@misc{5441,
  abstract     = {We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.},
  author       = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Goharshady, Amir and Pavlogiannis, Andreas},
  issn         = {2664-1690},
  pages        = {24},
  publisher    = {IST Austria},
  title        = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}},
  doi          = {10.15479/AT:IST-2015-340-v1-1},
  year         = {2015},
}

@misc{5442,
  abstract     = {We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural properties that arise in program analysis.
We consider that each component of the concurrent system is a graph with constant treewidth, and it is known that the controlflow graphs of most programs have constant treewidth. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis problems (e.g., alias analysis). The study of multiple queries allows us to consider the tradeoff between the resource usage of the \emph{one-time} preprocessing and for \emph{each individual} query. The traditional approaches construct the product graph of all components and apply the best-known graph algorithm on the product. In the traditional approach, even the answer to a single query requires the transitive closure computation (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time.

Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, 
each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results that show that the worst-case running times of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (such as improving 
the worst-case bounds for the shortest path problem in general graphs whose current best-known bound has not been improved in five decades). Finally, we provide a prototype implementation of our algorithms which significantly outperforms the existing algorithmic methods on several benchmarks.},
  author       = {Anonymous, 1 and Anonymous, 2 and Anonymous, 3 and Anonymous, 4},
  issn         = {2664-1690},
  pages        = {22},
  publisher    = {IST Austria},
  title        = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}},
  year         = {2015},
}

@misc{5443,
  abstract     = {POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.},
  author       = {Chatterjee, Krishnendu and Chmelik, Martin and Davies, Jessica},
  issn         = {2664-1690},
  pages        = {23},
  publisher    = {IST Austria},
  title        = {{A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs}},
  doi          = {10.15479/AT:IST-2015-325-v2-1},
  year         = {2015},
}

@misc{5444,
  abstract     = {A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.},
  author       = {Reiter, Johannes and Makohon-Moore, Alvin and Gerold, Jeffrey and Bozic, Ivana and Chatterjee, Krishnendu and Iacobuzio-Donahue, Christine and Vogelstein, Bert and Nowak, Martin},
  issn         = {2664-1690},
  pages        = {25},
  publisher    = {IST Austria},
  title        = {{Reconstructing robust phylogenies of metastatic cancers}},
  doi          = {10.15479/AT:IST-2015-399-v1-1},
  year         = {2015},
}

@misc{5549,
  abstract     = {This repository contains the experimental part of the CAV 2015 publication Counterexample Explanation by Learning Small Strategies in Markov Decision Processes.
We extended the probabilistic model checker PRISM to represent strategies of Markov Decision Processes as Decision Trees.
The archive contains a java executable version of the extended tool (prism_dectree.jar) together with a few examples of the PRISM benchmark library.
To execute the program, please have a look at the README.txt, which provides instructions and further information on the archive.
The archive contains scripts that (if run often enough) reproduces the data presented in the publication.},
  author       = {Fellner, Andreas},
  keywords     = {Markov Decision Process, Decision Tree, Probabilistic Verification, Counterexample Explanation},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Experimental part of CAV 2015 publication: Counterexample Explanation by Learning Small Strategies in Markov Decision Processes}},
  doi          = {10.15479/AT:ISTA:28},
  year         = {2015},
}

@article{5804,
  abstract     = {We present here the first integer-based algorithm for constructing a well-defined lattice sphere specified by integer radius and integer center. The algorithm evolves from a unique correspondence between the lattice points comprising the sphere and the distribution of sum of three square numbers in integer intervals. We characterize these intervals to derive a useful set of recurrences, which, in turn, aids in efficient computation. Each point of the lattice sphere is determined by resorting to only a few primitive operations in the integer domain. The symmetry of its quadraginta octants provides an added advantage by confining the computation to its prima quadraginta octant. Detailed theoretical analysis and experimental results have been furnished to demonstrate its simplicity and elegance.},
  author       = {Biswas, Ranita and Bhowmick, Partha},
  issn         = {0304-3975},
  journal      = {Theoretical Computer Science},
  number       = {4},
  pages        = {56--72},
  publisher    = {Elsevier},
  title        = {{From prima quadraginta octant to lattice sphere through primitive integer operations}},
  doi          = {10.1016/j.tcs.2015.11.018},
  volume       = {624},
  year         = {2015},
}

