@article{3818, abstract = {Rigorous analysis of synaptic transmission in the central nervous system requires access to presynaptic terminals. However, cortical terminals have been largely inaccessible to presynaptic patch-clamp recording, due to their small size. Using improved patch-clamp techniques in brain slices, we recorded from mossy fiber terminals in the CA3 region of the hippocampus, which have a diameter of 2-5 microm. The major steps of improvement were the enhanced visibility provided by high-numerical aperture objectives and infrared illumination, the development of vibratomes with minimal vertical blade vibrations and the use of sucrose-based solutions for storage and cutting. Based on these improvements, we describe a protocol that allows us to routinely record from hippocampal mossy fiber boutons. Presynaptic recordings can be obtained in slices from both rats and mice. Presynaptic recordings can be also obtained in slices from transgenic mice in which terminals are labeled with enhanced green fluorescent protein.}, author = {Bischofberger, Josef and Engel, Dominique and Li, Liyi and Geiger, Jörg R and Peter Jonas}, journal = {Nature Protocols}, number = {4}, pages = {2075 -- 81}, publisher = {Nature Publishing Group}, title = {{Patch-clamp recording from mossy fiber terminals in hippocampal slices}}, doi = {10.1038/nprot.2006.312 }, volume = {1}, year = {2006}, } @inproceedings{3890, abstract = {We consider two-player infinite games played on graphs. The games are concurrent, in that at each state the players choose their moves simultaneously and independently, and stochastic, in that the moves determine a probability distribution for the successor state. The value of a game is the maximal probability with which a player can guarantee the satisfaction of her objective. We show that the values of concurrent games with w-regular objectives expressed as parity conditions can be decided in NP boolean AND coNP. This result substantially improves the best known previous bound of 3EXPTIME. It also shows that the full class of concurrent parity games is no harder than the special case of turn-based stochastic reachability games, for which NP boolean AND coNP is the best known bound. While the previous, more restricted NP boolean AND coNP results for graph games relied on the existence of particularly simple (pure memoryless) optimal strategies, in concurrent games with parity objectives optimal strategies may not exist, and epsilon-optimal strategies (which achieve the value of the game within a parameter epsilon > 0) require in general both randomization and infinite memory. Hence our proof must rely on a more detailed analysis of strategies and, in addition to the main result, yields two results that are interesting on their own. First, we show that there exist epsilon-optimal strategies that in the limit coincide with memoryless strategies; this parallels the celebrated result of Mertens-Neyman for concurrent games with limit-average objectives. Second, we complete the characterization of the memory requirements for epsilon-optimal strategies for concurrent games with parity conditions, by showing that memoryless strategies suffice for epsilon-optimality for coBachi conditions.}, author = {Krishnendu Chatterjee and de Alfaro, Luca and Thomas Henzinger}, pages = {678 -- 687}, publisher = {SIAM}, title = {{The complexity of quantitative concurrent parity games}}, doi = {10.1145/1109557.1109631}, year = {2006}, } @inproceedings{3889, abstract = {We study observation-based strategies for two-player turn-based games on graphs with omega-regular objectives. An observation-based strategy relies on imperfect information about the history of a play, namely, on the past sequence of observations. Such games occur in the synthesis of a controller that does not see the private state of the plant. Our main results are twofold. First, we give a fixed-point algorithm for computing the set of states from which a player can win with a deterministic observation-based strategy for any omega-regular objective. The fixed point is computed in the lattice of antichains of state sets. This algorithm has the advantages of being directed by the objective and of avoiding an explicit subset construction on the game graph. Second, we give an algorithm for computing the set of states from which a player can win with probability 1 with a randomized observation-based strategy for a Buchi objective. This set is of interest because in the absence of perfect information, randomized strategies are more powerful than deterministic ones. We show that our algorithms are optimal by proving matching lower bounds.}, author = {Krishnendu Chatterjee and Doyen, Laurent and Thomas Henzinger and Raskin, Jean-François}, pages = {287 -- 302}, publisher = {Springer}, title = {{Algorithms for omega-regular games with imperfect information}}, doi = {10.1007/11874683_19}, volume = {4207}, year = {2006}, } @inproceedings{3891, abstract = {We study infinite stochastic games played by two-players over a finite state space, with objectives specified by sets of infinite traces. The games are concurrent (players make moves simultaneously and independently), stochastic (the next state is determined by a probability distribution that depends on the current state and chosen moves of the players) and infinite (proceeds for infinite number of rounds). The analysis of concurrent stochastic games can be classified into: quantitative analysis, analyzing the optimum value of the game; and qualitative analysis, analyzing the set of states with optimum value 1. We consider concurrent games with tail objectives, i.e., objectives that are independent of the finite-prefix of traces, and show that the class of tail objectives are strictly richer than the omega-regular objectives. We develop new proof techniques to extend several properties of concurrent games with omega-regular objectives to concurrent games with tail objectives. We prove the positive limit-one property for tail objectives, that states for all concurrent games if the optimum value for a player is positive for a tail objective Phi at some state, then there is a state where the optimum value is 1 for Phi, for the player. We also show that the optimum values of zero-sum (strictly conflicting objectives) games with tail objectives can be related to equilibrium values of nonzero-sum (not strictly conflicting objectives) games with simpler reachability objectives. A consequence of our analysis presents a polynomial time reduction of the quantitative analysis of tail objectives to the qualitative analysis for the sub-class of one-player stochastic games (Markov decision processes).}, author = {Krishnendu Chatterjee}, pages = {256 -- 270}, publisher = {Springer}, title = {{Concurrent games with tail objectives}}, doi = {10.1007/11874683_17}, volume = {4207}, year = {2006}, } @inproceedings{3888, abstract = {A stochastic graph game is played by two players on a game graph with probabilistic transitions. We consider stochastic graph games with omega-regular winning conditions specified as Rabin or Streett objectives. These games are NP-complete and coNP-complete, respectively. The value of the game for a player at a state s given an objective Phi is the maximal probability with which the player can guarantee the satisfaction of Phi from s. We present a strategy-improvement algorithm to compute values in stochastic Rabin games, where an improvement step involves solving Markov decision processes (MDPs) and nonstochastic Rabin games. The algorithm also computes values for stochastic Streett games but does not directly yield an optimal strategy for Streett objectives. We then show how to obtain an optimal strategy for Streett objectives by solving certain nonstochastic Streett games.}, author = {Krishnendu Chatterjee and Thomas Henzinger}, pages = {375 -- 389}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Strategy improvement for stochastic Rabin and Streett games}}, doi = {10.1007/11817949_25}, volume = {4137}, year = {2006}, } @article{3908, abstract = {It is commonly believed that both the average length and the frequency of microsatellites correlate with genome size. We have estimated the frequency and the average length for 69 perfect dinucleotide microsatellites in an insect with an exceptionally large genome: Chorthippus biguttulus (Orthoptera, Acrididae). Dinucleotide microsatellites are not more frequent in C. biguttulus, but repeat arrays are 1.4 to 2 times longer than in other insect species. The average repeat number in C. biguttulus lies in the range of higher vertebrates. Natural populations are highly variable. At least 30 alleles per locus were found and the expected heterozygosity is above 0.95 at all three loci studied. In contrast, the observed heterozygosity is much lower (≤0.51), which could be caused by long null alleles.}, author = {Ustinova, Jana and Achmann, Roland and Cremer, Sylvia and Mayer, Frieder}, journal = {Journal of Molecular Evolution}, number = {2}, pages = {158 -- 167}, publisher = {Springer}, title = {{Long repeats in a huge gemome: microsatellite loci in the grasshopper Chorthippus biguttulus}}, doi = {10.1007/s00239-005-0022-6}, volume = {62}, year = {2006}, } @article{3934, abstract = {T cells develop in the thymus in a highly specialized cellular and extracellular microenvironment. The basement membrane molecule, laminin-5 (LN-5), is predominantly found in the medulla of the human thymic lobules. Using high-resolution light microscopy, we show here that LN-5 is localized in a bi-membranous conduit-like structure, together with other typical basement membrane components including collagen type IV, nidogen and perlecan. Other interstitial matrix components, such as fibrillin-1 or -2, tenascin-C or fibrillar collagen types, were also associated with these structures. Three-dimensional (3D) confocal microscopy suggested a tubular structure, whereas immunoelectron and transmission electron microscopy showed that the core of these tubes contained fibrillar collagens enwrapped by the LN-5-containing membrane. These medullary conduits are surrounded by thymic epithelial cells, which in vitro were found to bind LN-5, but also fibrillin and tenascin-C. Dendritic cells were also detected in close vicinity to the conduits. Both of these stromal cell types express major histocompatibility complex (MHC) class II molecules capable of antigen presentation. The conduits are connected to blood vessels but, with an average diameter of 2 mum, they are too small to transport cells. However, evidence is provided that smaller molecules such as a 10 kDa dextran, but not large molecules (>500 kDa), can be transported in the conduits. These results clearly demonstrate that a conduit system, which is also known from secondary lymphatic organs such as lymph nodes and spleen, is present in the medulla of the human thymus, and that it might serve to transport small blood-borne molecules or chemokines to defined locations within the medulla.}, author = {Drumea-Mirancea, Mihaela and Wessels, Johannes T and Müller, Claudia A and Essl, Mike and Eble, Johannes A and Tolosa, Eva and Koch, Manuel and Reinhardt, Dieter P and Michael Sixt and Sorokin, Lydia and Stierhof, York-Dieter and Schwarz, Heinz and Klein, Gerd}, journal = {Journal of Cell Science}, number = {Pt 7}, pages = {1396 -- 1405}, publisher = {Company of Biologists}, title = {{Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules}}, doi = {10.1242/​jcs.02840}, volume = {119}, year = {2006}, } @article{3935, abstract = {Integrins regulate cell behavior through the assembly of multiprotein complexes at the site of cell adhesion. Parvins are components of such a multiprotein complex. They consist of three members (alpha-, beta-, and gamma-parvin), form a functional complex with integrin-linked kinase (ILK) and PINCH, and link integrins to the actin cytoskeleton. Whereas alpha- and beta-parvins are widely expressed, gamma-parvin has been reported to be expressed in hematopoietic organs. In the present study, we report the expression pattern of the parvins in hematopoietic cells and the phenotypic analysis of gamma-parvin-deficient mice. Whereas alpha-parvin is not expressed in hematopoietic cells, beta-parvin is only found in myeloid cells and gamma-parvin is present in both cells of the myeloid and lymphoid lineages, where it binds ILK. Surprisingly, loss of gamma-parvin expression had no effect on blood cell differentiation, proliferation, and survival and no consequence for the T-cell-dependent antibody response and lymphocyte and dendritic cell migration. These data indicate that despite the high expression of gamma-parvin in hematopoietic cells it must play a more subtle role for blood cell homeostasis.}, author = {Chu, Haiyan and Thievessen, Ingo and Michael Sixt and Lämmermann, Tim and Waisman, Ari and Braun, Attila and Noegel, Angelika A and Fässler, Reinhard}, journal = {Molecular and Cellular Biology}, number = {5}, pages = {1817 -- 1825}, publisher = {American Society for Microbiology}, title = {{γ-Parvin is dispensable for hematopoiesis, leukocyte trafficking, and T-cell-dependent antibody response}}, doi = {10.1128/MCB.26.5.1817-1825.2006}, volume = {26}, year = {2006}, } @article{3936, abstract = {At least eight of the twelve known members of the beta1 integrin family are expressed on hematopoietic cells. Among these, the VCAM-1 receptor alpha4beta1 has received most attention as a main factor mediating firm adhesion to the endothelium during blood cell extravasation. Therapeutic trials are ongoing into the use of antibodies and small molecule inhibitors to target this interaction and hence obtain anti-inflammatory effects. However, extravasation is only one possible process that is mediated by beta1 integrins and there is evidence that they also mediate leukocyte retention and positioning in the tissue, lymphocyte activation and possibly migration within the interstitium. Genetic mouse models where integrins are selectively deleted on blood cells have been used to investigate these functions and further studies will be invaluable to critically evaluate therapeutic trials.}, author = {Michael Sixt and Bauer, Martina and Lämmermann, Tim and Fässler, Reinhard}, journal = {Current Opinion in Cell Biology}, number = {5}, pages = {482 -- 490}, publisher = {Elsevier}, title = {{β1 integrins: zip codes and signaling relay for blood cells}}, doi = {10.1016/j.ceb.2006.08.007}, volume = {18}, year = {2006}, } @article{4140, abstract = {Wnt11 is a key signal, determining cell polarization and migration during vertebrate gastrulation. It is known that Wnt11 functionally interacts with several signaling components, the homologues of which control planar cell polarity in Drosophila melanogaster. Although in D. melanogaster these components are thought to polarize cells by asymmetrically localizing at the plasma membrane, it is not yet clear whether their subcellular localization plays a similarly important role in vertebrates. We show that in zebrafish embryonic cells, Wnt11 locally functions at the plasma membrane by accumulating its receptor, Frizzled 7, on adjacent sites of cell contacts. Wnt11-induced Frizzled 7 accumulations recruit the intracellular Wnt signaling mediator Dishevelled, as well as Wnt11 itself, and locally increase cell contact persistence. This increase in cell contact persistence is mediated by the local interaction of Wnt11, Frizzled 7, and the atypical cadherin Flamingo at the plasma membrane, and it does not require the activity of further downstream effectors of Wnt11 signaling, such as RhoA and Rok2. We propose that Wnt11, by interacting with Frizzled 7 and Flamingo, modulates local cell contact persistence to coordinate cell movements during gastrulation.