@inproceedings{5963, abstract = {There has been significant progress in understanding the parallelism inherent to iterative sequential algorithms: for many classic algorithms, the depth of the dependence structure is now well understood, and scheduling techniques have been developed to exploit this shallow dependence structure for efficient parallel implementations. A related, applied research strand has studied methods by which certain iterative task-based algorithms can be efficiently parallelized via relaxed concurrent priority schedulers. These allow for high concurrency when inserting and removing tasks, at the cost of executing superfluous work due to the relaxed semantics of the scheduler. In this work, we take a step towards unifying these two research directions, by showing that there exists a family of relaxed priority schedulers that can efficiently and deterministically execute classic iterative algorithms such as greedy maximal independent set (MIS) and matching. Our primary result shows that, given a randomized scheduler with an expected relaxation factor of k in terms of the maximum allowed priority inversions on a task, and any graph on n vertices, the scheduler is able to execute greedy MIS with only an additive factor of \poly(k) expected additional iterations compared to an exact (but not scalable) scheduler. This counter-intuitive result demonstrates that the overhead of relaxation when computing MIS is not dependent on the input size or structure of the input graph. Experimental results show that this overhead can be clearly offset by the gain in performance due to the highly scalable scheduler. In sum, we present an efficient method to deterministically parallelize iterative sequential algorithms, with provable runtime guarantees in terms of the number of executed tasks to completion.}, author = {Alistarh, Dan-Adrian and Brown, Trevor A and Kopinsky, Justin and Nadiradze, Giorgi}, booktitle = {Proceedings of the 2018 ACM Symposium on Principles of Distributed Computing - PODC '18}, isbn = {9781450357951}, location = {Egham, United Kingdom}, pages = {377--386}, publisher = {ACM Press}, title = {{Relaxed schedulers can efficiently parallelize iterative algorithms}}, doi = {10.1145/3212734.3212756}, year = {2018}, } @inproceedings{5965, abstract = {Relaxed concurrent data structures have become increasingly popular, due to their scalability in graph processing and machine learning applications (\citeNguyen13, gonzalez2012powergraph ). Despite considerable interest, there exist families of natural, high performing randomized relaxed concurrent data structures, such as the popular MultiQueue~\citeMQ pattern for implementing relaxed priority queue data structures, for which no guarantees are known in the concurrent setting~\citeAKLN17. Our main contribution is in showing for the first time that, under a set of analytic assumptions, a family of relaxed concurrent data structures, including variants of MultiQueues, but also a new approximate counting algorithm we call the MultiCounter, provides strong probabilistic guarantees on the degree of relaxation with respect to the sequential specification, in arbitrary concurrent executions. We formalize these guarantees via a new correctness condition called distributional linearizability, tailored to concurrent implementations with randomized relaxations. Our result is based on a new analysis of an asynchronous variant of the classic power-of-two-choices load balancing algorithm, in which placement choices can be based on inconsistent, outdated information (this result may be of independent interest). We validate our results empirically, showing that the MultiCounter algorithm can implement scalable relaxed timestamps.}, author = {Alistarh, Dan-Adrian and Brown, Trevor A and Kopinsky, Justin and Li, Jerry Z. and Nadiradze, Giorgi}, booktitle = {Proceedings of the 30th on Symposium on Parallelism in Algorithms and Architectures - SPAA '18}, isbn = {9781450357999}, location = {Vienna, Austria}, pages = {133--142}, publisher = {ACM Press}, title = {{Distributionally linearizable data structures}}, doi = {10.1145/3210377.3210411}, year = {2018}, } @inproceedings{5967, abstract = {The Big Match is a multi-stage two-player game. In each stage Player 1 hides one or two pebbles in his hand, and his opponent has to guess that number; Player 1 loses a point if Player 2 is correct, and otherwise he wins a point. As soon as Player 1 hides one pebble, the players cannot change their choices in any future stage. Blackwell and Ferguson (1968) give an ε-optimal strategy for Player 1 that hides, in each stage, one pebble with a probability that depends on the entire past history. Any strategy that depends just on the clock or on a finite memory is worthless. The long-standing natural open problem has been whether every strategy that depends just on the clock and a finite memory is worthless. We prove that there is such a strategy that is ε-optimal. In fact, we show that just two states of memory are sufficient. }, author = {Hansen, Kristoffer Arnsfelt and Ibsen-Jensen, Rasmus and Neyman, Abraham}, booktitle = {Proceedings of the 2018 ACM Conference on Economics and Computation - EC '18}, isbn = {9781450358293}, location = {Ithaca, NY, United States}, pages = {149--150}, publisher = {ACM Press}, title = {{The Big Match with a clock and a bit of memory}}, doi = {10.1145/3219166.3219198}, year = {2018}, } @inproceedings{5966, abstract = {The transactional conflict problem arises in transactional systems whenever two or more concurrent transactions clash on a data item. While the standard solution to such conflicts is to immediately abort one of the transactions, some practical systems consider the alternative of delaying conflict resolution for a short interval, which may allow one of the transactions to commit. The challenge in the transactional conflict problem is to choose the optimal length of this delay interval so as to minimize the overall running time penalty for the conflicting transactions. In this paper, we propose a family of optimal online algorithms for the transactional conflict problem. Specifically, we consider variants of this problem which arise in different implementations of transactional systems, namely "requestor wins'' and "requestor aborts'' implementations: in the former, the recipient of a coherence request is aborted, whereas in the latter, it is the requestor which has to abort. Both strategies are implemented by real systems. We show that the requestor aborts case can be reduced to a classic instance of the ski rental problem, while the requestor wins case leads to a new version of this classical problem, for which we derive optimal deterministic and randomized algorithms. Moreover, we prove that, under a simplified adversarial model, our algorithms are constant-competitive with the offline optimum in terms of throughput. We validate our algorithmic results empirically through a hardware simulation of hardware transactional memory (HTM), showing that our algorithms can lead to non-trivial performance improvements for classic concurrent data structures.}, author = {Alistarh, Dan-Adrian and Haider, Syed Kamran and Kübler, Raphael and Nadiradze, Giorgi}, booktitle = {Proceedings of the 30th on Symposium on Parallelism in Algorithms and Architectures - SPAA '18}, isbn = {9781450357999}, location = {Vienna, Austria}, pages = {383--392}, publisher = {ACM Press}, title = {{The transactional conflict problem}}, doi = {10.1145/3210377.3210406}, year = {2018}, } @article{5975, abstract = {We consider the recent formulation of the algorithmic Lov ́asz Local Lemma [N. Har-vey and J. Vondr ́ak, inProceedings of FOCS, 2015, pp. 1327–1345; D. Achlioptas and F. Iliopoulos,inProceedings of SODA, 2016, pp. 2024–2038; D. Achlioptas, F. Iliopoulos, and V. Kolmogorov,ALocal Lemma for Focused Stochastic Algorithms, arXiv preprint, 2018] for finding objects that avoid“bad features,” or “flaws.” It extends the Moser–Tardos resampling algorithm [R. A. Moser andG. Tardos,J. ACM, 57 (2010), 11] to more general discrete spaces. At each step the method picks aflaw present in the current state and goes to a new state according to some prespecified probabilitydistribution (which depends on the current state and the selected flaw). However, the recent formu-lation is less flexible than the Moser–Tardos method since it requires a specific flaw selection rule,whereas the algorithm of Moser and Tardos allows an arbitrary rule (and thus can potentially beimplemented more efficiently). We formulate a new “commutativity” condition and prove that it issufficient for an arbitrary rule to work. It also enables an efficient parallelization under an additionalassumption. We then show that existing resampling oracles for perfect matchings and permutationsdo satisfy this condition.