@article{2443, abstract = {The mode of action of auxin is based on its non-uniform distribution within tissues and organs. Despite the wide use of several auxin analogues in research and agriculture, little is known about the specificity of different auxin-related transport and signalling processes towards these compounds. Using seedlings of Arabidopsis thaliana and suspension-cultured cells of Nicotiana tabacum (BY-2), the physiological activity of several auxin analogues was investigated, together with their capacity to induce auxin-dependent gene expression, to inhibit endocytosis and to be transported across the plasma membrane. This study shows that the specificity criteria for different auxin-related processes vary widely. Notably, the special behaviour of some synthetic auxin analogues suggests that they might be useful tools in investigations of the molecular mechanism of auxin action. Thus, due to their differential stimulatory effects on DR5 expression, indole-3-propionic (IPA) and 2,4,5-trichlorophenoxy acetic (2,4,5-T) acids can serve in studies of TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALLING F-BOX (TIR1/AFB)-mediated auxin signalling, and 5-fluoroindole-3-acetic acid (5-F-IAA) can help to discriminate between transcriptional and non-transcriptional pathways of auxin signalling. The results demonstrate that the major determinants for the auxin-like physiological potential of a particular compound are very complex and involve its chemical and metabolic stability, its ability to distribute in tissues in a polar manner and its activity towards auxin signalling machinery.}, author = {Simon, Sibu and Kubeš, Martin and Baster, Pawel and Robert, Stéphanie and Dobrev, Petre and Friml, Jirí and Petrášek, Jan and Zažímalová, Eva}, journal = {New Phytologist}, number = {4}, pages = {1034 -- 1048}, publisher = {Wiley}, title = {{Defining the selectivity of processes along the auxin response chain: A study using auxin analogues}}, doi = {10.1111/nph.12437}, volume = {200}, year = {2013}, } @inproceedings{2181, abstract = {There is a trade-off between performance and correctness in implementing concurrent data structures. Better performance may be achieved at the expense of relaxing correctness, by redefining the semantics of data structures. We address such a redefinition of data structure semantics and present a systematic and formal framework for obtaining new data structures by quantitatively relaxing existing ones. We view a data structure as a sequential specification S containing all "legal" sequences over an alphabet of method calls. Relaxing the data structure corresponds to defining a distance from any sequence over the alphabet to the sequential specification: the k-relaxed sequential specification contains all sequences over the alphabet within distance k from the original specification. In contrast to other existing work, our relaxations are semantic (distance in terms of data structure states). As an instantiation of our framework, we present two simple yet generic relaxation schemes, called out-of-order and stuttering relaxation, along with several ways of computing distances. We show that the out-of-order relaxation, when further instantiated to stacks, queues, and priority queues, amounts to tolerating bounded out-of-order behavior, which cannot be captured by a purely syntactic relaxation (distance in terms of sequence manipulation, e.g. edit distance). We give concurrent implementations of relaxed data structures and demonstrate that bounded relaxations provide the means for trading correctness for performance in a controlled way. The relaxations are monotonic which further highlights the trade-off: increasing k increases the number of permitted sequences, which as we demonstrate can lead to better performance. Finally, since a relaxed stack or queue also implements a pool, we actually have new concurrent pool implementations that outperform the state-of-the-art ones.}, author = {Henzinger, Thomas A and Kirsch, Christoph and Payer, Hannes and Sezgin, Ali and Sokolova, Ana}, booktitle = {Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language}, isbn = {978-1-4503-1832-7}, location = {Rome, Italy}, pages = {317 -- 328}, publisher = {ACM}, title = {{Quantitative relaxation of concurrent data structures}}, doi = {10.1145/2429069.2429109}, year = {2013}, } @inproceedings{1385, abstract = {It is often difficult to correctly implement a Boolean controller for a complex system, especially when concurrency is involved. Yet, it may be easy to formally specify a controller. For instance, for a pipelined processor it suffices to state that the visible behavior of the pipelined system should be identical to a non-pipelined reference system (Burch-Dill paradigm). We present a novel procedure to efficiently synthesize multiple Boolean control signals from a specification given as a quantified first-order formula (with a specific quantifier structure). Our approach uses uninterpreted functions to abstract details of the design. We construct an unsatisfiable SMT formula from the given specification. Then, from just one proof of unsatisfiability, we use a variant of Craig interpolation to compute multiple coordinated interpolants that implement the Boolean control signals. Our method avoids iterative learning and back-substitution of the control functions. We applied our approach to synthesize a controller for a simple two-stage pipelined processor, and present first experimental results.