {We introduce a diagrammatic Monte Carlo approach to angular momentum properties of quantum many-particle systems possessing a macroscopic number of degrees of freedom. The treatment is based on a diagrammatic expansion that merges the usual Feynman diagrams with the angular momentum diagrams known from atomic and nuclear structure theory, thereby incorporating the non-Abelian algebra inherent to quantum rotations. Our approach is applicable at arbitrary coupling, is free of systematic errors and of finite-size effects, and naturally provides access to the impurity Green function. We exemplify the technique by obtaining an all-coupling solution of the angulon model; however, the method is quite general and can be applied to a broad variety of systems in which particles exchange quantum angular momentum with their many-body environment.}, author = {Bighin, Giacomo and Tscherbul, Timur and Lemeshko, Mikhail}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Diagrammatic Monte Carlo approach to angular momentum in quantum many-particle systems}}, doi = {10.1103/physrevlett.121.165301}, volume = {121}, year = {2018}, } @article{417, abstract = {We introduce a Diagrammatic Monte Carlo (DiagMC) approach to complex molecular impurities with rotational degrees of freedom interacting with a many-particle environment. The treatment is based on the diagrammatic expansion that merges the usual Feynman diagrams with the angular momentum diagrams known from atomic and nuclear structure theory, thereby incorporating the non-Abelian algebra inherent to quantum rotations. Our approach works at arbitrary coupling, is free of systematic errors and of finite size effects, and naturally provides access to the impurity Green function. We exemplify the technique by obtaining an all-coupling solution of the angulon model, however, the method is quite general and can be applied to a broad variety of quantum impurities possessing angular momentum degrees of freedom. }, author = {Bighin, Giacomo and Tscherbul, Timur and Lemeshko, Mikhail}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Diagrammatic Monte Carlo approach to rotating molecular impurities}}, doi = {10.1103/PhysRevLett.121.165301}, volume = {121}, year = {2018}, } @article{412, abstract = {Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterised compared to that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing Tandem Affinity Purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat. Among the confirmed interactors, we found two putative homologues of the clathrin-coat uncoating factor auxilin previously described in non-plant systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in A. thaliana caused an arrest of seedling growth and development. This was concomitant with inhibited endocytosis due to blocking of clathrin recruitment after the initial step of adaptor protein binding to the plasma membrane. By contrast, auxilin-like(1/2) loss-of-function lines did not present endocytosis-related developmental or cellular phenotypes under normal growth conditions. This work contributes to the on-going characterization of the endocytotic machinery in plants and provides a robust tool for conditionally and specifically interfering with CME in A. thaliana.}, author = {Adamowski, Maciek and Narasimhan, Madhumitha and Kania, Urszula and Glanc, Matous and De Jaeger, Geert and Friml, Jirí}, issn = {1532-298X}, journal = {The Plant Cell}, number = {3}, pages = {700 -- 716}, publisher = {American Society of Plant Biologists}, title = {{A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors in Arabidopsis}}, doi = {10.1105/tpc.17.00785}, volume = {30}, year = {2018}, } @article{5914, abstract = {With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task.}, author = {Rangel Guerrero, Dámaris K and Donnett, James G. and Csicsvari, Jozsef L and Kovács, Krisztián}, journal = {eNeuro}, number = {4}, publisher = {Society of Neuroscience}, title = {{Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning}}, doi = {10.1523/ENEURO.0087-18.2018}, volume = {5}, year = {2018}, } @article{402, abstract = {During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.}, author = {Brown, Markus and Assen, Frank P and Leithner, Alexander F and Abe, Jun and Schachner, Helga and Asfour, Gabriele and Bagó Horváth, Zsuzsanna and Stein, Jens and Uhrin, Pavel and Sixt, Michael K and Kerjaschki, Dontscho}, journal = {Science}, number = {6382}, pages = {1408 -- 1411}, publisher = {American Association for the Advancement of Science}, title = {{Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice}}, doi = {10.1126/science.aal3662}, volume = {359}, year = {2018}, } @phdthesis{395, abstract = {Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. }, author = {Tarlungeanu, Dora-Clara}, issn = {2663-337X}, pages = {88}, publisher = {Institute of Science and Technology Austria}, title = {{The branched chain amino acids in autism spectrum disorders }}, doi = {10.15479/AT:ISTA:th_992}, year = {2018}, } @phdthesis{51, abstract = {Asymmetries have long been known about in the central nervous system. From gross anatomical differences, such as the presence of the parapineal organ in only one hemisphere of the developing zebrafish, to more subtle differences in activity between both hemispheres, as seen in freely roaming animals or human participants under PET and fMRI imaging analysis. The presence of asymmetries has been demonstrated to have huge behavioural implications, with their disruption often leading to the generation of neurological disorders, memory problems, changes in personality, and in an organism's health and well-being. For my Ph.D. work I aimed to tackle two important avenues of research. The first being the process of input-side dependency in the hippocampus, with the goal of finding a key gene responsible for its development (Gene X). The second project was to do with experience-induced laterality formation in the hippocampus. Specifically, how laterality in the synapse density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental enrichment. Through unilateral tracer injections into the CA3, I was able to selectively measure the properties of synapses within the CA1 and investigate how they differed based upon which hemisphere the presynaptic neurone originated. Having found the existence of a previously unreported reversed (left-isomerism) i.v. mutant, through morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate a key gene responsible for the process of left or right determination of inputs to the CA1 s.r.. This work relates to the previous finding of input-side dependent asymmetry in the wild-type rodent, where the origin of the projecting neurone to the CA1 will determine the morphology of a synapse, to a greater degree than the hemisphere in which the projection terminates. Using left- and right-isomerism i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like (Evl) as a potential target for Gene X. In relation to this topic, I also highlight my work in the recently published paper of how knockout of PirB can lead to a lack of input-side dependency in the murine hippocampus. For the second question, I show that the environmental enrichment paradigm will lead to an asymmetry in the synapse densities in the hippocampus of mice. I also highlight that the nature of the enrichment is of less consequence than the process of enrichment itself. I demonstrate that the CA3 region will dramatically alter its projection targets, in relation to environmental stimulation, with the asymmetry in synaptic density, caused by enrichment, relying heavily on commissural fibres. I also highlight the vital importance of input-side dependent asymmetry, as a necessary component of experience-dependent laterality formation in the CA1 s.r.. However, my results suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism also at play. Upon further investigation, I highlight the significant, and highly important, finding that the changes seen in the CA1 s.r. were predominantly caused through projections from the left-CA3, with the right-CA3 having less involvement in this mechanism.}, author = {Case, Matthew J}, issn = {2663-337X}, pages = {186}, publisher = {Institute of Science and Technology Austria}, title = {{From the left to the right: A tale of asymmetries, environments, and hippocampal development}}, doi = {10.15479/AT:ISTA:th_1032}, year = {2018}, } @phdthesis{10, abstract = {Genomic imprinting is an epigenetic process that leads to parent of origin-specific gene expression in a subset of genes. Imprinted genes are essential for brain development, and deregulation of imprinting is associated with neurodevelopmental diseases and the pathogenesis of psychiatric disorders. However, the cell-type specificity of imprinting at single cell resolution, and how imprinting and thus gene dosage regulates neuronal circuit assembly is still largely unknown. Here, MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic imprinting at single cell level. By visualizing MADM-induced uniparental disomies (UPDs) in distinct colors at single cell level in genetic mosaic animals, this experimental paradigm provides a unique quantitative platform to systematically assay the UPD-mediated imbalances in imprinted gene expression at unprecedented resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics analysis was established and applied to systematically map cell-type-specific ‘imprintomes’ in the mouse brain. The results revealed that parental-specific expression of imprinted genes per se is rarely cell-type-specific even at the individual cell level. Conversely, when we extended the comparison to downstream responses resulting from imbalanced imprinted gene expression, we discovered an unexpectedly high degree of cell-type specificity. Furthermore, we determined a novel function of genomic imprinting in cortical astrocyte production and in olfactory bulb (OB) granule cell