@article{751, abstract = {The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.}, author = {Matsubayashi, Yutaka and Louani, Adam and Dragu, Anca and Sanchez Sanchez, Besaiz and Serna Morales, Eduardo and Yolland, Lawrence and György, Attila and Vizcay, Gema and Fleck, Roland and Heddleston, John and Chew, Teng and Siekhaus, Daria E and Stramer, Brian}, issn = {09609822}, journal = {Current Biology}, number = {22}, pages = {3526 -- 3534e.4}, publisher = {Cell Press}, title = {{A moving source of matrix components is essential for De Novo basement membrane formation}}, doi = {10.1016/j.cub.2017.10.001}, volume = {27}, year = {2017}, } @article{7725, abstract = {Phenotypic plasticity is the ability of an individual genotype to alter aspects of its phenotype depending on the current environment. It is central to the persistence, resistance and resilience of populations facing variation in physical or biological factors. Genetic variation in plasticity is pervasive, which suggests its local adaptation is plausible. Existing studies on the adaptation of plasticity typically focus on single traits and a few populations, while theory about interactions among genes (for example, pleiotropy) suggests that a multi-trait, landscape scale (for example, multiple populations) perspective is required. We present data from a landscape scale, replicated, multi-trait experiment using a classic predator–prey system centred on the water flea Daphnia pulex. We find predator regime-driven differences in genetic variation of multivariate plasticity. These differences are associated with strong divergent selection linked to a predation regime. Our findings are evidence for local adaptation of plasticity, suggesting that responses of populations to environmental variation depend on the conditions in which they evolved in the past.}, author = {Reger, Julia and Lind, Martin I. and Robinson, Matthew Richard and Beckerman, Andrew P.}, issn = {2397-334X}, journal = {Nature Ecology & Evolution}, pages = {100--107}, publisher = {Springer Nature}, title = {{Predation drives local adaptation of phenotypic plasticity}}, doi = {10.1038/s41559-017-0373-6}, volume = {2}, year = {2017}, } @article{7727, abstract = {Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses (Equus caballus) to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males (n = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.}, author = {Burger, D. and Thomas, S. and Aepli, H. and Dreyer, M. and Fabre, G. and Marti, E. and Sieme, H. and Robinson, Matthew Richard and Wedekind, C.}, issn = {0962-8452}, journal = {Proceedings of the Royal Society B: Biological Sciences}, number = {1868}, publisher = {The Royal Society}, title = {{Major histocompatibility complex-linked social signalling affects female fertility}}, doi = {10.1098/rspb.2017.1824}, volume = {284}, year = {2017}, } @article{7728, abstract = {Meta-analyses of genome-wide association studies, which dominate genetic discovery, are based on data from diverse historical time periods and populations. Genetic scores derived from genome-wide association studies explain only a fraction of the heritability estimates obtained from whole-genome studies on single populations, known as the ‘hidden heritability’ puzzle. Using seven sampling populations (n = 35,062), we test whether hidden heritability is attributed to heterogeneity across sampling populations and time, showing that estimates are substantially smaller across populations compared with within populations. We show that the hidden heritability varies substantially: from zero for height to 20% for body mass index, 37% for education, 40% for age at first birth and up to 75% for number of children. Simulations demonstrate that our results are more likely to reflect heterogeneity in phenotypic measurement or gene–environment interactions than genetic heterogeneity. These findings have substantial implications for genetic discovery, suggesting that large homogenous datasets are required for behavioural phenotypes and that gene–environment interaction may be a central challenge for genetic discovery.}, author = {Tropf, Felix C. and Lee, S. Hong and Verweij, Renske M. and Stulp, Gert and van der Most, Peter J. and de Vlaming, Ronald and Bakshi, Andrew and Briley, Daniel A. and Rahal, Charles and Hellpap, Robert and Iliadou, Anastasia N. and Esko, Tõnu and Metspalu, Andres and Medland, Sarah E. and Martin, Nicholas G. and Barban, Nicola and Snieder, Harold and Robinson, Matthew Richard and Mills, Melinda C.}, issn = {2397-3374}, journal = {Nature Human Behaviour}, number = {10}, pages = {757--765}, publisher = {Springer Nature}, title = {{Hidden heritability due to heterogeneity across seven populations}}, doi = {10.1038/s41562-017-0195-1}, volume = {1}, year = {2017}, } @article{7729, abstract = {Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in ∼140,000 participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between −2.3 and −5.2 phenotypic SDs for complete inbreeding; P<0.001). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.}, author = {Yengo, Loic and Zhu, Zhihong and Wray, Naomi R. and Weir, Bruce S. and Yang, Jian and Robinson, Matthew Richard and Visscher, Peter M.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {32}, pages = {8602--8607}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Detection and quantification of inbreeding depression for complex traits from SNP data}}, doi = {10.1073/pnas.1621096114}, volume = {114}, year = {2017}, } @article{7731, abstract = {Genetic association studies in admixed populations are underrepresented in the genomics literature, with a key concern for researchers being the adequate control of spurious associations due to population structure. Linear mixed models (LMMs) are well suited for genome-wide association studies (GWAS) because they account for both population stratification and cryptic relatedness and achieve increased statistical power by jointly modeling all genotyped markers. Additionally, Bayesian LMMs allow for more flexible assumptions about the underlying distribution of genetic effects, and can concurrently estimate the proportion of phenotypic variance explained by genetic markers. Using three recently published Bayesian LMMs, Bayes R, BSLMM, and BOLT-LMM, we investigate an existing data set on eye (n = 625) and skin (n = 684) color from Cape Verde, an island nation off West Africa that is home to individuals with a broad range of phenotypic values for eye and skin color due to the mix of West African and European ancestry. We use simulations to demonstrate the utility of Bayesian LMMs for mapping loci and studying the genetic architecture of quantitative traits in admixed populations. The Bayesian LMMs provide evidence for two new pigmentation loci: one for eye color (AHRR) and one for skin color (DDB1).}, author = {Lloyd-Jones, Luke R. and Robinson, Matthew Richard and Moser, Gerhard and Zeng, Jian and Beleza, Sandra and Barsh, Gregory S. and Tang, Hua and Visscher, Peter M.}, issn = {0016-6731}, journal = {Genetics}, number = {2}, pages = {1113--1126}, publisher = {Genetics Society of America}, title = {{Inference on the genetic basis of eye and skin color in an admixed population via Bayesian linear mixed models}}, doi = {10.1534/genetics.116.193383}, volume = {206}, year = {2017}, } @article{7733, abstract = {Sections PDFPDF Tools Share Abstract Background: Gene discovery has provided remarkable biological insights into amyotrophic lateral sclerosis (ALS). One challenge for clinical application of genetic testing is critical evaluation of the significance of reported variants. Methods: We use whole exome sequencing (WES) to develop a clinically relevant approach to identify a subset of ALS patients harboring likely pathogenic mutations. In parallel, we assess if DNA methylation can be used to screen for pathogenicity of novel variants since a methylation signature has been shown to associate with the pathogenic C9orf72 expansion, but has not been explored for other ALS mutations. Australian patients identified with ALS‐relevant variants were cross‐checked with population databases and case reports to critically assess whether they were “likely causal,” “uncertain significance,” or “unlikely causal.” Results: Published ALS variants were identified in >10% of patients; however, in only 3% of patients (4/120) could these be confidently considered pathogenic (in SOD1 and TARDBP). We found no evidence for a differential DNA methylation signature in these mutation carriers. Conclusions: The use of WES in a typical ALS clinic demonstrates a critical approach to variant assessment with the capability to combine cohorts to enhance the largely unknown genetic basis of ALS.}, author = {Garton, Fleur C. and Benyamin, Beben and Zhao, Qiongyi and Liu, Zhijun and Gratten, Jacob and Henders, Anjali K. and Zhang, Zong-Hong and Edson, Janette and Furlong, Sarah and Morgan, Sarah and Heggie, Susan and Thorpe, Kathryn and Pfluger, Casey and Mather, Karen A. and Sachdev, Perminder S. and McRae, Allan F. and Robinson, Matthew Richard and Shah, Sonia and Visscher, Peter M. and Mangelsdorf, Marie and Henderson, Robert D. and Wray, Naomi R. and McCombe, Pamela A.}, issn = {2324-9269}, journal = {Molecular Genetics & Genomic Medicine}, number = {4}, pages = {418--428}, publisher = {Wiley}, title = {{Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort}}, doi = {10.1002/mgg3.302}, volume = {5}, year = {2017}, } @article{7755, abstract = {We give a bird's-eye view of the plastic deformation of crystals aimed at the statistical physics community, as well as a broad introduction to the statistical theories of forced rigid systems aimed at the plasticity community. Memory effects in magnets, spin glasses, charge density waves, and dilute colloidal suspensions are discussed in relation to the onset of plastic yielding in crystals. Dislocation avalanches and complex dislocation tangles are discussed via a brief introduction to the renormalization group and scaling. Analogies to emergent scale invariance in fracture, jamming, coarsening, and a variety of depinning transitions are explored. Dislocation dynamics in crystals challenge nonequilibrium statistical physics. Statistical physics provides both cautionary tales of subtle memory effects in nonequilibrium systems and systematic tools designed to address complex scale-invariant behavior on multiple length scales and timescales.