}, author = {Kolmogorov, Vladimir}, issn = {1095-7111}, journal = {SIAM Journal on Computing}, number = {6}, pages = {2029--2056}, publisher = {Society for Industrial & Applied Mathematics (SIAM)}, title = {{Commutativity in the algorithmic Lovász local lemma}}, doi = {10.1137/16m1093306}, volume = {47}, year = {2018}, } @inproceedings{5964, abstract = {A standard design pattern found in many concurrent data structures, such as hash tables or ordered containers, is an alternation of parallelizable sections that incur no data conflicts and critical sections that must run sequentially and are protected with locks. A lock can be viewed as a queue that arbitrates the order in which the critical sections are executed, and a natural question is whether we can use stochastic analysis to predict the resulting throughput. As a preliminary evidence to the affirmative, we describe a simple model that can be used to predict the throughput of coarse-grained lock-based algorithms. We show that our model works well for CLH lock, and we expect it to work for other popular lock designs such as TTAS, MCS, etc.}, author = {Aksenov, Vitaly and Alistarh, Dan-Adrian and Kuznetsov, Petr}, booktitle = {Proceedings of the 2018 ACM Symposium on Principles of Distributed Computing - PODC '18}, isbn = {9781450357951}, location = {Egham, United Kingdom}, pages = {411--413}, publisher = {ACM Press}, title = {{Brief Announcement: Performance prediction for coarse-grained locking}}, doi = {10.1145/3212734.3212785}, year = {2018}, } @article{5971, abstract = {We consider a Wigner-type ensemble, i.e. large hermitian N×N random matrices H=H∗ with centered independent entries and with a general matrix of variances Sxy=𝔼∣∣Hxy∣∣2. The norm of H is asymptotically given by the maximum of the support of the self-consistent density of states. We establish a bound on this maximum in terms of norms of powers of S that substantially improves the earlier bound 2∥S∥1/2∞ given in [O. Ajanki, L. Erdős and T. Krüger, Universality for general Wigner-type matrices, Prob. Theor. Rel. Fields169 (2017) 667–727]. The key element of the proof is an effective Markov chain approximation for the contributions of the weighted Dyck paths appearing in the iterative solution of the corresponding Dyson equation.}, author = {Erdös, László and Mühlbacher, Peter}, issn = {2010-3271}, journal = {Random matrices: Theory and applications}, publisher = {World Scientific Publishing}, title = {{Bounds on the norm of Wigner-type random matrices}}, doi = {10.1142/s2010326319500096}, year = {2018}, } @article{5984, abstract = {G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.}, author = {Morri, Maurizio and Sanchez-Romero, Inmaculada and Tichy, Alexandra-Madelaine and Kainrath, Stephanie and Gerrard, Elliot J. and Hirschfeld, Priscila and Schwarz, Jan and Janovjak, Harald L}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Optical functionalization of human class A orphan G-protein-coupled receptors}}, doi = {10.1038/s41467-018-04342-1}, volume = {9}, year = {2018}, } @article{5976, abstract = {We propose FlexMaps, a novel framework for fabricating smooth shapes out of flat, flexible panels with tailored mechanical properties. We start by mapping the 3D surface onto a 2D domain as in traditional UV mapping to design a set of deformable flat panels called FlexMaps. For these panels, we design and obtain specific mechanical properties such that, once they are assembled, the static equilibrium configuration matches the desired 3D shape. FlexMaps can be fabricated from an almost rigid material, such as wood or plastic, and are made flexible in a controlled way by using computationally designed spiraling microstructures.}, author = {Malomo, Luigi and Perez Rodriguez, Jesus and Iarussi, Emmanuel and Pietroni, Nico and Miguel, Eder and Cignoni, Paolo and Bickel, Bernd}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {Association for Computing Machinery (ACM)}, title = {{FlexMaps: Computational design of flat flexible shells for shaping 3D objects}}, doi = {10.1145/3272127.3275076}, volume = {37}, year = {2018}, } @article{5983, abstract = {We study a quantum impurity possessing both translational and internal rotational degrees of freedom interacting with a bosonic bath. Such a system corresponds to a “rotating polaron,” which can be used to model, e.g., a rotating molecule immersed in an ultracold Bose gas or superfluid helium. We derive the Hamiltonian of the rotating polaron and study its spectrum in the weak- and strong-coupling regimes using a combination of variational, diagrammatic, and mean-field approaches. We reveal how the coupling between linear and angular momenta affects stable quasiparticle states, and demonstrate that internal rotation leads to an enhanced self-localization in the translational degrees of freedom.}, author = {Yakaboylu, Enderalp and Midya, Bikashkali and Deuchert, Andreas and Leopold, Nikolai K and Lemeshko, Mikhail}, issn = {2469-9969}, journal = {Physical Review B}, number = {22}, publisher = {American Physical Society}, title = {{Theory of the rotating polaron: Spectrum and self-localization}}, doi = {10.1103/physrevb.98.224506}, volume = {98}, year = {2018}, } @article{5982, abstract = {In the present work, we detail a fast and simple solution-based method to synthesize hexagonal SnSe2 nanoplates (NPLs) and their use to produce crystallographically textured SnSe2 nanomaterials. We also demonstrate that the same strategy can be used to produce orthorhombic SnSe nanostructures and nanomaterials. NPLs are grown through a screw dislocation-driven mechanism. This mechanism typically results in pyramidal structures, but we demonstrate here that the growth from multiple dislocations results in flower-like structures. Crystallographically textured SnSe2 bulk nanomaterials obtained from the hot pressing of these SnSe2 structures display highly anisotropic charge and heat transport properties and thermoelectric (TE) figures of merit limited by relatively low electrical conductivities. To improve this parameter, SnSe2 NPLs are blended here with metal nanoparticles. The electrical conductivities of the blends are significantly improved with respect to bare SnSe2 NPLs, what translates into a three-fold increase of the TE Figure of merit, reaching unprecedented ZT values up to 0.65.}, author = {Zhang, Yu and Liu, Yu and Lim, Khak Ho and Xing, Congcong and Li, Mengyao and Zhang, Ting and Tang, Pengyi and Arbiol, Jordi and Llorca, Jordi and Ng, Ka Ming and Ibáñez, Maria and Guardia, Pablo and Prato, Mirko and Cadavid, Doris and Cabot, Andreu}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {52}, pages = {17063--17068}, publisher = {Wiley}, title = {{Tin diselenide molecular precursor for solution-processable thermoelectric materials}}, doi = {10.1002/anie.201809847}, volume = {57}, year = {2018}, } @inproceedings{5978, abstract = {We consider the MAP-inference problem for graphical models,which is a valued constraint satisfaction problem defined onreal numbers with a natural summation operation. We proposea family of relaxations (different from the famous Sherali-Adams hierarchy), which naturally define lower bounds for itsoptimum. This family always contains a tight relaxation andwe give an algorithm able to find it and therefore, solve theinitial non-relaxed NP-hard problem.The relaxations we consider decompose the original probleminto two non-overlapping parts: an easy LP-tight part and adifficult one. For the latter part a combinatorial solver must beused. As we show in our experiments, in a number of applica-tions the second, difficult part constitutes only a small fractionof the whole problem. This property allows to significantlyreduce the computational time of the combinatorial solver andtherefore solve problems which were out of reach before.}, author = {Haller, Stefan and Swoboda, Paul and Savchynskyy, Bogdan}, booktitle = {Proceedings of the 32st AAAI Conference on Artificial Intelligence}, location = {New Orleans, LU, United States}, pages = {6581--6588}, publisher = {AAAI Press}, title = {{Exact MAP-inference by confining combinatorial search with LP relaxation}}, year = {2018}, } @article{5990, abstract = {A Ge–Si core–shell nanowire is used to realize a Josephson field‐effect transistor with highly transparent contacts to superconducting leads. By changing the electric field, access to two distinct regimes, not combined before in a single device, is gained: in the accumulation mode the device is highly transparent and the supercurrent is carried by multiple subbands, while near depletion, the supercurrent is carried by single‐particle levels of a strongly coupled quantum dot operating in the few‐hole regime. These results establish Ge–Si nanowires as an important platform for hybrid superconductor–semiconductor physics and Majorana fermions.