@article{3166, abstract = {There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors. Reviewers: this article was reviewed by Prof. William Martin, Prof. Eors Szathmary (nominated by Dr. Gaspar Jekely) and Dr. Adam Kun (nominated by Dr. Sandor Pongor)}, author = {Vladar, Harold}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Amino acid fermentation at the origin of the genetic code}}, doi = {10.1186/1745-6150-7-6}, volume = {7}, year = {2012}, } @article{3167, author = {Weber, Michele}, journal = {Science}, number = {6077}, pages = {32--34}, publisher = {American Association for the Advancement of Science}, title = {{NextGen speaks 13 }}, doi = {10.1126/science.336.6077.32}, volume = {336}, year = {2012}, } @article{3168, abstract = {The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a mathematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the combinatorial complexity by quotienting the reachable set of molecular species into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently, we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper, we prove that this quotienting yields a sufficient condition for weak lumpability (that is to say that the quotient system is still Markovian for a given set of initial distributions) and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system (which means that the conditional probability of being in a given state in the original system knowing that we are in its equivalence class is an invariant of the system). We illustrate the framework on a case study of the epidermal growth factor (EGF)/insulin receptor crosstalk.}, author = {Feret, Jérôme and Henzinger, Thomas A and Koeppl, Heinz and Petrov, Tatjana}, journal = {Theoretical Computer Science}, pages = {137 -- 164}, publisher = {Elsevier}, title = {{Lumpability abstractions of rule based systems}}, doi = {10.1016/j.tcs.2011.12.059}, volume = {431}, year = {2012}, } @article{3242, abstract = {Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).}, author = {Konrad, Matthias and Vyleta, Meghan and Theis, Fabian and Stock, Miriam and Tragust, Simon and Klatt, Martina and Drescher, Verena and Marr, Carsten and Ugelvig, Line V and Cremer, Sylvia}, journal = {PLoS Biology}, number = {4}, publisher = {Public Library of Science}, title = {{Social transfer of pathogenic fungus promotes active immunisation in ant colonies}}, doi = {10.1371/journal.pbio.1001300}, volume = {10}, year = {2012}, } @article{3243, abstract = {Wie wandelt sich das Berufsbild in Wissenschaftlichen Bibliotheken? Patrick Danowski gibt seine Einschätzung ab. }, author = {Danowski, Patrick}, issn = {1607-7172}, journal = {Büchereiperspektiven}, number = {1}, pages = {11}, publisher = {Büchereiverband Österreichs}, title = {{Zwischen Technologie und Information}}, volume = {2012}, year = {2012}, } @article{3244, abstract = {Bibliothekare haben die Aufgabe, sich mit neuen Medienformen auseinanderzusetzen. }, author = {Danowski, Patrick}, issn = {1869 -1137}, journal = {BuB - Forum Bibliothek und Information}, number = {4}, pages = {284}, publisher = {Fachzeitschrift des BIB – Berufsverband Information Bibliothek}, title = {{Die Zeit des Abwartens ist vorbei!}}, volume = {64}, year = {2012}, } @article{3245, abstract = {How cells orchestrate their behavior during collective migration is a long-standing question. Using magnetic tweezers to apply mechanical stimuli to Xenopus mesendoderm cells, Weber etal. (2012) now reveal, in this issue of Developmental Cell, a cadherin-mediated mechanosensitive response that promotes cell polarization and movement persistence during the collective mesendoderm migration in gastrulation.}, author = {Behrndt, Martin and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {1}, pages = {3 -- 4}, publisher = {Cell Press}, title = {{Spurred by resistance mechanosensation in collective migration}}, doi = {10.1016/j.devcel.2011.12.018}, volume = {22}, year = {2012}, } @article{3246, abstract = {Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis.}, author = {Barone, Vanessa and Heisenberg, Carl-Philipp J}, journal = {Current Opinion in Cell Biology}, number = {1}, pages = {148 -- 153}, publisher = {Elsevier}, title = {{Cell adhesion in embryo morphogenesis}}, doi = {10.1016/j.ceb.2011.11.006}, volume = {24}, year = {2012}, } @article{3247, abstract = {The Brazilian Merganser is a very rare and threatened species that nowadays inhabits only a few protected areas and their surroundings in the Brazilian territory. In order to estimate the remaining genetic diversity and population structure in this species, two mitochondrial genes were sequenced in 39 individuals belonging to two populations and in one individual collected in Argentina in 1950. We found a highly significant divergence between two major remaining populations of Mergus octosetaceus, which suggests a historical population structure in this species. Furthermore, two deeply divergent lineages were found in a single location, which could due to current or historical secondary contact. Based on the available genetic data, we point out future directions which would contribute to design strategies for conservation and management of this threatened species.