}, author = {Sethna, James P. and Bierbaum, Matthew K. and Dahmen, Karin A. and Goodrich, Carl Peter and Greer, Julia R. and Hayden, Lorien X. and Kent-Dobias, Jaron P. and Lee, Edward D. and Liarte, Danilo B. and Ni, Xiaoyue and Quinn, Katherine N. and Raju, Archishman and Rocklin, D. Zeb and Shekhawat, Ashivni and Zapperi, Stefano}, issn = {1531-7331}, journal = {Annual Review of Materials Research}, pages = {217--246}, publisher = {Annual Reviews}, title = {{Deformation of crystals: Connections with statistical physics}}, doi = {10.1146/annurev-matsci-070115-032036}, volume = {47}, year = {2017}, } @article{7756, abstract = {We study the shear jamming of athermal frictionless soft spheres, and find that in the thermodynamic limit, a shear-jammed state exists with different elastic properties from the isotropically-jammed state. For example, shear-jammed states can have a non-zero residual shear stress in the thermodynamic limit that arises from long-range stress-stress correlations. As a result, the ratio of the shear and bulk moduli, which in isotropically-jammed systems vanishes as the jamming transition is approached from above, instead approaches a constant. Despite these striking differences, we argue that in a deeper sense, the shear jamming and isotropic jamming transitions actually have the same symmetry, and that the differences can be fully understood by rotating the six-dimensional basis of the elastic modulus tensor.}, author = {Baity-Jesi, Marco and Goodrich, Carl Peter and Liu, Andrea J. and Nagel, Sidney R. and Sethna, James P.}, issn = {0022-4715}, journal = {Journal of Statistical Physics}, number = {3-4}, pages = {735--748}, publisher = {Springer Nature}, title = {{Emergent SO(3) symmetry of the frictionless shear jamming transition}}, doi = {10.1007/s10955-016-1703-9}, volume = {167}, year = {2017}, } @article{7757, abstract = {Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.}, author = {Rocks, Jason W. and Pashine, Nidhi and Bischofberger, Irmgard and Goodrich, Carl Peter and Liu, Andrea J. and Nagel, Sidney R.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {10}, pages = {2520--2525}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Designing allostery-inspired response in mechanical networks}}, doi = {10.1073/pnas.1612139114}, volume = {114}, year = {2017}, } @article{7758, abstract = {Controlling motion at the microscopic scale is a fundamental goal in the development of biologically inspired systems. We show that the motion of active, self-propelled colloids can be sufficiently controlled for use as a tool to assemble complex structures such as braids and weaves out of microscopic filaments. Unlike typical self-assembly paradigms, these structures are held together by geometric constraints rather than adhesive bonds. The out-of-equilibrium assembly that we propose involves precisely controlling the 2D motion of active colloids so that their path has a nontrivial topology. We demonstrate with proof-of-principle Brownian dynamics simulations that, when the colloids are attached to long semiflexible filaments, this motion causes the filaments to braid. The ability of the active particles to provide sufficient force necessary to bend the filaments into a braid depends on a number of factors, including the self-propulsion mechanism, the properties of the filament, and the maximum curvature in the braid. Our work demonstrates that nonequilibrium assembly pathways can be designed using active particles.}, author = {Goodrich, Carl Peter and Brenner, Michael P.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {2}, pages = {257--262}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Using active colloids as machines to weave and braid on the micrometer scale}}, doi = {10.1073/pnas.1608838114}, volume = {114}, year = {2017}, } @article{459, abstract = {The social insects bees, wasps, ants, and termites are species-rich, occur in many habitats, and often constitute a large part of the biomass. Many are also invasive, including species of termites, the red imported fire ant, and the Argentine ant. While invasive social insects have been a problem in Southern Europe for some time, Central Europa was free of invasive ant species until recently because most ants are adapted to warmer climates. Only in the 1990s, did Lasius neglectus, a close relative