@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}, } @techreport{5686, author = {Danowski, Patrick}, pages = {5}, title = {{An Austrian proposal for the Classification of Open Access Tuples (COAT) - Distinguish different Open Access types beyond colors}}, doi = {10.5281/zenodo.1244154}, 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}, }