}, author = {Witzel, Sabine and Zimyanin, Vitaly and Carreira Barbosa, Filipa and Tada, Masazumi and Heisenberg, Carl-Philipp J}, journal = {Journal of Cell Biology}, number = {5}, pages = {791 -- 802}, publisher = {Rockefeller University Press}, title = {{Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane}}, doi = {10.1083/jcb.200606017}, volume = {175}, year = {2006}, } @article{4145, abstract = {The detection of microRNAs (miRNAs) at single-cell resolution is important for studying the role of these posttranscriptional regulators. Here, we use a dual-fluorescent green fluorescent protein (GFP)-reporter/monomeric red fluorescent protein (mRFP)-sensor (DFRS) plasmid, injected into zebrafish blastomeres or electroporated into defined tissues of mouse embryos in utero or ex utero, to monitor the dynamics of specific miRNAs in individual live cells. This approach reveals, for example, that in the developing mouse central nervous system,, miR-124a is expressed not only in postmitotic neurons but also in neuronal progenitor cells. Collectively, our results demonstrate that acute administration of DFRS plasmids.offers an alternative to previous in situ hybridization and transgenic approaches and allows the monitoring of miRNA appearance and disappearance in defined cell lineages during vertebrate development.}, author = {Tonelli, Davide and Calegari, Frederico and Fei, Ji and Nomura, Tadashi and Osumi, Noriko and Heisenberg, Carl-Philipp J and Huttner, Wieland}, journal = {Biotechniques}, number = {6}, pages = {727 -- 732}, publisher = {Informa Healthcare}, title = {{Single-cell detection of microRNAs in developing vertebrate embryos after acute administration of a dual-fluorescence reporter/sensor plasmid}}, doi = {10.2144/000112296}, volume = {41}, year = {2006}, } @article{4176, abstract = {During vertebrate gastrulation, a well-orchestrated series of morphogenetic changes leads to the formation of the three germ layers: the ectoderm, mesoderm and endoderm. The analysis of gene expression patterns during gastrulation has been central to the identification of genes involved in germ layer formation. However, many proteins are regulated on a translational or post-translational level and are thus undetectable by gene expression analysis. Therefore, we developed a 2D-gel-based comparative proteomic approach to target proteins involved in germ layer morphogenesis during zebrafish gastrulation. Proteomes of ectodermal and mesendodermal progenitor cells were compared and 35 significantly regulated proteins were identified by mass spectrometry, including several proteins with predicted functions in cytoskeletal organization. A comparison of our proteomic results with data obtained in an accompanying microarray-based gene expression analysis revealed no significant overlap, confirming the complementary nature of proteomics and transcriptomics. The regulation of ezrin2, which was identified based on a reduction in spot intensity in mesendodermal cells, was independently validated. Furthermore, we show that ezrin2 is activated by phosphorylation in mesendodermal cells and is required for proper germ layer morphogenesis. We demonstrate the feasibility of proteomics in zebrafish, concluding that proteomics is a valuable tool for analysis of early development.}, author = {Link, Vinzenz and Carvalho, Lara and Castanon, Irinka and Stockinger, Petra and Shevchenko, Andrej and Heisenberg, Carl-Philipp J}, journal = {Journal of Cell Science}, number = {10}, pages = {2073 -- 2083}, publisher = {Company of Biologists}, title = {{Identification of regulators of germ layer morphogenesis using proteomics in zebrafish}}, doi = {10.1242/jcs.02928}, volume = {119}, year = {2006}, } @article{4173, abstract = {Background: Zebrafish (D. rerio) has become a powerful and widely used model system for the analysis of vertebrate embryogenesis and organ development. While genetic methods are readily available in zebrafish, protocols for two dimensional (2D) gel electrophoresis and proteomics have yet to be developed. Results: As a prerequisite to carry out proteomic experiments with early zebrafish embryos, we developed a method to efficiently remove the yolk from large batches of embryos. This method enabled high resolution 2D gel electrophoresis and improved Western blotting considerably. Here, we provide detailed protocols for proteomics in zebrafish from sample preparation to mass spectrometry (MS), including a comparison of databases for MS identification of zebrafish proteins. Conclusion: The provided protocols for proteomic analysis of early embryos enable research to be taken in novel directions in embryogenesis.}, author = {Link, Vinzenz and Shevchenko, Andrej and Heisenberg, Carl-Philipp J}, journal = {BMC Developmental Biology}, pages = {1 -- 9}, publisher = {BioMed Central}, title = {{Proteomics of early zebrafish embryos}}, doi = {10.1186/1471-213X-6-1}, volume = {6}, year = {2006}, } @article{4178, abstract = {Detailed reconstruction of the spatiotemporal history of embryonic cells is key to understanding tissue formation processes but is often complicated by the large number of cells involved, particularly so in vertebrates. Through a combination of high-resolution time-lapse lineage tracing and antibody staining, we have analyzed the movement of mesencephalic and metencephalic cell populations in the early zebrafish embryo. To facilitate the analysis of our cell tracking data, we have created TracePilot, a software tool that allows interactive manipulation and visualization of tracking data. We demonstrate its utility by showing novel visualizations of cell movement in the developing zebrafish brain. TracePilot (http://www.mpi-cbg.de/tracepilot) is Java-based, available free of charge, and has a program structure that allows the incorporation of additional analysis tools.}, author = {Langenberg, Tobias and Dracz, Tadeusz and Oates, Andrew and Heisenberg, Carl-Philipp J and Brand, Michael}, journal = {Developmental Dynamics}, number = {4}, pages = {928 -- 933}, publisher = {Wiley-Blackwell}, title = {{Analysis and visualization of cell movement in the developing zebrafish brain}}, doi = {10.1002/dvdy.20692}, volume = {235}, year = {2006}, } @article{4184, abstract = {Epithelial morphogenesis depends on coordinated changes in cell shape, a process that is still poorly understood. During zebrafish epiboly and Drosophila dorsal closure, cell-shape changes at the epithelial margin are of critical importance. Here evidence is provided for a conserved mechanism of local actin and myosin 2 recruitment during theses events. It was found that during epiboly of the zebrafish embryo, the movement of the outer epithelium (enveloping layer) over the yolk cell surface involves the constriction of marginal cells. This process depends on the recruitment of actin and myosin 2 within the yolk cytoplasm along the margin of the enveloping layer. Actin and myosin 2 recruitment within the yolk cytoplasm requires the Ste20-like kinase Msn1, an orthologue of Drosophila Misshapen. Similarly, in Drosophila, actin and myosin 2 localization and cell constriction at the margin of the epidermis mediate dorsal closure and are controlled by Misshapen. Thus, this study has characterized a conserved mechanism underlying coordinated cell-shape changes during epithelial morphogenesis.}, author = {Köppen, Mathias and Fernández, Beatriz and Carvalho, Lara and Jacinto, António and Heisenberg, Carl-Philipp J}, journal = {Development}, number = {14}, pages = {2671 -- 2681}, publisher = {Company of Biologists}, title = {{Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila}}, doi = {doi: 10.1242/dev.02439}, volume = {133}, year = {2006}, } @article{4218, abstract = {The molecular and cellular mechanisms governing cell motility and directed migration in response to the chemokine SDF-1 are largely unknown. Here, we demonstrate that zebrafish primordial germ cells whose migration is guided by SDF-1 generate bleb-like protrusions that are powered by cytoplasmic flow. Protrusions are formed at sites of higher levels of free calcium where activation of myosin contraction occurs. Separation of the acto-myosin cortex from the plasma membrane at these sites is followed by a flow of cytoplasm into the forming bleb. We propose that polarized activation of the receptor CXCR4 leads to a rise in free calcium that in turn activates myosin contraction in the part of the cell responding to higher levels of the ligand SDF-1. The biased formation of new protrusions in a particular region of the cell in response to SDF-1 defines the leading edge and the direction of cell migration.}, author = {Blaser, Heiko and Reichman Fried, Michal and Castanon, Irinka and Dumstrei, Karin and Marlow, Florence and Kawakami, Koichi and Solnica Krezel, Lilianna and Heisenberg, Carl-Philipp J and Raz, Erez}, journal = {Developmental Cell}, number = {5}, pages = {613 -- 627}, publisher = {Cell Press}, title = {{Migration of zebrafish primordial germ cells: A role for myosin contraction and cytoplasmic flow}}, doi = {10.1016/j.devcel.2006.09.023}, volume = {11}, year = {2006}, } @article{4237, abstract = {The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the Population. One important class of regulatory functions is the theta-logistic, which generalizes the logistic equation. Using this model as a motivation, this paper introduces a simple dynamical reformulation that generalizes many growth functions. The reformulation consists of two equations, one for population size, and one for the growth rate. Furthermore, the model shows that although population is density-dependent, the dynamics of the growth rate does not depend either on population size, nor on the carrying capacity. Actually, the growth equation is uncoupled from the population size equation, and the model has only two parameters, a Malthusian parameter rho and a competition coefficient theta. Distinct sign combinations of these parameters reproduce not only the family of theta-logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations, among other possibilities. It is also shown that, except for two critical points, there is a general size-scaling relation that includes those appearing in the most important allometric theories, including the recently proposed Metabolic Theory of Ecology. With this model, several issues of general interest are discussed such as the growth of animal population, extinctions, cell growth and allometry, and the effect of environment over a population. (c) 2005 Elsevier Ltd. All rights reserved.}, author = {de Vladar, Harold}, journal = {Journal of Theoretical Biology}, number = {2}, pages = {245 -- 256}, publisher = {Elsevier}, title = {{Density-dependence as a size-independent regulatory mechanism}}, doi = {3802}, volume = {238}, year = {2006}, } @article{4235, author = {Harold Vladar and González,J. A}, journal = {Journal of Theoretical Biology}, pages = {91 -- 109}, publisher = {Elsevier}, title = {{Dynamic response of cancer under the influence of immunological activity and therapy}}, year = {2006}, } @article{4248, abstract = {In finite populations, genetic drift generates interference between selected loci, causing advantageous alleles to be found more often on different chromosomes than on the same chromosome, which reduces the rate of adaptation. This “Hill–Robertson effect” generates indirect selection to increase recombination rates. We present a new method to quantify the strength of this selection. Our model represents a new beneficial allele (A) entering a population as a single copy, while another beneficial allele (B) is sweeping at another locus. A third locus affects the recombination rate between selected loci. Using a branching process model, we calculate the probability distribution of the number of copies of A on the different genetic backgrounds, after it is established but while it is still rare. Then, we use a deterministic model to express the change in frequency of the recombination modifier, due to hitchhiking, as A goes to fixation. We show that this method can give good estimates of selection for recombination. Moreover, it shows that recombination is selected through two different effects: it increases the fixation probability of new alleles, and it accelerates selective sweeps. The relative importance of these two effects depends on the relative times of occurrence of the beneficial alleles.}, author = {Roze, Denis and Nicholas Barton}, journal = {Genetics}, number = {3}, pages = {1793 -- 1811}, publisher = {Genetics Society of America}, title = {{The Hill-Robertson effect and the evolution of recombination}}, doi = {10.1534/genetics.106.058586 }, volume = {173}, year = {2006}, } @misc{4250, abstract = {A recent analysis has shown that divergence between human and chimpanzee varies greatly across the genome. Although this is consistent with ‘hybridisation’ between the diverging human and chimp lineages, such observations can be explained more simply by the null model of allopatric speciation.}, author = {Nicholas Barton}, booktitle = {Current Biology}, number = {16}, pages = {647 -- 650}, publisher = {Cell Press}, title = {{Evolutionary Biology: How did the human species form?}}, doi = {10.1016/j.cub.2006.07.032}, volume = {16}, year = {2006}, } @inproceedings{4359, author = {Thomas Wies and Kuncak, Viktor and Lam,Patrick and Podelski,Andreas and Rinard,Martin}, pages = {157 -- 173}, publisher = {Springer}, title = {{Field Constraint Analysis}}, doi = {1551}, year = {2006}, } @inproceedings{4373, author = {Maler, Oded and Dejan Nickovic and Pnueli,Amir}, pages = {2 -- 16}, publisher = {Springer}, title = {{Real Time Temporal Logic: Past, Present, Future}}, doi = {1571}, year = {2006}, } @inproceedings{4374, author = {Maler, Oded and Dejan Nickovic and Pnueli,Amir}, pages = {274 -- 289}, publisher = {Springer}, title = {{From MITL to Timed Automata}}, doi = {1570}, year = {2006}, } @inproceedings{4406, abstract = {We propose and evaluate a new algorithm for checking the universality of nondeterministic finite automata. In contrast to the standard algorithm, which uses the subset construction to explicitly determinize the automaton, we keep the determinization step implicit. Our algorithm computes the least fixed point of a monotone function on the lattice of antichains of state sets. We evaluate the performance of our algorithm experimentally using the random automaton model recently proposed by Tabakov and Vardi. We show that on the difficult instances of this probabilistic model, the antichain algorithm outperforms the standard one by several orders of magnitude. We also show how variations of the antichain method can be used for solving the language-inclusion problem for nondeterministic finite automata, and the emptiness problem for alternating finite automata.}, author = {De Wulf, Martin and Doyen, Laurent and Thomas Henzinger and Raskin, Jean-François}, pages = {17 -- 30}, publisher = {Springer}, title = {{Antichains: A new algorithm for checking universality of finite automata}}, doi = {10.1007/11817963_5}, volume = {4144}, year = {2006}, } @inproceedings{4401, author = {Alur, Rajeev and Pavol Cerny and Zdancewic,Steve}, pages = {107 -- 118}, publisher = {Springer}, title = {{Preserving Secrecy Under Refinement}}, doi = {1543}, year = {2006}, } @inproceedings{4437, abstract = {The synthesis of reactive systems requires the solution of two-player games on graphs with ω-regular objectives. When the objective is specified by a linear temporal logic formula or nondeterministic Büchi automaton, then previous algorithms for solving the game require the construction of an equivalent deterministic automaton. However, determinization for automata on infinite words is extremely complicated, and current implementations fail to produce deterministic automata even for relatively small inputs. We show how to construct, from a given nondeterministic Büchi automaton, an equivalent nondeterministic parity automaton that is good for solving games with objective . The main insight is that a nondeterministic automaton is good for solving games if it fairly simulates the equivalent deterministic automaton. In this way, we omit the determinization step in game solving and reactive synthesis. The fact that our automata are nondeterministic makes them surprisingly simple, amenable to symbolic implementation, and allows an incremental search for winning strategies.