}, author = {Ridderbos, Joost and Brauns, Matthias and Shen, Jie and de Vries, Folkert K. and Li, Ang and Bakkers, Erik P. A. M. and Brinkman, Alexander and Zwanenburg, Floris A.}, issn = {0935-9648}, journal = {Advanced Materials}, number = {44}, publisher = {Wiley}, title = {{Josephson effect in a few-hole quantum dot}}, doi = {10.1002/adma.201802257}, volume = {30}, year = {2018}, } @article{5980, abstract = {The problem of private set-intersection (PSI) has been traditionally treated as an instance of the more general problem of multi-party computation (MPC). Consequently, in order to argue security, or compose these protocols one has to rely on the general theory that was developed for the purpose of MPC. The pursuit of efficient protocols, however, has resulted in designs that exploit properties pertaining to PSI. In almost all practical applications where a PSI protocol is deployed, it is expected to be executed multiple times, possibly on related inputs. In this work we initiate a dedicated study of PSI in the multi-interaction (MI) setting. In this model a server sets up the common system parameters and executes set-intersection multiple times with potentially different clients. We discuss a few attacks that arise when protocols are naïvely composed in this manner and, accordingly, craft security definitions for the MI setting and study their inter-relation. Finally, we suggest a set of protocols that are MI-secure, at the same time almost as efficient as their parent, stand-alone, protocols.}, author = {Chatterjee, Sanjit and Kamath Hosdurg, Chethan and Kumar, Vikas}, journal = {American Institute of Mathematical Sciences}, number = {1}, pages = {17--47}, publisher = {AIMS}, title = {{Private set-intersection with common set-up}}, doi = {10.3934/amc.2018002}, volume = {12}, year = {2018}, } @article{5998, abstract = {Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM.}, author = {Velicky, Philipp and Meinhardt, Gudrun and Plessl, Kerstin and Vondra, Sigrid and Weiss, Tamara and Haslinger, Peter and Lendl, Thomas and Aumayr, Karin and Mairhofer, Mario and Zhu, Xiaowei and Schütz, Birgit and Hannibal, Roberta L. and Lindau, Robert and Weil, Beatrix and Ernerudh, Jan and Neesen, Jürgen and Egger, Gerda and Mikula, Mario and Röhrl, Clemens and Urban, Alexander E. and Baker, Julie and Knöfler, Martin and Pollheimer, Jürgen}, issn = {1553-7404}, journal = {PLOS Genetics}, number = {10}, publisher = {Public Library of Science}, title = {{Genome amplification and cellular senescence are hallmarks of human placenta development}}, doi = {10.1371/journal.pgen.1007698}, volume = {14}, year = {2018}, } @article{5995, abstract = {Motivation Computational prediction of the effect of mutations on protein stability is used by researchers in many fields. The utility of the prediction methods is affected by their accuracy and bias. Bias, a systematic shift of the predicted change of stability, has been noted as an issue for several methods, but has not been investigated systematically. Presence of the bias may lead to misleading results especially when exploring the effects of combination of different mutations. Results Here we use a protocol to measure the bias as a function of the number of introduced mutations. It is based on a self-consistency test of the reciprocity the effect of a mutation. An advantage of the used approach is that it relies solely on crystal structures without experimentally measured stability values. We applied the protocol to four popular algorithms predicting change of protein stability upon mutation, FoldX, Eris, Rosetta and I-Mutant, and found an inherent bias. For one program, FoldX, we manage to substantially reduce the bias using additional relaxation by Modeller. Authors using algorithms for predicting effects of mutations should be aware of the bias described here.}, author = {Usmanova, Dinara R and Bogatyreva, Natalya S and Ariño Bernad, Joan and Eremina, Aleksandra A and Gorshkova, Anastasiya A and Kanevskiy, German M and Lonishin, Lyubov R and Meister, Alexander V and Yakupova, Alisa G and Kondrashov, Fyodor and Ivankov, Dmitry}, issn = {1367-4803}, journal = {Bioinformatics}, number = {21}, pages = {3653--3658}, publisher = {Oxford University Press }, title = {{Self-consistency test reveals systematic bias in programs for prediction change of stability upon mutation}}, doi = {10.1093/bioinformatics/bty340}, volume = {34}, year = {2018}, } @article{5992, abstract = {Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow.}, author = {Dolati, Setareh and Kage, Frieda and Mueller, Jan and Müsken, Mathias and Kirchner, Marieluise and Dittmar, Gunnar and Sixt, Michael K and Rottner, Klemens and Falcke, Martin}, issn = {1939-4586}, journal = {Molecular Biology of the Cell}, number = {22}, pages = {2674--2686}, publisher = {American Society for Cell Biology }, title = {{On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility}}, doi = {10.1091/mbc.e18-02-0082}, volume = {29}, year = {2018}, } @article{6010, abstract = {The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.}, author = {Garrido-Charad, Florencia and Vega Zuniga, Tomas A and Gutiérrez-Ibáñez, Cristián and Fernandez, Pedro and López-Jury, Luciana and González-Cabrera, Cristian and Karten, Harvey J. and Luksch, Harald and Marín, Gonzalo J.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {32}, pages = {E7615--E7623}, publisher = {National Academy of Sciences}, title = {{“Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network}}, doi = {10.1073/pnas.1804517115}, volume = {115}, year = {2018}, } @article{6003, abstract = {Digital fabrication devices are powerful tools for creating tangible reproductions of 3D digital models. Most available printing technologies aim at producing an accurate copy of a tridimensional shape. However, fabrication technologies can also be used to create a stylistic representation of a digital shape. We refer to this class of methods as ‘stylized fabrication methods’. These methods abstract geometric and physical features of a given shape to create an unconventional representation, to produce an optical illusion or to devise a particular interaction with the fabricated model. In this state‐of‐the‐art report, we classify and overview this broad and emerging class of approaches and also propose possible directions for future research.}, author = {Bickel, Bernd and Cignoni, Paolo and Malomo, Luigi and Pietroni, Nico}, issn = {0167-7055}, journal = {Computer Graphics Forum}, number = {6}, pages = {325--342}, publisher = {Wiley}, title = {{State of the art on stylized fabrication}}, doi = {10.1111/cgf.13327}, volume = {37}, year = {2018}, } @article{6002, abstract = {The Bogoliubov free energy functional is analysed. The functional serves as a model of a translation-invariant Bose gas at positive temperature. We prove the existence of minimizers in the case of repulsive interactions given by a sufficiently regular two-body potential. Furthermore, we prove the existence of a phase transition in this model and provide its phase diagram.}, author = {Napiórkowski, Marcin M and Reuvers, Robin and Solovej, Jan Philip}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {1037--1090}, publisher = {Springer Nature}, title = {{The Bogoliubov free energy functional I: Existence of minimizers and phase diagram}}, doi = {10.1007/s00205-018-1232-6}, volume = {229}, year = {2018}, } @article{5996, abstract = {In pipes, turbulence sets in despite the linear stability of the laminar Hagen–Poiseuille flow. The Reynolds number ( ) for which turbulence first appears in a given experiment – the ‘natural transition point’ – depends on imperfections of the set-up, or, more precisely, on the magnitude of finite amplitude perturbations. At onset, turbulence typically only occupies a certain fraction of the flow, and this fraction equally is found to differ from experiment to experiment. Despite these findings, Reynolds proposed that after sufficiently long times, flows may settle to steady conditions: below a critical velocity, flows should (regardless of initial conditions) always return to laminar, while above this velocity, eddying motion should persist. As will be shown, even in pipes several thousand diameters long, the spatio-temporal intermittent flow patterns observed at the end of the pipe strongly depend on the initial conditions, and there is no indication that different flow patterns would eventually settle to a (statistical) steady state. Exploiting the fact that turbulent puffs do not age (i.e. they are memoryless), we