generation. These results suggest important functional implication of genomic imprinting for generating cell-type diversity in the brain. In addition, MADM provides a powerful tool to study candidate genes by concomitant genetic manipulation and fluorescent labelling of single cells. MADM-based candidate gene approach was utilized to identify potential imprinted genes involved in the generation of cortical astrocytes and OB granule cells. We investigated p57Kip2, a maternally expressed gene and known cell cycle regulator. Although we found that p57Kip2 does not play a role in these processes, we detected an unexpected function of the paternal allele previously thought to be silent. Finally, we took advantage of a key property of MADM which is to allow unambiguous investigation of environmental impact on single cells. The experimental pipeline based on FACS and RNA-seq analysis of MADM-labeled cells was established to probe the functional differences of single cell loss of gene function compared to global loss of function on a transcriptional level. With this method, both common and distinct responses were isolated due to cell-autonomous and non-autonomous effects acting on genotypically identical cells. As a result, transcriptional changes were identified which result solely from the surrounding environment. Using the MADM technology to study genomic imprinting at single cell resolution, we have identified cell-type-specific gene expression, novel gene function and the impact of environment on single cell transcriptomes. Together, these provide important insights to the understanding of mechanisms regulating cell-type specificity and thus diversity in the brain.}, author = {Laukoter, Susanne}, issn = {2663-337X}, pages = {1 -- 139}, publisher = {Institute of Science and Technology Austria}, title = {{Role of genomic imprinting in cerebral cortex development}}, doi = {10.15479/AT:ISTA:th1057}, year = {2018}, } @phdthesis{323, abstract = {In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. }, author = {Leithner, Alexander F}, issn = {2663-337X}, pages = {99}, publisher = {Institute of Science and Technology Austria}, title = {{Branched actin networks in dendritic cell biology}}, doi = {10.15479/AT:ISTA:th_998}, year = {2018}, } @phdthesis{539, abstract = {The whole life cycle of plants as well as their responses to environmental stimuli is governed by a complex network of hormonal regulations. A number of studies have demonstrated an essential role of both auxin and cytokinin in the regulation of many aspects of plant growth and development including embryogenesis, postembryonic organogenic processes such as root, and shoot branching, root and shoot apical meristem activity and phyllotaxis. Over the last decades essential knowledge on the key molecular factors and pathways that spatio-temporally define auxin and cytokinin activities in the plant body has accumulated. However, how both hormonal pathways are interconnected by a complex network of interactions and feedback circuits that determines the final outcome of the individual hormone actions is still largely unknown. Root system architecture establishment and in particular formation of lateral organs is prime example of developmental process at whose regulation both auxin and cytokinin pathways converge. To dissect convergence points and pathways that tightly balance auxin - cytokinin antagonistic activities that determine the root branching pattern transcriptome profiling was applied. Genome wide expression analyses of the xylem pole pericycle, a tissue giving rise to lateral roots, led to identification of genes that are highly responsive to combinatorial auxin and cytokinin treatments and play an essential function in the auxin-cytokinin regulated root branching. SYNERGISTIC AUXIN CYTOKININ 1 (SYAC1) gene, which encodes for a protein of unknown function, was detected among the top candidate genes of which expression was synergistically up-regulated by simultaneous hormonal treatment. Plants with modulated SYAC1 activity exhibit severe defects in the root system establishment and attenuate developmental responses to both auxin and cytokinin. To explore the biological function of the SYAC1, we employed different strategies including expression pattern analysis, subcellular localization and phenotypic analyses of the syac1 loss-of-function and gain-of-function transgenic lines along with the identification of the SYAC1 interaction partners. Detailed functional characterization revealed that SYAC1 acts as a developmentally specific regulator of the secretory pathway to control deposition of cell wall components and thereby rapidly fine tune elongation growth.