@phdthesis{1405, abstract = {Motivated by the analysis of highly dynamic message-passing systems, i.e. unbounded thread creation, mobility, etc. we present a framework for the analysis of depth-bounded systems. Depth-bounded systems are one of the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. Even though they are infinite state systems depth-bounded systems are well-structured, thus can be analyzed algorithmically. We give an interpretation of depth-bounded systems as graph-rewriting systems. This gives more flexibility and ease of use to apply depth-bounded systems to other type of systems like shared memory concurrency. First, we develop an adequate domain of limits for depth-bounded systems, a prerequisite for the effective representation of downward-closed sets. Downward-closed sets are needed by forward saturation-based algorithms to represent potentially infinite sets of states. Then, we present an abstract interpretation framework to compute the covering set of well-structured transition systems. Because, in general, the covering set is not computable, our abstraction over-approximates the actual covering set. Our abstraction captures the essence of acceleration based-algorithms while giving up enough precision to ensure convergence. We have implemented the analysis in the PICASSO tool and show that it is accurate in practice. Finally, we build some further analyses like termination using the covering set as starting point.}, author = {Zufferey, Damien}, issn = {2663-337X}, pages = {134}, publisher = {Institute of Science and Technology Austria}, title = {{Analysis of dynamic message passing programs}}, doi = {10.15479/at:ista:1405}, year = {2013}, } @inproceedings{2847, abstract = {Depth-Bounded Systems form an expressive class of well-structured transition systems. They can model a wide range of concurrent infinite-state systems including those with dynamic thread creation, dynamically changing communication topology, and complex shared heap structures. We present the first method to automatically prove fair termination of depth-bounded systems. Our method uses a numerical abstraction of the system, which we obtain by systematically augmenting an over-approximation of the system’s reachable states with a finite set of counters. This numerical abstraction can be analyzed with existing termination provers. What makes our approach unique is the way in which it exploits the well-structuredness of the analyzed system. We have implemented our work in a prototype tool and used it to automatically prove liveness properties of complex concurrent systems, including nonblocking algorithms such as Treiber’s stack and several distributed processes. Many of these examples are beyond the scope of termination analyses that are based on traditional counter abstractions.}, author = {Bansal, Kshitij and Koskinen, Eric and Wies, Thomas and Zufferey, Damien}, editor = {Piterman, Nir and Smolka, Scott}, location = {Rome, Italy}, pages = {62 -- 77}, publisher = {Springer}, title = {{Structural Counter Abstraction}}, doi = {10.1007/978-3-642-36742-7_5}, volume = {7795}, 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{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}, } @inproceedings{2445, abstract = {We develop program synthesis techniques that can help programmers fix concurrency-related bugs. We make two new contributions to synthesis for concurrency, the first improving the efficiency of the synthesized code, and the second improving the efficiency of the synthesis procedure itself. The first contribution is to have the synthesis procedure explore a variety of (sequential) semantics-preserving program transformations. Classically, only one such transformation has been considered, namely, the insertion of synchronization primitives (such as locks). Based on common manual bug-fixing techniques used by Linux device-driver developers, we explore additional, more efficient transformations, such as the reordering of independent instructions. The second contribution is to speed up the counterexample-guided removal of concurrency bugs within the synthesis procedure by considering partial-order traces (instead of linear traces) as counterexamples. A partial-order error trace represents a set of linear (interleaved) traces of a concurrent program all of which lead to the same error. By eliminating a partial-order error trace, we eliminate in a single iteration of the synthesis procedure all linearizations of the partial-order trace. We evaluated our techniques on several simplified examples of real concurrency bugs that occurred in Linux device drivers.}, author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun and Ryzhyk, Leonid and Tarrach, Thorsten}, location = {St. Petersburg, Russia}, pages = {951 -- 967}, publisher = {Springer}, title = {{Efficient synthesis for concurrency by semantics-preserving transformations}}, doi = {10.1007/978-3-642-39799-8_68}, volume = {8044}, year = {2013}, } @article{2926, abstract = {To fight infectious diseases, host immune defenses are employed at multiple levels. Sanitary behavior, such as pathogen avoidance and removal, acts as a first line of defense to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care toward pathogen-exposed group members [2]. One of the most common behaviors is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores; it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behavior extends the current understanding of grooming and the establishment of social immunity in insect societies.}, author = {Tragust, Simon and Mitteregger, Barbara and Barone, Vanessa and Konrad, Matthias and Ugelvig, Line V and Cremer, Sylvia}, journal = {Current Biology}, number = {1}, pages = {76 -- 82}, publisher = {Cell Press}, title = {{Ants disinfect fungus-exposed brood by oral uptake and spread of their poison}}, doi = {10.1016/j.cub.2012.11.034}, volume = {23}, year = {2013}, } @inproceedings{2305, abstract = {We study the complexity of central controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize both the expected mean-payoff performance of the system and its stability. e argue that the basic theoretical notion of expressing the stability in terms of the variance of the mean-payoff (called global variance in our paper) is not always sufficient, since it ignores possible instabilities on respective runs. For this reason we propose alernative definitions of stability, which we call local and hybrid variance, and which express how rewards on each run deviate from the run's own mean-payoff and from the expected mean-payoff, respectively. We show that a strategy ensuring both the expected mean-payoff and the variance below given bounds requires randomization and memory, under all the above semantics of variance. We then look at the problem of determining whether there is a such a strategy. For the global variance, we show that the problem is in PSPACE, and that the answer can be approximated in pseudo-polynomial time. For the hybrid variance, the analogous decision problem is in NP, and a polynomial-time approximating algorithm also exists. For local variance, we show that the decision problem is in NP. Since the overall performance can be traded for stability (and vice versa), we also present algorithms for approximating the associated Pareto curve in all the three cases. Finally, we study a special case of the decision problems, where we require a given expected mean-payoff together with zero variance. Here we show that the problems can be all solved in polynomial time.