continuously recreate the puff sequence exiting the pipe at the pipe entrance, and in doing so introduce periodic boundary conditions for the puff pattern. This procedure allows us to study the evolution of the flow patterns for arbitrary long times, and we find that after times in excess of advective time units, indeed a statistical steady state is reached. Although the resulting flows remain spatio-temporally intermittent, puff splitting and decay rates eventually reach a balance, so that the turbulent fraction fluctuates around a well-defined level which only depends on . In accordance with Reynolds’ proposition, we find that at lower (here 2020), flows eventually always resume to laminar, while for higher ( ), turbulence persists. The critical point for pipe flow hence falls in the interval of $2020 , which is in very good agreement with the recently proposed value of . The latter estimate was based on single-puff statistics and entirely neglected puff interactions. Unlike in typical contact processes where such interactions strongly affect the percolation threshold, in pipe flow, the critical point is only marginally influenced. Interactions, on the other hand, are responsible for the approach to the statistical steady state. As shown, they strongly affect the resulting flow patterns, where they cause ‘puff clustering’, and these regions of large puff densities are observed to travel across the puff pattern in a wave-like fashion.}, author = {Vasudevan, Mukund and Hof, Björn}, issn = {1469-7645}, journal = {Journal of Fluid Mechanics}, pages = {76--94}, publisher = {Cambridge University Press}, title = {{The critical point of the transition to turbulence in pipe flow}}, doi = {10.1017/jfm.2017.923}, volume = {839}, year = {2018}, } @article{5993, abstract = {In this article, we consider the termination problem of probabilistic programs with real-valued variables. Thequestions concerned are: qualitative ones that ask (i) whether the program terminates with probability 1(almost-sure termination) and (ii) whether the expected termination time is finite (finite termination); andquantitative ones that ask (i) to approximate the expected termination time (expectation problem) and (ii) tocompute a boundBsuch that the probability not to terminate afterBsteps decreases exponentially (con-centration problem). To solve these questions, we utilize the notion of ranking supermartingales, which isa powerful approach for proving termination of probabilistic programs. In detail, we focus on algorithmicsynthesis of linear ranking-supermartingales over affine probabilistic programs (Apps) with both angelic anddemonic non-determinism. An important subclass of Apps is LRApp which is defined as the class of all Appsover which a linear ranking-supermartingale exists.Our main contributions are as follows. Firstly, we show that the membership problem of LRApp (i) canbe decided in polynomial time for Apps with at most demonic non-determinism, and (ii) isNP-hard and inPSPACEfor Apps with angelic non-determinism. Moreover, theNP-hardness result holds already for Appswithout probability and demonic non-determinism. Secondly, we show that the concentration problem overLRApp can be solved in the same complexity as for the membership problem of LRApp. Finally, we show thatthe expectation problem over LRApp can be solved in2EXPTIMEand isPSPACE-hard even for Apps withoutprobability and non-determinism (i.e., deterministic programs). Our experimental results demonstrate theeffectiveness of our approach to answer the qualitative and quantitative questions over Apps with at mostdemonic non-determinism.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Novotný, Petr and Hasheminezhad, Rouzbeh}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {2}, publisher = {Association for Computing Machinery (ACM)}, title = {{Algorithmic analysis of qualitative and quantitative termination problems for affine probabilistic programs}}, doi = {10.1145/3174800}, volume = {40}, year = {2018}, } @article{5999, abstract = {We introduce for each quiver Q and each algebraic oriented cohomology theory A, the cohomological Hall algebra (CoHA) of Q, as the A-homology of the moduli of representations of the preprojective algebra of Q. This generalizes the K-theoretic Hall algebra of commuting varieties defined by Schiffmann-Vasserot. When A is the Morava K-theory, we show evidence that this algebra is a candidate for Lusztig's reformulated conjecture on modular representations of algebraic groups. We construct an action of the preprojective CoHA on the A-homology of Nakajima quiver varieties. We compare this with the action of the Borel subalgebra of Yangian when A is the intersection theory. We also give a shuffle algebra description of this CoHA in terms of the underlying formal group law of A. As applications, we obtain a shuffle description of the Yangian. }, author = {Yang, Yaping and Zhao, Gufang}, issn = {0024-6115}, journal = {Proceedings of the London Mathematical Society}, number = {5}, pages = {1029--1074}, publisher = {Oxford University Press}, title = {{The cohomological Hall algebra of a preprojective algebra}}, doi = {10.1112/plms.12111}, volume = {116}, year = {2018}, } @article{5989, abstract = {Schistosomes are the causative agents of schistosomiasis, a neglected tropical disease affecting over 230 million people worldwide.Additionally to their major impact on human health, they are also models of choice in evolutionary biology. These parasitic flatwormsare unique among the common hermaphroditic trematodes as they have separate sexes. This so-called “evolutionary scandal”displays a female heterogametic genetic sex-determination system (ZZ males and ZW females), as well as a pronounced adult sexualdimorphism. These phenotypic differences are determined by a shared set of genes in both sexes, potentially leading to intralocussexual conflicts. To resolve these conflicts in sexually selected traits, molecular mechanisms such as sex-biased gene expression couldoccur, but parent-of-origin gene expression also provides an alternative. In this work we investigated the latter mechanism, that is,genes expressed preferentially from either the maternal or the paternal allele, inSchistosoma mansonispecies. To this end, tran-scriptomes from male and female hybrid adults obtained by strain crosses were sequenced. Strain-specific single nucleotide poly-morphism (SNP) markers allowed us to discriminate the parental origin, while reciprocal crosses helped to differentiate parentalexpression from strain-specific expression. We identified genes containing SNPs expressed in a parent-of-origin manner consistentwith paternal and maternal imprints. Although the majority of the SNPs was identified in mitochondrial and Z-specific loci, theremaining SNPs found in male and female transcriptomes were situated in genes that have the potential to explain sexual differencesin schistosome parasites. Furthermore, we identified and validated four new Z-specific scaffolds.}, author = {Kincaid-Smith, Julien and Picard, Marion A L and Cosseau, Céline and Boissier, Jérôme and Severac, Dany and Grunau, Christoph and Toulza, Eve}, issn = {1759-6653}, journal = {Genome Biology and Evolution}, number = {3}, pages = {840--856}, publisher = {Oxford University Press}, title = {{Parent-of-Origin-Dependent Gene Expression in Male and Female Schistosome Parasites}}, doi = {10.1093/gbe/evy037}, volume = {10}, year = {2018}, } @inproceedings{6031, abstract = {We introduce Clover, a new library for efficient computation using low-precision data, providing mathematical routines required by fundamental methods in optimization and sparse recovery. Our library faithfully implements variants of stochastic quantization that guarantee convergence at low precision, and supports data formats from 4-bit quantized to 32-bit IEEE-754 on current Intel processors. In particular, we show that 4-bit can be implemented efficiently using Intel AVX despite the lack of native support for this data format. Experimental results with dot product, matrix-vector multiplication (MVM), gradient descent (GD), and iterative hard thresholding (IHT) demonstrate that the attainable speedups are in many cases close to linear with respect to the reduction of precision due to reduced data movement. Finally, for GD and IHT, we show examples of absolute speedup achieved by 4-bit versus 32-bit, by iterating until a given target error is achieved.