}, author = {Thomas Henzinger and Piterman, Nir}, pages = {395 -- 410}, publisher = {Springer}, title = {{Solving games without determinization}}, doi = {10.1007/11874683_26}, volume = {4207}, year = {2006}, } @inproceedings{4436, abstract = {We present an assume-guarantee interface algebra for real-time components. In our formalism a component implements a set of task sequences that share a resource. A component interface consists of an arrival rate function and a latency for each task sequence, and a capacity function for the shared resource. The interface specifies that the component guarantees certain task latencies depending on assumptions about task arrival rates and allocated resource capacities. Our algebra defines compatibility and refinement relations on interfaces. Interface compatibility can be checked on partial designs, even when some component interfaces are yet unknown. In this case interface composition computes as new assumptions the weakest constraints on the unknown components that are necessary to satisfy the specified guarantees. Interface refinement is defined in a way that ensures that compatible interfaces can be refined and implemented independently. Our algebra thus formalizes an interface-based design methodology that supports both the incremental addition of new components and the independent stepwise refinement of existing components. We demonstrate the flexibility and efficiency of the framework through simulation experiments.}, author = {Thomas Henzinger and Matic, Slobodan}, pages = {253 -- 266}, publisher = {IEEE}, title = {{An interface algebra for real-time components}}, doi = {10.1109/RTAS.2006.11}, year = {2006}, } @inproceedings{4432, abstract = {We add freeze quantifiers to the game logic ATL in order to specify real-time objectives for games played on timed structures. We define the semantics of the resulting logic TATL by restricting the players to physically meaningful strategies, which do not prevent time from diverging. We show that TATL can be model checked over timed automaton games. We also specify timed optimization problems for physically meaningful strategies, and we show that for timed automaton games, the optimal answers can be approximated to within any degree of precision.}, author = {Thomas Henzinger and Prabhu, Vinayak S}, pages = {1 -- 17}, publisher = {Springer}, title = {{Timed alternating-time temporal logic}}, doi = {10.1007/11867340_1}, volume = {4202}, year = {2006}, } @inproceedings{4431, abstract = {We summarize some current trends in embedded systems design and point out some of their characteristics, such as the chasm between analytical and computational models, and the gap between safety-critical and best-effort engineering practices. We call for a coherent scientific foundation for embedded systems design, and we discuss a few key demands on such a foundation: the need for encompassing several manifestations of heterogeneity, and the need for constructivity in design. We believe that the development of a satisfactory Embedded Systems Design Science provides a timely challenge and opportunity for reinvigorating computer science.}, author = {Thomas Henzinger and Sifakis, Joseph}, pages = {1 -- 15}, publisher = {Springer}, title = {{The embedded systems design challenge}}, doi = {10.1007/11813040_1}, volume = {4085}, year = {2006}, } @article{4451, abstract = {One source of complexity in the μ-calculus is its ability to specify an unbounded number of switches between universal (AX) and existential (EX) branching modes. We therefore study the problems of satisfiability, validity, model checking, and implication for the universal and existential fragments of the μ-calculus, in which only one branching mode is allowed. The universal fragment is rich enough to express most specifications of interest, and therefore improved algorithms are of practical importance. We show that while the satisfiability and validity problems become indeed simpler for the existential and universal fragments, this is, unfortunately, not the case for model checking and implication. We also show the corresponding results for the alternation-free fragment of the μ-calculus, where no alternations between least and greatest fixed points are allowed. Our results imply that efforts to find a polynomial-time model-checking algorithm for the μ-calculus can be replaced by efforts to find such an algorithm for the universal or existential fragment.}, author = {Thomas Henzinger and Kupferman, Orna and Majumdar, Ritankar S}, journal = {Theoretical Computer Science}, number = {2}, pages = {173 -- 186}, publisher = {Elsevier}, title = {{On the universal and existential fragments of the mu-calculus}}, doi = {10.1016/j.tcs.2005.11.015}, volume = {354}, year = {2006}, } @inproceedings{4523, abstract = {We consider the problem if a given program satisfies a specified safety property. Interesting programs have infinite state spaces, with inputs ranging over infinite domains, and for these programs the property checking problem is undecidable. Two broad approaches to property checking are testing and verification. Testing tries to find inputs and executions which demonstrate violations of the property. Verification tries to construct a formal proof which shows that all executions of the program satisfy the property. Testing works best when errors are easy to find, but it is often difficult to achieve sufficient coverage for correct programs. On the other hand, verification methods are most successful when proofs are easy to find, but they are often inefficient at discovering errors. We propose a new algorithm, Synergy, which combines testing and verification. Synergy unifies several ideas from the literature, including counterexample-guided model checking, directed testing, and partition refinement.This paper presents a description of the Synergy algorithm, its theoretical properties, a comparison with related algorithms, and a prototype implementation called Yogi.}, author = {Gulavani, Bhargav S and Thomas Henzinger and Kannan, Yamini and Nori, Aditya V and Rajamani, Sriram K}, pages = {117 -- 127}, publisher = {ACM}, title = {{Synergy: A new algorithm for property checking}}, doi = {10.1145/1181775.1181790}, year = {2006}, } @inproceedings{4526, abstract = {We designed and implemented a new programming language called Hierarchical Timing Language (HTL) for hard realtime systems. Critical timing constraints are specified within the language,and ensured by the compiler. Programs in HTL are extensible in two dimensions without changing their timing behavior: new program modules can be added, and individual program tasks can be refined. The mechanism supporting time invariance under parallel composition is that different program modules communicate at specified instances of time. Time invariance under refinement is achieved by conservative scheduling of the top level. HTL is a coordination language, in that individual tasks can be implemented in "foreign" languages. As a case study, we present a distributed HTL implementation of an automotive steer-by-wire controller.}, author = {Ghosal, Arkadeb and Thomas Henzinger and Iercan, Daniel and Kirsch, Christoph M and Sangiovanni-Vincentelli, Alberto}, pages = {132 -- 141}, publisher = {ACM}, title = {{A hierarchical coordination language for interacting real-time tasks}}, doi = {10.1145/1176887.1176907}, year = {2006}, } @inproceedings{4528, abstract = {Computational modeling of biological systems is becoming increasingly common as scientists attempt to understand biological phenomena in their full complexity. Here we distinguish between two types of biological models mathematical and computational - according to their different representations of biological phenomena and their diverse potential. We call the approach of constructing computational models of biological systems executable biology, as it focuses on the design of executable computer algorithms that mimic biological phenomena. We give an overview of the main modeling efforts in this direction, and discuss some of the new challenges that executable biology poses for computer science and biology. We argue that for executable biology to reach its full potential as a mainstream biological technique, formal and algorithmic approaches must be integrated into biological research, driving biology towards a more precise engineering discipline.}, author = {Fisher, Jasmin and Thomas Henzinger}, pages = {1675 -- 1682}, publisher = {IEEE}, title = {{Executable biology}}, doi = {10.1109/WSC.2006.322942}, year = {2006}, } @inproceedings{4539, abstract = {Games on graphs with ω-regular objectives provide a model for the control and synthesis of reactive systems. Every ω-regular objective can be decomposed into a safety part and a liveness part. The liveness part ensures that something good happens “eventually.” Two main strengths of the classical, infinite-limit formulation of liveness are robustness (independence from the granularity of transitions) and simplicity (abstraction of complicated time bounds). However, the classical liveness formulation suffers from the drawback that the time until something good happens may be unbounded. A stronger formulation of liveness, so-called finitary liveness, overcomes this drawback, while still retaining robustness and simplicity. Finitary liveness requires that there exists an unknown, fixed bound b such that something good happens within b transitions. While for one-shot liveness (reachability) objectives, classical and finitary liveness coincide, for repeated liveness (Büchi) objectives, the finitary formulation is strictly stronger. In this work we study games with finitary parity and Streett (fairness) objectives. We prove the determinacy of these games, present algorithms for solving these games, and characterize the memory requirements of winning strategies. Our algorithms can be used, for example, for synthesizing controllers that do not let the response time of a system increase without bound.}, author = {Krishnendu Chatterjee and Thomas Henzinger}, pages = {257 -- 271}, publisher = {Springer}, title = {{Finitary winning in omega-regular games}}, doi = {10.1007/11691372_17}, volume = {3920}, year = {2006}, } @inproceedings{4538, abstract = {A stochastic graph game is played by two players on a game graph with probabilistic transitions. We consider stochastic graph games with ω-regular winning conditions specified as parity objectives. These games lie in NP ∩ coNP. We present a strategy improvement algorithm for stochastic parity games; this is the first non-brute-force algorithm for solving these games. From the strategy improvement algorithm we obtain a randomized subexponential-time algorithm to solve such games.}, author = {Krishnendu Chatterjee and Thomas Henzinger}, pages = {512 -- 523}, publisher = {Springer}, title = {{Strategy improvement and randomized subexponential algorithms for stochastic parity games}}, doi = {10.1007/11672142_42}, volume = {3884}, year = {2006}, } @inproceedings{4551, abstract = {We consider Markov decision processes (MDPs) with multiple discounted reward objectives. Such MDPs occur in design problems where one wishes to simultaneously optimize several criteria, for example, latency and power. The possible trade-offs between the different objectives are characterized by the Pareto curve. We show that every Pareto-optimal point can be achieved by a memoryless strategy; however, unlike in the single-objective case, the memoryless strategy may require randomization. Moreover, we show that the Pareto curve can be approximated in polynomial time in the size of the MDP. Additionally, we study the problem if a given value vector is realizable by any strategy, and show that it can be decided in polynomial time; but the question whether it is realizable by a deterministic memoryless strategy is NP-complete. These results provide efficient algorithms for design exploration in MDP models with multiple objectives. This research was supported in part by the AFOSR MURI grant F49620-00-1-0327, and the NSF grants CCR-0225610, CCR-0234690, and CCR-0427202. }, author = {Krishnendu Chatterjee and Majumdar, Ritankar S and Thomas Henzinger}, pages = {325 -- 336}, publisher = {Springer}, title = {{Markov decision processes with multiple objectives}}, doi = {10.1007/11672142_26}, volume = {3884}, year = {2006}, } @article{4550, abstract = {In 2-player non-zero-sum games, Nash equilibria capture the options for rational behavior if each player attempts to maximize her payoff. In contrast to classical game theory, we consider lexicographic objectives: first, each player tries to maximize her own payoff, and then, the player tries to minimize the opponent's payoff. Such objectives arise naturally in the verification of systems with multiple components. There, instead of proving that each component satisfies its specification no matter how the other components behave, it sometimes suffices to prove that each component satisfies its specification provided that the other components satisfy their specifications. We say that a Nash equilibrium is secure if it is an equilibrium with respect to the lexicographic objectives of both players. We prove that in graph games with Borel winning conditions, which include the games that arise in verification, there may be several Nash equilibria, but there is always a unique maximal payoff profile of a secure equilibrium. We show how this equilibrium can be computed in the case of ω-regular winning conditions, and we characterize the memory requirements of strategies that achieve the equilibrium.}, author = {Krishnendu Chatterjee and Thomas Henzinger and Jurdziński, Marcin}, journal = {Theoretical Computer Science}, number = {1-2}, pages = {67 -- 82}, publisher = {Elsevier}, title = {{Games with secure equilibria}}, doi = {10.1016/j.tcs.2006.07.032}, volume = {365}, year = {2006}, } @inproceedings{4549, abstract = {We present a compositional theory of system verification, where specifications assign real-numbered costs to systems. These costs can express a wide variety of quantitative system properties, such as resource consumption, price, or a measure of how well a system satisfies its specification. The theory supports the composition of systems and specifications, and the hiding of variables. Boolean refinement relations are replaced by real-numbered distances between descriptions of a system at different levels of detail. We show that the classical Boolean rules for compositional reasoning have quantitative counterparts in our setting. While our general theory allows costs to be specified by arbitrary cost functions, we also consider a class of linear cost functions, which give rise to an instance of our framework where all operations are computable in polynomial time.