@inproceedings{6175, abstract = {We consider the problem of expected cost analysis over nondeterministic probabilistic programs, which aims at automated methods for analyzing the resource-usage of such programs. Previous approaches for this problem could only handle nonnegative bounded costs. However, in many scenarios, such as queuing networks or analysis of cryptocurrency protocols, both positive and negative costs are necessary and the costs are unbounded as well. In this work, we present a sound and efficient approach to obtain polynomial bounds on the expected accumulated cost of nondeterministic probabilistic programs. Our approach can handle (a) general positive and negative costs with bounded updates in variables; and (b) nonnegative costs with general updates to variables. We show that several natural examples which could not be handled by previous approaches are captured in our framework. Moreover, our approach leads to an efficient polynomial-time algorithm, while no previous approach for cost analysis of probabilistic programs could guarantee polynomial runtime. Finally, we show the effectiveness of our approach using experimental results on a variety of programs for which we efficiently synthesize tight resource-usage bounds.}, author = {Wang, Peixin and Fu, Hongfei and Goharshady, Amir Kafshdar and Chatterjee, Krishnendu and Qin, Xudong and Shi, Wenjun}, booktitle = {PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation}, keywords = {Program Cost Analysis, Program Termination, Probabilistic Programs, Martingales}, location = {Phoenix, AZ, United States}, pages = {204--220}, publisher = {Association for Computing Machinery}, title = {{Cost analysis of nondeterministic probabilistic programs}}, doi = {10.1145/3314221.3314581}, year = {2019}, } @article{7158, abstract = {Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth. Our main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goyal, Prateesh and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth}}, doi = {10.1145/3363525}, volume = {41}, year = {2019}, } @article{7014, abstract = {We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of nonrecursive programs. First, we apply ranking functions to recursion, resulting in measure functions. We show that measure functions provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in nonpolynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form $\mathcal{O}(n\log n)$ as well as $\mathcal{O}(n^r)$ where $r$ is not an integer. We present experimental results to demonstrate that our approach can obtain efficiently worst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the divide-and-conquer algorithm for the Closest-Pair problem, where we obtain $\mathcal{O}(n \log n)$ worst-case bound, and (ii) Karatsuba's algorithm for polynomial multiplication and Strassen's algorithm for matrix multiplication, where we obtain $\mathcal{O}(n^r)$ bound such that $r$ is not an integer and close to the best-known bounds for the respective algorithms.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Non-polynomial worst-case analysis of recursive programs}}, doi = {10.1145/3339984}, volume = {41}, year = {2019}, } @article{6380, abstract = {There is a huge gap between the speeds of modern caches and main memories, and therefore cache misses account for a considerable loss of efficiency in programs. The predominant technique to address this issue has been Data Packing: data elements that are frequently accessed within time proximity are packed into the same cache block, thereby minimizing accesses to the main memory. We consider the algorithmic problem of Data Packing on a two-level memory system. Given a reference sequence R of accesses to data elements, the task is to partition the elements into cache blocks such that the number of cache misses on R is minimized. The problem is notoriously difficult: it is NP-hard even when the cache has size 1, and is hard to approximate for any cache size larger than 4. Therefore, all existing techniques for Data Packing are based on heuristics and lack theoretical guarantees. In this work, we present the first positive theoretical results for Data Packing, along with new and stronger negative results. We consider the problem under the lens of the underlying access hypergraphs, which are hypergraphs of affinities between the data elements, where the order of an access hypergraph corresponds to the size of the affinity group. We study the problem parameterized by the treewidth of access hypergraphs, which is a standard notion in graph theory to measure the closeness of a graph to a tree. Our main results are as follows: We show there is a number q* depending on the cache parameters such that (a) if the access hypergraph of order q* has constant treewidth, then there is a linear-time algorithm for Data Packing; (b)the Data Packing problem remains NP-hard even if the access hypergraph of order q*-1 has constant treewidth. Thus, we establish a fine-grained dichotomy depending on a single parameter, namely, the highest order among access hypegraphs that have constant treewidth; and establish the optimal value q* of this parameter. Finally, we present an experimental evaluation of a prototype implementation of our algorithm. Our results demonstrate that, in practice, access hypergraphs of many commonly-used algorithms have small treewidth. We compare our approach with several state-of-the-art heuristic-based algorithms and show that our algorithm leads to significantly fewer cache-misses. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Okati, Nastaran and Pavlogiannis, Andreas}, issn = {2475-1421}, journal = {Proceedings of the ACM on Programming Languages}, number = {POPL}, publisher = {ACM}, title = {{Efficient parameterized algorithms for data packing}}, doi = {10.1145/3290366}, volume = {3}, year = {2019}, } @inproceedings{6056, abstract = {In today's programmable blockchains, smart contracts are limited to being deterministic and non-probabilistic. This lack of randomness is a consequential limitation, given that a wide variety of real-world financial contracts, such as casino games and lotteries, depend entirely on randomness. As a result, several ad-hoc random number generation approaches have been developed to be used in smart contracts. These include ideas such as using an oracle or relying on the block hash. However, these approaches are manipulatable, i.e. their output can be tampered with by parties who might not be neutral, such as the owner of the oracle or the miners.We propose a novel game-theoretic approach for generating provably unmanipulatable pseudorandom numbers on the blockchain. Our approach allows smart contracts to access a trustworthy source of randomness that does not rely on potentially compromised miners or oracles, hence enabling the creation of a new generation of smart contracts that are not limited to being non-probabilistic and can be drawn from the much more general class of probabilistic programs.}, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Pourdamghani, Arash}, booktitle = {IEEE International Conference on Blockchain and Cryptocurrency}, location = {Seoul, Korea}, publisher = {IEEE}, title = {{Probabilistic smart contracts: Secure randomness on the blockchain}}, doi = {10.1109/BLOC.2019.8751326}, year = {2019}, } @article{6627, abstract = {Cortical microtubule arrays in elongating epidermal cells in both the root and stem of plants have the propensity of dynamic reorientations that are correlated with the activation or inhibition of growth. Factors regulating plant growth, among them the hormone auxin, have been recognized as regulators of microtubule array orientations. Some previous work in the field has aimed at elucidating the causal relationship between cell growth, the signaling of auxin or other growth-regulating factors, and microtubule array reorientations, with various conclusions. Here, we revisit this problem of causality with a comprehensive set of experiments in Arabidopsis thaliana, using the now available pharmacological and genetic tools. We use isolated, auxin-depleted hypocotyls, an experimental system allowing for full control of both growth and auxin signaling. We demonstrate that reorientation of microtubules is not directly triggered by an auxin signal during growth activation. Instead, reorientation is triggered by the activation of the growth process itself and is auxin-independent in its nature. We discuss these findings in the context of previous relevant work, including that on the mechanical regulation of microtubule array orientation.}, author = {Adamowski, Maciek and Li, Lanxin and Friml, Jiří}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, number = {13}, publisher = {MDPI}, title = {{Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling}}, doi = {10.3390/ijms20133337}, volume = {20}, year = {2019}, } @article{6609, abstract = {Mechanical systems facilitate the development of a hybrid quantum technology comprising electrical, optical, atomic and acoustic degrees of freedom1, and entanglement is essential to realize quantum-enabled devices. Continuous-variable entangled fields—known as Einstein–Podolsky–Rosen (EPR) states—are spatially separated two-mode squeezed states that can be used for quantum teleportation and quantum communication2. In the optical domain, EPR states are typically generated using nondegenerate optical amplifiers3, and at microwave frequencies Josephson circuits can serve as a nonlinear medium4,5,6. An outstanding goal is to deterministically generate and distribute entangled states with a mechanical oscillator, which requires a carefully arranged balance between excitation, cooling and dissipation in an ultralow noise environment. Here we observe stationary emission of path-entangled microwave radiation from a parametrically driven 30-micrometre-long silicon nanostring oscillator, squeezing the joint field operators of two thermal modes by 3.40 decibels below the vacuum level. The motion of this micromechanical system correlates up to 50 photons per second per hertz, giving rise to a quantum discord that is robust with respect to microwave noise7. Such generalized quantum correlations of separable states are important for quantum-enhanced detection8 and provide direct evidence of the non-classical nature of the mechanical oscillator without directly measuring its state9. This noninvasive measurement scheme allows to infer information about otherwise inaccessible objects, with potential implications for sensing, open-system dynamics and fundamental tests of quantum gravity. In the future, similar on-chip devices could be used to entangle subsystems on very different energy scales, such as microwave and optical photons.