}, author = {Hofferek, Georg and Gupta, Ashutosh and Könighofer, Bettina and Jiang, Jie and Bloem, Roderick}, booktitle = {2013 Formal Methods in Computer-Aided Design}, location = {Portland, OR, United States}, pages = {77 -- 84}, publisher = {IEEE}, title = {{Synthesizing multiple boolean functions using interpolation on a single proof}}, doi = {10.1109/FMCAD.2013.6679394}, year = {2013}, } @article{11087, abstract = {Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell’s life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process.}, author = {Toyama, Brandon H. and Savas, Jeffrey N. and Park, Sung Kyu and Harris, Michael S. and Ingolia, Nicholas T. and Yates, John R. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {5}, pages = {971--982}, publisher = {Elsevier}, title = {{Identification of long-lived proteins reveals exceptional stability of essential cellular structures}}, doi = {10.1016/j.cell.2013.07.037}, volume = {154}, year = {2013}, } @inproceedings{2237, abstract = {We describe new extensions of the Vampire theorem prover for computing tree interpolants. These extensions generalize Craig interpolation in Vampire, and can also be used to derive sequence interpolants. We evaluated our implementation on a large number of examples over the theory of linear integer arithmetic and integer-indexed arrays, with and without quantifiers. When compared to other methods, our experiments show that some examples could only be solved by our implementation.}, author = {Blanc, Régis and Gupta, Ashutosh and Kovács, Laura and Kragl, Bernhard}, location = {Stellenbosch, South Africa}, pages = {173 -- 181}, publisher = {Springer}, title = {{Tree interpolation in Vampire}}, doi = {10.1007/978-3-642-45221-5_13}, volume = {8312}, year = {2013}, } @article{6130, abstract = {Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive immunity in prokaryotes. CRISPR–Cas9 has recently been used to generate insertion and deletion mutations in Caenorhabditis elegans, but not to create tailored changes (knock-ins). We show that the CRISPR–CRISPR-associated (Cas) system can be adapted for efficient and precise editing of the C. elegans genome. The targeted double-strand breaks generated by CRISPR are substrates for transgene-instructed gene conversion. This allows customized changes in the C. elegans genome by homologous recombination: sequences contained in the repair template (the transgene) are copied by gene conversion into the genome. The possibility to edit the C. elegans genome at selected locations will facilitate the systematic study of gene function in this widely used model organism.}, author = {Chen, Changchun and Fenk, Lorenz A. and de Bono, Mario}, issn = {1362-4962}, journal = {Nucleic Acids Research}, number = {20}, publisher = {Oxford University Press}, title = {{Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination}}, doi = {10.1093/nar/gkt805}, volume = {41}, year = {2013}, } @phdthesis{1406, abstract = {Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading.}, author = {Campinho, Pedro}, issn = {2663-337X}, pages = {123}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading}}, year = {2013}, } @article{2282, abstract = {Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.}, author = {Campinho, Pedro and Behrndt, Martin and Ranft, Jonas and Risler, Thomas and Minc, Nicolas and Heisenberg, Carl-Philipp J}, journal = {Nature Cell Biology}, pages = {1405 -- 1414}, publisher = {Nature Publishing Group}, title = {{Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly}}, doi = {10.1038/ncb2869}, volume = {15}, year = {2013}, } @article{2247, abstract = {Cooperative behavior, where one individual incurs a cost to help another, is a wide spread phenomenon. Here we study direct reciprocity in the context of the alternating Prisoner's Dilemma. We consider all strategies that can be implemented by one and two-state automata. We calculate the payoff matrix of all pairwise encounters in the presence of noise. We explore deterministic selection dynamics with and without mutation. Using different error rates and payoff values, we observe convergence to a small number of distinct equilibria. Two of them are uncooperative strict Nash equilibria representing always-defect (ALLD) and Grim. The third equilibrium is mixed and represents a cooperative alliance of several strategies, dominated by a strategy which we call Forgiver. Forgiver cooperates whenever the opponent has cooperated; it defects once when the opponent has defected, but subsequently Forgiver attempts to re-establish cooperation even if the opponent has defected again. Forgiver is not an evolutionarily stable strategy, but the alliance, which it rules, is asymptotically stable. For a wide range of parameter values the most commonly observed outcome is convergence to the mixed equilibrium, dominated by Forgiver. Our results show that although forgiving might incur a short-term loss it can lead to a long-term gain. Forgiveness facilitates stable cooperation in the presence of exploitation and noise.