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Forejt, Vojtěch and Kučera, Antonín}, booktitle = {28th Annual ACM/IEEE Symposium}, location = {New Orleans, LA, United States}, pages = {331 -- 340}, publisher = {IEEE}, title = {{Trading performance for stability in Markov decision processes}}, doi = {10.1109/LICS.2013.39}, year = {2013}, } @inproceedings{2820, abstract = {In this paper, we introduce the powerful framework of graph games for the analysis of real-time scheduling with firm deadlines. We introduce a novel instance of a partial-observation game that is suitable for this purpose, and prove decidability of all the involved decision problems. We derive a graph game that allows the automated computation of the competitive ratio (along with an optimal witness algorithm for the competitive ratio) and establish an NP-completeness proof for the graph game problem. For a given on-line algorithm, we present polynomial time solution for computing (i) the worst-case utility; (ii) the worst-case utility ratio w.r.t. a clairvoyant off-line algorithm; and (iii) the competitive ratio. A major strength of the proposed approach lies in its flexibility w.r.t. incorporating additional constraints on the adversary and/or the algorithm, including limited maximum or average load, finiteness of periods of overload, etc., which are easily added by means of additional instances of standard objective functions for graph games. }, author = {Chatterjee, Krishnendu and Kößler, Alexander and Schmid, Ulrich}, booktitle = {Proceedings of the 16th International conference on Hybrid systems: Computation and control}, isbn = {978-1-4503-1567-8 }, location = {Philadelphia, PA, United States}, pages = {163 -- 172}, publisher = {ACM}, title = {{Automated analysis of real-time scheduling using graph games}}, doi = {10.1145/2461328.2461356}, year = {2013}, } @inproceedings{2272, abstract = {We consider Conditional Random Fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) x1...xn is the sum of terms over intervals [i,j] where each term is non-zero only if the substring xi...xj equals a prespecified pattern α. Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively O(nL), O(nLℓmax) and O(nLmin{|D|,log(ℓmax+1)}) where L is the combined length of input patterns, ℓmax is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of (Ye et al., 2009) whose complexities are respectively O(nL|D|), O(n|Γ|L2ℓ2max) and O(nL|D|), where |Γ| is the number of input patterns. In addition, we give an efficient algorithm for sampling. Finally, we consider the case of non-positive weights. (Komodakis & Paragios, 2009) gave an O(nL) algorithm for computing the MAP. We present a modification that has the same worst-case complexity but can beat it in the best case. }, author = {Takhanov, Rustem and Kolmogorov, Vladimir}, booktitle = {ICML'13 Proceedings of the 30th International Conference on International}, location = {Atlanta, GA, USA}, number = {3}, pages = {145 -- 153}, publisher = {ML Research Press}, title = {{Inference algorithms for pattern-based CRFs on sequence data}}, volume = {28}, year = {2013}, } @article{2448, abstract = {Cell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN2 carrier in epidermal root tip cells under conditions normally triggering PIN2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots.}, author = {Remy, Estelle and Baster, Pawel and Friml, Jirí and Duque, Paula}, journal = {Plant Signaling & Behavior}, number = {10}, publisher = {Taylor & Francis}, title = {{ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs in Arabidopsis root tip}}, doi = {10.4161/psb.25688}, volume = {8}, year = {2013}, } @article{2853, abstract = {High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.}, author = {Refardt, Dominik and Bergmiller, Tobias and Kümmerli, Rolf}, issn = {1471-2954}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1759}, publisher = {The Royal Society}, title = {{Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection}}, doi = {10.1098/rspb.2012.3035}, volume = {280}, year = {2013}, } @misc{9751, abstract = {High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared to its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.}, author = {Refardt, Dominik and Bergmiller, Tobias and Kümmerli, Rolf}, publisher = {Dryad}, title = {{Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection}}, doi = {10.5061/dryad.b1q2n}, year = {2013}, } @article{7785, abstract = {Neural circuit assembly requires selection of specific cell fates, axonal trajectories, and synaptic targets. By analyzing the function of a secreted semaphorin, Sema-2b, in Drosophila olfactory receptor neuron (ORN) development, we identified multiple molecular and cellular mechanisms that link these events. Notch signaling limits Sema-2b expression to ventromedial ORN classes, within which Sema-2b cell-autonomously sensitizes ORN axons to external semaphorins. Central-brain-derived Sema-2a and Sema-2b attract Sema-2b-expressing axons to the ventromedial trajectory. In addition, Sema-2b/PlexB-mediated axon-axon interactions consolidate this trajectory choice and promote ventromedial axon-bundle formation. Selecting the correct developmental trajectory is ultimately essential for proper target choice. These findings demonstrate that Sema-2b couples ORN axon guidance to postsynaptic target neuron dendrite patterning well before the final target selection phase, and exemplify how a single guidance molecule can drive consecutive stages of neural circuit assembly with the help of sophisticated spatial and temporal regulation.}, author = {Joo, William J. and Sweeney, Lora Beatrice Jaeger and Liang, Liang and Luo, Liqun}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {673--686}, publisher = {Elsevier}, title = {{Linking cell fate, trajectory choice, and target selection: Genetic analysis of sema-2b in olfactory axon targeting}}, doi = {10.1016/j.neuron.2013.03.022}, volume = {78}, year = {2013}, } @techreport{2274, abstract = {Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto'92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system. In this work, we put forward an alternative concept for PoWs -- so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model, using graphs with high "pebbling complexity" and Merkle hash-trees. }, author = {Dziembowski, Stefan and Faust, Sebastian and Kolmogorov, Vladimir and Pietrzak, Krzysztof Z}, publisher = {IST Austria}, title = {{Proofs of Space}}, year = {2013}, } @article{15162, abstract = {Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP to evaluate a library of nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide range of biological pathways. We developed informatics techniques for generating dosage-independent phenotypic “fingerprints” for each compound, and for quantifying the likelihood that a compound's CP fingerprint corresponds to its annotated MOA. We identified groups of features that distinguish classes with closely related phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis vs. proteasome inhibitors. We tested several cases in which cytological profiles indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma ligand that acts as a proteasome inhibitor, using independent biochemical assays to confirm the MOAs predicted by the CP signatures. We also applied maximal-information statistics to identify correlations between cytological features and kinase inhibitory activities by combining the CP fingerprints of 24 kinase inhibitors with published data on their specificities against a diverse panel of kinases. The resulting analysis suggests a strategy for probing the biological functions of specific kinases by compiling cytological data from inhibitors of varying specificities.