of the common black garden ant, arrive in Germany. First described in 1990 based on individuals collected in Budapest, the species has since been detected for example in France, Germany, Spain, England, and Kyrgyzstan. The species is spread with soil during construction work or plantings, and L. neglectus therefore is often found in parks and botanical gardens. Another invasive ant now spreading in southern Germany is Formica fuscocinerea, which occurs along rivers, including in the sandy floodplains of the river Isar. As is typical of pioneer species, F. fuscocinerea quickly becomes extremely abundant and therefore causes problems for example on playgrounds in Munich. All invasive ant species are characterized by cooperation across nests, leading to strongly interconnected, very large super-colonies. The resulting dominance results in the extinction of native ant species as well as other arthropod species and thus in the reduction of biodiversity.}, author = {Cremer, Sylvia}, issn = {2366-2875}, journal = {Rundgespräche Forum Ökologie}, pages = {105 -- 116}, publisher = {Verlag Dr. Friedrich Pfeil}, title = {{Invasive Ameisen in Europa: Wie sie sich ausbreiten und die heimische Fauna verändern}}, volume = {46}, year = {2017}, } @article{463, abstract = {We investigate transient behaviors induced by magnetic fields on the dynamics of the flow of a ferrofluid in the gap between two concentric, independently rotating cylinders. Without applying any magnetic fields, we uncover emergence of flow states constituted by a combination of a localized spiral state (SPIl) in the top and bottom of the annulus and different multi-cell flow states (SPI2v, SPI3v) with toroidally closed vortices in the interior of the bulk (SPIl+2v = SPIl + SPI2v and SPIl+3v = SPIl + SPI3v). However, when a magnetic field is presented, we observe the transient behaviors between multi-cell states passing through two critical thresholds in a strength of an axial (transverse) magnetic field. Before the first critical threshold of a magnetic field strength, multi-stable states with different number of cells could be observed. After the first critical threshold, we find the transient behavior between the three- and two-cell flow states. For more strength of magnetic field or after the second critical threshold, we discover that multi-cell states are disappeared and a localized spiral state remains to be stimulated. The studied transient behavior could be understood by the investigation of various quantities including a modal kinetic energy, a mode amplitude of the radial velocity, wavenumber, angular momentum, and torque. In addition, the emergence of new flow states and the transient behavior between their states in ferrofluidic flows indicate that richer and potentially controllable dynamics through magnetic fields could be possible in ferrofluic flow.}, author = {Altmeyer, Sebastian and Do, Younghae and Ryu, Soorok}, issn = {10541500}, journal = {Chaos}, number = {11}, publisher = {AIP Publishing}, title = {{Transient behavior between multi-cell flow states in ferrofluidic Taylor-Couette flow}}, doi = {10.1063/1.5002771}, volume = {27}, year = {2017}, } @article{464, abstract = {The computation of the winning set for parity objectives and for Streett objectives in graphs as well as in game graphs are central problems in computer-aided verification, with application to the verification of closed systems with strong fairness conditions, the verification of open systems, checking interface compatibility, well-formedness of specifications, and the synthesis of reactive systems. We show how to compute the winning set on n vertices for (1) parity-3 (aka one-pair Streett) objectives in game graphs in time O(n5/2) and for (2) k-pair Streett objectives in graphs in time O(n2+nklogn). For both problems this gives faster algorithms for dense graphs and represents the first improvement in asymptotic running time in 15 years.}, author = {Chatterjee, Krishnendu and Henzinger, Monika H and Loitzenbauer, Veronika}, issn = {1860-5974}, journal = {Logical Methods in Computer Science}, number = {3}, publisher = {International Federation of Computational Logic}, title = {{Improved algorithms for parity and Streett objectives}}, doi = {10.23638/LMCS-13(3:26)2017}, volume = {13}, year = {2017}, } @article{465, abstract = {The edit distance between two words w 1 , w 2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w 1 to w 2 . The edit distance generalizes to languages L 1 , L 2 , where the edit distance from L 1 to L 2 is the minimal number k such that for every word from L 1 there exists a word in L 2 with edit distance at most k . We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for the following problems: (1) deciding whether, for a given threshold k , the edit distance from a pushdown automaton to a finite automaton is at most k , and (2) deciding whether the edit distance from a pushdown automaton