}, author = {Vilaça, Sibelle and Fernandes Redondo, Rodrigo A and Lins, Lívia and Santos, Fabrício}, journal = {Conservation Genetics}, number = {1}, pages = {293 -- 298}, publisher = {Springer}, title = {{Remaining genetic diversity in Brazilian Merganser (Mergus octosetaceus)}}, doi = {10.1007/s10592-011-0262-5}, volume = {13}, year = {2012}, } @article{3248, abstract = {We describe RTblob, a high speed vision system that detects objects in cluttered scenes based on their color and shape at a speed of over 800 frames/s. Because the system is available as open-source software and relies only on off-the-shelf PC hardware components, it can provide the basis for multiple application scenarios. As an illustrative example, we show how RTblob can be used in a robotic table tennis scenario to estimate ball trajectories through 3D space simultaneously from four cameras images at a speed of 200 Hz.}, author = {Lampert, Christoph and Peters, Jan}, issn = {1861-8219}, journal = {Journal of Real-Time Image Processing}, number = {1}, pages = {31 -- 41}, publisher = {Springer}, title = {{Real-time detection of colored objects in multiple camera streams with off-the-shelf hardware components}}, doi = {10.1007/s11554-010-0168-3}, volume = {7}, year = {2012}, } @article{3249, abstract = {Boolean notions of correctness are formalized by preorders on systems. Quantitative measures of correctness can be formalized by real-valued distance functions between systems, where the distance between implementation and specification provides a measure of "fit" or "desirability". We extend the simulation preorder to the quantitative setting by making each player of a simulation game pay a certain price for her choices. We use the resulting games with quantitative objectives to define three different simulation distances. The correctness distance measures how much the specification must be changed in order to be satisfied by the implementation. The coverage distance measures how much the implementation restricts the degrees of freedom offered by the specification. The robustness distance measures how much a system can deviate from the implementation description without violating the specification. We consider these distances for safety as well as liveness specifications. The distances can be computed in polynomial time for safety specifications, and for liveness specifications given by weak fairness constraints. We show that the distance functions satisfy the triangle inequality, that the distance between two systems does not increase under parallel composition with a third system, and that the distance between two systems can be bounded from above and below by distances between abstractions of the two systems. These properties suggest that our simulation distances provide an appropriate basis for a quantitative theory of discrete systems. We also demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes.}, author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun}, journal = {Theoretical Computer Science}, number = {1}, pages = {21 -- 35}, publisher = {Elsevier}, title = {{Simulation distances}}, doi = {10.1016/j.tcs.2011.08.002}, volume = {413}, year = {2012}, } @inproceedings{3250, abstract = {The Learning Parity with Noise (LPN) problem has recently found many applications in cryptography as the hardness assumption underlying the constructions of "provably secure" cryptographic schemes like encryption or authentication protocols. Being provably secure means that the scheme comes with a proof showing that the existence of an efficient adversary against the scheme implies that the underlying hardness assumption is wrong. LPN based schemes are appealing for theoretical and practical reasons. On the theoretical side, LPN based schemes offer a very strong security guarantee. The LPN problem is equivalent to the problem of decoding random linear codes, a problem that has been extensively studied in the last half century. The fastest known algorithms run in exponential time and unlike most number-theoretic problems used in cryptography, the LPN problem does not succumb to known quantum algorithms. On the practical side, LPN based schemes are often extremely simple and efficient in terms of code-size as well as time and space requirements. This makes them prime candidates for light-weight devices like RFID tags, which are too weak to implement standard cryptographic primitives like the AES block-cipher. This talk will be a gentle introduction to provable security using simple LPN based schemes as examples. Starting from pseudorandom generators and symmetric key encryption, over secret-key authentication protocols, and, if time admits, touching on recent constructions of public-key identification, commitments and zero-knowledge proofs.