}, author = {Woehrmann, Marcos H. and Bray, Walter M. and Durbin, James K. and Nisam, Sean C. and Michael, Alicia Kathleen and Glassey, Emerson and Stuart, Joshua M. and Lokey, R. Scott}, issn = {1742-2051}, journal = {Molecular BioSystems}, keywords = {Molecular Biology, Biotechnology}, number = {11}, publisher = {Royal Society of Chemistry}, title = {{Large-scale cytological profiling for functional analysis of bioactive compounds}}, doi = {10.1039/c3mb70245f}, volume = {9}, year = {2013}, } @article{10387, abstract = {We report numerical simulations of membrane tubulation driven by large colloidal particles. Using Monte Carlo simulations we study how the process depends on particle size and binding strength, and present accurate free energy calculations to sort out how tube formation compares with the competing budding process. We find that tube formation is a result of the collective behavior of the particles adhering on the surface, and it occurs for binding strengths that are smaller than those required for budding. We also find that long linear aggregates of particles forming on the membrane surface act as nucleation seeds for tubulation by lowering the free energy barrier associated to the process.}, author = {Šarić, Anđela and Cacciuto, Angelo}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {18}, publisher = {American Physical Society}, title = {{Mechanism of membrane tube formation induced by adhesive nanocomponents}}, doi = {10.1103/physrevlett.109.188101}, volume = {109}, year = {2012}, } @article{10388, abstract = {Using computer simulations, we show that lipid membranes can mediate linear aggregation of spherical nanoparticles binding to it for a wide range of biologically relevant bending rigidities. This result is in net contrast with the isotropic aggregation of nanoparticles on fluid interfaces or the expected clustering of isotropic insertions in biological membranes. We present a phase diagram indicating where linear aggregation is expected and compute explicitly the free-energy barriers associated with linear and isotropic aggregation. Finally, we provide simple scaling arguments to explain this phenomenology.}, author = {Šarić, Anđela and Cacciuto, Angelo}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {11}, publisher = {American Physical Society}, title = {{Fluid membranes can drive linear aggregation of adsorbed spherical nanoparticles}}, doi = {10.1103/physrevlett.108.118101}, volume = {108}, year = {2012}, } @article{1055, abstract = {In July, 2011, a 32-year-old man presented with thoracic pain radiating to the left arm and upper dorsum, shortness of breath, and palpitations. He had had upper back tension for 6 months. Medical history was unremarkable apart from moderate nicotine use (two pack-years). Echocardiography, electrocardiography, and laboratory tests were unremarkable, excluding a cardiac event. CT of the chest after chest radiography showed a large bulla of 16 cm diameter in the right hemithorax (figure A). We did not detect radiological evidence of underlying pulmonary disease. The bulla wall was unremarkable and no structures were seen within the bulla.}, author = {Erne, Barbara and Graff, Mareike and Klemm, Wolfram and Danzl, Johann G and Leschber, Gunda}, journal = {The Lancet}, number = {9849}, publisher = {Elsevier}, title = {{Bulla in the lung}}, doi = {10.1016/S0140-6736(12)60690-4}, volume = {380}, year = {2012}, } @article{1056, abstract = {We prepare and study a metastable attractive Mott-insulator state formed with bosonic atoms in a three-dimensional optical lattice. Starting from a Mott insulator with Cs atoms at weak repulsive interactions, we use a magnetic Feshbach resonance to tune the interactions to large attractive values and produce a metastable state pinned by attractive interactions with a lifetime on the order of 10 s. We probe the (de)excitation spectrum via lattice modulation spectroscopy, measuring the interaction dependence of two- and three-body bound-state energies. As a result of increased on-site three-body loss we observe resonance broadening and suppression of tunneling processes that produce three-body occupation.}, author = {Mark, Manfred and Haller, Elmar and Lauber, Katharina and Danzl, Johann G and Janisch, Alexander and Büchler, Hans and Daley, Andrew and Nägerl, Hanns}, journal = {Physical Review Letters}, number = {21}, publisher = {American Physical Society}, title = {{Preparation and spectroscopy of a metastable mott-insulator state with attractive interactions}}, doi = {10.1103/PhysRevLett.108.215302}, volume = {108}, year = {2012}, } @inproceedings{10750, abstract = {The goal of this work is to study the superconducting coherence length in the fluctuation regime in cuprate superconductors. In this work we present cantilever torque magnetometry measurements of micron-size BSCCO flakes patterned with arrays of nanometer scale rings or holes. Using ultrasensitive dynamic torque magnetometry, oscillations in magnetization are observed near Tc as a function of the applied magnetic flux threading the array. Special effort was made to detect the oscillations in magnetization at temperatures above Tc, where the Nernst effect and magnetization measurements suggest the possibility of pairing. To constrain the magnitude of the coherence length in the fluctuation regime, we will present the dependence of the amplitude of the h/2e period oscillations as a function of temperature and hole size.}, author = {Polshyn, Hryhoriy and Budakian, Raffi}, booktitle = {APS March Meeting 2012}, issn = {0003-0503}, location = {Boston, MA, United States}, number = {1}, publisher = {American Physical Society}, title = {{Cantilever torque magnetometry study of multiply connected BSCCO arrays near Tc}}, volume = {57}, year = {2012}, } @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}, } @article{11089, abstract = {The Nuclear Envelope (NE) contains over 100 different proteins that associate with nuclear components such as chromatin, the lamina and the transcription machinery. Mutations in genes encoding NE proteins have been shown to result in tissue-specific defects and disease, suggesting cell-type specific differences in NE composition and function. Consistent with these observations, recent studies have revealed unexpected functions for numerous NE associated proteins during cell differentiation and development. Here we review the latest insights into the roles played by the NE in cell differentiation, development, disease and aging, focusing primarily on inner nuclear membrane (INM) proteins and nuclear pore components.