}, author = {Krishnendu Chatterjee and de Alfaro, Luca and Faella, Marco and Thomas Henzinger and Majumdar, Ritankar S and Stoelinga, Mariëlle}, pages = {179 -- 188}, publisher = {IEEE}, title = {{Compositional quantitative reasoning}}, doi = {10.1109/QEST.2006.11}, year = {2006}, } @inproceedings{4552, abstract = {A concurrent reachability game is a two-player game played on a graph: at each state, the players simultaneously and independently select moves; the two moves determine jointly a probability distribution over the successor states. The objective for player 1 consists in reaching a set of target states; the objective for player 2 is to prevent this, so that the game is zero-sum. Our contributions are two-fold. First, we present a simple proof of the fact that in concurrent reachability games, for all epsilon > 0, memoryless epsilon-optimal strategies exist. A memoryless strategy is independent of the history of plays, and an epsilon-optimal strategy achieves the objective with probability within epsilon of the value of the game. In contrast to previous proofs of this fact, which rely on the limit behavior of discounted games using advanced Puisieux series analysis, our proof is elementary and combinatorial. Second, we present a strategy-improvement (a.k.a. policy-iteration) algorithm for concurrent games with reachability objectives.}, author = {Krishnendu Chatterjee and de Alfaro, Luca and Thomas Henzinger}, pages = {291 -- 300}, publisher = {IEEE}, title = {{Strategy improvement for concurrent reachability games}}, doi = {10.1109/QEST.2006.48}, year = {2006}, } @inproceedings{4574, abstract = {Many software model checkers are based on predicate abstraction. If the verification goal depends on pointer structures, the approach does not work well, because it is difficult to find adequate predicate abstractions for the heap. In contrast, shape analysis, which uses graph-based heap abstractions, can provide a compact representation of recursive data structures. We integrate shape analysis into the software model checker Blast. Because shape analysis is expensive, we do not apply it globally. Instead, we ensure that, like predicates, shape graphs are computed and stored locally, only where necessary for proving the verification goal. To achieve this, we extend lazy abstraction refinement, which so far has been used only for predicate abstractions, to three-valued logical structures. This approach does not only increase the precision of model checking, but it also increases the efficiency of shape analysis. We implemented the technique by extending Blast with calls to Tvla.}, author = {Beyer, Dirk and Thomas Henzinger and Théoduloz, Grégory}, pages = {532 -- 546}, publisher = {Springer}, title = {{Lazy shape analysis}}, doi = {10.1007/11817963_48}, volume = {4144}, year = {2006}, } @unpublished{573, abstract = {Mitchison and Jozsa recently suggested that the "chained-Zeno" counterfactual computation protocol recently proposed by Hosten et al. is counterfactual for only one output of the computer. This claim was based on the existing abstract algebraic definition of counterfactual computation, and indeed according to this definition, their argument is correct. However, a more general definition (physically adequate) for counterfactual computation is implicitly assumed by Hosten et. al. Here we explain in detail why the protocol is counterfactual and how the "history tracking" method of the existing description inadequately represents the physics underlying the protocol. Consequently, we propose a modified definition of counterfactual computation. Finally, we comment on one of the most interesting aspects of the error-correcting protocol. }, author = {Hosten, Onur and Rakher, Matthew and Barreiro, Julio and Peters, Nicholas and Kwiat, Paul}, pages = {12}, publisher = {ArXiv}, title = {{Counterfactual computation revisited}}, year = {2006}, } @unpublished{574, abstract = {Vaidman, in a recent article adopts the method of 'quantum weak measurements in pre- and postselected ensembles' to ascertain whether or not the chained-Zeno counterfactual computation scheme proposed by Hosten et al. is counterfactual; which has been the topic of a debate on the definition of counterfactuality. We disagree with his conclusion, which brings up some interesting aspects of quantum weak measurements and some concerns about the way they are interpreted. }, author = {Hosten, Onur and Kwiat, Paul}, pages = {2}, publisher = {ArXiv}, title = {{Weak measurements and counterfactual computation}}, year = {2006}, } @inproceedings{578, abstract = {A source of single photons allows secure quantum key distribution, in addition, to being a critical resource for linear optics quantum computing. We describe our progress on deterministically creating single photons from spontaneous parametric downconversion, an extension of the Pittman, Jacobs and Franson scheme [Phys. Rev A, v66, 042303 (2002)]. Their idea was to conditionally prepare single photons by measuring one member of a spontaneously emitted photon pair and storing the remaining conditionally prepared photon until a predetermined time, when it would be "deterministically" released from storage. Our approach attempts to improve upon this by recycling the pump pulse in order to decrease the possibility of multiple-pair generation, while maintaining a high probability of producing a single pair. Many of the challenges we discuss are central to other quantum information technologies, including the need for low-loss optical storage, switching and detection, and fast feed-forward control.}, author = {Peters, Nicholas A and Arnold, Keith J and VanDevender, Aaron P and Jeffrey, Evan R and Rangarajan, Radhika and Onur Hosten and Barreiro, Julio T and Altepeter, Joseph B and Kwiat, Paul G}, publisher = {SPIE}, title = {{Towards a quasi-deterministic single-photon source}}, doi = {10.1117/12.684702}, volume = {6305}, year = {2006}, } @inproceedings{577, abstract = {Visible light photon counters (VLPCs) and solid-state photomultipliers (SSPMs) are high-efficiency single-photon detectors which have multi-photon counting capability. While both the VLPCs and the SSPMs have inferred internal quantum efficiencies above 93%, the actual measured values for both the detectors were in fact limited to less than 88%, attributed to in-coupling losses. We are currently improving this overall detection efficiency via a) custom anti-reflection coating the detectors and the in-coupling fibers, b) implementing a novel cryogenic design to reduce transmission losses and, c) using low-noise electronics to obtain a better signal-to-noise ratio.}, author = {Rangarajan, Radhika and Altepeter, Joseph B and Jeffrey, Evan R and Stoutimore, Micah J and Peters, Nicholas A and Onur Hosten and Kwiat, Paul G}, publisher = {SPIE}, title = {{High-efficiency single-photon detectors}}, doi = {10.1117/12.686117}, volume = {6372}, year = {2006}, } @article{579, abstract = {The logic underlying the coherent nature of quantum information processing often deviates from intuitive reasoning, leading to surprising effects. Counterfactual computation constitutes a striking example: the potential outcome of a quantum computation can be inferred, even if the computer is not run 1. Relying on similar arguments to interaction-free measurements 2 (or quantum interrogation3), counterfactual computation is accomplished by putting the computer in a superposition of 'running' and 'not running' states, and then interfering the two histories. Conditional on the as-yet-unknown outcome of the computation, it is sometimes possible to counterfactually infer information about the solution. Here we demonstrate counterfactual computation, implementing Grover's search algorithm with an all-optical approach4. It was believed that the overall probability of such counterfactual inference is intrinsically limited1,5, so that it could not perform better on average than random guesses. However, using a novel 'chained' version of the quantum Zeno effect6, we show how to boost the counterfactual inference probability to unity, thereby beating the random guessing limit. Our methods are general and apply to any physical system, as illustrated by a discussion of trapped-ion systems. Finally, we briefly show that, in certain circumstances, counterfactual computation can eliminate errors induced by decoherence. }, author = {Onur Hosten and Rakher, Matthew T and Barreiro, Julio T and Peters, Nicholas A and Kwiat, Paul G}, journal = {Nature}, number = {7079}, pages = {949 -- 952}, publisher = {Nature Publishing Group}, title = {{Counterfactual quantum computation through quantum interrogation}}, doi = {10.1038/nature04523}, volume = {439}, year = {2006}, } @inproceedings{583, abstract = {Visible light photon counters (VLPCs) and solid-state photomultipliers (SSPMs) facilitate efficient single-photon detection. We are attempting to improve their efficiency, previously limited to < 88% by coupling losses, via anti-reflection coatings, better electronics and cryogenics.}, author = {Rangarajan, Radhika and Peters, Nicholas A and Onur Hosten and Altepeter, Joseph B and Jeffrey, Evan R and Kwiat, Paul G}, publisher = {IEEE}, title = {{Improved single-photon detection}}, doi = {10.1109/CLEO.2006.4628641}, year = {2006}, } @article{6151, author = {Salecker, Iris and Häusser, Michael and de Bono, Mario}, issn = {1469-221X}, journal = {EMBO reports}, number = {6}, pages = {585--589}, publisher = {Wiley}, title = {{On the axonal road to circuit function and behaviour: Workshop on the assembly and function of neuronal circuits}}, doi = {10.1038/sj.embor.7400713}, volume = {7}, year = {2006}, } @article{6152, author = {Rogers, Candida and Persson, Annelie and Cheung, Benny and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {7}, pages = {649--659}, publisher = {Elsevier}, title = {{Behavioral motifs and neural pathways coordinating O2 responses and aggregation in C. elegans}}, doi = {10.1016/j.cub.2006.03.023}, volume = {16}, year = {2006}, } @article{7328, abstract = {An experimental technique for measuring the current density distribution with a resolution smaller than the channel/rib scale of the flow field in polymer electrolyte fuel cells (PEFCs) is presented. The electron conductors in a plane perpendicular to the channel direction are considered as two-dimensional resistors. Hence, the current density is obtained from the solution of Laplace's equation with the potentials at current collector and reaction layer as boundary conditions. Using ohmic drop for calculating the local current, detailed knowledge of all resistances involved is of prime importance. In particular, the contact resistance between the gas diffusion layer (GDL) and flow field rib, as well as GDL bulk conductivity, are strongly dependent on clamping pressure. They represent a substantial amount of the total ohmic drop and therefore require careful consideration. The detailed experimental setup as well as the concise procedure for quantitative data evaluation is described. Finally, the method is applied successfully to a cell operated on pure oxygen and air up to high current densities. The results show that electrical and ionic resistances seem to govern the current distribution at low current regimes, whereas mass transport limitations locally hamper the current production at high loads.}, author = {Freunberger, Stefan Alexander and Reum, Mathias and Evertz, Jörg and Wokaun, Alexander and Büchi, Felix N.}, issn = {0013-4651}, journal = {Journal of The Electrochemical Society}, number = {11}, publisher = {The Electrochemical Society}, title = {{Measuring the current distribution in PEFCs with sub-millimeter resolution}}, doi = {10.1149/1.2345591}, volume = {153}, year = {2006}, } @article{7327, abstract = {Propagation of performance changes to adjacent cells in polymer electrolyte fuel cell stacks is studied by means of voltage monitoring and local current density measurements in peripheral cells of the stack. A technical fuel cell stack has been modified by implementing two independent reactant and coolant supplies in order to deliberately change the performance of one cell (anomalous cell) and study the coupling phenomena to adjacent cells (coupling cells), while keeping the working conditions of the later cell-group unaltered. Two anomalies are studied: (i) air starvation and (ii) thermal anomaly, in a single anomalous cell in the stack and their coupling to adjacent cells. The results have shown that anomalies inducing considerable changes in the local current density of the anomalous cell (such as air starvation) propagate to adjacent cells affecting their performance. The propagation of local current density changes takes place via the common bipolar plate due to its finite thickness and in-plane conductivity. Consequently, anomalies which do not strongly influence the local current density distribution (such as a thermal anomaly under the studied working conditions) do not propagate to adjacent cells.}, author = {Santis, Marco and Freunberger, Stefan Alexander and Papra, Matthias and Wokaun, Alexander and Büchi, Felix N.}, issn = {0378-7753}, journal = {Journal of Power Sources}, number = {2}, pages = {1076--1083}, publisher = {Elsevier}, title = {{Experimental investigation of coupling phenomena in polymer electrolyte fuel cell stacks}}, doi = {10.1016/j.jpowsour.2006.06.007}, volume = {161}, year = {2006}, } @inproceedings{7326, abstract = {Often the properties of a single cell are considered as representative for a complete polymer electrolyte fuel cell stack or even a fuel cell system. In some cases this comes close, however, in many real cases differences on several scales become important. Cell interaction phenomena in fuel cell stacks that arise from inequalities between adjacent cells are investigated in detail experimentally. For that, a specialized 2-cell stack with advanced localized diagnostics was developed. The results show that inequalities propagate by electrical coupling, inhomogeneous cell polarization and inducing in-plane current in the common bipolar plate. The effects of the different loss-mechanisms are analyzed and quantified. }, author = {Büchi, Felix N. and Freunberger, Stefan Alexander and Santis, Marco}, booktitle = {ECS Transactions}, location = {Cancun, Mexico}, number = {1}, pages = {963--968}, publisher = {ECS}, title = {{What is learned beyond the scale of single cells?}}, doi = {10.1149/1.2356215}, volume = {3}, year = {2006}, } @article{7329, abstract = {A novel measurement principle for measuring the current distribution in polymer electrolyte fuel cells (PEFCs) is introduced. It allows, in contrast to all other known techniques, for the first time for a resolution smaller than the channel/rib scale of the flow field in PEFCs. The current density is obtained by considering the electron conductors in the cell as a two-dimensional resistor with the voltage drop caused by the current. The method was applied to a cell operated on oxygen up to high current densities. The results show that the ohmic resistances govern the current distribution in the low current regime, whereas mass transport limitations hamper the current production under the land at high loads.}, author = {Freunberger, Stefan Alexander and Reum, Mathias and Wokaun, Alexander and Büchi, Felix N.