}, author = {Zagorsky, Benjamin and Reiter, Johannes and Chatterjee, Krishnendu and Nowak, Martin}, journal = {PLoS One}, number = {12}, publisher = {Public Library of Science}, title = {{Forgiver triumphs in alternating prisoner's dilemma }}, doi = {10.1371/journal.pone.0080814}, volume = {8}, year = {2013}, } @article{2858, abstract = {Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases.}, author = {Reiter, Johannes and Božić, Ivana and Allen, Benjamin and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Evolutionary Applications}, number = {1}, pages = {34 -- 45}, publisher = {Wiley-Blackwell}, title = {{The effect of one additional driver mutation on tumor progression}}, doi = {10.1111/eva.12020}, volume = {6}, year = {2013}, } @article{2816, abstract = {In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics.}, author = {Božić, Ivana and Reiter, Johannes and Allen, Benjamin and Antal, Tibor and Chatterjee, Krishnendu and Shah, Preya and Moon, Yo and Yaqubie, Amin and Kelly, Nicole and Le, Dung and Lipson, Evan and Chapman, Paul and Diaz, Luis and Vogelstein, Bert and Nowak, Martin}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Evolutionary dynamics of cancer in response to targeted combination therapy}}, doi = {10.7554/eLife.00747}, volume = {2}, year = {2013}, } @inproceedings{2000, abstract = {In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.}, author = {Reiter, Johannes and Božić, Ivana and Chatterjee, Krishnendu and Nowak, Martin}, booktitle = {Proceedings of 25th Int. Conf. on Computer Aided Verification}, location = {St. Petersburg, Russia}, pages = {101 -- 106}, publisher = {Springer}, title = {{TTP: Tool for tumor progression}}, doi = {10.1007/978-3-642-39799-8_6}, volume = {8044}, year = {2013}, } @article{22508, abstract = {High-resolution space-time stochastic models for precipitation are crucial for hydrological applications related to flood risk and water resources management. In this study, we present a new stochastic space-time model, STREAP, which is capable of reproducing essential features of the statistical structure of precipitation in space and time for a wide range of scales, and at the same time can be used for continuous simulation. The model is based on a three-stage hierarchical structure that mimics the precipitation formation process. The stages describe the storm arrival process, the temporal evolution of areal mean precipitation intensity and wet area, and the evolution in time of the two-dimensional storm structure. Each stage of the model is based on appropriate stochastic modeling techniques spanning from point processes, multivariate stochastic simulation and random fields. Details of the calibration and simulation procedures in each stage are provided so that they can be easily reproduced. STREAP is applied to a case study in Switzerland using 7 years of high-resolution (2 × 2 km2; 5 min) data from weather radars. The model is also compared with a popular parsimonious space-time stochastic model based on point processes (space-time Neyman-Scott) which it outperforms mainly because of a better description of spatial precipitation. The model validation and comparison is based on an extensive evaluation of both areal and point scale statistics at hydrologically relevant temporal scales, focusing mainly on the reproduction of the probability distributions of rainfall intensities, correlation structure, and the reproduction of intermittency and wet spell duration statistics. The results shows that a more accurate description of the space-time structure of precipitation fields in stochastic models such as STREAP does indeed lead to a better performance for properties and at scales which are not used in model calibration.}, author = {Paschalis, Athanasios and Molnar, Peter and Fatichi, Simone and Burlando, Paolo}, issn = {1944-7973}, journal = {Water Resources Research}, number = {12}, pages = {8400--8417}, publisher = {American Geophysical Union}, title = {{A stochastic model for high-resolution space-time precipitation simulation}}, doi = {10.1002/2013wr014437}, volume = {49}, year = {2013}, } @article{22552, abstract = {Dynamic vegetation models have been widely used for analyzing ecosystem dynamics and their interactions with climate. Their performance has been tested extensively against observations and by model intercomparison studies. In the present analysis, Lund-Potsdam-Jena General Ecosystem Simulator (LPJ-GUESS), a state-of-the-art ecosystem model, was evaluated by performing a global sensitivity analysis. The study aims at examining potential model limitations, particularly with regard to long-term applications. A detailed sensitivity analysis based on variance decomposition is presented to investigate structural model assumptions and to highlight processes and parameters that cause the highest variability in the output. First- and total-order