}, author = {Barzanjeh, Shabir and Redchenko, Elena and Peruzzo, Matilda and Wulf, Matthias and Lewis, Dylan and Arnold, Georg M and Fink, Johannes M}, journal = {Nature}, pages = {480--483}, publisher = {Nature Publishing Group}, title = {{Stationary entangled radiation from micromechanical motion}}, doi = {10.1038/s41586-019-1320-2}, volume = {570}, year = {2019}, } @article{12, abstract = {Molding is a popular mass production method, in which the initial expenses for the mold are offset by the low per-unit production cost. However, the physical fabrication constraints of the molding technique commonly restrict the shape of moldable objects. For a complex shape, a decomposition of the object into moldable parts is a common strategy to address these constraints, with plastic model kits being a popular and illustrative example. However, conducting such a decomposition requires considerable expertise, and it depends on the technical aspects of the fabrication technique, as well as aesthetic considerations. We present an interactive technique to create such decompositions for two-piece molding, in which each part of the object is cast between two rigid mold pieces. Given the surface description of an object, we decompose its thin-shell equivalent into moldable parts by first performing a coarse decomposition and then utilizing an active contour model for the boundaries between individual parts. Formulated as an optimization problem, the movement of the contours is guided by an energy reflecting fabrication constraints to ensure the moldability of each part. Simultaneously, the user is provided with editing capabilities to enforce aesthetic guidelines. Our interactive interface provides control of the contour positions by allowing, for example, the alignment of part boundaries with object features. Our technique enables a novel workflow, as it empowers novice users to explore the design space, and it generates fabrication-ready two-piece molds that can be used either for casting or industrial injection molding of free-form objects.}, author = {Nakashima, Kazutaka and Auzinger, Thomas and Iarussi, Emmanuel and Zhang, Ran and Igarashi, Takeo and Bickel, Bernd}, journal = {ACM Transaction on Graphics}, number = {4}, publisher = {ACM}, title = {{CoreCavity: Interactive shell decomposition for fabrication with two-piece rigid molds}}, doi = {10.1145/3197517.3201341}, volume = {37}, year = {2018}, } @article{1215, abstract = {Two generalizations of Itô formula to infinite-dimensional spaces are given. The first one, in Hilbert spaces, extends the classical one by taking advantage of cancellations when they occur in examples and it is applied to the case of a group generator. The second one, based on the previous one and a limit procedure, is an Itô formula in a special class of Banach spaces having a product structure with the noise in a Hilbert component; again the key point is the extension due to a cancellation. This extension to Banach spaces and in particular the specific cancellation are motivated by path-dependent Itô calculus.}, author = {Flandoli, Franco and Russo, Francesco and Zanco, Giovanni A}, journal = {Journal of Theoretical Probability}, number = {2}, pages = {789--826}, publisher = {Springer}, title = {{Infinite-dimensional calculus under weak spatial regularity of the processes}}, doi = {10.1007/s10959-016-0724-2}, volume = {31}, year = {2018}, } @inproceedings{273, abstract = {The accuracy of information retrieval systems is often measured using complex loss functions such as the average precision (AP) or the normalized discounted cumulative gain (NDCG). Given a set of positive and negative samples, the parameters of a retrieval system can be estimated by minimizing these loss functions. However, the non-differentiability and non-decomposability of these loss functions does not allow for simple gradient based optimization algorithms. This issue is generally circumvented by either optimizing a structured hinge-loss upper bound to the loss function or by using asymptotic methods like the direct-loss minimization framework. Yet, the high computational complexity of loss-augmented inference, which is necessary for both the frameworks, prohibits its use in large training data sets. To alleviate this deficiency, we present a novel quicksort flavored algorithm for a large class of non-decomposable loss functions. We provide a complete characterization of the loss functions that are amenable to our algorithm, and show that it includes both AP and NDCG based loss functions. Furthermore, we prove that no comparison based algorithm can improve upon the computational complexity of our approach asymptotically. We demonstrate the effectiveness of our approach in the context of optimizing the structured hinge loss upper bound of AP and NDCG loss for learning models for a variety of vision tasks. We show that our approach provides significantly better results than simpler decomposable loss functions, while requiring a comparable training time.