@article{5807,
  author       = {Biswas, Ranita and Bhowmick, Partha},
  issn         = {0304-3975},
  journal      = {Theoretical Computer Science},
  number       = {11},
  pages        = {146--163},
  publisher    = {Elsevier},
  title        = {{On different topological classes of spherical geodesic paths and circles inZ3}},
  doi          = {10.1016/j.tcs.2015.09.003},
  volume       = {605},
  year         = {2015},
}

@article{5808,
  author       = {Biswas, Ranita and Bhowmick, Partha},
  issn         = {0178-2789},
  journal      = {The Visual Computer},
  number       = {6-8},
  pages        = {787--797},
  publisher    = {Springer Nature},
  title        = {{Layer the sphere}},
  doi          = {10.1007/s00371-015-1101-3},
  volume       = {31},
  year         = {2015},
}

@article{594,
  abstract     = {Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.},
  author       = {Sainsbury, Sarah and Bernecky, Carrie A and Cramer, Patrick},
  issn         = {1471-0080},
  journal      = {Nature Reviews Molecular Cell Biology},
  number       = {3},
  pages        = {129 -- 143},
  publisher    = {Springer Nature},
  title        = {{Structural basis of transcription initiation by RNA polymerase II}},
  doi          = {10.1038/nrm3952},
  volume       = {16},
  year         = {2015},
}

@article{6118,
  abstract     = {Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.},
  author       = {Fenk, Lorenz A. and de Bono, Mario},
  issn         = {0027-8424},
  journal      = {Proceedings of the National Academy of Sciences},
  number       = {27},
  pages        = {E3525--E3534},
  publisher    = {National Academy of Sciences},
  title        = {{Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity}},
  doi          = {10.1073/pnas.1423808112},
  volume       = {112},
  year         = {2015},
}

@article{6120,
  abstract     = {Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.},
  author       = {Laurent, Patrick and Soltesz, Zoltan and Nelson, Geoffrey M and Chen, Changchun and Arellano-Carbajal, Fausto and Levy, Emmanuel and de Bono, Mario},
  issn         = {2050-084X},
  journal      = {eLife},
  publisher    = {eLife Sciences Publications},
  title        = {{Decoding a neural circuit controlling global animal state in C. elegans}},
  doi          = {10.7554/elife.04241},
  volume       = {4},
  year         = {2015},
}

@article{19805,
  abstract     = {Understanding the role of electron correlations in strong spin-orbit transition-metal oxides is key to the realization of numerous exotic phases including spin-orbit–assisted Mott insulators, correlated topological solids, and prospective new high-temperature superconductors. To date, most attention has been focused on the 5d iridium-based oxides. We instead consider the Pt-based delafossite oxide PtCoO2. Our transport measurements, performed on single-crystal samples etched to well-defined geometries using focused ion beam techniques, yield a room temperature resistivity of only 2.1 microhm·cm (μΩ-cm), establishing PtCoO2 as the most conductive oxide known. From angle-resolved photoemission and density functional theory, we show that the underlying Fermi surface is a single cylinder of nearly hexagonal cross-section, with very weak dispersion along kz. Despite being predominantly composed of d-orbital character, the conduction band is remarkably steep, with an average effective mass of only 1.14me. Moreover, the sharp spectral features observed in photoemission remain well defined with little additional broadening for more than 500 meV below EF, pointing to suppressed electron-electron scattering. Together, our findings establish PtCoO2 as a model nearly-free–electron system in a 5d delafossite transition-metal oxide.},
  author       = {Kushwaha, Pallavi and Sunko, Veronika and Moll, Philip J. W. and Bawden, Lewis and Riley, Jonathon M. and Nandi, Nabhanila and Rosner, Helge and Schmidt, Marcus P. and Arnold, Frank and Hassinger, Elena and Kim, Timur K. and Hoesch, Moritz and Mackenzie, Andrew P. and King, Phil D. C.},
  issn         = {2375-2548},
  journal      = {Science Advances},
  number       = {9},
  publisher    = {American Association for the Advancement of Science},
  title        = {{Nearly free electrons in a 5d delafossite oxide metal}},
  doi          = {10.1126/sciadv.1500692},
  volume       = {1},
  year         = {2015},
}