}, author = {Stojanov, Alen and Smith, Tyler Michael and Alistarh, Dan-Adrian and Puschel, Markus}, booktitle = {2018 IEEE International Workshop on Signal Processing Systems}, location = {Cape Town, South Africa}, publisher = {IEEE}, title = {{Fast quantized arithmetic on x86: Trading compute for data movement}}, doi = {10.1109/SiPS.2018.8598402}, volume = {2018-October}, year = {2018}, } @inproceedings{25, abstract = {Partially observable Markov decision processes (POMDPs) are the standard models for planning under uncertainty with both finite and infinite horizon. Besides the well-known discounted-sum objective, indefinite-horizon objective (aka Goal-POMDPs) is another classical objective for POMDPs. In this case, given a set of target states and a positive cost for each transition, the optimization objective is to minimize the expected total cost until a target state is reached. In the literature, RTDP-Bel or heuristic search value iteration (HSVI) have been used for solving Goal-POMDPs. Neither of these algorithms has theoretical convergence guarantees, and HSVI may even fail to terminate its trials. We give the following contributions: (1) We discuss the challenges introduced in Goal-POMDPs and illustrate how they prevent the original HSVI from converging. (2) We present a novel algorithm inspired by HSVI, termed Goal-HSVI, and show that our algorithm has convergence guarantees. (3) We show that Goal-HSVI outperforms RTDP-Bel on a set of well-known examples.}, author = {Horák, Karel and Bošanský, Branislav and Chatterjee, Krishnendu}, booktitle = {Proceedings of the Twenty-Seventh International Joint Conference on Artificial Intelligence}, location = {Stockholm, Sweden}, pages = {4764 -- 4770}, publisher = {IJCAI}, title = {{Goal-HSVI: Heuristic search value iteration for goal-POMDPs}}, doi = {10.24963/ijcai.2018/662}, volume = {2018-July}, year = {2018}, } @inproceedings{24, abstract = {Partially-observable Markov decision processes (POMDPs) with discounted-sum payoff are a standard framework to model a wide range of problems related to decision making under uncertainty. Traditionally, the goal has been to obtain policies that optimize the expectation of the discounted-sum payoff. A key drawback of the expectation measure is that even low probability events with extreme payoff can significantly affect the expectation, and thus the obtained policies are not necessarily risk-averse. An alternate approach is to optimize the probability that the payoff is above a certain threshold, which allows obtaining risk-averse policies, but ignores optimization of the expectation. We consider the expectation optimization with probabilistic guarantee (EOPG) problem, where the goal is to optimize the expectation ensuring that the payoff is above a given threshold with at least a specified probability. We present several results on the EOPG problem, including the first algorithm to solve it.}, author = {Chatterjee, Krishnendu and Elgyütt, Adrian and Novotny, Petr and Rouillé, Owen}, location = {Stockholm, Sweden}, pages = {4692 -- 4699}, publisher = {IJCAI}, title = {{Expectation optimization with probabilistic guarantees in POMDPs with discounted-sum objectives}}, doi = {10.24963/ijcai.2018/652}, volume = {2018}, year = {2018}, } @inproceedings{34, abstract = {Partially observable Markov decision processes (POMDPs) are widely used in probabilistic planning problems in which an agent interacts with an environment using noisy and imprecise sensors. We study a setting in which the sensors are only partially defined and the goal is to synthesize “weakest” additional sensors, such that in the resulting POMDP, there is a small-memory policy for the agent that almost-surely (with probability 1) satisfies a reachability objective. We show that the problem is NP-complete, and present a symbolic algorithm by encoding the problem into SAT instances. We illustrate trade-offs between the amount of memory of the policy and the number of additional sensors on a simple example. We have implemented our approach and consider three classical POMDP examples from the literature, and show that in all the examples the number of sensors can be significantly decreased (as compared to the existing solutions in the literature) without increasing the complexity of the policies.}, author = {Chatterjee, Krishnendu and Chemlík, Martin and Topcu, Ufuk}, location = {Delft, Netherlands}, pages = {47 -- 55}, publisher = {AAAI Press}, title = {{Sensor synthesis for POMDPs with reachability objectives}}, volume = {2018}, year = {2018}, } @article{18, abstract = {An N-superconcentrator is a directed, acyclic graph with N input nodes and N output nodes such that every subset of the inputs and every subset of the outputs of same cardinality can be connected by node-disjoint paths. It is known that linear-size and bounded-degree superconcentrators exist. We prove the existence of such superconcentrators with asymptotic density 25.3 (where the density is the number of edges divided by N). The previously best known densities were 28 [12] and 27.4136 [17].}, author = {Kolmogorov, Vladimir and Rolinek, Michal}, issn = {0381-7032}, journal = {Ars Combinatoria}, number = {10}, pages = {269 -- 304}, publisher = {Charles Babbage Research Centre}, title = {{Superconcentrators of density 25.3}}, volume = {141}, year = {2018}, } @article{6355, abstract = {We prove that any cyclic quadrilateral can be inscribed in any closed convex C1-curve. The smoothness condition is not required if the quadrilateral is a rectangle.}, author = {Akopyan, Arseniy and Avvakumov, Sergey}, issn = {2050-5094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Any cyclic quadrilateral can be inscribed in any closed convex smooth curve}}, doi = {10.1017/fms.2018.7}, volume = {6}, year = {2018}, } @inproceedings{6195, abstract = {In the context of robotic manipulation and grasping, the shift from a view that is static (force closure of a single posture) and contact-deprived (only contact for force closure is allowed, everything else is obstacle) towards a view that is dynamic and contact-rich (soft manipulation) has led to an increased interest in soft hands. These hands can easily exploit environmental constraints and object surfaces without risk, and safely interact with humans, but present also some challenges. Designing them is difficult, as well as predicting, modelling, and “programming” their interactions with the objects and the environment. This paper tackles the problem of simulating them in a fast and effective way, leveraging on novel and existing simulation technologies. We present a triple-layered simulation framework where dynamic properties such as stiffness are determined from slow but accurate FEM simulation data once, and then condensed into a lumped parameter model that can be used to fast simulate soft fingers and soft hands. We apply our approach to the simulation of soft pneumatic fingers.}, author = {Pozzi, Maria and Miguel Villalba, Eder and Deimel, Raphael and Malvezzi, Monica and Bickel, Bernd and Brock, Oliver and Prattichizzo, Domenico}, isbn = {9781538630815}, location = {Brisbane, Australia}, publisher = {IEEE}, title = {{Efficient FEM-based simulation of soft robots modeled as kinematic chains}}, doi = {10.1109/icra.2018.8461106}, year = {2018}, } @inproceedings{6941, abstract = {Bitcoin has become the most successful cryptocurrency ever deployed, and its most distinctive feature is that it is decentralized. Its underlying protocol (Nakamoto consensus) achieves this by using proof of work, which has the drawback that it causes the consumption of vast amounts of energy to maintain the ledger. Moreover, Bitcoin mining dynamics have become less distributed over time. Towards addressing these issues, we propose SpaceMint, a cryptocurrency based on proofs of space instead of proofs of work. Miners in SpaceMint dedicate disk space rather than computation. We argue that SpaceMint’s design solves or alleviates several of Bitcoin’s issues: most notably, its large energy consumption. SpaceMint also rewards smaller miners fairly according to their contribution to the network, thus incentivizing more distributed participation. This paper adapts proof of space to enable its use in cryptocurrency, studies the attacks that can arise against a Bitcoin-like blockchain that uses proof of space, and proposes a new blockchain format and transaction types to address these attacks. Our prototype shows that initializing 1 TB for mining takes about a day (a one-off setup cost), and miners spend on average just a fraction of a second per block mined. Finally, we provide a game-theoretic analysis modeling SpaceMint as an extensive game (the canonical game-theoretic notion for games that take place over time) and show that this stylized game satisfies a strong equilibrium notion, thereby arguing for SpaceMint ’s stability and consensus.