}, author = {Gomez-Cavazos, J Sebastian and HETZER, Martin W}, issn = {0955-0674}, journal = {Current Opinion in Cell Biology}, keywords = {Cell Biology}, number = {6}, pages = {775--783}, publisher = {Elsevier}, title = {{Outfits for different occasions: tissue-specific roles of Nuclear Envelope proteins}}, doi = {10.1016/j.ceb.2012.08.008}, volume = {24}, year = {2012}, } @article{11091, abstract = {Neoplastic cells are often characterized by specific morphological abnormalities of the nuclear envelope (NE), which have been used for cancer diagnosis for more than a century. The NE is a double phospholipid bilayer that encapsulates the nuclear genome, regulates all nuclear trafficking of RNAs and proteins and prevents the passive diffusion of macromolecules between the nucleoplasm and the cytoplasm. Whether there is a consequence to the proper functioning of the cell and loss of structural integrity of the nucleus remains unclear. Using live cell imaging, we characterize a phenomenon wherein nuclei of several proliferating human cancer cell lines become temporarily ruptured during interphase. Strikingly, NE rupturing was associated with the mislocalization of nucleoplasmic and cytoplasmic proteins and, in the most extreme cases, the entrapment of cytoplasmic organelles in the nuclear interior. In addition, we observed the formation of micronuclei-like structures during interphase and the movement of chromatin out of the nuclear space. The frequency of these NE rupturing events was higher in cells in which the nuclear lamina, a network of intermediate filaments providing mechanical support to the NE, was not properly formed. Our data uncover the existence of a NE instability that has the potential to change the genomic landscape of cancer cells.}, author = {Vargas, Jesse D. and Hatch, Emily M. and Anderson, Daniel J. and HETZER, Martin W}, issn = {1949-1042}, journal = {Nucleus}, keywords = {Cell Biology}, number = {1}, pages = {88--100}, publisher = {Taylor & Francis}, title = {{Transient nuclear envelope rupturing during interphase in human cancer cells}}, doi = {10.4161/nucl.18954}, volume = {3}, year = {2012}, } @article{11093, abstract = {Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem cells (ESCs) but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ESCs into neuroprogenitors. We found that the addition of Nup210 to NPCs does not affect nuclear transport but is required for the induction of genes that are essential for cell differentiation. Our results identify a single change in NPC composition as an essential step in cell differentiation and establish a role for Nup210 in gene expression regulation and cell fate determination.}, author = {D'Angelo, Maximiliano A. and Gomez-Cavazos, J. Sebastian and Mei, Arianna and Lackner, Daniel H. and HETZER, Martin W}, issn = {1534-5807}, journal = {Developmental Cell}, keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology}, number = {2}, pages = {446--458}, publisher = {Elsevier}, title = {{A change in nuclear pore complex composition regulates cell differentiation}}, doi = {10.1016/j.devcel.2011.11.021}, volume = {22}, year = {2012}, } @article{11092, abstract = {To combat the functional decline of the proteome, cells use the process of protein turnover to replace potentially impaired polypeptides with new functional copies. We found that extremely long-lived proteins (ELLPs) did not turn over in postmitotic cells of the rat central nervous system. These ELLPs were associated with chromatin and the nuclear pore complex, the central transport channels that mediate all molecular trafficking in and out of the nucleus. The longevity of these proteins would be expected to expose them to potentially harmful metabolites, putting them at risk of accumulating damage over extended periods of time. Thus, it is possible that failure to maintain proper levels and functional integrity of ELLPs in nonproliferative cells might contribute to age-related deterioration in cell and tissue function.}, author = {Savas, Jeffrey N. and Toyama, Brandon H. and Xu, Tao and Yates, John R. and HETZER, Martin W}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6071}, pages = {942--942}, publisher = {American Association for the Advancement of Science}, title = {{Extremely long-lived nuclear pore proteins in the rat brain}}, doi = {10.1126/science.1217421}, volume = {335}, year = {2012}, } @article{11090, abstract = {Nuclear export of mRNAs is thought to occur exclusively through nuclear pore complexes. In this issue of Cell, Speese et al. identify an alternate pathway for mRNA export in muscle cells where ribonucleoprotein complexes involved in forming neuromuscular junctions transit the nuclear envelope by fusing with and budding through the nuclear membrane.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {4}, pages = {733--735}, publisher = {Elsevier}, title = {{RNP export by nuclear envelope budding}}, doi = {10.1016/j.cell.2012.04.018}, volume = {149}, year = {2012}, } @article{113, abstract = {Although liquids typically flow around intruding objects, a counterintuitive phenomenon occurs in dense suspensions of micrometre-sized particles: they become liquid-like when perturbed lightly, but harden when driven strongly. Rheological experiments have investigated how such thickening arises under shear, and linked it to hydrodynamic interactions or granular dilation. However, neither of these mechanisms alone can explain the ability of suspensions to generate very large, positive normal stresses under impact. To illustrate the phenomenon, such stresses can be large enough to allow a person to run across a suspension without sinking, and far exceed the upper limit observed under shear or extension. Here we show that these stresses originate from an impact-generated solidification front that transforms an initially compressible particle matrix into a rapidly growing jammed region, ultimately leading to extraordinary amounts of momentum absorption. Using high-speed videography, embedded force sensing and X-ray imaging, we capture the detailed dynamics of this process as it decelerates a metal rod hitting a suspension of cornflour (cornstarch) in water. We develop a model for the dynamic solidification and its effect on the surrounding suspension that reproduces the observed behaviour quantitatively. Our findings suggest that prior interpretations of the impact resistance as dominated by shear thickening need to be revisited.}, author = {Waitukaitis, Scott R and Jaeger, Heinrich}, journal = {Nature}, number = {7406}, pages = {205 -- 209}, publisher = {Nature Publishing Group}, title = {{Impact-activated solidification of dense suspensions via dynamic jamming fronts}}, doi = {10.1038/nature11187}, volume = {487}, year = {2012}, } @article{114, abstract = {We report on an investigation of the solidification of a cornstarch and water suspension during normal impact on its surface. We find that a finite time after impact, the suspension displays characteristics reminiscent of a solid, including localized stress transmission, the development of a yield stress, and some elastic energy storage. The time dependence of these characteristics depends on the thickness of the cornstarch layer, showing that the solidification is a dynamic process driven by the impacting object. These findings confirm previous speculations that rapidly applied normal stress transforms the normally fluid-like suspension into a temporarily jammed solid and draw a clear distinction between the effects of normal stress and shear stress in dense suspensions.