@article{1981,
  abstract     = {Variation in mitochondrial DNA is often assumed to be neutral and is used to construct the genealogical relationships among populations and species. However, if extant variation is the result of episodes of positive selection, these genealogies may be incorrect, although this information itself may pro-vide biologically and evolutionary meaningful information. In fact, positive Darwinian selection has been detected in the mitochondrial-encoded subunits that comprise complex I from diverse taxa with seemingly dissimilar bioenergetic life histories, but the functional implications of the selected sites are unknown. Complex I produces roughly 40% of the proton flux that is used to synthesize ATP from ADP, and a functional model based on the high-resolution structure of complex I described a unique biomechanical apparatus for proton translocation. We reported positive selection at sites in this apparatus during the evolution of Pacific salmon, and it appeared this was also the case in published reports from other taxa, but a comparison among studies was difficult because different statistical tests were used to detect selection and oftentimes, specific sites were not reported. Here we review the literature of positive selection in mitochondrial genomes, the statistical tests used to detect selection, and the structural and functional models that are currently available to study the physiological implications of selection. We then search for signatures of positive selection among the coding mitochondrial genomes of 237 species with a common set of tests and verify that the ND5 subunit of complex I is a repeated target of positive Darwinian selection in diverse taxa. We propose a novel hypothesis to explain the results based on their bioenergetic life histories and provide a guide for laboratory and field studies to test this hypothesis.},
  author       = {Garvin, Michael and Bielawski, Joseph and Sazanov, Leonid A and Gharrett, Anthony},
  journal      = {Journal of Zoological Systematics and Evolutionary Research},
  number       = {1},
  pages        = {1 -- 17},
  publisher    = {Wiley},
  title        = {{Review and meta-analysis of natural selection in mitochondrial complex I in metazoans}},
  doi          = {10.1111/jzs.12079},
  volume       = {53},
  year         = {2015},
}

@inproceedings{1992,
  abstract     = {We present a method and a tool for generating succinct representations of sets of concurrent traces. We focus on trace sets that contain all correct or all incorrect permutations of events from a given trace. We represent trace sets as HB-Formulas that are Boolean combinations of happens-before constraints between events. To generate a representation of incorrect interleavings, our method iteratively explores interleavings that violate the specification and gathers generalizations of the discovered interleavings into an HB-Formula; its complement yields a representation of correct interleavings.

We claim that our trace set representations can drive diverse verification, fault localization, repair, and synthesis techniques for concurrent programs. We demonstrate this by using our tool in three case studies involving synchronization synthesis, bug summarization, and abstraction refinement based verification. In each case study, our initial experimental results have been promising.

In the first case study, we present an algorithm for inferring missing synchronization from an HB-Formula representing correct interleavings of a given trace. The algorithm applies rules to rewrite specific patterns in the HB-Formula into locks, barriers, and wait-notify constructs. In the second case study, we use an HB-Formula representing incorrect interleavings for bug summarization. While the HB-Formula itself is a concise counterexample summary, we present additional inference rules to help identify specific concurrency bugs such as data races, define-use order violations, and two-stage access bugs. In the final case study, we present a novel predicate learning procedure that uses HB-Formulas representing abstract counterexamples to accelerate counterexample-guided abstraction refinement (CEGAR). In each iteration of the CEGAR loop, the procedure refines the abstraction to eliminate multiple spurious abstract counterexamples drawn from the HB-Formula.},
  author       = {Gupta, Ashutosh and Henzinger, Thomas A and Radhakrishna, Arjun and Samanta, Roopsha and Tarrach, Thorsten},
  isbn         = {978-1-4503-3300-9},
  location     = {Mumbai, India},
  pages        = {433 -- 444},
  publisher    = {ACM},
  title        = {{Succinct representation of concurrent trace sets}},
  doi          = {10.1145/2676726.2677008},
  year         = {2015},
}

@article{1993,
  abstract     = {The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens. },
  author       = {Konrad, Matthias and Grasse, Anna V and Tragust, Simon and Cremer, Sylvia},
  issn         = {1471-2954},
  journal      = {Proceedings of the Royal Society of London Series B Biological Sciences},
  number       = {1799},
  publisher    = {The Royal Society},
  title        = {{Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host}},
  doi          = {10.1098/rspb.2014.1976},
  volume       = {282},
  year         = {2015},
}