}, issn = {1388-2481}, journal = {Electrochemistry Communications}, number = {9}, pages = {1435--1438}, publisher = {Elsevier}, title = {{Expanding current distribution measurement in PEFCs to sub-millimeter resolution}}, doi = {10.1016/j.elecom.2006.05.032}, volume = {8}, year = {2006}, } @article{7330, abstract = {Polymer electrolyte fuel cells (PE fuel cells) working with air at low stoichiometries (<2.0) and standard electrochemical components show a high degree of inhomogeneity in the current density distribution over the active area. An inhomogeneous current density distribution leads to a non-uniform utilization of the active area, which could negatively affect the time of life of the cells. Furthermore, it is also believed to lower cell performance. In this work, the homogenization of the current density, realized by means of tailored cathodes with along-the-air-channel redistributed catalyst loadings, is investigated. The air stoichiometry range for which a homogenization of the current density is achieved depends upon the gradient with which the catalyst is redistributed along the air channel. A gentle increasing catalyst loading profile homogenizes the current density at relatively higher air stoichiometries, while a steeper profile is suited better for lower air stoichiometries. The results show that a homogenization of the current density by means of redistributed catalyst loading has negative effects on cell performance. Model calculations corroborate the experimental findings on homogenization of the current density and deliver an explanation for the decrease in cell performance.}, author = {Santis, M. and Freunberger, Stefan Alexander and Reiner, A. and Büchi, F.N.}, issn = {0013-4686}, journal = {Electrochimica Acta}, number = {25}, pages = {5383--5393}, publisher = {Elsevier}, title = {{Homogenization of the current density in polymer electrolyte fuel cells by in-plane cathode catalyst gradients}}, doi = {10.1016/j.electacta.2006.02.008}, volume = {51}, year = {2006}, } @article{7332, abstract = {A quasi-two-dimensional, along-the-channel mass and heat-transfer model for a proton exchange membrane fuel cell (PEFC) is described and validated against experimental current distribution data. The model is formulated in a dimensional manner, i.e., local transport phenomena are treated one-dimensional in through-plane direction and coupled in-plane by convective transport in the gas and coolant channels. Thus, a two-dimensional slice running through the repetitive unit of a cell from the anode channel via membrane-electrode assembly (MEA) and cathode channel to the coolant channel and from inlet to outlet is modeled. The aim of the work is to elucidate the influence of operating conditions such as feed gas humidities and stoichiometric ratios on the along-the-channel current density distribution and to identify the distinct underlying voltage loss mechanisms. Furthermore, a complicated technical flow field is modeled by a combination of co- and counterflow subdomains and compared with experimental current densities.}, author = {Freunberger, Stefan Alexander and Santis, Marco and Schneider, Ingo A. and Wokaun, Alexander and Büchi, Felix N.}, issn = {0013-4651}, journal = {Journal of The Electrochemical Society}, number = {2}, publisher = {The Electrochemical Society}, title = {{In-plane effects in large-scale PEMFCs}}, doi = {10.1149/1.2150150}, volume = {153}, year = {2006}, } @article{7331, abstract = {A previously developed mathematical model for water management and current density distribution in a polymer electrolyte fuel cell (PEFCs) is employed to investigate the effects of cooling strategies on cell performance. The model describes a two-dimensional slice through the cell along the channels and through the entire cell sandwich including the coolant channels and the bipolar plate. Arbitrary flow arrangements of fuel, oxidant, and coolant stream directions can be described. Due to the serious impact of temperature on all processes in the PEFC, both the relative direction of the coolant stream to the gas streams and its mass flow turns out to significantly affect the cell performance. Besides influencing the electrochemical reaction and all kinds of mass transfer temperature, variations predominantly alter the local membrane hydration distribution and subseqently its conductivity.}, author = {Freunberger, Stefan Alexander and Wokaun, Alexander and Büchi, Felix N.}, issn = {0013-4651}, journal = {Journal of The Electrochemical Society}, number = {5}, publisher = {The Electrochemical Society}, title = {{In-plane effects in large-scale PEFCs: II. The influence of cooling strategy on cell performance}}, doi = {10.1149/1.2185282}, volume = {153}, year = {2006}, } @article{854, abstract = {Phylogenetic relationships between the extinct woolly mammoth (Mammuthus primigenius), and the Asian (Elephas maximus) and African savanna (Loxodonta africana) elephants remain unresolved. Here, we report the sequence of the complete mitochondrial genome (16,842 base pairs) of a woolly mammoth extracted from permafrost-preserved remains from the Pleistocene epoch - the oldest mitochondrial genome sequence determined to date. We demonstrate that well-preserved mitochondrial genome fragments, as long as ∼1,600-1700 base pairs, can be retrieved from pre-Holocene remains of an extinct species. Phylogenetic reconstruction of the Elephantinae clade suggests that M. primigenius and E. maximus are sister species that diverged soon after their common ancestor split from the L. africana lineage. Low nucleotide diversity found between independently determined mitochondrial genomic sequences of woolly mammoths separated geographically and in time suggests that north-eastern Siberia was occupied by a relatively homogeneous population of M. primigenius throughout the late Pleistocene.}, author = {Rogaev, Evgeny I and Moliaka, Yuri K and Malyarchuk, Boris A and Fyodor Kondrashov and Derenko, Miroslava V and Chumakov, Ilya M and Grigorenko, Anastasia P}, journal = {PLoS Biology}, number = {3}, pages = {0403 -- 0410}, publisher = {Public Library of Science}, title = {{Complete mitochondrial genome and phylogeny of pleistocene mammoth Mammuthus primigenius}}, doi = {10.1371/journal.pbio.0040073}, volume = {4}, year = {2006}, } @article{868, abstract = {Background: The glyoxylate cycle is thought to be present in bacteria, protists, plants, fungi, and nematodes, but not in other Metazoa. However, activity of the glyoxylate cycle enzymes, malate synthase (MS) and isocitrate lyase (ICL), in animal tissues has been reported. In order to clarify the status of the MS and ICL genes in animals and get an insight into their evolution, we undertook a comparative-genomic study. Results: Using sequence similarity searches, we identified MS genes in arthropods, echinoderms, and vertebrates, including platypus and opossum, but not in the numerous sequenced genomes of placental mammals. The regions of the placental mammals' genomes expected to code for malate synthase, as determined by comparison of the gene orders in vertebrate genomes, show clear similarity to the opossum MS sequence but contain stop codons, indicating that the MS gene became a pseudogene in placental mammals. By contrast, the ICL gene is undetectable in animals other than the nematodes that possess a bifunctional, fused ICL-MS gene. Examination of phylogenetic trees of MS and ICL suggests multiple horizontal gene transfer events that probably went in both directions between several bacterial and eukaryotic lineages. The strongest evidence was obtained for the acquisition of the bifunctional ICL-MS gene from an as yet unknown bacterial source with the corresponding operonic organization by the common ancestor of the nematodes. Conclusion: The distribution of the MS and ICL genes in animals suggests that either they encode alternative enzymes of the glyoxylate cycle that are not orthologous to the known MS and ICL or the animal MS acquired a new function that remains to be characterized. Regardless of the ultimate solution to this conundrum, the genes for the glyoxylate cycle enzymes present a remarkable variety of evolutionary events including unusual horizontal gene transfer from bacteria to animals.}, author = {Fyodor Kondrashov and Koonin, Eugene V and Morgunov, Igor G and Finogenova, Tatiana V and Kondrashova, Marie N}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Evolution of glyoxylate cycle enzymes in Metazoa Evidence of multiple horizontal transfer events and pseudogene formation}}, doi = {10.1186/1745-6150-1-31}, volume = {1}, year = {2006}, } @article{873, abstract = {New genes commonly appear through complete or partial duplications of pre-existing genes. Duplications of long DNA segments are constantly produced by rare mutations, may become fixed in a population by selection or random drift, and are subject to divergent evolution of the paralogous sequences after fixation, although gene conversion can impede this process. New data shed some light on each of these processes. Mutations which involve duplications can occur through at least two different mechanisms, backward strand slippage during DNA replication and unequal crossing-over. The background rate of duplication of a complete gene in humans is 10-9-10-10 per generation, although many genes located within hot-spots of large-scale mutation are duplicated much more often. Many gene duplications affect fitness strongly, and are responsible, through gene dosage effects, for a number of genetic diseases. However, high levels of intrapopulation polymorphism caused by presence or absence of long, gene-containing DNA segments imply that some duplications are not under strong selection. The polymorphism to fixation ratios appear to be approximately the same for gene duplications and for presumably selectively neutral nucleotide substitutions, which, according to the McDonald-Kreitman test, is consistent with selective neutrality of duplications. However, this pattern can also be due to negative selection against most of segregating duplications and positive selection for at least some duplications which become fixed. Patterns in post-fixation evolution of duplicated genes do not easily reveal the causes of fixations. Many gene duplications which became fixed recently in a variety of organisms were positively selected because the increased expression of the corresponding genes was beneficial. The effects of gene dosage provide a unified framework for studying all phases of the life history of a gene duplication. Application of well-known methods of evolutionary genetics to accumulating data on new, polymorphic, and fixed duplication will enhance our understanding of the role of natural selection in the evolution by gene duplication.}, author = {Fyodor Kondrashov and Kondrashov, Alexey S}, journal = {Journal of Theoretical Biology}, number = {2}, pages = {141 -- 151}, publisher = {Elsevier}, title = {{Role of selection in fixation of gene duplications}}, doi = {10.1016/j.jtbi.2005.08.033}, volume = {239}, year = {2006}, } @article{8489, abstract = {Structure elucidation of proteins by either NMR or X‐ray crystallography often requires the screening of a large number of samples for promising protein constructs and optimum solution conditions. For large‐scale screening of protein samples in solution, robust methods are needed that allow a rapid assessment of the folding of a polypeptide under diverse sample conditions. Here we present HET‐SOFAST NMR, a highly sensitive new method for semi‐quantitative characterization of the structural compactness and heterogeneity of polypeptide chains in solution. On the basis of one‐dimensional 1H HET‐SOFAST NMR data, obtained on well‐folded, molten globular, partially‐ and completely unfolded proteins, we define empirical thresholds that can be used as quantitative benchmarks for protein compactness. For 15N‐enriched protein samples, two‐dimensional 1H‐15N HET‐SOFAST correlation spectra provide site‐specific information about the structural heterogeneity along the polypeptide chain.}, author = {Schanda, Paul and Forge, Vincent and Brutscher, Bernhard}, issn = {0749-1581}, journal = {Magnetic Resonance in Chemistry}, number = {S1}, pages = {S177--S184}, publisher = {Wiley}, title = {{HET-SOFAST NMR for fast detection of structural compactness and heterogeneity along polypeptide chains}}, doi = {10.1002/mrc.1825}, volume = {44}, year = {2006}, } @article{8488, abstract = {We demonstrate for different protein samples that three-dimensional HNCO and HNCA correlation spectra may be recorded in a few minutes acquisition time using the band-selective excitation short-transient sequences presented here. This opens new perspectives for the NMR structural investigation of unstable protein samples and real-time site-resolved studies of protein kinetics.}, author = {Schanda, Paul and Van Melckebeke, Hélène and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {28}, pages = {9042--9043}, publisher = {American Chemical Society}, title = {{Speeding up three-dimensional protein NMR experiments to a few minutes}}, doi = {10.1021/ja062025p}, volume = {128}, year = {2006}, } @article{8490, abstract = {We demonstrate the feasibility of recording 1H–15N correlation spectra of proteins in only one second of acquisition time. The experiment combines recently proposed SOFAST-HMQC with Hadamard-type 15N frequency encoding. This allows site-resolved real-time NMR studies of kinetic processes in proteins with an increased time resolution. The sensitivity of the experiment is sufficient to be applicable to a wide range of molecular systems available at millimolar concentration on a high magnetic field spectrometer.}, author = {Schanda, Paul and Brutscher, Bernhard}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, keywords = {Nuclear and High Energy Physics, Biophysics, Biochemistry, Condensed Matter Physics}, number = {2}, pages = {334--339}, publisher = {Elsevier}, title = {{Hadamard frequency-encoded SOFAST-HMQC for ultrafast two-dimensional protein NMR}}, doi = {10.1016/j.jmr.2005.10.007}, volume = {178}, year = {2006}, } @article{8514, abstract = {We study the extent to which the Hausdorff dimension of a compact subset of an infinite-dimensional Banach space is affected by a typical mapping into a finite-dimensional space. It is possible that the dimension drops under all such mappings, but the amount by which it typically drops is controlled by the ‘thickness exponent’ of the set, which was defined by Hunt and Kaloshin (Nonlinearity12 (1999), 1263–1275). More precisely, let $X$ be a compact subset of a Banach space $B$ with thickness exponent $\tau$ and Hausdorff dimension $d$. Let $M$ be any subspace of the (locally) Lipschitz functions from $B$ to $\mathbb{R}^{m}$ that contains the space of bounded linear functions. We prove that for almost every (in the sense of prevalence) function $f \in M$, the Hausdorff dimension of $f(X)$ is at least $\min\{ m, d / (1 + \tau) \}$. We also prove an analogous result for a certain part of the dimension spectra of Borel probability measures supported on $X$. The factor $1 / (1 + \tau)$ can be improved to $1 / (1 + \tau / 2)$ if $B$ is a Hilbert space. Since dimension cannot increase under a (locally) Lipschitz function, these theorems become dimension preservation results when $\tau = 0$. We conjecture that many of the attractors associated with the evolution equations of mathematical physics have thickness exponent zero. We also discuss the sharpness of our results in the case $\tau > 0$.}, author = {OTT, WILLIAM and HUNT, BRIAN and Kaloshin, Vadim}, issn = {0143-3857}, journal = {Ergodic Theory and Dynamical Systems}, number = {3}, pages = {869--891}, publisher = {Cambridge University Press}, title = {{The effect of projections on fractal sets and measures in Banach spaces}}, doi = {10.1017/s0143385705000714}, volume = {26}, year = {2006}, } @inproceedings{8515, abstract = {We consider the evolution of a set carried by a space periodic incompressible stochastic flow in a Euclidean space. We report on three main results obtained in [8, 9, 10] concerning long time behaviour for a typical realization of the stochastic flow. First, at time t most of the particles are at a distance of order √t away from the origin. Moreover, we prove a Central Limit Theorem for the evolution of a measure carried by the flow, which holds for almost every realization of the flow. Second, we show the existence of a zero measure full Hausdorff dimension set of points, which escape to infinity at a linear rate. Third, in the 2-dimensional case, we study the set of points visited by the original set by time t. Such a set, when scaled down by the factor of t, has a limiting non random shape.