@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}, } @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{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}, } @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{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{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{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{1715, abstract = {Background: Cell-to-cell communication at the synapse involves synaptic transmission as well as signaling mediated by growth factors, which provide developmental and plasticity cues. There is evidence that a retrograde, presynaptic transforming growth factor-β (TGF-β) signaling event regulates synapse development and function in Drosophila. Results: Here we show that a postsynaptic TGF-β signaling event occurs during larval development. The type I receptor Thick veins (Tkv) and the R-Smad transcription factor Mothers-against-dpp (Mad) are localized postsynaptically in the muscle. Furthermore, Mad phosphorylation occurs in regions facing the presynaptic active zones of neurotransmitter release within the postsynaptic subsynaptic reticulum (SSR). In order to monitor in real time the levels of TGF-β signaling in the synapse during synaptic transmission, we have established a FRAP assay to measure Mad nuclear import/export in the muscle. We show that Mad nuclear trafficking depends on stimulation of the muscle. Conclusions: Our data suggest a mechanism linking synaptic transmission and postsynaptic TGF-β signaling that may coordinate nerve-muscle development and function.}, author = {Dudu, Veronika and Bittig, Thomas and Entchev, Eugeni and Kicheva, Anna and Julicher, Frank and González Gaitán, Marcos}, journal = {Current Biology}, number = {7}, pages = {625 -- 635}, publisher = {Cell Press}, title = {{Postsynaptic mad signaling at the Drosophila neuromuscular junction}}, doi = {10.1016/j.cub.2006.02.061}, volume = {16}, year = {2006}, } @article{1745, abstract = {SiGe islands grown by deposition of 10 monolayers of Ge on Si(0 0 1) at 740 °C were investigated by using a combination of selective wet chemical etching and atomic force microscopy. The used etchant, a solution consisting of ammonium hydroxide and hydrogen peroxide, shows a high selectivity of Ge over SixGe1-x and is characterized by relatively slow etching rates for Si-rich alloys. By performing successive etching experiments on the same sample area, we are able to gain a deeper insight into the lateral displacement the islands undergo during post growth annealing.}, author = {Georgios Katsaros and Rastelli, Armando and Stoffel, Mathieu and Isella, Giovanni and Von Känel, Hans and Bittner, Alexander M and Tersoff, Jerry and Denker, Ulrich and Schmidt, Oliver G and Costantini, Giovanni and Kern, Klaus}, journal = {Surface Science}, number = {12}, pages = {2608 -- 2613}, publisher = {Elsevier}, title = {{Investigating the lateral motion of SiGe islands by selective chemical etching}}, doi = {10.1016/j.susc.2006.04.027}, volume = {600}, year = {2006}, } @article{1746, abstract = {A microscopic picture for the GaAs overgrowth of self-organized InAs/GaAs(001) quantum dots is developed. Scanning tunneling microscopy measurements reveal two capping regimes: the first being characterized by a dot shrinking and a backward pyramid-to-dome shape transition. This regime is governed by fast dynamics resulting in island morphologies close to thermodynamic equilibrium. The second regime is marked by a true overgrowth and is controlled by kinetically limited surface diffusion processes. A simple model is developed to describe the observed structural changes which are rationalized in terms of energetic minimization driven by lattice mismatch and alloying.}, author = {Costantini, Giovanni and Rastelli, Armando and Manzano, Carlos and Acosta-Diaz, P and Songmuang, Rudeeson and Georgios Katsaros and Schmidt, Oliver G and Kern, Klaus}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Interplay between thermodynamics and kinetics in the capping of InAs/GaAs (001) quantum dots}}, doi = {10.1103/PhysRevLett.96.226106}, volume = {96}, year = {2006}, } @article{1747, abstract = {We report on recent advances in the understanding of surface processes occurring during growth and post-growth annealing of strained islands which may find application as self-assembled quantum dots. We investigate the model system SiGe/Si(0 0 1) by a new approach based on "reading the footprints" which islands leave on the substrate during their growth and evolution. Such footprints consist of trenches carved in the Si substrate. We distinguish between surface footprints and footprints buried below the islands. The former allow us to discriminate islands which are in the process of growing from those which are shrinking. Islands with steep morphologies grow at the expense of smaller and shallower islands, consistent with the kinetics of anomalous coarsening. While shrinking, islands change their shape according to thermodynamic predictions. Buried footprints are investigated by removing the SiGe epilayer by means of selective wet chemical etching. Their reading shows that: (i) during post-growth annealing islands move laterally because of surface-mediated Si-Ge intermixing; (ii) a tree-ring structure of trenches is created by dislocated islands during their "cyclic" growth. This allows us to distinguish coherent from dislocated islands and to establish whether the latter are the result of island coalescence.