}, author = {Pietrzak, Krzysztof Z}, location = {Špindlerův Mlýn, Czech Republic}, pages = {99 -- 114}, publisher = {Springer}, title = {{Cryptography from learning parity with noise}}, doi = {10.1007/978-3-642-27660-6_9}, volume = {7147}, year = {2012}, } @inproceedings{3251, abstract = {Many infinite state systems can be seen as well-structured transition systems (WSTS), i.e., systems equipped with a well-quasi-ordering on states that is also a simulation relation. WSTS are an attractive target for formal analysis because there exist generic algorithms that decide interesting verification problems for this class. Among the most popular algorithms are acceleration-based forward analyses for computing the covering set. Termination of these algorithms can only be guaranteed for flattable WSTS. Yet, many WSTS of practical interest are not flattable and the question whether any given WSTS is flattable is itself undecidable. We therefore propose an analysis that computes the covering set and captures the essence of acceleration-based algorithms, but sacrifices precision for guaranteed termination. Our analysis is an abstract interpretation whose abstract domain builds on the ideal completion of the well-quasi-ordered state space, and a widening operator that mimics acceleration and controls the loss of precision of the analysis. We present instances of our framework for various classes of WSTS. Our experience with a prototype implementation indicates that, despite the inherent precision loss, our analysis often computes the precise covering set of the analyzed system.}, author = {Zufferey, Damien and Wies, Thomas and Henzinger, Thomas A}, location = {Philadelphia, PA, USA}, pages = {445 -- 460}, publisher = {Springer}, title = {{Ideal abstractions for well structured transition systems}}, doi = {10.1007/978-3-642-27940-9_29}, volume = {7148}, year = {2012}, } @inproceedings{3252, abstract = {We study the automatic synthesis of fair non-repudiation protocols, a class of fair exchange protocols, used for digital contract signing. First, we show how to specify the objectives of the participating agents, the trusted third party (TTP) and the protocols as path formulas in Linear Temporal Logic (LTL) and prove that the satisfaction of the objectives of the agents and the TTP imply satisfaction of the protocol objectives. We then show that weak (co-operative) co-synthesis and classical (strictly competitive) co-synthesis fail in synthesizing these protocols, whereas assume-guarantee synthesis (AGS) succeeds. We demonstrate the success of assume-guarantee synthesis as follows: (a) any solution of assume-guarantee synthesis is attack-free; no subset of participants can violate the objectives of the other participants without violating their own objectives; (b) the Asokan-Shoup-Waidner (ASW) certified mail protocol that has known vulnerabilities is not a solution of AGS; and (c) the Kremer-Markowitch (KM) non-repudiation protocol is a solution of AGS. To our knowledge this is the first application of synthesis to fair non-repudiation protocols, and our results show how synthesis can generate correct protocols and automatically discover vulnerabilities. The solution to assume-guarantee synthesis can be computed efficiently as the secure equilibrium solution of three-player graph games. © 2012 Springer-Verlag.}, author = {Chatterjee, Krishnendu and Raman, Vishwanath}, location = {Philadelphia, PA, USA}, pages = {152 -- 168}, publisher = {Springer}, title = {{Synthesizing protocols for digital contract signing}}, doi = {10.1007/978-3-642-27940-9_11}, volume = {7148}, year = {2012}, } @inproceedings{3253, abstract = {We describe a framework for reasoning about programs with lists carrying integer numerical data. We use abstract domains to describe and manipulate complex constraints on configurations of these programs mixing constraints on the shape of the heap, sizes of the lists, on the multisets of data stored in these lists, and on the data at their different positions. Moreover, we provide powerful techniques for automatic validation of Hoare-triples and invariant checking, as well as for automatic synthesis of invariants and procedure summaries using modular inter-procedural analysis. The approach has been implemented in a tool called Celia and experimented successfully on a large benchmark of programs.