}, author = {Kaloshin, Vadim and DOLGOPYAT, D. and KORALOV, L.}, booktitle = {XIVth International Congress on Mathematical Physics}, isbn = {9789812562012}, location = {Lisbon, Portugal}, pages = {290--295}, publisher = {World Scientific}, title = {{Long time behaviour of periodic stochastic flows}}, doi = {10.1142/9789812704016_0026}, year = {2006}, } @article{8513, author = {Kaloshin, Vadim and Saprykina, Maria}, issn = {1553-5231}, journal = {Discrete & Continuous Dynamical Systems - A}, number = {2}, pages = {611--640}, publisher = {American Institute of Mathematical Sciences (AIMS)}, title = {{Generic 3-dimensional volume-preserving diffeomorphisms with superexponential growth of number of periodic orbits}}, doi = {10.3934/dcds.2006.15.611}, volume = {15}, year = {2006}, } @article{869, abstract = {The impact of synonymous nucleotide substitutions on fitness in mammals remains controversial. Despite some indications of selective constraint, synonymous sites are often assumed to be neutral, and the rate of their evolution is used as a proxy for mutation rate. We subdivide all sites into four classes in terms of the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold synonymous sites and intron sites residing outside transposable elements. The distribution of the rate of evolution across all synonymous sites is trimodal. Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed by G, is ∼10% below that at such intron sites. In contrast, rate of evolution at postCpreG synonymous sites is ∼30% above that at such intron sites. Finally, synonymous and intron postC and preG sites evolve at similar rates. The relationship between the levels of polymorphism at the corresponding synonymous and intron sites is very similar to that between their rates of evolution. Within every class, synonymous sites are occupied by G or C much more often than intron sites, whose nucleotide composition is consistent with neutral mutation-drift equilibrium. These patterns suggest that synonymous sites are under weak selection in favor of G and C, with the average coefficient s∼0.25/Ne∼10-5, where Ne is the effective population size. Such selection decelerates evolution and reduces variability at sites with symmetric mutation, but has the opposite effects at sites where the favored nucleotides are more mutable. The amino-acid composition of proteins dictates that many synonymous sites are CpGprone, which causes them, on average, to evolve faster and to be more polymorphic than intron sites. An average genotype carries ∼107 suboptimal nucleotides at synonymous sites, implying synergistic epistasis in selection against them.}, author = {Fyodor Kondrashov and Ogurtsov, Aleksey Yu and Kondrashov, Alexey S}, journal = {Journal of Theoretical Biology}, number = {4}, pages = {616 -- 626}, publisher = {Elsevier}, title = {{Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites}}, doi = {10.1016/j.jtbi.2005.10.020}, volume = {240}, year = {2006}, } @article{903, abstract = {Background: Carcinogenesis typically involves multiple somatic mutations in caretaker (DNA repair) and gatekeeper (tumor suppressors and oncogenes) genes. Analysis of mutation spectra of the tumor suppressor that is most commonly mutated in human cancers, p53, unexpectedly suggested that somatic evolution of the p53 gene during tumorigenesis is dominated by positive selection for gain of function. This conclusion is supported by accumulating experimental evidence of evolution of new functions of p53 in tumors. These findings prompted a genome-wide analysis of possible positive selection during tumor evolution. Methods: A comprehensive analysis of probable somatic mutations in the sequences of Expressed Sequence Tags (ESTs) from malignant tumors and normal tissues was performed in order to access the prevalence of positive selection in cancer evolution. For each EST, the numbers of synonymous and non-synonymous substitutions were calculated. In order to identify genes with a signature of positive selection in cancers, these numbers were compared to: i) expected numbers and ii) the numbers for the respective genes in the ESTs from normal tissues. Results: We identified 112 genes with a signature of positive selection in cancers, i.e., a significantly elevated ratio of non-synonymous to synonymous substitutions, in tumors as compared to 37 such genes in an approximately equal-sized EST collection from normal tissues. A substantial fraction of the tumor-specific positive-selection candidates have experimentally demonstrated or strongly predicted links to cancer. Conclusion: The results of EST analysis should be interpreted with extreme caution given the noise introduced by sequencing errors and undetected polymorphisms. Furthermore, an inherent limitation of EST analysis is that multiple mutations amenable to statistical analysis can be detected only in relatively highly expressed genes. Nevertheless, the present results suggest that positive selection might affect a substantial number of genes during tumorigenic somatic evolution.}, author = {Babenko, Vladimir N and Basu, Malay K and Fyodor Kondrashov and Rogozin, Igor B and Koonin, Eugene V}, journal = {BMC Cancer}, publisher = {BioMed Central}, title = {{Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis}}, doi = {10.1186/1471-2407-6-36}, volume = {6}, year = {2006}, } @article{9505, abstract = {Cytosine methylation, a common form of DNA modification that antagonizes transcription, is found at transposons and repeats in vertebrates, plants and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within a large fraction of A. thaliana genes. Methylation within genes is conspicuously biased away from gene ends, suggesting a dependence on RNA polymerase transit. Genic methylation is strongly influenced by transcription: moderately transcribed genes are most likely to be methylated, whereas genes at either extreme are least likely. In turn, transcription is influenced by methylation: short methylated genes are poorly expressed, and loss of methylation in the body of a gene leads to enhanced transcription. Our results indicate that genic transcription and DNA methylation are closely interwoven processes.}, author = {Zilberman, Daniel and Gehring, Mary and Tran, Robert K. and Ballinger, Tracy and Henikoff, Steven}, issn = {1546-1718}, journal = {Nature Genetics}, number = {1}, pages = {61--69}, publisher = {Nature Publishing Group}, title = {{Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription}}, doi = {10.1038/ng1929}, volume = {39}, year = {2006}, } @article{13430, abstract = {Dynamic self-assembly (DySA) processes occurring outside of thermodynamic equilibrium underlie many forms of adaptive and intellligent behaviors in natural systems. Relatively little, however, is known about the principles that govern DySA and the ways in which it can be extended to artificial ensembles. This article discusses recent advances in both the theory and the practice of nonequilibrium self-assembly. It is argued that a union of ideas from thermodynamics and dynamic systems' theory can provide a general description of DySA. In parallel, heuristic design rules can be used to construct DySA systems of increasing complexities based on a variety of suitable interactions/potentials on length scales from nanoscopic to macroscopic. Applications of these rules to magnetohydrodynamic DySA are also discussed.}, author = {Fialkowski, Marcin and Bishop, Kyle J. M. and Klajn, Rafal and Smoukov, Stoyan K. and Campbell, Christopher J. and Grzybowski, Bartosz A.}, issn = {1520-6106}, journal = {The Journal of Physical Chemistry B}, keywords = {Materials Chemistry, Surfaces, Coatings and Films, Physical and Theoretical Chemistry}, number = {6}, pages = {2482--2496}, publisher = {American Chemical Society}, title = {{Principles and implementations of dissipative (dynamic) self-assembly}}, doi = {10.1021/jp054153q}, volume = {110}, year = {2006}, } @article{13428, abstract = {Mixtures of oppositely charged nanoparticles of various sizes and charge ratios precipitate only at the point of electroneutrality. This phenomenonspecific to the nanoscale and reminiscent of threshold precipitation of ionsis a consequence of the formation of core-and-shell nanoparticle aggregates, in which the shells are composed of like-charged particles and are stabilized by efficient electrostatic screening.}, author = {Kalsin, Alexander M. and Kowalczyk, Bartlomiej and Smoukov, Stoyan K. and Klajn, Rafal and Grzybowski, Bartosz A.}, issn = {1520-5126}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {47}, pages = {15046--15047}, publisher = {American Chemical Society}, title = {{Ionic-like behavior of oppositely charged nanoparticles}}, doi = {10.1021/ja0642966}, volume = {128}, year = {2006}, } @article{13429, abstract = {The fruitful core: Organic syntheses reported in the literature from 1850 to 2004 are analyzed with mathematical tools from network theory and statistical physics. There is a set of substances (the core) from which the majority of other organic compounds can be made (see picture; red: core, blue: periphery, green: islands). Search algorithms are used to identify small optimal sets of maximally useful chemicals.}, author = {Bishop, Kyle J. M. and Klajn, Rafal and Grzybowski, Bartosz A.}, issn = {1521-3773}, journal = {Angewandte Chemie International Edition}, keywords = {General Chemistry, Catalysis}, number = {32}, pages = {5348--5354}, publisher = {Wiley}, title = {{The core and most useful molecules in organic chemistry}}, doi = {10.1002/anie.200600881}, volume = {45}, year = {2006}, } @article{11120, abstract = {The nuclear envelope (NE) is a highly specialized membrane that delineates the eukaryotic cell nucleus. It is composed of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) and, in metazoa, the lamina. The NE not only regulates the trafficking of macromolecules between nucleoplasm and cytosol but also provides anchoring sites for chromatin and the cytoskeleton. Through these interactions, the NE helps position the nucleus within the cell and chromosomes within the nucleus, thereby regulating the expression of certain genes. The NE is not static, rather it is continuously remodeled during cell division. The most dramatic example of NE reorganization occurs during mitosis in metazoa when the NE undergoes a complete cycle of disassembly and reformation. Despite the importance of the NE for eukaryotic cell life, relatively little is known about its biogenesis or many of its functions. We thus are far from understanding the molecular etiology of a diverse group of NE-associated diseases.}, author = {HETZER, Martin W and Walther, Tobias C. and Mattaj, Iain W.}, issn = {1530-8995}, journal = {Annual Review of Cell and Developmental Biology}, keywords = {Cell Biology, Developmental Biology}, pages = {347--380}, publisher = {Annual Reviews}, title = {{Pushing the envelope: Structure, function, and dynamics of the nuclear periphery}}, doi = {10.1146/annurev.cellbio.21.090704.151152}, volume = {21}, year = {2005}, } @inproceedings{11698, abstract = {We give a short survey of the use of hyperlink analysis in web search engine ranking and sketch other applications of hyperlink analysis in the web space.}, author = {Henzinger, Monika H}, booktitle = {Proceedings of the 16th ACM conference on Hypertext and hypermedia}, isbn = {9781595931689}, keywords = {Hyperlink Analysis, World Wide Web}, location = {Salzburg, Austria}, pages = {1--3}, publisher = {Association for Computing Machinery}, title = {{Hyperlink analysis on the world wide web}}, doi = {10.1145/1083356.1083357}, year = {2005}, } @article{11904, abstract = {Many daily activities present information in the form of a stream of text, and often people can benefit from additional information on the topic discussed. TV broadcast news can be treated as one such stream of text; in this paper we discuss finding news articles on the web that are relevant to news currently being broadcast. We evaluated a variety of algorithms for this problem, looking at the impact of inverse document frequency, stemming, compounds, history, and query length on the relevance and coverage of news articles returned in real time during a broadcast. We also evaluated several postprocessing techniques for improving the precision, including reranking using additional terms, reranking by document similarity, and filtering on document similarity. For the best algorithm, 84–91% of the articles found were relevant, with at least 64% of the articles being on the exact topic of the broadcast. In addition, a relevant article was found for at least 70% of the topics.}, author = {Henzinger, Monika H and Chang, Bay-Wei and Milch, Brian and Brin, Sergey}, issn = {1573-1413}, journal = {World Wide Web}, number = {2}, pages = {101--126}, publisher = {Springer Nature}, title = {{Query-free news search}}, doi = {10.1007/s11280-004-4870-6}, volume = {8}, year = {2005}, } @article{11763, abstract = {We present the first polylog-competitive online algorithm for the general multicast admission control and routing problem in the throughput model. The ratio of the number of requests accepted by the optimum offline algorithm to the expected number of requests accepted by our algorithm is O((log n + log log M)(log n + log M) log n), where M is the number of multicast groups and n is the number of nodes in the graph. We show that this is close to optimum by presenting an Ω(log n log M) lower bound on this ratio for any randomized online algorithm against an oblivious adversary, when M is much larger than the link capacities. Our lower bound applies even in the restricted case where the link capacities are much larger than bandwidth requested by a single multicast. We also present a simple proof showing that it is impossible to be competitive against an adaptive online adversary. As in the previous online routing algorithms, our algorithm uses edge-costs when deciding on which is the best path to use. In contrast to the previous competitive algorithms in the throughput model, our cost is not a direct function of the edge load. The new cost definition allows us to decouple the effects of routing and admission decisions of different multicast groups.}, author = {Goel, Ashish and Henzinger, Monika H and Plotkin, Serge}, issn = {0196-6774}, journal = {Journal of Algorithms}, number = {1}, pages = {1--20}, publisher = {Elsevier}, title = {{An online throughput-competitive algorithm for multicast routing and admission control}}, doi = {10.1016/j.jalgor.2004.11.001}, volume = {55}, year = {2005}, } @article{12657, abstract = {An enhanced temperature-index glacier melt model, incorporating incoming shortwave radiation and albedo, is presented. The model is an attempt to combine the high temporal resolution and accuracy of physically based melt models with the lower data requirements and computational simplicity of empirical melt models, represented by the ‘degree-day’ method and its variants. The model is run with both measured and modelled radiation data, to test its applicability to glaciers with differing data availability. Five automatic weather stations were established on Haut Glacier d’Arolla, Switzerland, between May and September 2001. Reference surface melt rates were calculated using a physically based energy-balance melt model. The performance of the enhanced temperature-index model was tested at each of the four validation stations by comparing predicted hourly melt rates with reference melt rates. Predictions made with three other temperature-index models were evaluated in the same way for comparison. The enhanced temperature-index model offers significant improvements over the other temperature-index models, and accounts for 90–95% of the variation in the reference melt rate. The improvement is lower, but still significant, when the model is forced by modelled shortwave radiation data, thus offering a better alternative to existing models that require only temperature data input.