to a finite automaton is finite. }, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Otop, Jan}, issn = {18605974}, journal = {Logical Methods in Computer Science}, number = {3}, publisher = {International Federation of Computational Logic}, title = {{Edit distance for pushdown automata}}, doi = {10.23638/LMCS-13(3:23)2017}, volume = {13}, year = {2017}, } @article{466, abstract = {We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem. }, author = {Chatterjee, Krishnendu and Křetínská, Zuzana and Kretinsky, Jan}, issn = {18605974}, journal = {Logical Methods in Computer Science}, number = {2}, publisher = {International Federation of Computational Logic}, title = {{Unifying two views on multiple mean-payoff objectives in Markov decision processes}}, doi = {10.23638/LMCS-13(2:15)2017}, volume = {13}, year = {2017}, } @article{467, abstract = {Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata or in any other known decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata, which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in runtime verification. We establish an almost-complete decidability picture for the basic decision problems about nested weighted automata and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {15293785}, journal = {ACM Transactions on Computational Logic (TOCL)}, number = {4}, publisher = {ACM}, title = {{Nested weighted automata}}, doi = {10.1145/3152769}, volume = {18}, year = {2017}, } @article{470, abstract = {This paper presents a method for simulating water surface waves as a displacement field on a 2D domain. Our method relies on Lagrangian particles that carry packets of water wave energy; each packet carries information about an entire group of wave trains, as opposed to only a single wave crest. Our approach is unconditionally stable and can simulate high resolution geometric details. This approach also presents a straightforward interface for artistic control, because it is essentially a particle system with intuitive parameters like wavelength and amplitude. Our implementation parallelizes well and runs in real time for moderately challenging scenarios.}, author = {Jeschke, Stefan and Wojtan, Christopher J}, issn = {07300301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Water wave packets}}, doi = {10.1145/3072959.3073678}, volume = {36}, year = {2017}, } @article{471, abstract = {We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds. }, author = {Daca, Przemyslaw and Henzinger, Thomas A and Kretinsky, Jan and Petrov, Tatjana}, issn = {15293785}, journal = {ACM Transactions on Computational Logic (TOCL)}, number = {2}, publisher = {ACM}, title = {{Faster statistical model checking for unbounded temporal properties}}, doi = {10.1145/3060139}, volume = {18}, year = {2017}, } @article{472, abstract = {α-Synuclein is a presynaptic protein the function of which has yet to be identified, but its neuronal content increases in patients of synucleinopa-thies including Parkinson’s disease. Chronic overexpression of α-synuclein reportedly expresses various phenotypes of synaptic dysfunction, but the primary target of its toxicity has not been determined. To investigate this, we acutely loaded human recombinant α-synuclein or its pathological mutants in their monomeric forms into the calyces of Held presynaptic terminals in slices from auditorily mature and immature rats of either sex. Membrane capacitance measurements revealed significant and specific inhibitory effects of WT monomeric α-synuclein on vesicle endocytosis throughout development. However, the α-synuclein A53T mutant affected vesicle endocytosis only at immature calyces, where as the A30P mutant had no effect throughout. The endocytic impairment by WTα-synuclein was rescued by intraterminal coloading of the microtubule (MT) polymerization blocker nocodazole. Furthermore, it was reversibly rescued by presynaptically loaded photostatin-1, a pho-toswitcheable inhibitor of MT polymerization, inalight-wavelength-dependent manner. Incontrast, endocyticinhibition by the A53T mutant at immature calyces was not rescued by nocodazole. Functionally, presynaptically loaded WT α-synuclein had no effect on basal synaptic transmission evoked at a low frequency, but significantly attenuated exocytosis and impaired the fidelity of neurotransmission during prolonged high-frequency stimulation. We conclude that monomeric WTα-synuclein primarily inhibits vesicle endocytosis via MT overassembly, thereby impairing high-frequency neurotransmission.}, author = {Eguchi, Kohgaku and Taoufiq, Zachari and Thorn Seshold, Oliver and Trauner, Dirk and Hasegawa, Masato and Takahashi, Tomoyuki}, issn = {02706474}, journal = {European Journal of Neuroscience}, number = {25}, pages = {6043 -- 6052}, publisher = {Wiley-Blackwell}, title = {{Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of held}}, doi = {10.1523/JNEUROSCI.0179-17.2017}, volume = {37}, year = {2017}, }