sensitivity indices were calculated for selected parameters using Sobol's methodology. In order to elucidate the role of climate on model sensitivity, different climate forcings were used based on observations from Switzerland. The results clearly indicate a very high sensitivity of LPJ-GUESS to photosynthetic parameters. Intrinsic quantum efficiency alone is able to explain about 60% of the variability in vegetation carbon fluxes and pools for a wide range of climate forcings. Processes related to light harvesting were also found to be important together with parameters affecting forest structure (growth, establishment, and mortality). The model shows minor sensitivity to hydrological and soil texture parameters, questioning its skills in representing spatial vegetation heterogeneity at regional or watershed scales. In the light of these results, we discuss the deficiencies of LPJ-GUESS and possibly that of other, structurally similar, dynamic vegetation models and we highlight potential directions for further model improvements.}, author = {Pappas, Christoforos and Fatichi, Simone and Leuzinger, Sebastian and Wolf, Annett and Burlando, Paolo}, issn = {2169-8961}, journal = {Journal of Geophysical Research: Biogeosciences}, number = {2}, pages = {505--528}, publisher = {American Geophysical Union}, title = {{Sensitivity analysis of a process‐based ecosystem model: Pinpointing parameterization and structural issues}}, doi = {10.1002/jgrg.20035}, volume = {118}, year = {2013}, } @article{450, abstract = {Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F1, F2, F3) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations.}, author = {Pickup, Melinda and Field, David and Rowell, David and Young, Andrew}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1750}, publisher = {Royal Society}, title = {{Source population characteristics affect heterosis following genetic rescue of fragmented plant populations}}, doi = {10.1098/rspb.2012.2058}, volume = {280}, year = {2013}, } @article{22476, abstract = {Projections of the future carbon and water cycles rely on knowledge on how forests will respond to rising atmospheric CO2. Experiments with elevated CO2 are logistically challenging and carbon pools and fluxes are difficult to measure and upscale due to their spatiotemporal heterogeneity. Therefore, it is important to combine the knowledge derived from experimental results with modeling. Here, we systematically compare data from a free air CO2 enrichment (FACE) experiment in a mature deciduous forest in Switzerland with realizations from an ecohydrological model (Tethys–Chloris). We test whether a mechanistic ecohydrological model is able to simulate physiological plant responses under ambient and elevated CO2 concentration. We overcome measurement limitations by quantifying differences in response to ambient and elevated CO2 over ten years. The reliability of model realizations is demonstrated by comparing simulations with field observations of stomatal conductance, sap flow, leaf and fruit litter, and stem growth. The model successfully captures the observed CO2-induced difference in stomatal conductance and transpiration and its sensitivity to atmospheric demand, as well as qualitative changes in soil moisture. The simulated differences between CO2 scenarios generally fall within the uncertainty of experimental observations, both for the carbon and water balance. Simulated total evapotranspiration is 2.8% (18 mm yr−1) lower and soil moisture 1.2% higher in the CO2-enriched scenario. Latent and sensible heat are modified by ca. 1 W m−2. Net primary production is simulated to increase by 19.8% and allocation to stem growth is 53 gC yr−1 m−2 higher in the elevated CO2 scenario, which represents the limit of the detection threshold of the experiment. Results show that while ecohydrological models can be used to reliably simulate multi-year energy, water, and carbon fluxes at the stand level, testing carbon allocation remains critical with current accuracy of field measurements. Uncertainties due to the simplified carbon allocation scheme are shown to be more significant for carbon than for energy and water fluxes. Generally, we conclude that for this type of forest, differences in annual energy and water fluxes induced by elevated CO2 are likely to be less than 10%.}, author = {Fatichi, Simone and Leuzinger, Sebastian}, issn = {1873-2240}, journal = {Agricultural and Forest Meteorology}, keywords = {Ecohydrological modeling, Plant water relations, FACE experiments, Forest productivity, CO2 enrichment, Swiss Canopy Crane}, pages = {144--157}, publisher = {Elsevier}, title = {{Reconciling observations with modeling: The fate of water and carbon allocation in a mature deciduous forest exposed to elevated CO2}}, doi = {10.1016/j.agrformet.2013.02.005}, volume = {174-175}, year = {2013}, } @article{22475, abstract = {This study extends a stochastic downscaling methodology to generation of an ensemble of hourly time series of meteorological variables that express possible future climate conditions at a point-scale. The stochastic downscaling uses general circulation