}, author = {Pellicciotti, Francesca and Brock, Ben and Strasser, Ulrich and Burlando, Paolo and Funk, Martin and Corripio, Javier}, issn = {1727-5652}, journal = {Journal of Glaciology}, number = {175}, pages = {573--587}, publisher = {Cambridge University Press}, title = {{An enhanced temperature-index glacier melt model including the shortwave radiation balance: Development and testing for Haut Glacier d’Arolla, Switzerland}}, doi = {10.3189/172756505781829124}, volume = {51}, year = {2005}, } @article{1298, abstract = {Genetically encoded fluorescent probes of neural activity represent new promising tools for systems neuroscience. Here, we present a comparative in vivo analysis of 10 different genetically encoded calcium indicators, as well as the pH-sensitive synapto-pHluorin. We analyzed their fluorescence changes in presynaptic boutons of the Drosophila larval neuromuscular junction. Robust neural activity did not result in any or noteworthy fluorescence changes when Flash-Pericam, Camgaroo-1, and Camgaroo-2 were expressed. However, calculated on the raw data, fractional fluorescence changes up to 18% were reported by synapto-pHluorin, Yellow Cameleon 2.0, 2.3, and 3.3, Inverse-Pericam, GCaMP1.3, GCaMP1.6, and the troponin C-based calcium sensor TN-L15. The response characteristics of all of these indicators differed considerably from each other, with GCaMP1.6 reporting high rates of neural activity with the largest and fastest fluorescence changes. However, GCaMP1.6 suffered from photobleaching, whereas the fluorescence signals of the double-chromophore indicators were in general smaller but more photostable and reproducible, with TN-L15 showing the fastest rise of the signals at lower activity rates. We show for GCaMP1.3 and YC3.3 that an expanded range of neural activity evoked fairly linear fluorescence changes and a corresponding linear increase in the signal-to-noise ratio (SNR). The expression level of the indicator biased the signal kinetics and SNR, whereas the signal amplitude was independent. The presented data will be useful for in vivo experiments with respect to the selection of an appropriate indicator, as well as for the correct interpretation of the optical signals.}, author = {Reiff, Dierk F and Ihring, Alexandra and Guerrero, Giovanna and Isacoff, Ehud Y and Maximilian Jösch and Nakai, Junichi and Borst, Alexander}, journal = {Journal of Neuroscience}, number = {19}, pages = {4766 -- 4778}, publisher = {Society for Neuroscience}, title = {{In vivo performance of genetically encoded indicators of neural activity in flies}}, doi = {10.1523/JNEUROSCI.4900-04.2005}, volume = {25}, year = {2005}, } @article{1447, abstract = {Building on a recent paper [8], here we argue that the combinatorics of matroids are intimately related to the geometry and topology of toric hyperkähler varieties. We show that just like toric varieties occupy a central role in Stanley’s proof for the necessity of McMullen’s conjecture (or g-inequalities) about the classification of face vectors of simplicial polytopes, the topology of toric hyperkähler varieties leads to new restrictions on face vectors of matroid complexes. Namely in this paper we will give two proofs that the injectivity part of the Hard Lefschetz theorem survives for toric hyperkähler varieties. We explain how this implies the g-inequalities for rationally representable matroids. We show how the geometrical intuition in the first proof, coupled with results of Chari [3], leads to a proof of the g-inequalities for general matroid complexes, which is a recent result of Swartz [20]. The geometrical idea in the second proof will show that a pure O-sequence should satisfy the g-inequalities, thus showing that our result is in fact a consequence of a long-standing conjecture of Stanley.}, author = {Tamas Hausel}, journal = {Open Mathematics}, number = {1}, pages = {26 -- 38}, publisher = {Central European Science Journals}, title = {{Quaternionic geometry of matroids}}, doi = {10.2478/BF02475653}, volume = {3}, year = {2005}, } @inbook{1444, abstract = {The paper surveys the mirror symmetry conjectures of Hausel-Thaddeus and Hausel-Rodriguez-Villegas concerning the equality of certain Hodge numbers of SL(n, ℂ) vs. PGL(n, ℂ) flat connections and character varieties for curves, respectively. Several new results and conjectures and their relations to works of Hitchin, Gothen, Garsia-Haiman and Earl-Kirwan are explained. These use the representation theory of finite groups of Lie-type via the arithmetic of character varieties and lead to an unexpected conjecture for a Hard Lefschetz theorem for their cohomology.}, author = {Tamas Hausel}, booktitle = {Geometric Methods in Algebra and Number Theory}, pages = {193 -- 217}, publisher = {Springer}, title = {{Mirror symmetry and Langlands duality in the non-Abelian Hodge theory of a curve}}, doi = {10.1007/0-8176-4417-2_9}, volume = {235}, year = {2005}, } @article{1463, abstract = {We study an integration theory in circle equivariant cohomology in order to prove a theorem relating the cohomology ring of a hyperkähler quotient to the cohomology ring of the quotient by a maximal abelian subgroup, analogous to a theorem of Martin for symplectic quotients. We discuss applications of this theorem to quiver varieties, and compute as an example the ordinary and equivariant cohomology rings of a hyperpolygon space.}, author = {Tamas Hausel and Proudfoot, Nicholas J}, journal = {Topology}, number = {1}, pages = {231 -- 248}, publisher = {Elsevier}, title = {{Abelianization for hyperkähler quotients}}, doi = {10.1016/j.top.2004.04.002}, volume = {44}, year = {2005}, } @article{1742, abstract = {The effects of substrate temperature, growth rate, and postgrowth annealing on the composition of Ge islands grown on Si(001) were investigated with a combination of selective wet chemical etching and atomic force microscopy. A simple kinetic model comprising only surface diffusion processes can explain all the experimentally observed compositional profiles for pyramid and dome islands grown in the 560-620°C range. From this model three-dimensional compositional maps were extracted. By performing annealing experiments a change in the composition of the domes was observed. This could be explained as the result of the islands' movement induced by alloying-driven energy minimization. Also in this case kinetically hindered bulk diffusion processes are not needed to explain the experimental observations.}, author = {Georgios Katsaros and Costantini, Giovanni and Stoffel, Mathieu and Esteban, Rubén and Bittner, Alexander M and Rastelli, Armando and Denker, Ulrich and Schmidt, Oliver G and Kern, Klaus}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {19}, publisher = {American Physical Society}, title = {{Kinetic origin of island intermixing during the growth of Ge on Si (001)}}, doi = {10.1103/PhysRevB.72.195320}, volume = {72}, year = {2005}, } @article{1740, abstract = {A systematic study of the morphology of self-organized islands in the InAs/GaAs(0 0 1) and Ge/Si(0 0 1) systems is presented, based on high-resolution scanning tunneling microscopy measurements. We demonstrate that in both cases two main island families coexist: smaller pyramids bound by one type of shallow facets and larger multifaceted domes. Their structure and facet orientation are precisely determined, thus solving a highly debated argument in the case of InAs/GaAs(0 0 1). The comparison between the two material systems reveals the existence of striking similarities that extend even to the nature of island precursors and to the islands that form when depositing InGaAs or GeSi alloys. The implications of these observations on a possible universal description of the Stranski-Krastanow growth mode are discussed with respect to recent theoretical results.}, author = {Costantini, Giovanni and Rastelli, Armando and Manzano, Carlos and Acosta-Diaz, P and Georgios Katsaros and Songmuang, Rudeeson and Schmidt, Oliver G and Von Känel, Hans and Kern, Klaus}, journal = {Journal of Crystal Growth}, number = {1-4}, pages = {38 -- 45}, publisher = {Elsevier}, title = {{Pyramids and domes in the InAs/GaAs (0 0 1) and Ge/Si (0 0 1) systems}}, doi = {10.1016/j.jcrysgro.2004.12.047}, volume = {278}, year = {2005}, } @article{1743, abstract = {Laterally aligned multilayer GeSiSi islands grown on a patterned Si (001) substrate are disclosed by selective etching of Si in a KOH solution. This procedure allows us to visualize the vertical alignment of the islands in a three-dimensional perspective. Our technique reveals that partly coalesced double islands in the initial layer do not merge together, but instead gradually reproduce into well-separated double islands in upper layers. We attribute this effect to very thin spacer layers, which efficiently transfer the strain modulation of each island through the spacer layer to the surface. The etching rate of Si is reduced in tensile strained regions, which helps to preserve sufficient Si between the stacked islands to form a periodic array of freestanding and vertically modulated heterostructure pillars.}, author = {Zhong, Zheyang and Georgios Katsaros and Stoffel, Mathieu and Costantini, Giovanni and Kern, Klaus and Schmidt, Oliver G and Jin-Phillipp, Neng Y and Bauer, Günther}, journal = {Applied Physics Letters}, number = {26}, pages = {1 -- 3}, publisher = {American Institute of Physics}, title = {{Periodic pillar structures by Si etching of multilayer GeSi/Si islands}}, doi = {10.1063/1.2150278}, volume = {87}, year = {2005}, } @article{1744, abstract = {This paper presents optical duobinary and dicode signalling, as alternatives to the binary format, in order to improve the transmission performance in the presense of non-linear effects in a dense wavelength division multiplex (WDM) optical system. Duobinary signalling is applied to an optical system to explore the reduction of stimulated Brillouin scattering (SBS) effects. Duobinary signalling suppresses the SBS effects, and an eye-opening improvement of 0.25 to 1.2 dB is achieved relative to binary transmission over a range of input power levels. An experimental study demonstrates that duobinary modulation suppresses the four wave mixing (FWM) products of a dense WDM system by a maximum of 3 dB. The suppression is maintained over a range of channel spacings. An investigation of the impact of fibre dispersion on FWM products under binary, duobinary and dicode modulation in a dense WDM system is then performed, with interchannel spacing and optical power variation. This leads to the development of a set of guidelines for the application areas, in which it is appropriate to use duobinary or dicode modulation in WDM systems as a means of mitigating the impact of FWM.}, author = {Georgios Katsaros and Darwazeh, Izzat Z and Lane, Phil M}, journal = {IEE Proceedings - Optoelectronics}, number = {6}, pages = {344 -- 352}, publisher = {Institute of Electrical Engineers}, title = {{Non linear transmission effects in duobinary and dicode optical systems}}, doi = {10.1049/ip-opt:20045067}, volume = {152}, year = {2005}, } @article{1741, abstract = {SiGe islands move laterally on a Si(001) substrate during in situ postgrowth annealing. This surprising behavior is revealed by an analysis of the substrate surface morphology after island removal using wet chemical etching. We explain the island motion by asymmetric surface-mediated alloying. Material leaves one side of the island by surface diffusion, and mixes with additional Si from the surrounding surface as it redeposits on the other side. Thus the island moves laterally while becoming larger and more dilute.}, author = {Denker, Ulrich and Rastelli, Armando and Stoffel, Mathieu and Tersoff, Jerry and Georgios Katsaros and Costantini, Giovanni and Kern, Klaus and Jin-Phillipp, Neng Y and Jesson, David E and Schmidt, Oliver G}, journal = {Physical Review Letters}, number = {21}, publisher = {American Physical Society}, title = {{Lateral motion of SiGe islands driven by surface-mediated alloying}}, doi = {10.1103/PhysRevLett.94.216103}, volume = {94}, year = {2005}, } @article{1795, abstract = {Background: Murine leukemia virus (MLV) vector particles can be pseudotyped with a truncated variant of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) and selectively target gene transfer to human cells expressing both CD4 and an appropriate co-receptor. Vector transduction mimics the HIV-1 entry process and is therefore a safe tool to study HIV-1 entry. Results: Using FLY cells, which express the MLV gag and pol genes, we generated stable producer cell lines that express the HIV-1 envelope gene and a retroviral vector genome encoding the green fluorescent protein (GFP). The BH10 or 89.6 P HIV-1 Env was expressed from a bicistronic vector which allowed the rapid selection of stable cell lines. A codon-usage-optimized synthetic env gene permitted high, Rev-independent Env expression. Vectors generated by these producer cells displayed different sensitivity to entry inhibitors. Conclusion: These data illustrate that MLV/HIV-1 vectors are a valuable screening system for entry inhibitors or neutralizing antisera generated by vaccines.}, author = {Sandra Siegert and Thaler, Sonja and Wagner, Ralf and Schnierle, Barbara S}, journal = {AIDS Research and Therapy}, number = {1}, publisher = {BioMed Central}, title = {{Assessment of HIV-1 entry inhibitors by MLV/HIV-1 pseudotyped vectors}}, doi = {10.1186/1742-6405-2-7}, volume = {2}, year = {2005}, } @article{1962, abstract = { Complex I of respiratory chains plays a central role in bioenergetics and is implicated in many human neurodegenerative diseases. An understanding of its mechanism requires a knowledge of the organization of redox centers. The arrangement of iron-sulfur clusters in the hydrophilic domain of complex I from Thermus thermophilus has been determined with the use of x-ray crystallography. One binuclear and six tetranuclear clusters are arranged, maximally 14 angstroms apart, in an 84-angstrom-long electron transfer chain. The binuclear cluster N1a and the tetranuclear cluster N7 are not in this pathway. Cluster N1a may play a role in the prevention of oxidative damage. The structure provides a framework for the interpretation of the large amounts of data accumulated on complex I.}, author = {Hinchliffe, Philip and Leonid Sazanov}, journal = {Science}, number = {5735}, pages = {771 -- 774}, publisher = {American Association for the Advancement of Science}, title = {{Biochemistry: Organization of iron-sulfur clusters in respiratory complex I}}, doi = {10.1126/science.1113988}, volume = {309}, year = {2005}, } @book{210, abstract = {Harold Davenport was one of the truly great mathematicians of the twentieth century. Based on lectures he gave at the University of Michigan in the early 1960s, this book is concerned with the use of analytic methods in the study of integer solutions to Diophantine equations and Diophantine inequalities. It provides an excellent introduction to a timeless area of number theory that is still as widely researched today as it was when the book originally appeared. The three main themes of the book are Waring's problem and the representation of integers by diagonal forms, the solubility in integers of systems of forms in many variables, and the solubility in integers of diagonal inequalities. For the second edition of the book a comprehensive foreword has been added in which three prominent authorities describe the modern context and recent developments. A thorough bibliography has also been added.