}, author = {Park, Sunoo and Kwon, Albert and Fuchsbauer, Georg and Gazi, Peter and Alwen, Joel F and Pietrzak, Krzysztof Z}, booktitle = {22nd International Conference on Financial Cryptography and Data Security}, isbn = {9783662583869}, issn = {1611-3349}, location = {Nieuwpoort, Curacao}, pages = {480--499}, publisher = {Springer Nature}, title = {{SpaceMint: A cryptocurrency based on proofs of space}}, doi = {10.1007/978-3-662-58387-6_26}, volume = {10957}, year = {2018}, } @article{6497, abstract = {T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations.}, author = {Moalli, Federica and Ficht, Xenia and Germann, Philipp and Vladymyrov, Mykhailo and Stolp, Bettina and de Vries, Ingrid and Lyck, Ruth and Balmer, Jasmin and Fiocchi, Amleto and Kreutzfeldt, Mario and Merkler, Doron and Iannacone, Matteo and Ariga, Akitaka and Stoffel, Michael H. and Sharpe, James and Bähler, Martin and Sixt, Michael K and Diz-Muñoz, Alba and Stein, Jens V.}, issn = {1540-9538}, journal = {The Journal of Experimental Medicine}, number = {7}, pages = {1869–1890}, publisher = {Rockefeller University Press}, title = {{The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells}}, doi = {10.1084/jem.20170896}, volume = {2015}, year = {2018}, } @article{6499, abstract = {Expansion microscopy is a recently introduced imaging technique that achieves super‐resolution through physically expanding the specimen by ~4×, after embedding into a swellable gel. The resolution attained is, correspondingly, approximately fourfold better than the diffraction limit, or ~70 nm. This is a major improvement over conventional microscopy, but still lags behind modern STED or STORM setups, whose resolution can reach 20–30 nm. We addressed this issue here by introducing an improved gel recipe that enables an expansion factor of ~10× in each dimension, which corresponds to an expansion of the sample volume by more than 1,000‐fold. Our protocol, which we termed X10 microscopy, achieves a resolution of 25–30 nm on conventional epifluorescence microscopes. X10 provides multi‐color images similar or even superior to those produced with more challenging methods, such as STED, STORM, and iterative expansion microscopy (iExM). X10 is therefore the cheapest and easiest option for high‐quality super‐resolution imaging currently available. X10 should be usable in any laboratory, irrespective of the machinery owned or of the technical knowledge.}, author = {Truckenbrodt, Sven M and Maidorn, Manuel and Crzan, Dagmar and Wildhagen, Hanna and Kabatas, Selda and Rizzoli, Silvio O}, issn = {1469-3178}, journal = {EMBO reports}, number = {9}, publisher = {EMBO}, title = {{X10 expansion microscopy enables 25‐nm resolution on conventional microscopes}}, doi = {10.15252/embr.201845836}, volume = {19}, year = {2018}, } @inproceedings{7123, abstract = {Population protocols are a popular model of distributed computing, in which n agents with limited local state interact randomly, and cooperate to collectively compute global predicates. Inspired by recent developments in DNA programming, an extensive series of papers, across different communities, has examined the computability and complexity characteristics of this model. Majority, or consensus, is a central task in this model, in which agents need to collectively reach a decision as to which one of two states A or B had a higher initial count. Two metrics are important: the time that a protocol requires to stabilize to an output decision, and the state space size that each agent requires to do so. It is known that majority requires Ω(log log n) states per agent to allow for fast (poly-logarithmic time) stabilization, and that O(log2 n) states are sufficient. Thus, there is an exponential gap between the space upper and lower bounds for this problem. This paper addresses this question. On the negative side, we provide a new lower bound of Ω(log n) states for any protocol which stabilizes in O(n1–c) expected time, for any constant c > 0. This result is conditional on monotonicity and output assumptions, satisfied by all known protocols. Technically, it represents a departure from previous lower bounds, in that it does not rely on the existence of dense configurations. Instead, we introduce a new generalized surgery technique to prove the existence of incorrect executions for any algorithm which would contradict the lower bound. Subsequently, our lower bound also applies to general initial configurations, including ones with a leader. On the positive side, we give a new algorithm for majority which uses O(log n) states, and stabilizes in O(log2 n) expected time. Central to the algorithm is a new leaderless phase clock technique, which allows agents to synchronize in phases of Θ(n log n) consecutive interactions using O(log n) states per agent, exploiting a new connection between population protocols and power-of-two-choices load balancing mechanisms. We also employ our phase clock to build a leader election algorithm with a state space of size O(log n), which stabilizes in O(log2 n) expected time.}, author = {Alistarh, Dan-Adrian and Aspnes, James and Gelashvili, Rati}, booktitle = {Proceedings of the 29th Annual ACM-SIAM Symposium on Discrete Algorithms}, isbn = {9781611975031}, location = {New Orleans, LA, United States}, pages = {2221--2239}, publisher = {ACM}, title = {{Space-optimal majority in population protocols}}, doi = {10.1137/1.9781611975031.144}, year = {2018}, } @article{9917, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, issn = {2056-3744}, journal = {Evolution Letters}, number = {4}, pages = {297--309}, publisher = {Wiley}, title = {{Clines on the seashore: The genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.1002/evl3.74}, volume = {2}, year = {2018}, } @article{9915, abstract = {The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favor reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence.}, author = {Hollander, Johan and Montaño-Rendón, Mauricio and Bianco, Giuseppe and Yang, Xi and Westram, Anja M and Duvaux, Ludovic and Reid, David G. and Butlin, Roger K.}, issn = {2056-3744}, journal = {Evolution Letters}, number = {6}, pages = {557--566}, publisher = {Wiley}, title = {{Are assortative mating and genital divergence driven by reinforcement?}}, doi = {10.1002/evl3.85}, volume = {2}, year = {2018}, } @article{8618, abstract = {The reversibly switchable fluorescent proteins (RSFPs) commonly used for RESOLFT nanoscopy have been developed from fluorescent proteins of the GFP superfamily. These proteins are bright, but exhibit several drawbacks such as relatively large size, oxygen-dependence, sensitivity to low pH, and limited switching speed. Therefore, RSFPs from other origins with improved properties need to be explored. Here, we report the development of two RSFPs based on the LOV domain of the photoreceptor protein YtvA from Bacillus subtilis. LOV domains obtain their fluorescence by association with the abundant cellular cofactor flavin mononucleotide (FMN). Under illumination with blue and ultraviolet light, they undergo a photocycle, making these proteins inherently photoswitchable. Our first improved variant, rsLOV1, can be used for RESOLFT imaging, whereas rsLOV2 proved useful for STED nanoscopy of living cells with a resolution of down to 50 nm. In addition to their smaller size compared to GFP-related proteins (17 kDa instead of 27 kDa) and their usability at low pH, rsLOV1 and rsLOV2 exhibit faster switching kinetics, switching on and off 3 times faster than rsEGFP2, the fastest-switching RSFP reported to date. Therefore, LOV-domain-based RSFPs have potential for applications where the switching speed of GFP-based proteins is limiting.}, author = {Gregor, Carola and Sidenstein, Sven C. and Andresen, Martin and Sahl, Steffen J. and Danzl, Johann G and Hell, Stefan W.}, issn = {2045-2322}, journal = {Scientific Reports}, keywords = {Multidisciplinary}, publisher = {Springer Nature}, title = {{Novel reversibly switchable fluorescent proteins for RESOLFT and STED nanoscopy engineered from the bacterial photoreceptor YtvA}}, doi = {10.1038/s41598-018-19947-1}, volume = {8}, year = {2018}, } @article{10881, abstract = {Strigolactones (SLs) are a relatively recent addition to the list of plant hormones that control different aspects of plant development. SL signalling is perceived by an α/β hydrolase, DWARF 14 (D14). A close homolog of D14, KARRIKIN INSENSTIVE2 (KAI2), is involved in perception of an uncharacterized molecule called karrikin (KAR). Recent studies in Arabidopsis identified the SUPPRESSOR OF MAX2 1 (SMAX1) and SMAX1-LIKE 7 (SMXL7) to be potential SCF–MAX2 complex-mediated proteasome targets of KAI2 and D14, respectively. Genetic studies on SMXL7 and SMAX1 demonstrated distinct developmental roles for each, but very little is known about these repressors in terms of their sequence features. In this study, we performed an extensive comparative analysis of SMXLs and determined their phylogenetic and evolutionary history in the plant lineage. Our results show that SMXL family members can be sub-divided into four distinct phylogenetic clades/classes, with an ancient SMAX1. Further, we identified the clade-specific motifs that have evolved and that might act as determinants of SL-KAR signalling specificity. These specificities resulted from functional diversities among the clades. Our results suggest that a gradual co-evolution of SMXL members with their upstream receptors D14/KAI2 provided an increased specificity to both the SL perception and response in land plants.