}, author = {Bouajjani, Ahmed and Dragoi, Cezara and Enea, Constantin and Sighireanu, Mihaela}, location = {Philadelphia, PA, USA}, pages = {1 -- 22}, publisher = {Springer}, title = {{Abstract domains for automated reasoning about list manipulating programs with infinite data}}, doi = {10.1007/978-3-642-27940-9_1}, volume = {7148}, year = {2012}, } @article{3254, abstract = {The theory of graph games with ω-regular winning conditions is the foundation for modeling and synthesizing reactive processes. In the case of stochastic reactive processes, the corresponding stochastic graph games have three players, two of them (System and Environment) behaving adversarially, and the third (Uncertainty) behaving probabilistically. We consider two problems for stochastic graph games: the qualitative problem asks for the set of states from which a player can win with probability 1 (almost-sure winning); and the quantitative problem asks for the maximal probability of winning (optimal winning) from each state. We consider ω-regular winning conditions formalized as Müller winning conditions. We present optimal memory bounds for pure (deterministic) almost-sure winning and optimal winning strategies in stochastic graph games with Müller winning conditions. We also study the complexity of stochastic Müller games and show that both the qualitative and quantitative analysis problems are PSPACE-complete. Our results are relevant in synthesis of stochastic reactive processes.}, author = {Chatterjee, Krishnendu}, journal = {Information and Computation}, pages = {29 -- 48}, publisher = {Elsevier}, title = {{The complexity of stochastic Müller games}}, doi = {10.1016/j.ic.2011.11.004}, volume = {211}, year = {2012}, } @inproceedings{3255, abstract = {In this paper we survey results of two-player games on graphs and Markov decision processes with parity, mean-payoff and energy objectives, and the combination of mean-payoff and energy objectives with parity objectives. These problems have applications in verification and synthesis of reactive systems in resource-constrained environments.}, author = {Chatterjee, Krishnendu and Doyen, Laurent}, location = {Lednice, Czech Republic}, pages = {37 -- 46}, publisher = {Springer}, title = {{Games and Markov decision processes with mean payoff parity and energy parity objectives}}, doi = {10.1007/978-3-642-25929-6_3}, volume = {7119}, year = {2012}, } @article{3256, abstract = {We use a distortion to define the dual complex of a cubical subdivision of ℝ n as an n-dimensional subcomplex of the nerve of the set of n-cubes. Motivated by the topological analysis of high-dimensional digital image data, we consider such subdivisions defined by generalizations of quad- and oct-trees to n dimensions. Assuming the subdivision is balanced, we show that mapping each vertex to the center of the corresponding n-cube gives a geometric realization of the dual complex in ℝ n.}, author = {Edelsbrunner, Herbert and Kerber, Michael}, journal = {Discrete & Computational Geometry}, number = {2}, pages = {393 -- 414}, publisher = {Springer}, title = {{Dual complexes of cubical subdivisions of ℝn}}, doi = {10.1007/s00454-011-9382-4}, volume = {47}, year = {2012}, } @article{3257, abstract = {Consider a convex relaxation f̂ of a pseudo-Boolean function f. We say that the relaxation is totally half-integral if f̂(x) is a polyhedral function with half-integral extreme points x, and this property is preserved after adding an arbitrary combination of constraints of the form x i=x j, x i=1-x j, and x i=γ where γ∈{0,1,1/2} is a constant. A well-known example is the roof duality relaxation for quadratic pseudo-Boolean functions f. We argue that total half-integrality is a natural requirement for generalizations of roof duality to arbitrary pseudo-Boolean functions. Our contributions are as follows. First, we provide a complete characterization of totally half-integral relaxations f̂ by establishing a one-to-one correspondence with bisubmodular functions. Second, we give a new characterization of bisubmodular functions. Finally, we show some relationships between general totally half-integral relaxations and relaxations based on the roof duality. On the conceptual level, our results show that bisubmodular functions provide a natural generalization of the roof duality approach to higher-order terms. This can be viewed as a non-submodular analogue of the fact that submodular functions generalize the s-t minimum cut problem with non-negative weights to higher-order terms.}, author = {Kolmogorov, Vladimir}, journal = {Discrete Applied Mathematics}, number = {4-5}, pages = {416 -- 426}, publisher = {Elsevier}, title = {{Generalized roof duality and bisubmodular functions}}, doi = {10.1016/j.dam.2011.10.026}, volume = {160}, year = {2012}, } @article{3258, abstract = {CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.}, author = {Kim, Sooyun and Guzmán, José and Hu, Hua and Jonas, Peter M}, issn = {1546-1726}, journal = {Nature Neuroscience}, number = {4}, pages = {600 -- 606}, publisher = {Nature Publishing Group}, title = {{Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons}}, doi = {10.1038/nn.3060}, volume = {15}, year = {2012}, }