}, author = {Waitukaitis, Scott R and Jaeger, Heinrich}, journal = {Revista Cubana de Fisica}, number = {1E}, pages = {1E31 -- 1E33}, publisher = {Universidad de La Habana}, title = {{Solidification of a cornstarch and water suspension}}, volume = {29}, year = {2012}, } @inproceedings{11656, abstract = {Suppose your sole interest in recommending a product to me is to maximize the amount paid to you by the seller for a sequence of recommendations. How should you recommend optimally if I become more inclined to ignore you with each irrelevant recommendation you make? Finding an answer to this question is a key challenge in all forms of marketing that rely on and explore social ties; ranging from personal recommendations to viral marketing. We prove that even if the recommendee regains her initial trust on each successful recommendation, the expected revenue the recommender can make over an infinite period due to payments by the seller is bounded. This can only be overcome when the recommendee also incrementally regains trust during periods without any recommendation. Here, we see a connection to "banner blindness," suggesting that showing fewer ads can lead to a higher long-term revenue.}, author = {Dütting, Paul and Henzinger, Monika H and Weber, Ingmar}, booktitle = {Proceedings of the 21st ACM international conference on Information and knowledge management}, isbn = {9781450311564}, location = {Maui, HI, United States}, pages = {2268--2286}, publisher = {Association for Computing Machinery}, title = {{Maximizing revenue from strategic recommendations under decaying trust}}, doi = {10.1145/2396761.2398621}, year = {2012}, } @article{11751, abstract = {The Seebeck coefficients, electrical resistivities, total thermal conductivities, and magnetization are reported for temperatures between 5 and 350 K for n-type Bi0.88Sb0.12 nano-composite alloys made by Ho-doping at the 0, 1, and 3 % atomic levels. The alloys were prepared using a dc hot-pressing method, and are shown to be single phase for both Ho contents with grain sizes on the average of 900 nm. We find the parent compound has a maximum of ZT = 0.28 at 231 K, while doping 1 % Ho increases the maximum ZT to 0.31 at 221 K and the 3 % doped sample suppresses the maximum ZT = 0.24 at a temperature of 260 K.}, author = {Lukas, K. C. and Joshi, G. and Modic, Kimberly A and Ren, Z. F. and Opeil, C. P.}, issn = {1573-4803}, journal = {Journal of Materials Science}, number = {15}, pages = {5729--5734}, publisher = {Springer Nature}, title = {{Thermoelectric properties of Ho-doped Bi0.88Sb0.12}}, doi = {10.1007/s10853-012-6463-6}, volume = {47}, year = {2012}, } @inproceedings{11794, abstract = {We study individual rational, Pareto optimal, and incentive compatible mechanisms for auctions with heterogeneous items and budget limits. For multi-dimensional valuations we show that there can be no deterministic mechanism with these properties for divisible items. We use this to show that there can also be no randomized mechanism that achieves this for either divisible or indivisible items. For single-dimensional valuations we show that there can be no deterministic mechanism with these properties for indivisible items, but that there is a randomized mechanism that achieves this for either divisible or indivisible items. The impossibility results hold for public budgets, while the mechanism allows private budgets, which is in both cases the harder variant to show. While all positive results are polynomial-time algorithms, all negative results hold independent of complexity considerations.}, author = {Dütting, Paul and Henzinger, Monika H and Starnberger, Martin}, booktitle = {8th International Workshop on Internet and Network Economics}, isbn = {9783642353109}, issn = {1611-3349}, location = {Liverpool, United Kingdom}, pages = {44–57}, publisher = {Springer Nature}, title = {{Auctions with heterogeneous items and budget limits}}, doi = {10.1007/978-3-642-35311-6_4}, volume = {7695}, year = {2012}, } @inproceedings{11795, abstract = {We study multiple keyword sponsored search auctions with budgets. Each keyword has multiple ad slots with a click-through rate. The bidders have additive valuations, which are linear in the click-through rates, and budgets, which are restricting their overall payments. Additionally, the number of slots per keyword assigned to a bidder is bounded. We show the following results: (1) We give the first mechanism for multiple keywords, where click-through rates differ among slots. Our mechanism is incentive compatible in expectation, individually rational in expectation, and Pareto optimal. (2) We study the combinatorial setting, where each bidder is only interested in a subset of the keywords. We give an incentive compatible, individually rational, Pareto optimal, and deterministic mechanism for identical click-through rates. (3) We give an impossibility result for incentive compatible, individually rational, Pareto optimal, and deterministic mechanisms for bidders with diminishing marginal valuations.}, author = {Colini-Baldeschi, Riccardo and Henzinger, Monika H and Leonardi, Stefano and Starnberger, Martin}, booktitle = {39th International Colloquium on Automata, Languages, and Programming}, isbn = {9783642315848}, issn = {0302-9743}, location = {Warwick, United Kingdom}, pages = {1–12}, publisher = {Springer Nature}, title = {{On multiple keyword sponsored search auctions with budgets}}, doi = {10.1007/978-3-642-31585-5_1}, volume = {7392}, year = {2012}, } @article{11964, abstract = {A detailed investigation on the direct arylation of benzene with aryl bromides by using first-row transition metals under high-temperature/high-pressure (high-T/p) conditions is described. By employing a parallel reactor platform for rapid reaction screening and discovery at elevated temperatures, various metal/ligand/base combinations were evaluated for their ability to enable biaryl formation through C-H activation. The combination of cobalt(III) acetylacetonate and lithium bis(trimethylsilyl)amide was subjected to further process intensification at 200 °C (15 bar), allowing a significant reduction of the catalyst/base loading and a dramatic increase in catalytic efficiency (turnover frequency) by a factor of 1000 compared to traditional protocols. The high-throughput screening additionally identified novel nickel- and copper-based metal/ligand combinations that favored an amination pathway competing with C-H activation, with the addition of ligands, such as 1,10-phenanthroline, having a profound influence on the selectivity. In addition to metal-based catalysts, high-T/p process windows were also successfully applied to transition-metal-free systems, utilizing 1,10-phenanthroline as organocatalyst.