}, author = {Mohapatra, Pritish and Rolinek, Michal and Jawahar, C V and Kolmogorov, Vladimir and Kumar, M Pawan}, booktitle = {2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition}, isbn = {9781538664209}, location = {Salt Lake City, UT, USA}, pages = {3693--3701}, publisher = {IEEE}, title = {{Efficient optimization for rank-based loss functions}}, doi = {10.1109/cvpr.2018.00389}, year = {2018}, } @article{275, abstract = {Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified > 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.}, author = {Brown, Markus and Johnson, Louise and Leone, Dario and Májek, Peter and Vaahtomeri, Kari and Senfter, Daniel and Bukosza, Nora and Schachner, Helga and Asfour, Gabriele and Langer, Brigitte and Hauschild, Robert and Parapatics, Katja and Hong, Young and Bennett, Keiryn and Kain, Renate and Detmar, Michael and Sixt, Michael K and Jackson, David and Kerjaschki, Dontscho}, journal = {Journal of Cell Biology}, number = {6}, pages = {2205 -- 2221}, publisher = {Rockefeller University Press}, title = {{Lymphatic exosomes promote dendritic cell migration along guidance cues}}, doi = {10.1083/jcb.201612051}, volume = {217}, year = {2018}, } @article{276, abstract = {Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo.}, author = {Frick, Corina and Dettinger, Philip and Renkawitz, Jörg and Jauch, Annaïse and Berger, Christoph and Recher, Mike and Schroeder, Timm and Mehling, Matthias}, journal = {PLoS One}, number = {6}, publisher = {Public Library of Science}, title = {{Nano-scale microfluidics to study 3D chemotaxis at the single cell level}}, doi = {10.1371/journal.pone.0198330}, volume = {13}, year = {2018}, } @article{277, abstract = {Arabidopsis and human ARM protein interact with telomerase. Deregulated mRNA levels of DNA repair and ribosomal protein genes in an Arabidopsis arm mutant suggest non-telomeric ARM function. The human homolog ARMC6 interacts with hTRF2. Abstract: Telomerase maintains telomeres and has proposed non-telomeric functions. We previously identified interaction of the C-terminal domain of Arabidopsis telomerase reverse transcriptase (AtTERT) with an armadillo/β-catenin-like repeat (ARM) containing protein. Here we explore protein–protein interactions of the ARM protein, AtTERT domains, POT1a, TRF-like family and SMH family proteins, and the chromatin remodeling protein CHR19 using bimolecular fluorescence complementation (BiFC), yeast two-hybrid (Y2H) analysis, and co-immunoprecipitation. The ARM protein interacts with both the N- and C-terminal domains of AtTERT in different cellular compartments. ARM interacts with CHR19 and TRF-like I family proteins that also bind AtTERT directly or through interaction with POT1a. The putative human ARM homolog co-precipitates telomerase activity and interacts with hTRF2 protein in vitro. Analysis of Arabidopsis arm mutants shows no obvious changes in telomere length or telomerase activity, suggesting that ARM is not essential for telomere maintenance. The observed interactions with telomerase and Myb-like domain proteins (TRF-like family I) may therefore reflect possible non-telomeric functions. Transcript levels of several DNA repair and ribosomal genes are affected in arm mutants, and ARM, likely in association with other proteins, suppressed expression of XRCC3 and RPSAA promoter constructs in luciferase reporter assays. In conclusion, ARM can participate in non-telomeric functions of telomerase, and can also perform its own telomerase-independent functions.}, author = {Dokládal, Ladislav and Benková, Eva and Honys, David and Dupláková, Nikoleta and Lee, Lan and Gelvin, Stanton and Sýkorová, Eva}, journal = {Plant Molecular Biology}, number = {5}, pages = {407 -- 420}, publisher = {Springer}, title = {{An armadillo-domain protein participates in a telomerase interaction network}}, doi = {10.1007/s11103-018-0747-4}, volume = {97}, year = {2018}, } @article{279, abstract = {Background: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Results: Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes. Conclusions: In summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments.}, author = {Zapata, Luis and Pich, Oriol and Serrano, Luis and Kondrashov, Fyodor and Ossowski, Stephan and Schaefer, Martin}, journal = {Genome Biology}, publisher = {BioMed Central}, title = {{Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome}}, doi = {10.1186/s13059-018-1434-0}, volume = {19}, year = {2018}, } @article{280, abstract = {Flowers have a species-specific functional life span that determines the time window in which pollination, fertilization and seed set can occur. The stigma tissue plays a key role in flower receptivity by intercepting pollen and initiating pollen tube growth toward the ovary. In this article, we show that a developmentally controlled cell death programme terminates the functional life span of stigma cells in Arabidopsis. We identified the leaf senescence regulator ORESARA1 (also known as ANAC092) and the previously uncharacterized KIRA1 (also known as ANAC074) as partially redundant transcription factors that modulate stigma longevity by controlling the expression of programmed cell death-associated genes. KIRA1 expression is sufficient to induce cell death and terminate floral receptivity, whereas lack of both KIRA1 and ORESARA1 substantially increases stigma life span. Surprisingly, the extension of stigma longevity is accompanied by only a moderate extension of flower receptivity, suggesting that additional processes participate in the control of the flower's receptive life span.