}, author = {Hurny, Andrej}, issn = {2663-337X}, pages = {147}, publisher = {Institute of Science and Technology Austria}, title = {{Identification and characterization of novel auxin-cytokinin cross-talk components}}, doi = {10.15479/AT:ISTA:th_930}, year = {2018}, } @phdthesis{48, abstract = {The hippocampus is a key brain region for spatial memory and navigation and is needed at all stages of memory, including encoding, consolidation, and recall. Hippocampal place cells selectively discharge at specific locations of the environment to form a cognitive map of the space. During the rest period and sleep following spatial navigation and/or learning, the waking activity of the place cells is reactivated within high synchrony events. This reactivation is thought to be important for memory consolidation and stabilization of the spatial representations. The aim of my thesis was to directly test whether the reactivation content encoded in firing patterns of place cells is important for consolidation of spatial memories. In particular, I aimed to test whether, in cases when multiple spatial memory traces are acquired during learning, the specific disruption of the reactivation of a subset of these memories leads to the selective disruption of the corresponding memory traces or through memory interference the other learned memories are disrupted as well. In this thesis, using a modified cheeseboard paradigm and a closed-loop recording setup with feedback optogenetic stimulation, I examined how the disruption of the reactivation of specific spiking patterns affects consolidation of the corresponding memory traces. To obtain multiple distinctive memories, animals had to perform a spatial task in two distinct cheeseboard environments and the reactivation of spiking patterns associated with one of the environments (target) was disrupted after learning during four hours rest period using a real-time decoding method. This real-time decoding method was capable of selectively affecting the firing rates and cofiring correlations of the target environment-encoding cells. The selective disruption led to behavioural impairment in the memory tests after the rest periods in the target environment but not in the other undisrupted control environment. In addition, the map of the target environment was less stable in the impaired memory tests compared to the learning session before than the map of the control environment. However, when the animal relearned the task, the same map recurred in the target environment that was present during learning before the disruption. Altogether my work demonstrated that the reactivation content is important: assembly-related disruption of reactivation can lead to a selective memory impairment and deficiency in map stability. These findings indeed suggest that reactivated assembly patterns reflect processes associated with the consolidation of memory traces. }, author = {Gridchyn, Igor}, issn = {2663-337X}, pages = {104}, publisher = {Institute of Science and Technology Austria}, title = {{Reactivation content is important for consolidation of spatial memory}}, doi = {10.15479/AT:ISTA:th_1042}, year = {2018}, } @phdthesis{9, abstract = {Immune cells migrating to the sites of infection navigate through diverse tissue architectures and switch their migratory mechanisms upon demand. However, little is known about systemic regulators that could allow the acquisition of these mechanisms. We performed a genetic screen in Drosophila melanogaster to identify regulators of germband invasion by embryonic macrophages into the confined space between the ectoderm and mesoderm. We have found that bZIP circadian transcription factors (TFs) Kayak (dFos) and Vrille (dNFIL3) have opposite effects on macrophage germband infiltration: Kayak facilitated and Vrille inhibited it. These TFs are enriched in the macrophages during migration and genetically interact to control it. Kayak sets a less coordinated mode of migration of the macrophage group and increases the probability and length of Levy walks. Intriguingly, the motility of kayak mutant macrophages was also strongly affected during initial germband invasion but not along another less confined route. Inhibiting Rho1 signaling within the tail ectoderm partially rescued the Kayak mutant phenotype, strongly suggesting that migrating macrophages have to overcome a barrier imposed by the stiffness of the ectoderm. Also, Kayak appeared to be important for the maintenance of the round cell shape and the rear edge translocation of the macrophages invading the germband. Complementary to this, the cortical actin cytoskeleton of Kayak- deficient macrophages was strongly affected. RNA sequencing revealed the filamin Cheerio and tetraspanin TM4SF to be downstream of Kayak. Chromatin immunoprecipitation and immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Indeed, Cheerio, TM4SF and Diaphanous are required within macrophages for germband invasion, and expression of constitutively active Diaphanous in macrophages was able to rescue the kayak mutant phenotype. Moreover, Cher and Diaphanous are also reduced in the macrophages overexpressing Vrille. We hypothesize that Kayak, through its targets, increases actin polymerization and cortical tension in macrophages and thus allows extra force generation necessary for macrophage dissemination and migration through confined stiff tissues, while Vrille counterbalances it.