}, author = {Pieber, Bartholomäus and Cantillo, David and Kappe, C. Oliver}, issn = {1521-3765}, journal = {Chemistry – A European Journal}, number = {16}, pages = {5047--5055}, publisher = {Wiley}, title = {{Direct arylation of benzene with aryl bromides using high‐temperature/high‐pressure process windows: Expanding the scope of C-H activation chemistry}}, doi = {10.1002/chem.201103748}, volume = {18}, year = {2012}, } @article{11963, abstract = {Peroxides and ethers in flow: 2-Carbonyl-substituted phenols and β-ketoesters react safely with ethers in a microreactor environment using a copper catalyst and an organic peroxide (TBHP). This protocol results in unsymmetrical acetal scaffolds not easily available otherwise (see scheme).}, author = {Kumar, G. Sathish and Pieber, Bartholomäus and Reddy, K. Rajender and Kappe, C. Oliver}, issn = {1521-3765}, journal = {Chemistry - A European Journal}, number = {20}, pages = {6124--6128}, publisher = {Wiley}, title = {{Copper-catalyzed formation of C-O bonds by direct α-C-H bond activation of ethers using stoichiometric amounts of peroxide in batch and continuous-flow formats}}, doi = {10.1002/chem.201200815}, volume = {18}, year = {2012}, } @article{12644, abstract = {In the Dry Andes of central Chile, summer water resources originate mostly from snowmelt and ice melt. We use the physically based, spatially distributed hydrological model TOPKAPI to study the exchange between glaciers and climate in the upper Aconcagua River Basin during the summer season and identify the model parameters that are robust and transferable and those that are more dependent on calibration. TOPKAPI has recently been adapted to incorporate an enhanced temperature index approach for snow and ice melting. We suggest a calibration procedure that allows calibration of parameters in three steps by separating parameters governing distinct processes. We evaluate the parameters' transferability in time and in space by applying the model at two spatial scales. TOPKAPI's ability to simulate the relevant processes is tested against meteorological, ablation, and glacier runoff data measured on Juncal Norte Glacier during two glacier ablation seasons. The model was applied successfully to the climatic setting of the Dry Andes once its parameters were recalibrated. We found a clear distinction between parameters that are stable in time and those that need recalibration. The parameters of the melt model are transferable from one season to the other, while the parameters governing the extrapolation of meteorological input data and the routing of glacier meltwater need recalibration from one season to the other. Sensitivity analysis revealed that the model is most sensitive to the temperature lapse rate governing the extrapolation of air temperature from point measurements to the glacier scale and to the melt parameter that multiplies the shortwave radiation balance.}, author = {Ragettli, S. and Pellicciotti, Francesca}, issn = {0043-1397}, journal = {Water Resources Research}, number = {3}, publisher = {American Geophysical Union}, title = {{Calibration of a physically based, spatially distributed hydrological model in a glacierized basin: On the use of knowledge from glaciometeorological processes to constrain model parameters}}, doi = {10.1029/2011wr010559}, volume = {48}, year = {2012}, } @article{12646, abstract = {Assessment of water resources from remote mountainous catchments plays a crucial role for the development of rural areas in or in the vicinity of mountain ranges. The scarcity of data, however, prevents the application of standard approaches that are based on data-driven models. The Hindu Kush–Karakoram–Himalaya mountain range is a crucial area in terms of water resources, but our understanding of the response of its high-elevation catchments to a changing climate is hindered by lack of hydro-meteorological and cryospheric data. Hydrological modeling is challenging here because internal inconsistencies—such as an underestimation of precipitation input that can be compensated for by an overestimation of meltwater—might be hidden due to the complexity of feedback mechanisms that govern melt and runoff generation in such basins. Data scarcity adds to this difficulty by preventing the application of systematic calibration procedures that would allow identification of the parameter set that could guarantee internal consistency in the simulation of the single hydrological components. In this work, we use simulations from the Hunza River Basin in the Karakoram region obtained with the hydrological model TOPKAPI to quantify the predictive power of discharge and snow-cover data sets, as well as the combination of both. We also show that short-term measurements of meteorological variables such as radiative fluxes, wind speed, relative humidity, and air temperature from glacio-meteorological experiments are crucial for a correct parameterization of surface melt processes. They enable detailed simulations of the energy fluxes governing glacier–atmosphere interaction and the resulting ablation through energy-balance modeling. These simulations are used to derive calibrated parameters for the simplified snow and glacier routines in TOPKAPI. We demonstrate that such parameters are stable in space and time in similar climatic regions, thus reducing the number of parameters requiring calibration.}, author = {Pellicciotti, Francesca and Buergi, Cyrill and Immerzeel, Walter Willem and Konz, Markus and Shrestha, Arun B.}, issn = {1994-7151}, journal = {Mountain Research and Development}, number = {1}, pages = {39--50}, publisher = {International Mountain Society}, title = {{Challenges and uncertainties in hydrological modeling of remote Hindu Kush–Karakoram–Himalayan (HKH) basins: Suggestions for calibration strategies}}, doi = {10.1659/mrd-journal-d-11-00092.1}, volume = {32}, year = {2012}, } @article{12647, abstract = {Accurate quantification of the spatial distribution of precipitation in mountain regions is crucial for assessments of water resources and for the understanding of high-altitude hydrology, yet it is one of the largest unknowns due to the lack of high-altitude observations. The Hunza basin in Pakistan contains very large glacier systems, which, given the melt, cannot persist unless precipitation (snow input) is much higher than what is observed at the meteorological stations, mostly located in mountain valleys. Several studies, therefore, suggest strong positive vertical precipitation lapse rates; in the present study, we quantify this lapse rate by using glaciers as a proxy. We assume a neutral mass balance for the glaciers for the period from 2001 to 2003, and we inversely model the precipitation lapse by balancing the total accumulation in the catchment area and the ablation over the glacier area for the 50 largest glacier systems in the Hunza basin in the Karakoram. Our results reveal a vertical precipitation lapse rate that equals 0.21 ± 0.12% m−1, with a maximum precipitation at an elevation of 5500 masl. We showed that the total annual basin precipitation (828 mm) is 260% higher than what is estimated based on interpolated observations (319 mm); this has major consequences for hydrological modeling and water resource assessments in general. Our results were validated by using previously published studies on individual glaciers as well as the water balance of the Hunza basin. The approach is more widely applicable in mountain ranges where precipitation measurements at high altitude are lacking.