@article{1997,
  abstract     = {We prove that the three-state toric homogeneous Markov chain model has Markov degree two. In algebraic terminology this means, that a certain class of toric ideals is generated by quadratic binomials. This was conjectured by Haws, Martin del Campo, Takemura and Yoshida, who proved that they are generated by degree six binomials.},
  author       = {Noren, Patrik},
  journal      = {Journal of Symbolic Computation},
  number       = {May-June},
  pages        = {285 -- 296},
  publisher    = {Elsevier},
  title        = {{The three-state toric homogeneous Markov chain model has Markov degree two}},
  doi          = {10.1016/j.jsc.2014.09.014},
  volume       = {68/Part 2},
  year         = {2015},
}

@article{2006,
  abstract     = {The monotone secant conjecture posits a rich class of polynomial systems, all of whose solutions are real. These systems come from the Schubert calculus on flag manifolds, and the monotone secant conjecture is a compelling generalization of the Shapiro conjecture for Grassmannians (Theorem of Mukhin, Tarasov, and Varchenko). We present some theoretical evidence for this conjecture, as well as computational evidence obtained by 1.9 teraHertz-years of computing, and we discuss some of the phenomena we observed in our data. },
  author       = {Hein, Nicolas and Hillar, Christopher and Martin Del Campo Sanchez, Abraham and Sottile, Frank and Teitler, Zach},
  journal      = {Experimental Mathematics},
  number       = {3},
  pages        = {261 -- 269},
  publisher    = {Taylor & Francis},
  title        = {{The monotone secant conjecture in the real Schubert calculus}},
  doi          = {10.1080/10586458.2014.980044},
  volume       = {24},
  year         = {2015},
}

@article{2008,
  abstract     = {The paper describes a generalized iterative proportional fitting procedure that can be used for maximum likelihood estimation in a special class of the general log-linear model. The models in this class, called relational, apply to multivariate discrete sample spaces that do not necessarily have a Cartesian product structure and may not contain an overall effect. When applied to the cell probabilities, the models without the overall effect are curved exponential families and the values of the sufficient statistics are reproduced by the MLE only up to a constant of proportionality. The paper shows that Iterative Proportional Fitting, Generalized Iterative Scaling, and Improved Iterative Scaling fail to work for such models. The algorithm proposed here is based on iterated Bregman projections. As a by-product, estimates of the multiplicative parameters are also obtained. An implementation of the algorithm is available as an R-package.},
  author       = {Klimova, Anna and Rudas, Tamás},
  journal      = {Scandinavian Journal of Statistics},
  number       = {3},
  pages        = {832 -- 847},
  publisher    = {Wiley},
  title        = {{Iterative scaling in curved exponential families}},
  doi          = {10.1111/sjos.12139},
  volume       = {42},
  year         = {2015},
}

@article{2014,
  abstract     = {The concepts of faithfulness and strong-faithfulness are important for statistical learning of graphical models. Graphs are not sufficient for describing the association structure of a discrete distribution. Hypergraphs representing hierarchical log-linear models are considered instead, and the concept of parametric (strong-) faithfulness with respect to a hypergraph is introduced. Strong-faithfulness ensures the existence of uniformly consistent parameter estimators and enables building uniformly consistent procedures for a hypergraph search. The strength of association in a discrete distribution can be quantified with various measures, leading to different concepts of strong-faithfulness. Lower and upper bounds for the proportions of distributions that do not satisfy strong-faithfulness are computed for different parameterizations and measures of association.},
  author       = {Klimova, Anna and Uhler, Caroline and Rudas, Tamás},
  journal      = {Computational Statistics & Data Analysis},
  number       = {7},
  pages        = {57 -- 72},
  publisher    = {Elsevier},
  title        = {{Faithfulness and learning hypergraphs from discrete distributions}},
  doi          = {10.1016/j.csda.2015.01.017},
  volume       = {87},
  year         = {2015},
}

@article{2025,
  abstract     = {Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins.},
  author       = {Kawada, Daiki and Kobayashi, Hiromu and Tomita, Tsuyoshi and Nakata, Eisuke and Nagano, Makoto and Siekhaus, Daria E and Toshima, Junko and Toshimaa, Jiro},
  journal      = {Biochimica et Biophysica Acta - Molecular Cell Research},
  number       = {1},
  pages        = {144 -- 156},
  publisher    = {Elsevier},
  title        = {{The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins}},
  doi          = {10.1016/j.bbamcr.2014.10.009},
  volume       = {1853},
  year         = {2015},
}