}, author = {Belyaeva, Vera}, issn = {2663-337X}, pages = {96}, publisher = {Institute of Science and Technology Austria}, title = {{Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo }}, doi = {10.15479/AT:ISTA:th1064}, year = {2018}, } @phdthesis{6266, 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:th_1055}, year = {2018}, } @phdthesis{50, abstract = {The Wnt/planar cell polarity (Wnt/PCP) pathway determines planar polarity of epithelial cells in both vertebrates and invertebrates. The role that Wnt/PCP signaling plays in mesenchymal contexts, however, is only poorly understood. While previous studies have demonstrated the capacity of Wnt/PCP signaling to polarize and guide directed migration of mesenchymal cells, it remains unclear whether endogenous Wnt/PCP signaling performs these functions instructively, as it does in epithelial cells. Here we developed a light-switchable version of the Wnt/PCP receptor Frizzled 7 (Fz7) to unambiguously distinguish between an instructive and a permissive role of Wnt/PCP signaling for the directional collective migration of mesendoderm progenitor cells during zebrafish gastrulation. We show that prechordal plate (ppl) cell migration is defective in maternal-zygotic fz7a and fz7b (MZ fz7a,b) double mutant embryos, and that Fz7 functions cell-autonomously in this process by promoting ppl cell protrusion formation and directed migration. We further show that local activation of Fz7 can direct ppl cell migration both in vitro and in vivo. Surprisingly, however, uniform Fz7 activation is sufficient to fully rescue the ppl cell migration defect in MZ fz7a,b mutant embryos, indicating that Wnt/PCP signaling functions permissively rather than instructively in directed mesendoderm cell migration during zebrafish gastrulation.}, author = {Capek, Daniel}, issn = {2663-337X}, pages = {95}, publisher = {Institute of Science and Technology Austria}, title = {{Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration}}, doi = {10.15479/AT:ISTA:TH_1031}, year = {2018}, } @phdthesis{26, abstract = {Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.}, author = {Steinrück, Magdalena}, issn = {2663-337X}, pages = {109}, publisher = {Institute of Science and Technology Austria}, title = {{The influence of sequence context on the evolution of bacterial gene expression}}, doi = {10.15479/AT:ISTA:th1059}, year = {2018}, } @article{5816, abstract = {Solid-state qubit manipulation and read-out fidelities are reaching fault-tolerance, but quantum error correction requires millions of physical qubits and therefore a scalable quantum computer architecture. To solve signal-line bandwidth and fan-out problems, microwave sources required for qubit manipulation might be embedded close to the qubit chip, typically operating at temperatures below 4 K. Here, we perform the first low temperature measurements of a 130 nm BiCMOS based SiGe voltage controlled oscillator at cryogenic temperature. We determined the frequency and output power dependence on temperature and magnetic field up to 5 T and measured the temperature influence on its noise performance. The device maintains its full functionality from 300 K to 4 K. The carrier frequency at 4 K increases by 3% with respect to the carrier frequency at 300 K, and the output power at 4 K increases by 10 dB relative to the output power at 300 K. The frequency tuning range of approximately 20% remains unchanged between 300 K and 4 K. In an in-plane magnetic field of 5 T, the carrier frequency shifts by only 0.02% compared to the frequency at zero magnetic field.}, author = {Hollmann, Arne and Jirovec, Daniel and Kucharski, Maciej and Kissinger, Dietmar and Fischer, Gunter and Schreiber, Lars R.}, issn = {00346748}, journal = {Review of Scientific Instruments}, number = {11}, publisher = {AIP Publishing}, title = {{30 GHz-voltage controlled oscillator operating at 4 K}}, doi = {10.1063/1.5038258}, volume = {89}, year = {2018}, } @phdthesis{6263, abstract = {Antibiotic resistance can emerge spontaneously through genomic mutation and render treatment ineffective. To counteract this process, in addition to the discovery and description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand its determinantsis needed. To address this challenge, this thesisuncoversnew genetic determinants of resistance evolvability using a customized robotic setup, exploressystematic ways in which resistance evolution is perturbed due to dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates the evolutionary fate of one specific type of evolvability modifier -a stress-induced mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order to identify them, we first developedan automated high-throughput feedback-controlled protocol whichkeeps the population size and selection pressure