}, author = {Immerzeel, Walter Willem and Pellicciotti, Francesca and Shrestha, Arun B.}, issn = {1994-7151}, journal = {Mountain Research and Development}, keywords = {General Environmental Science, Development, Environmental Chemistry}, number = {1}, pages = {30--38}, publisher = {International Mountain Society}, title = {{Glaciers as a proxy to quantify the spatial distribution of precipitation in the Hunza basin}}, doi = {10.1659/mrd-journal-d-11-00097.1}, volume = {32}, year = {2012}, } @article{12648, abstract = {Distributed glacier melt models generally assume that the glacier surface consists of bare exposed ice and snow. In reality, many glaciers are wholly or partially covered in layers of debris that tend to suppress ablation rates. In this paper, an existing physically based point model for the ablation of debris-covered ice is incorporated in a distributed melt model and applied to Haut Glacier d'Arolla, Switzerland, which has three large patches of debris cover on its surface. The model is based on a 10 m resolution digital elevation model (DEM) of the area; each glacier pixel in the DEM is defined as either bare or debris-covered ice, and may be covered in snow that must be melted off before ice ablation is assumed to occur. Each debris-covered pixel is assigned a debris thickness value using probability distributions based on over 1000 manual thickness measurements. Locally observed meteorological data are used to run energy balance calculations in every pixel, using an approach suitable for snow, bare ice or debris-covered ice as appropriate. The use of the debris model significantly reduces the total ablation in the debris-covered areas, however the precise reduction is sensitive to the temperature extrapolation used in the model distribution because air near the debris surface tends to be slightly warmer than over bare ice. Overall results suggest that the debris patches, which cover 10% of the glacierized area, reduce total runoff from the glacierized part of the basin by up to 7%.}, author = {Reid, T. D. and Carenzo, M. and Pellicciotti, Francesca and Brock, B. W.}, issn = {0148-0227}, journal = {Journal of Geophysical Research: Atmospheres}, keywords = {Paleontology, Space and Planetary Science, Earth and Planetary Sciences (miscellaneous), Atmospheric Science, Earth-Surface Processes, Geochemistry and Petrology, Soil Science, Water Science and Technology, Ecology, Aquatic Science, Forestry, Oceanography, Geophysics}, number = {D18}, publisher = {American Geophysical Union}, title = {{Including debris cover effects in a distributed model of glacier ablation}}, doi = {10.1029/2012jd017795}, volume = {117}, year = {2012}, } @inproceedings{1384, abstract = {Software model checking, as an undecidable problem, has three possible outcomes: (1) the program satisfies the specification, (2) the program does not satisfy the specification, and (3) the model checker fails. The third outcome usually manifests itself in a space-out, time-out, or one component of the verification tool giving up; in all of these failing cases, significant computation is performed by the verification tool before the failure, but no result is reported. We propose to reformulate the model-checking problem as follows, in order to have the verification tool report a summary of the performed work even in case of failure: given a program and a specification, the model checker returns a condition Ψ - usually a state predicate - such that the program satisfies the specification under the condition Ψ - that is, as long as the program does not leave the states in which Ψ is satisfied. In our experiments, we investigated as one major application of conditional model checking the sequential combination of model checkers with information passing. We give the condition that one model checker produces, as input to a second conditional model checker, such that the verification problem for the second is restricted to the part of the state space that is not covered by the condition, i.e., the second model checker works on the problems that the first model checker could not solve. Our experiments demonstrate that repeated application of conditional model checkers, passing information from one model checker to the next, can significantly improve the verification results and performance, i.e., we can now verify programs that we could not verify before.}, author = {Beyer, Dirk and Henzinger, Thomas A and Keremoglu, Mehmet and Wendler, Philipp}, booktitle = {Proceedings of the ACM SIGSOFT 20th International Symposium on the Foundations of Software Engineering}, location = {Cary, NC, USA}, publisher = {ACM}, title = {{Conditional model checking: A technique to pass information between verifiers}}, doi = {10.1145/2393596.2393664}, year = {2012}, } @article{1472, abstract = {For G = GL 2, PGL 2, SL 2 we prove that the perverse filtration associated with the Hitchin map on the rational cohomology of the moduli space of twisted G-Higgs bundles on a compact Riemann surface C agrees with the weight filtration on the rational cohomology of the twisted G character variety of C when the cohomologies are identified via non-Abelian Hodge theory. The proof is accomplished by means of a study of the topology of the Hitchin map over the locus of integral spectral curves.}, author = {De Cataldo, Mark A and Tamas Hausel and Migliorini, Luca}, journal = {Annals of Mathematics}, number = {3}, pages = {1329 -- 1407}, publisher = {Princeton University Press}, title = {{Topology of hitchin systems and Hodge theory of character varieties: The case A 1}}, doi = {10.4007/annals.2012.175.3.7}, volume = {175}, year = {2012}, } @article{1471, abstract = {Given a possibly reducible and non-reduced spectral cover π: X → C over a smooth projective complex curve C we determine the group of connected components of the Prym variety Prym(X/C). As an immediate application we show that the finite group of n-torsion points of the Jacobian of C acts trivially on the cohomology of the twisted SL n-Higgs moduli space up to the degree which is predicted by topological mirror symmetry. In particular this yields a new proof of a result of Harder-Narasimhan, showing that this finite group acts trivially on the cohomology of the twisted SL n stable bundle moduli space.}, author = {Tamas Hausel and Pauly, Christian}, journal = {Geometry and Topology}, number = {3}, pages = {1609 -- 1638}, publisher = {University of Warwick}, title = {{Prym varieties of spectral covers}}, doi = {10.2140/gt.2012.16.1609}, volume = {16}, year = {2012}, } @article{171, abstract = {For given non-zero integers a, b, q we investigate the density of solutions (x, y) ∈ ℤ2 to the binary cubic congruence ax2 + by3 ≡ 0 mod q, and use it to establish the Manin conjecture for a singular del Pezzo surface of degree 2 defined over ℚ.