}, author = {Moturu, Taraka Ramji and Thula, Sravankumar and Singh, Ravi Kumar and Nodzyński, Tomasz and Vařeková, Radka Svobodová and Friml, Jiří and Simon, Sibu}, issn = {1460-2431}, journal = {Journal of Experimental Botany}, keywords = {Plant Science, Physiology}, number = {9}, pages = {2367--2378}, publisher = {Oxford University Press}, title = {{Molecular evolution and diversification of the SMXL gene family}}, doi = {10.1093/jxb/ery097}, volume = {69}, year = {2018}, } @article{10880, abstract = {Acquisition of evolutionary novelties is a fundamental process for adapting to the external environment and invading new niches and results in the diversification of life, which we can see in the world today. How such novel phenotypic traits are acquired in the course of evolution and are built up in developing embryos has been a central question in biology. Whole-genome duplication (WGD) is a process of genome doubling that supplies raw genetic materials and increases genome complexity. Recently, it has been gradually revealed that WGD and subsequent fate changes of duplicated genes can facilitate phenotypic evolution. Here, we review the current understanding of the relationship between WGD and the acquisition of evolutionary novelties. We show some examples of this link and discuss how WGD and subsequent duplicated genes can facilitate phenotypic evolution as well as when such genomic doubling can be advantageous for adaptation.}, author = {Yuuta, Moriyama and Koshiba-Takeuchi, Kazuko}, issn = {2041-2657}, journal = {Briefings in Functional Genomics}, keywords = {Genetics, Molecular Biology, Biochemistry, General Medicine}, number = {5}, pages = {329--338}, publisher = {Oxford University Press}, title = {{Significance of whole-genome duplications on the emergence of evolutionary novelties}}, doi = {10.1093/bfgp/ely007}, volume = {17}, year = {2018}, } @misc{9930, abstract = {Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g. outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e. focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally-suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasises that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.}, author = {Westram, Anja M and Rafajlović, Marina and Chaube, Pragya and Faria, Rui and Larsson, Tomas and Panova, Marina and Ravinet, Mark and Blomberg, Anders and Mehlig, Bernhard and Johannesson, Kerstin and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Clines on the seashore: the genomic architecture underlying rapid divergence in the face of gene flow}}, doi = {10.5061/dryad.bp25b65}, year = {2018}, } @misc{9929, abstract = {The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favour reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence.}, author = {Hollander, Johan and Montaño-Rendón, Mauricio and Bianco, Giuseppe and Yang, Xi and Westram, Anja M and Duvaux, Ludovic and Reid, David G. and Butlin, Roger K.}, publisher = {Dryad}, title = {{Data from: Are assortative mating and genital divergence driven by reinforcement?}}, doi = {10.5061/dryad.51sd2p5}, year = {2018}, } @inproceedings{10882, abstract = {We introduce Intelligent Annotation Dialogs for bounding box annotation. We train an agent to automatically choose a sequence of actions for a human annotator to produce a bounding box in a minimal amount of time. Specifically, we consider two actions: box verification [34], where the annotator verifies a box generated by an object detector, and manual box drawing. We explore two kinds of agents, one based on predicting the probability that a box will be positively verified, and the other based on reinforcement learning. We demonstrate that (1) our agents are able to learn efficient annotation strategies in several scenarios, automatically adapting to the image difficulty, the desired quality of the boxes, and the detector strength; (2) in all scenarios the resulting annotation dialogs speed up annotation compared to manual box drawing alone and box verification alone, while also outperforming any fixed combination of verification and drawing in most scenarios; (3) in a realistic scenario where the detector is iteratively re-trained, our agents evolve a series of strategies that reflect the shifting trade-off between verification and drawing as the detector grows stronger.}, author = {Uijlings, Jasper and Konyushkova, Ksenia and Lampert, Christoph and Ferrari, Vittorio}, booktitle = {2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition}, isbn = {9781538664209}, issn = {2575-7075}, location = {Salt Lake City, UT, United States}, pages = {9175--9184}, publisher = {IEEE}, title = {{Learning intelligent dialogs for bounding box annotation}}, doi = {10.1109/cvpr.2018.00956}, year = {2018}, } @inproceedings{6558, abstract = {This paper studies the problem of distributed stochastic optimization in an adversarial setting where, out of m machines which allegedly compute stochastic gradients every iteration, an α-fraction are Byzantine, and may behave adversarially. Our main result is a variant of stochastic gradient descent (SGD) which finds ε-approximate minimizers of convex functions in T=O~(1/ε²m+α²/ε²) iterations. In contrast, traditional mini-batch SGD needs T=O(1/ε²m) iterations, but cannot tolerate Byzantine failures. Further, we provide a lower bound showing that, up to logarithmic factors, our algorithm is information-theoretically optimal both in terms of sample complexity and time complexity.}, author = {Alistarh, Dan-Adrian and Allen-Zhu, Zeyuan and Li, Jerry}, booktitle = {Advances in Neural Information Processing Systems}, location = {Montreal, Canada}, pages = {4613--4623}, publisher = {Neural Information Processing Systems Foundation}, title = {{Byzantine stochastic gradient descent}}, volume = {2018}, year = {2018}, } @article{6032, abstract = {The main result of this article is a generalization of the classical blossom algorithm for finding perfect matchings. Our algorithm can efficiently solve Boolean CSPs where each variable appears in exactly two constraints (we call it edge CSP) and all constraints are even Δ-matroid relations (represented by lists of tuples). As a consequence of this, we settle the complexity classification of planar Boolean CSPs started by Dvorak and Kupec. Using a reduction to even Δ-matroids, we then extend the tractability result to larger classes of Δ-matroids that we call efficiently coverable. It properly includes classes that were known to be tractable before, namely, co-independent, compact, local, linear, and binary, with the following caveat:We represent Δ-matroids by lists of tuples, while the last two use a representation by matrices. Since an n ×n matrix can represent exponentially many tuples, our tractability result is not strictly stronger than the known algorithm for linear and binary Δ-matroids.