}, author = {Gao, Zhen and Daneva, Anna and Salanenka, Yuliya and Van Durme, Matthias and Huysmans, Marlies and Lin, Zongcheng and De Winter, Freya and Vanneste, Steffen and Karimi, Mansour and Van De Velde, Jan and Vandepoele, Klaas and Van De Walle, Davy and Dewettinck, Koen and Lambrecht, Bart and Nowack, Moritz}, journal = {Nature Plants}, number = {6}, pages = {365 -- 375}, publisher = {Nature Publishing Group}, title = {{KIRA1 and ORESARA1 terminate flower receptivity by promoting cell death in the stigma of Arabidopsis}}, doi = {10.1038/s41477-018-0160-7}, volume = {4}, year = {2018}, } @article{282, abstract = {Adaptive introgression is common in nature and can be driven by selection acting on multiple, linked genes. We explore the effects of polygenic selection on introgression under the infinitesimal model with linkage. This model assumes that the introgressing block has an effectively infinite number of genes, each with an infinitesimal effect on the trait under selection. The block is assumed to introgress under directional selection within a native population that is genetically homogeneous. We use individual-based simulations and a branching process approximation to compute various statistics of the introgressing block, and explore how these depend on parameters such as the map length and initial trait value associated with the introgressing block, the genetic variability along the block, and the strength of selection. Our results show that the introgression dynamics of a block under infinitesimal selection is qualitatively different from the dynamics of neutral introgression. We also find that in the long run, surviving descendant blocks are likely to have intermediate lengths, and clarify how the length is shaped by the interplay between linkage and infinitesimal selection. Our results suggest that it may be difficult to distinguish introgression of single loci from that of genomic blocks with multiple, tightly linked and weakly selected loci.}, author = {Sachdeva, Himani and Barton, Nicholas H}, journal = {Genetics}, number = {4}, pages = {1279 -- 1303}, publisher = {Genetics Society of America}, title = {{Introgression of a block of genome under infinitesimal selection}}, doi = {10.1534/genetics.118.301018}, volume = {209}, year = {2018}, } @article{283, abstract = {Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors.}, author = {Ceinos, Rosa Maria and Frigato, Elena and Pagano, Cristina and Frohlich, Nadine and Negrini, Pietro and Cavallari, Nicola and Vallone, Daniela and Fuselli, Silvia and Bertolucci, Cristiano and Foulkes, Nicholas S}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{Mutations in blind cavefish target the light regulated circadian clock gene period 2}}, doi = {10.1038/s41598-018-27080-2}, volume = {8}, 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}, } @inproceedings{285, abstract = {In graph theory, as well as in 3-manifold topology, there exist several width-type parameters to describe how "simple" or "thin" a given graph or 3-manifold is. These parameters, such as pathwidth or treewidth for graphs, or the concept of thin position for 3-manifolds, play an important role when studying algorithmic problems; in particular, there is a variety of problems in computational 3-manifold topology - some of them known to be computationally hard in general - that become solvable in polynomial time as soon as the dual graph of the input triangulation has bounded treewidth. In view of these algorithmic results, it is natural to ask whether every 3-manifold admits a triangulation of bounded treewidth. We show that this is not the case, i.e., that there exists an infinite family of closed 3-manifolds not admitting triangulations of bounded pathwidth or treewidth (the latter implies the former, but we present two separate proofs). We derive these results from work of Agol and of Scharlemann and Thompson, by exhibiting explicit connections between the topology of a 3-manifold M on the one hand and width-type parameters of the dual graphs of triangulations of M on the other hand, answering a question that had been raised repeatedly by researchers in computational 3-manifold topology. In particular, we show that if a closed, orientable, irreducible, non-Haken 3-manifold M has a triangulation of treewidth (resp. pathwidth) k then the Heegaard genus of M is at most 48(k+1) (resp. 4(3k+1)).}, author = {Huszár, Kristóf and Spreer, Jonathan and Wagner, Uli}, issn = {1868-8969}, location = {Budapest, Hungary}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{On the treewidth of triangulated 3-manifolds}}, doi = {10.4230/LIPIcs.SoCG.2018.46}, volume = {99}, 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}, }