approximately constant for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic concentration. We implementedthis protocol on a customized liquid handling robot and propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100 generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more compared to less sensitive ones. Our data uncover that deletions of certain genes which do not affect mutation rate,including efflux pump components, a chaperone and severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution. Sequencing analysis of evolved populations indicates that epistasis with resistance mutations is the most likelyexplanation. This work could inspire treatment strategies in which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model, toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations. We show that in silicothis also leads to slower resistance evolution. We see and confirm with experiments that increased mutation rates, apart from speeding up evolution, also leadto high reproducibility of phenotypic adaptation in a context of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier –a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under periodic selectionakin to clinical treatment. We set up a deterministic infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and evaluate various treatment schemes in how well they maintain a stress-induced mutator allele. In particular,a high diversity of stresses is crucial for the persistence of the mutator allele. This leads to a general trade-off where exactly those diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular mechanisms involved in antibiotic resistance evolution and could inspire new strategies for slowing down its rate. }, author = {Lukacisinova, Marta}, issn = {2663-337X}, pages = {91}, publisher = {Institute of Science and Technology Austria}, title = {{Genetic determinants of antibiotic resistance evolution}}, doi = {10.15479/AT:ISTA:th1072}, year = {2018}, } @article{544, abstract = {Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.}, author = {György, Attila and Roblek, Marko and Ratheesh, Aparna and Valosková, Katarina and Belyaeva, Vera and Wachner, Stephanie and Matsubayashi, Yutaka and Sanchez Sanchez, Besaiz and Stramer, Brian and Siekhaus, Daria E}, journal = {G3: Genes, Genomes, Genetics}, number = {3}, pages = {845 -- 857}, publisher = {Genetics Society of America}, title = {{Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues}}, doi = {10.1534/g3.117.300452}, volume = {8}, year = {2018}, } @article{612, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network.}, author = {Luján, Rafael and Aguado, Carolina and Ciruela, Francisco and Cózar, Javier and Kleindienst, David and De La Ossa, Luis and Bettler, Bernhard and Wickman, Kevin and Watanabe, Masahiko and Shigemoto, Ryuichi and Fukazawa, Yugo}, journal = {Brain Structure and Function}, number = {3}, pages = {1565 -- 1587}, publisher = {Springer}, title = {{Differential association of GABAB receptors with their effector ion channels in Purkinje cells}}, doi = {10.1007/s00429-017-1568-y}, volume = {223}, year = {2018}, } @article{21, abstract = {Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations}, author = {Espinoza Martinez, Claudia and Guzmán, José and Zhang, Xiaomin and Jonas, Peter M}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus}}, doi = {10.1038/s41467-018-06899-3}, volume = {9}, year = {2018}, } @inproceedings{66, abstract = {Crypto-currencies are digital assets designed to work as a medium of exchange, e.g., Bitcoin, but they are susceptible to attacks (dishonest behavior of participants). A framework for the analysis of attacks in crypto-currencies requires (a) modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior; (b) concurrent interactions between participants; and (c) analysis of long-term monetary gains. Traditional game-theoretic approaches for the analysis of security protocols consider either qualitative temporal properties such as safety and termination, or the very special class of one-shot (stateless) games. However, to analyze general attacks on protocols for crypto-currencies, both stateful analysis and quantitative objectives are necessary. In this work our main contributions are as follows: (a) we show how a class of concurrent mean-payo games, namely ergodic games, can model various attacks that arise naturally in crypto-currencies; (b) we present the first practical implementation of algorithms for ergodic games that scales to model realistic problems for crypto-currencies; and (c) we present experimental results showing that our framework can handle games with thousands of states and millions of transitions.