}, author = {Timothy Browning and Baier, Stephan}, journal = {Journal fur die Reine und Angewandte Mathematik}, number = {680}, pages = {1 -- 65}, publisher = {Walter de Gruyter}, title = {{Inhomogeneous cubic congruences and rational points on del Pezzo surfaces}}, doi = {https://doi.org/10.1515/crelle.2012.039}, volume = {2013}, year = {2012}, } @article{1725, abstract = {The spatial organization of cell fates during development involves the interpretation of morphogen gradients by cellular signaling cascades and transcriptional networks. Recent studies use biophysical models, genetics, and quantitative imaging to unravel how tissue-level morphogen behavior arises from subcellular events. Moreover, data from several systems show that morphogen gradients, downstream signaling, and the activity of cell-intrinsic transcriptional networks change dynamically during pattern formation. Studies from Drosophila and now also vertebrates suggest that transcriptional network dynamics are central to the generation of gene expression patterns. Together, this leads to the view that pattern formation is an emergent behavior that results from the coordination of events occurring across molecular, cellular, and tissue scales. The development of novel approaches to study this complex process remains a challenge.}, author = {Anna Kicheva and Cohen, Michael H and Briscoe, James}, journal = {Science}, number = {6104}, pages = {210 -- 212}, publisher = {American Association for the Advancement of Science}, title = {{Developmental pattern formation: Insights from physics and biology}}, doi = {10.1126/science.1225182}, volume = {338}, year = {2012}, } @article{1757, abstract = {Self-assembled Ge wires with a height of only 3 unit cells and a length of up to 2 micrometers were grown on Si(001) by means of a catalyst-free method based on molecular beam epitaxy. The wires grow horizontally along either the [100] or the [010] direction. On atomically flat surfaces, they exhibit a highly uniform, triangular cross section. A simple thermodynamic model accounts for the existence of a preferential base width for longitudinal expansion, in quantitative agreement with the experimental findings. Despite the absence of intentional doping, the first transistor-type devices made from single wires show low-resistive electrical contacts and single-hole transport at sub-Kelvin temperatures. In view of their exceptionally small and self-defined cross section, these Ge wires hold promise for the realization of hole systems with exotic properties and provide a new development route for silicon-based nanoelectronics.}, author = {Zhang, Jianjun and Georgios Katsaros and Montalenti, Francesco and Scopece, Daniele and Rezaev, Roman O and Mickel, Christine H and Rellinghaus, Bernd and Miglio, Leo P and De Franceschi, Silvano and Rastelli, Armando and Schmidt, Oliver G}, journal = {Physical Review Letters}, number = {8}, publisher = {American Physical Society}, title = {{Monolithic growth of ultrathin Ge nanowires on Si(001) }}, doi = {10.1103/PhysRevLett.109.085502}, volume = {109}, year = {2012}, } @article{1758, abstract = {We studied the low-energy states of spin-1/2 quantum dots defined in InAs/InP nanowires and coupled to aluminum superconducting leads. By varying the superconducting gap Δ with a magnetic field B we investigated the transition from strong coupling Δ≪T K to weak-coupling Δ≫T K, where T K is the Kondo temperature. Below the critical field, we observe a persisting zero-bias Kondo resonance that vanishes only for low B or higher temperatures, leaving the room to more robust subgap structures at bias voltages between Δ and 2Δ. For strong and approximately symmetric tunnel couplings, a Josephson supercurrent is observed in addition to the Kondo peak. We ascribe the coexistence of a Kondo resonance and a superconducting gap to a significant density of intragap quasiparticle states, and the finite-bias subgap structures to tunneling through Shiba states. Our results, supported by numerical calculations, own relevance also in relation to tunnel-spectroscopy experiments aiming at the observation of Majorana fermions in hybrid nanostructures.}, author = {Lee, Eduardo J and Jiang, Xiaocheng and Aguado, Ramón and Georgios Katsaros and Lieber, Charles M and De Franceschi, Silvano}, journal = {Physical Review Letters}, number = {18}, publisher = {American Physical Society}, title = {{Zero-bias anomaly in a nanowire quantum dot coupled to superconductors}}, doi = {10.1103/PhysRevLett.109.186802}, volume = {109}, year = {2012}, } @article{1756, abstract = {We report on the electronic transport properties of multiple-gate devices fabricated from undoped silicon nanowires. Understanding and control of the relevant transport mechanisms was achieved by means of local electrostatic gating and temperature-dependent measurements. The roles of the source/drain contacts and of the silicon channel could be independently evaluated and tuned. Wrap gates surrounding the silicide-silicon contact interfaces were proved to be effective in inducing a full suppression of the contact Schottky barriers, thereby enabling carrier injection down to liquid helium temperature. By independently tuning the effective Schottky barrier heights, a variety of reconfigurable device functionalities could be obtained. In particular, the same nanowire device could be configured to work as a Schottky barrier transistor, a Schottky diode, or a p-n diode with tunable polarities. This versatility was eventually exploited to realize a NAND logic gate with gain well above one.}, author = {Mongillo, Massimo and Spathis, Panayotis N and Georgios Katsaros and Gentile, Pascal and De Franceschi, Silvano}, journal = {Nano Letters}, number = {6}, pages = {3074 -- 3079}, publisher = {American Chemical Society}, title = {{Multifunctional devices and logic gates with undoped silicon nanowires}}, doi = {10.1021/nl300930m}, volume = {12}, year = {2012}, } @article{1783, abstract = {Nonlinearity and entanglement are two important properties by which physical systems can be identified as nonclassical. We study the dynamics of the resonant interaction of up to N=3 two-level systems and a single mode of the electromagnetic field sharing a single excitation dynamically. We observe coherent vacuum Rabi oscillations and their nonlinear √N speedup by tracking the populations of all qubits and the resonator in time. We use quantum state tomography to show explicitly that the dynamics generates maximally entangled states of the W class in a time limited only by the collective interaction rate. We use an entanglement witness and the 3-tangle to characterize the state whose fidelity F=78% is limited in our experiments by crosstalk arising during the simultaneous qubit manipulations which is absent in a sequential approach with F=91%.}, author = {Mlynek, Jonas A and Abdumalikov, Abdufarrukh A and Johannes Fink and Steffen, L. Kraig and Baur, Matthias P and Lang, C and Van Loo, Arjan F and Wallraff, Andreas}, journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, number = {5}, publisher = {American Physical Society}, title = {{Demonstrating W-type entanglement of Dicke states in resonant cavity quantum electrodynamics}}, doi = {10.1103/PhysRevA.86.053838}, volume = {86}, year = {2012}, }