}, author = {Kazda, Alexandr and Kolmogorov, Vladimir and Rolinek, Michal}, journal = {ACM Transactions on Algorithms}, number = {2}, publisher = {ACM}, title = {{Even delta-matroids and the complexity of planar boolean CSPs}}, doi = {10.1145/3230649}, volume = {15}, year = {2018}, } @phdthesis{200, abstract = {This thesis is concerned with the inference of current population structure based on geo-referenced genetic data. The underlying idea is that population structure affects its spatial genetic structure. Therefore, genotype information can be utilized to estimate important demographic parameters such as migration rates. These indirect estimates of population structure have become very attractive, as genotype data is now widely available. However, there also has been much concern about these approaches. Importantly, genetic structure can be influenced by many complex patterns, which often cannot be disentangled. Moreover, many methods merely fit heuristic patterns of genetic structure, and do not build upon population genetics theory. Here, I describe two novel inference methods that address these shortcomings. In Chapter 2, I introduce an inference scheme based on a new type of signal, identity by descent (IBD) blocks. Recently, it has become feasible to detect such long blocks of genome shared between pairs of samples. These blocks are direct traces of recent coalescence events. As such, they contain ample signal for inferring recent demography. I examine sharing of IBD blocks in two-dimensional populations with local migration. Using a diffusion approximation, I derive formulas for an isolation by distance pattern of long IBD blocks and show that sharing of long IBD blocks approaches rapid exponential decay for growing sample distance. I describe an inference scheme based on these results. It can robustly estimate the dispersal rate and population density, which is demonstrated on simulated data. I also show an application to estimate mean migration and the rate of recent population growth within Eastern Europe. Chapter 3 is about a novel method to estimate barriers to gene flow in a two dimensional population. This inference scheme utilizes geographically localized allele frequency fluctuations - a classical isolation by distance signal. The strength of these local fluctuations increases on average next to a barrier, and there is less correlation across it. I again use a framework of diffusion of ancestral lineages to model this effect, and provide an efficient numerical implementation to fit the results to geo-referenced biallelic SNP data. This inference scheme is able to robustly estimate strong barriers to gene flow, as tests on simulated data confirm.}, author = {Ringbauer, Harald}, issn = {2663-337X}, pages = {146}, publisher = {Institute of Science and Technology Austria}, title = {{Inferring recent demography from spatial genetic structure}}, doi = {10.15479/AT:ISTA:th_963}, year = {2018}, } @article{1064, abstract = {In 1945, A.W. Goodman and R.E. Goodman proved the following conjecture by P. Erdős: Given a family of (round) disks of radii r1, … , rn in the plane, it is always possible to cover them by a disk of radius R= ∑ ri, provided they cannot be separated into two subfamilies by a straight line disjoint from the disks. In this note we show that essentially the same idea may work for different analogues and generalizations of their result. In particular, we prove the following: Given a family of positive homothetic copies of a fixed convex body K⊂ Rd with homothety coefficients τ1, … , τn> 0 , it is always possible to cover them by a translate of d+12(∑τi)K, provided they cannot be separated into two subfamilies by a hyperplane disjoint from the homothets.}, author = {Akopyan, Arseniy and Balitskiy, Alexey and Grigorev, Mikhail}, issn = {14320444}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {1001--1009}, publisher = {Springer}, title = {{On the circle covering theorem by A.W. Goodman and R.E. Goodman}}, doi = {10.1007/s00454-017-9883-x}, volume = {59}, year = {2018}, } @phdthesis{418, abstract = {The aim of this thesis was the development of new strategies for optical and optogenetic control of proliferative and pro-survival signaling, and characterizing them from the molecular mechanism up to cellular effects. These new light-based methods have unique features, such as red light as an activator, or the avoidance of gene delivery, which enable to overcome current limitations, such as light delivery to target tissues and feasibility as therapeutic approach. A special focus was placed on implementing these new light-based approaches in pancreatic β-cells, as β-cells are the key players in diabetes and especially their loss in number negatively affects disease progression. Currently no treatment options are available to compensate the lack of functional β-cells in diabetic patients. In a first approach, red-light-activated growth factor receptors, in particular receptor tyrosine kinases were engineered and characterized. Receptor activation with light allows spatio-temporal control compared to ligand-based activation, and especially red light exhibits deeper tissue penetration than other wavelengths of the visible spectrum. Red-light-activated receptor tyrosine kinases robustly activated major growth factor related signaling pathways with a high temporal resolution. Moreover, the remote activation of the proliferative MAPK/Erk pathway by red-light-activated receptor tyrosine kinases in a pancreatic β-cell line was also achieved, through one centimeter thick mouse tissue. Although red-light-activated receptor tyrosine kinases are particularly attractive for applications in animal models due to the deep tissue penetration of red light, a drawback, especially with regard to translation into humans, is the requirement of gene therapy. In a second approach an endogenous light-sensitive mechanism was identified and its potential to promote proliferative and pro-survival signals was explored, towards light-based tissue regeneration without the need for gene transfer. Blue-green light illumination was found to be sufficient for the activation of proliferation and survival promoting signaling pathways in primary pancreatic murine and human islets. Blue-green light also led to an increase in proliferation of primary islet cells, an effect which was shown to be mostly β-cell specific in human islets. Moreover, it was demonstrated that this approach of pancreatic β-cell expansion did not have any negative effect on the β-cell function, in particular on their insulin secretion capacity. In contrast, a trend for enhanced insulin secretion under high glucose conditions after illumination was detected. In order to unravel the detailed characteristics of this endogenous light-sensitive mechanism, the precise light requirements were determined. In addition, the expression of light sensing proteins, OPN3 and rhodopsin, was detected. The observed effects were found to be independent of handling effects such as temperature differences and cytochrome c oxidase dependent ATP increase, but they were found to be enhanced through the knockout of OPN3. The exact mechanism of how islets cells sense light and the identity of the photoreceptor remains unknown. Summarized two new light-based systems with unique features were established that enable the activation of proliferative and pro-survival signaling pathways. While red-light-activated receptor tyrosine kinases open a new avenue for optogenetics research, by allowing non-invasive control of signaling in vivo, the identified endogenous light-sensitive mechanism has the potential to be the basis of a gene therapy-free therapeutical approach for light-based β-cell expansion.}, author = {Gschaider-Reichhart, Eva}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Optical and optogenetic control of proliferation and survival }}, doi = {10.15479/AT:ISTA:th_913}, year = {2018}, } @article{1012, abstract = {We prove a new central limit theorem (CLT) for the difference of linear eigenvalue statistics of a Wigner random matrix H and its minor H and find that the fluctuation is much smaller than the fluctuations of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of H and H. In particular, our theorem identifies the fluctuation of Kerov's rectangular Young diagrams, defined by the interlacing eigenvalues ofH and H, around their asymptotic shape, the Vershik'Kerov'Logan'Shepp curve. Young diagrams equipped with the Plancherel measure follow the same limiting shape. For this, algebraically motivated, ensemble a CLT has been obtained in Ivanov and Olshanski [20] which is structurally similar to our result but the variance is different, indicating that the analogy between the two models has its limitations. Moreover, our theorem shows that Borodin's result [7] on the convergence of the spectral distribution of Wigner matrices to a Gaussian free field also holds in derivative sense.}, author = {Erdös, László and Schröder, Dominik J}, issn = {10737928}, journal = {International Mathematics Research Notices}, number = {10}, pages = {3255--3298}, publisher = {Oxford University Press}, title = {{Fluctuations of rectangular young diagrams of interlacing wigner eigenvalues}}, doi = {10.1093/imrn/rnw330}, volume = {2018}, year = {2018}, } @article{6006, abstract = {Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally-optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an over-approximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. We extend the abstraction-refinement methodology to labeled networks, where the objectives of the players are regular languages. Our experimental results demonstrate the effectiveness of the methodology. }, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {2073-4336}, journal = {Games}, number = {3}, publisher = {MDPI AG}, title = {{An abstraction-refinement methodology for reasoning about network games}}, doi = {10.3390/g9030039}, volume = {9}, year = {2018}, }