}, author = {Davenport, Harold and Browning, Timothy D}, pages = {140}, publisher = {Cambridge University Press}, title = {{Analytic Methods for Diophantine Equations and Diophantine Inequalities}}, doi = {10.1017/CBO9780511542893}, year = {2005}, } @article{211, abstract = {Let f ∈ ℤ[x] be a polynomial of degree d. The paucity of non-trivial positive integer solutions to the equation f(x1)+f(x 2)=f(x3)+f(x4) is established, provided that d ≤ 7$. Also the corresponding situation is investigated for equal sums of three like polynomials.}, author = {Timothy Browning}, journal = {Bulletin of the London Mathematical Society}, number = {6}, pages = {801 -- 808}, publisher = {John Wiley and Sons Ltd}, title = {{Equal sums of like polynomials}}, doi = {10.1112/S0024609305004741}, volume = {37}, year = {2005}, } @article{212, abstract = {For any n ≧ 2, let F ∈ ℤ [ x 1, … , xn ] be a form of degree d≧ 2, which produces a geometrically irreducible hypersurface in ℙn–1. This paper is concerned with the number N(F;B) of rational points on F = 0 which have height at most B. For any ε > 0 we establish the estimate N(F; B) = O(B n− 2+ ε ), whenever either n ≦ 5 or the hypersurface is not a union of lines. Here the implied constant depends at most upon d, n and ε.}, author = {Timothy Browning and Heath-Brown, Roger}, journal = {Journal fur die Reine und Angewandte Mathematik}, number = {584}, pages = {83 -- 115}, publisher = {Walter de Gruyter and Co }, title = {{Counting rational points on hypersurfaces}}, doi = {https://doi.org/10.1515/crll.2005.2005.584.83}, year = {2005}, } @article{214, abstract = {Given an absolutely irreducible ternary form F, the purpose of this paper is to produce better upper bounds for the number of integer solutions to the equation F=0, that are restricted to lie in very lopsided boxes. As an application of the main result, a new paucity estimate is obtained for equal sums of two like powers.}, author = {Timothy Browning and Heath-Brown, Roger}, journal = {Mathematische Zeitschrift}, number = {2}, pages = {233 -- 247}, publisher = {Unknown}, title = {{Plane curves in boxes and equal sums of two powers}}, doi = {10.1007/s00209-004-0719-z}, volume = {251}, year = {2005}, } @article{217, abstract = {We show that the number of nontrivial rational points of height at most B, which lie on the cubic surface x1 x2 x3 = x4 (x1 + x2 + x3)2, has order of magnitude B (log B)6. This agrees with Manin's conjecture.}, author = {Timothy Browning}, journal = {Journal of Number Theory}, number = {2}, pages = {242 -- 283}, publisher = {Elsevier}, title = {{The density of rational points on a certain singular cubic surface}}, doi = {10.1016/j.jnt.2005.11.007}, volume = {119}, year = {2005}, } @article{2307, abstract = {The human norepinephrine (NE) transporter (hNET) attenuates neuronal signaling by rapid NE clearance from the synaptic cleft, and NET is a target for cocaine and amphetamines as well as therapeutics for depression, obsessive-compulsive disorder, and post-traumatic stress disorder. In spite of its central importance in the nervous system, little is known about how NET substrates, such as NE, 1-methyl-4-tetrahydropyridinium (MPP+), or amphetamine, interact with NET at the molecular level. Nor do we understand the mechanisms behind the transport rate. Previously we introduced a fluorescent substrate similar to MPP+, which allowed separate and simultaneous binding and transport measurement (Schwartz, J. W., Blakely, R. D., and DeFelice, L. J. (2003) J. Biol. Chem. 278, 9768-9777). Here we use this substrate, 4-(4-(dimethylamino)styrl)-N-methyl-pyridinium (ASP+), in combination with green fluorescent protein-tagged hNETs to measure substrate-transporter stoichiometry and substrate binding kinetics. Calibrated confocal microscopy and fluorescence correlation spectroscopy reveal that hNETs, which are homo-multimers, bind one substrate molecule per transporter subunit. Substrate residence at the transporter, obtained from rapid on-off kinetics revealed in fluorescence correlation spectroscopy, is 526 μs. Substrate residence obtained by infinite dilution is 1000 times slower. This novel examination of substrate-transporter kinetics indicates that a single ASP + molecule binds and unbinds thousands of times before being transported or ultimately dissociated from hNET. Calibrated fluorescent images combined with mass spectroscopy give a transport rate of 0.06 ASP +/hNET-protein/s, thus 36,000 on-off binding events (and 36 actual departures) occur for one transport event. Therefore binding has a low probability of resulting in transport. We interpret these data to mean that inefficient binding could contribute to slow transport rates.}, author = {Schwartz, Joel W and Gaia Novarino and Piston, David W and DeFelice, Louis J}, journal = {Journal of Biological Chemistry}, number = {19}, pages = {19177 -- 19184}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Substrate binding stoichiometry and kinetics of the norepinephrine transporter}}, doi = {10.1074/jbc.M412923200}, volume = {280}, year = {2005}, } @book{2335, abstract = {This book contains a unique survey of the mathematically rigorous results about the quantum-mechanical many-body problem that have been obtained by the authors in the past seven years. It addresses a topic that is not only rich mathematically, using a large variety of techniques in mathematical analysis, but is also one with strong ties to current experiments on ultra-cold Bose gases and Bose-Einstein condensation. The book provides a pedagogical entry into an active area of ongoing research for both graduate students and researchers. It is an outgrowth of a course given by the authors for graduate students and post-doctoral researchers at the Oberwolfach Research Institute in 2004. The book also provides a coherent summary of the field and a reference for mathematicians and physicists active in research on quantum mechanics.}, author = {Lieb, Élliott and Seiringer, Robert and Solovej, Jan and Yngvason, Jakob}, isbn = {978-3-7643-7336-8}, pages = {VIII, 203}, publisher = {Birkhäuser Verlag}, title = {{The Mathematics of the Bose gas and its Condensation}}, doi = {10.1007/b137508}, volume = {34}, year = {2005}, } @inbook{2336, abstract = { Now that the low temperature properties of quantum-mechanical many-body systems (bosons) at low density, ρ, can be examined experimentally it is appropriate to revisit some of the formulas deduced by many authors 4–5 decades ago, and to explore new regimes not treated before. For systems with repulsive (i.e. positive) interaction potentials the experimental low temperature state and the ground state are effectively synonymous — and this fact is used in all modeling. In such cases, the leading term in the energy/particle is 2πħ2 aρ/m where a is the scattering length of the two-body potential. Owing to the delicate and peculiar nature of bosonic correlations (such as the strange N 7/5 law for charged bosons), four decades of research failed to establish this plausible formula rigorously. The only previous lower bound for the energy was found by Dyson in 1957, but it was 14 times too small. The correct asymptotic formula has been obtained by us and this work will be presented. The reason behind the mathematical difficulties will be emphasized. A different formula, postulated as late as 1971 by Schick, holds in two dimensions and this, too, will be shown to be correct. With the aid of the methodology developed to prove the lower bound for the homogeneous gas, several other problems have been successfully addressed. One is the proof by us that the Gross-Pitaevskii equation correctly describes the ground state in the ‘traps’ actually used in the experiments. For this system it is also possible to prove complete Bose condensation and superfluidity as we have shown. On the frontier of experimental developments is the possibility that a dilute gas in an elongated trap will behave like a one-dimensional system; we have proved this mathematically. Another topic is a proof that Foldy’s 1961 theory of a high density Bose gas of charged particles correctly describes its ground state energy; using this we can also prove the N 7/5 formula for the ground state energy of the two-component charged Bose gas proposed by Dyson in 1967. All of this is quite recent work and it is hoped that the mathematical methodology might be useful, ultimately, to solve more complex problems connected with these interesting systems.}, author = {Lieb, Élliott H and Robert Seiringer and Solovej, Jan P and Yngvason, Jakob}, booktitle = {Perspectives in Analysis}, editor = {Benedicks, Michael and Jones, Peter W and Smirnov, Stanislav and Winckler, Björn}, pages = {97 -- 183}, publisher = {Springer}, title = {{The quantum-mechanical many-body problem: The Bose gas}}, doi = {10.1007/3-540-30434-7_9}, volume = {27}, year = {2005}, } @article{2359, abstract = {The validity of substituting a c-number z for the k = 0 mode operator a0 is established rigorously in full generality, thereby verifying one aspect of Bogoliubov's 1947 theory. This substitution not only yields the correct value of thermodynamic quantities such as the pressure or ground state energy, but also the value of |z|2 that maximizes the partition function equals the true amount of condensation in the presence of a gauge-symmetry-breaking term. This point had previously been elusive.}, author = {Lieb, Élliott H and Robert Seiringer and Yngvason, Jakob}, journal = {Physical Review Letters}, number = {8}, publisher = {American Physical Society}, title = {{Justification of c-number substitutions in bosonic hamiltonians}}, doi = {10.1103/PhysRevLett.94.080401}, volume = {94}, year = {2005}, } @article{2362, abstract = {Recent developments in the physics of low-density trapped gases make it worthwhile to verify old, well-known results that, while plausible, were based on perturbation theory and assumptions about pseudopotentials. We use and extend recently developed techniques to give a rigorous derivation of the asymptotic formula for the ground-state energy of a dilute gas of N fermions interacting with a short-range, positive potential of scattering length a. For spin-12 fermions, this is E∼E0+(22m)2πNa, where E0 is the energy of the noninteracting system and is the density. A similar formula holds in two dimensions (2D), with a replaced by ln(a2). Obviously this 2D energy is not the expectation value of a density-independent pseudopotential.}, author = {Lieb, Élliott H and Robert Seiringer and Solovej, Jan P}, journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, number = {5}, publisher = {American Physical Society}, title = {{Ground state energy of the low density Fermi gas}}, doi = {10.1103/PhysRevA.71.053605}, volume = {71}, year = {2005}, } @article{2361, abstract = {The strong subadditivity of entropy plays a key role in several areas of physics and mathematics. It states that the entropy S[±]=- Tr(ϱlnϱ) of a density matrix ϱ123 on the product of three Hilbert spaces satisfies S[ϱ123]- S[ϱ12]≤S[ϱ23]-S[ϱ2]. We strengthen this to S[ϱ123]-S[ϱ12] ≤αnα(S[ϱ23α]-S[ϱ2α]), where the nα are weights and the ϱ23α are partitions of ϱ23. Correspondingly, there is a strengthening of the theorem that the map A|Trexp[L+lnA] is concave. As applications we prove some monotonicity and convexity properties of the Wehrl coherent state entropy and entropy inequalities for quantum gases.}, author = {Lieb, Élliott H and Robert Seiringer}, journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, number = {6}, publisher = {American Physical Society}, title = {{Stronger subadditivity of entropy}}, doi = {10.1103/PhysRevA.71.062329}, volume = {71}, year = {2005}, } @inproceedings{2428, abstract = {We consider an online version of the conflict-free coloring of a set of points on the line, where each newly inserted point must be assigned a color upon insertion, and at all times the coloring has to be conflict-free, in the sense that in every interval I there is a color that appears exactly once in I. We present several deterministic and randomized algorithms for achieving this goal, and analyze their performance, that is, the maximum number of colors that they need to use, as a function of the number n of inserted points. We first show that a natural and simple (deterministic) approach may perform rather poorly, requiring Ω(√n) colors in the worst case. We then modify this approach, to obtain an efficient deterministic algorithm that uses a maximum of Θ(log 2 n) colors. Next, we present two randomized solutions. The first algorithm requires an expected number of at most O(log 2 n) colors, and produces a coloring which is valid with high probability, and the second one, which is a variant of our efficient deterministic algorithm, requires an expected number of at most O(log n log log n) colors but always produces a valid coloring. We also analyze the performance of the simplest proposed algorithm when the points are inserted in a random order, and present an incomplete analysis that indicates that, with high probability, it uses only O(log n) colors. Finally, we show that in the extension of this problem to two dimensions, where the relevant ranges are disks, n colors may be required in the worst case. The average-case behavior for disks, and cases involving other planar ranges, are still open.}, author = {Fiat, Amos and Levy, Meital B and Matoušek, Jiří and Pach, Elchanan M and Sharir, Micha and Smorodinsky, Shakhar and Uli Wagner and Welzl, Emo}, pages = {545 -- 554}, publisher = {SIAM}, title = {{Online conflict-free coloring for intervals}}, doi = {10.1137/S0097539704446682}, year = {2005}, } @article{2427, abstract = {Intersection graphs of disks and of line segments, respectively, have been well studied, because of both practical applications and theoretically interesting properties of these graphs. Despite partial results, the complexity status of the Clique problem for these two graph classes is still open. Here, we consider the Clique problem for intersection graphs of ellipses, which, in a sense, interpolate between disks and line segments, and show that the problem is APX-hard in that case. Moreover, this holds even if for all ellipses, the ratio of the larger over the smaller radius is some prescribed number. Furthermore, the reduction immediately carries over to intersection graphs of triangles. To our knowledge, this is the first hardness result for the Clique problem in intersection graphs of convex objects with finite description complexity. We also describe a simple approximation algorithm for the case of ellipses for which the ratio of radii is bounded.}, author = {Ambühl, Christoph and Uli Wagner}, journal = {Theory of Computing Systems}, number = {3}, pages = {279 -- 292}, publisher = {Springer}, title = {{The Clique problem in intersection graphs of ellipses and triangles}}, doi = {10.1007/s00224-005-1141-6}, volume = {38}, year = {2005}, } @article{2455, abstract = {Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specif ic manner. Here we show that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Our data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.}, author = {Billou, Ikram and Xu, Jian and Wildwater, Marjolein and Willemsen, Viola and Paponov, Ivan A and Jirí Friml and Heldstra, Renze and Aida, Mitsuhiro and Palme, Klaus J and Scheres, Ben}, journal = {Nature}, number = {7021}, pages = {39 -- 44}, publisher = {Nature Publishing Group}, title = {{The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots}}, doi = {10.1038/nature03184}, volume = {433}, year = {2005}, }