model (GCM) realizations and an hourly weather generator, the Advanced WEather GENerator (AWE-GEN). Marginal distributions of factors of change are computed for several climate statistics using a Bayesian methodology that can weight GCM realizations based on the model relative performance with respect to a historical climate and a degree of disagreement in projecting future conditions. A Monte Carlo technique is used to sample the factors of change from their respective marginal distributions. As a comparison with traditional approaches, factors of change are also estimated by averaging GCM realizations. With either approach, the derived factors of change are applied to the climate statistics inferred from historical observations to re-evaluate parameters of the weather generator. The re-parameterized generator yields hourly time series of meteorological variables that can be considered to be representative of future climate conditions. In this study, the time series are generated in an ensemble mode to fully reflect the uncertainty of GCM projections, climate stochasticity, as well as uncertainties of the downscaling procedure. Applications of the methodology in reproducing future climate conditions for the periods of 2000–2009, 2046–2065 and 2081–2100, using the period of 1962–1992 as the historical baseline are discussed for the location of Firenze (Italy). The inferences of the methodology for the period of 2000–2009 are tested against observations to assess reliability of the stochastic downscaling procedure in reproducing statistics of meteorological variables at different time scales.}, author = {Fatichi, Simone and Ivanov, V. Y. and Caporali, E.}, issn = {1432-0894}, journal = {Climate Dynamics}, keywords = {Stochastic downscaling, Weather generator, Uncertainty assessment, Firenze, Italy}, pages = {1841--1861}, publisher = {Springer Nature}, title = {{Assessment of a stochastic downscaling methodology in generating an ensemble of hourly future climate time series}}, doi = {10.1007/s00382-012-1627-2}, volume = {40}, year = {2013}, } @article{2811, abstract = {In pipe, channel, and boundary layer flows turbulence first occurs intermittently in space and time: at moderate Reynolds numbers domains of disordered turbulent motion are separated by quiescent laminar regions. Based on direct numerical simulations of pipe flow we argue here that the spatial intermittency has its origin in a nearest neighbor interaction between turbulent regions. We further show that in this regime turbulent flows are intrinsically intermittent with a well-defined equilibrium turbulent fraction but without ever assuming a steady pattern. This transition scenario is analogous to that found in simple models such as coupled map lattices. The scaling observed implies that laminar intermissions of the turbulent flow will persist to arbitrarily large Reynolds numbers.}, author = {Avila, Marc and Hof, Björn}, journal = {Physical Review E}, number = {6}, publisher = {American Physical Society}, title = {{Nature of laminar-turbulence intermittency in shear flows}}, doi = {10.1103/PhysRevE.87.063012}, volume = {87}, year = {2013}, } @inbook{10896, abstract = {Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals D-ribose and adenine, and the functional, and potential therapeutic, implications of doing so.}, author = {zur Nedden, Stephanie and Doney, Alexander S. and Frenguelli, Bruno G.}, booktitle = {Adenosine}, editor = {Masino, Susan and Boison, Detlev}, isbn = {9781461439028}, pages = {109--129}, publisher = {Springer}, title = {{The double-edged sword: Gaining Adenosine at the expense of ATP. How to balance the books}}, doi = {10.1007/978-1-4614-3903-5_6}, year = {2012}, } @inproceedings{10903, abstract = {We propose a logic-based framework for automated reasoning about sequential programs manipulating singly-linked lists and arrays with unbounded data. We introduce the logic SLAD, which allows combining shape constraints, written in a fragment of Separation Logic, with data and size constraints. We address the problem of checking the entailment between SLAD formulas, which is crucial in performing pre-post condition reasoning. Although this problem is undecidable in general for SLAD, we propose a sound and powerful procedure that is able to solve this problem for a large class of formulas, beyond the capabilities of existing techniques and tools. We prove that this procedure is complete, i.e., it is actually a decision procedure for this problem, for an important fragment of SLAD including known decidable logics. We implemented this procedure and shown its preciseness and its efficiency on a significant benchmark of formulas.}, author = {Bouajjani, Ahmed and Dragoi, Cezara and Enea, Constantin and Sighireanu, Mihaela}, booktitle = {Automated Technology for Verification and Analysis}, isbn = {9783642333859}, issn = {1611-3349}, location = {Thiruvananthapuram, India}, pages = {167--182}, publisher = {Springer}, title = {{Accurate invariant checking for programs manipulating lists and arrays with infinite data}}, doi = {10.1007/978-3-642-33386-6_14}, volume = {7561}, year = {2012}, }