}, author = {Chatterjee, Krishnendu and Goharshady, Amir and Ibsen-Jensen, Rasmus and Velner, Yaron}, isbn = {978-3-95977-087-3}, location = {Beijing, China}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Ergodic mean-payoff games for the analysis of attacks in crypto-currencies}}, doi = {10.4230/LIPIcs.CONCUR.2018.11}, volume = {118}, year = {2018}, } @inproceedings{311, abstract = {Smart contracts are computer programs that are executed by a network of mutually distrusting agents, without the need of an external trusted authority. Smart contracts handle and transfer assets of considerable value (in the form of crypto-currency like Bitcoin). Hence, it is crucial that their implementation is bug-free. We identify the utility (or expected payoff) of interacting with such smart contracts as the basic and canonical quantitative property for such contracts. We present a framework for such quantitative analysis of smart contracts. Such a formal framework poses new and novel research challenges in programming languages, as it requires modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior and modeling utilities which are not specified as standard temporal properties such as safety and termination. While game-theoretic incentives have been analyzed in the security community, their analysis has been restricted to the very special case of stateless games. However, to analyze smart contracts, stateful analysis is required as it must account for the different program states of the protocol. Our main contributions are as follows: we present (i)~a simplified programming language for smart contracts; (ii)~an automatic translation of the programs to state-based games; (iii)~an abstraction-refinement approach to solve such games; and (iv)~experimental results on real-world-inspired smart contracts.}, author = {Chatterjee, Krishnendu and Goharshady, Amir and Velner, Yaron}, location = {Thessaloniki, Greece}, pages = {739 -- 767}, publisher = {Springer}, title = {{Quantitative analysis of smart contracts}}, doi = {10.1007/978-3-319-89884-1_26}, volume = {10801}, year = {2018}, } @inproceedings{6340, abstract = {We present a secure approach for maintaining andreporting credit history records on the Blockchain. Our ap-proach removes third-parties such as credit reporting agen-cies from the lending process and replaces them with smartcontracts. This allows customers to interact directly with thelenders or banks while ensuring the integrity, unmalleabilityand privacy of their credit data. Additionally, each customerhas full control over complete or selective disclosure of hercredit records, eliminating the risk of privacy violations or databreaches. Moreover, our approach provides strong guaranteesfor the lenders as well. A lender can check both correctness andcompleteness of the credit data disclosed to her. This is the firstapproach that can perform all credit reporting tasks withouta central authority or changing the financial mechanisms*.}, author = {Goharshady, Amir Kafshdar and Behrouz, Ali and Chatterjee, Krishnendu}, booktitle = {Proceedings of the IEEE International Conference on Blockchain}, isbn = {978-1-5386-7975-3 }, location = {Halifax, Canada}, pages = {1343--1348}, publisher = {IEEE}, title = {{Secure Credit Reporting on the Blockchain}}, doi = {10.1109/Cybermatics_2018.2018.00231}, year = {2018}, } @article{6009, abstract = {We study algorithmic questions wrt algebraic path properties in concurrent systems, where the transitions of the system are labeled from a complete, closed semiring. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks. }, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Goharshady, Amir Kafshdar and Pavlogiannis, Andreas}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {3}, publisher = {Association for Computing Machinery (ACM)}, title = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}}, doi = {10.1145/3210257}, volume = {40}, year = {2018}, } @inproceedings{5977, abstract = {We consider the stochastic shortest path (SSP)problem for succinct Markov decision processes(MDPs), where the MDP consists of a set of vari-ables, and a set of nondeterministic rules that up-date the variables. First, we show that several ex-amples from the AI literature can be modeled assuccinct MDPs. Then we present computationalapproaches for upper and lower bounds for theSSP problem: (a) for computing upper bounds, ourmethod is polynomial-time in the implicit descrip-tion of the MDP; (b) for lower bounds, we present apolynomial-time (in the size of the implicit descrip-tion) reduction to quadratic programming. Our ap-proach is applicable even to infinite-state MDPs.Finally, we present experimental results to demon-strate the effectiveness of our approach on severalclassical examples from the AI literature.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir and Okati, Nastaran}, booktitle = {Proceedings of the Twenty-Seventh International Joint Conference on Artificial Intelligence}, isbn = {978-099924112-7}, issn = {10450823}, location = {Stockholm, Sweden}, pages = {4700--4707}, publisher = {IJCAI}, title = {{Computational approaches for stochastic shortest path on succinct MDPs}}, doi = {10.24963/ijcai.2018/653}, volume = {2018}, year = {2018}, }