}, author = {Rastelli, Armando and Stoffel, Mathieu and Georgios Katsaros and Tersoff, Jerry and Denker, Ulrich and Merdzhanova, Tsvetelina and Kar, Gouranga S and Costantini, Giovanni and Kern, Klaus and Von Känel, Hans and Schmidt, Oliver G}, journal = {Microelectronics Journal}, number = {12}, pages = {1471 -- 1476}, publisher = {Elsevier}, title = {{Reading the footprints of strained islands}}, doi = {10.1016/j.mejo.2006.05.029}, volume = {37}, year = {2006}, } @article{1748, abstract = {The authors apply selective wet chemical etching and atomic force microscopy to reveal the three-dimensional shape of SiGeSi (001) islands after capping with Si. Although the "self-assembled quantum dots" remain practically unaffected by capping in the temperature range of 300-450 °C, significant morphological changes take place on the Si surface. At 450 °C, the morphology of the capping layer (Si matrix) evolves toward an intriguing semifacetted structure, which we call a "ziggurat," giving the misleading impression of a stepped SiGe island shape.}, author = {Georgios Katsaros and Rastelli, Armando and Stoffel, Mathieu and Costantini, Giovanni and Schmidt, Oliver G and Kern, Klaus and Tersoff, Jerry and Müller, Elisabeth and Von Känel, Hans}, journal = {Applied Physics Letters}, number = {25}, publisher = {American Institute of Physics}, title = {{Evolution of buried semiconductor nanostructures and origin of stepped surface mounds during capping}}, doi = {10.1063/1.2405876}, volume = {89}, year = {2006}, } @article{1796, abstract = {Drugs that block the entry of human immunodeficiency virus type 1 (HIV-1) into host cells abrogate the establishment of a productive infection and should ideally diminish the chances of HIV-1 developing resistance. This review will give an overview of the mechanism by which the envelope glycoprotein mediates HIV-1 entry and will summarize current drug developments.}, author = {Sandra Siegert and Schnierle, Peter and Schnierle, Barbara S}, journal = {Mini-Reviews in Medicinal Chemistry}, number = {5}, pages = {557 -- 562}, publisher = {Bentham Science Publishers}, title = {{Novel anti-viral therapy: Drugs that block HIV entry at different target sites}}, doi = {10.2174/138955706776876267}, volume = {6}, year = {2006}, } @article{1961, abstract = {Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance of cluster N3, leading to the main redox pathway, and of the distal cluster Nia, a possible antioxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin, and it may be involved in iron-sulfur cluster regeneration in the complex. }, author = {Leonid Sazanov and Hinchliffe, Philip }, journal = {Science}, number = {5766}, pages = {1430 -- 1436}, publisher = {American Association for the Advancement of Science}, title = {{Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus}}, doi = {10.1126/science.1123809}, volume = {311}, year = {2006}, } @article{1966, abstract = {The hydrophilic domain (peripheral arm) of the proton-translocating NADH:quinone oxidoreductase (complex I) from the thermophilic organism Thermus thermophilus HB8 has been purified and characterized. The subcomplex is stable in sodium dodecyl sulfate up to 80 °C. Of nine iron-sulfur clusters, four to five (one or two binuclear and three tetranuclear) could be detected by EPR in the NADH-reduced enzyme. The preparation consists of eight different polypeptides. Seven of them have been positively identified by peptide mass mapping and N-terminal sequencing as known hydrophilic subunits of T. thermophilus complex I. The eighth polypeptide copurified with the subcomplex at all stages, is strongly associated with the other subunits, and is present in crystals of the subcomplex, used for X-ray data collection. Therefore, it has been identified as a novel complex I subunit and named Nqo15. It is encoded in a locus separate from the nqo operon, containing the 14 other known complex I genes. ORFs encoding Nqo15 homologues are present in the genomes of the closest relatives of T. thermophilus. Our data show that, contrary to previous assumptions, bacterial complex I can contain proteins in addition to a "core" complement of 14 subunits.}, author = {Hinchliffe, Philip and Carroll, Joe D and Leonid Sazanov}, journal = {Biochemistry}, number = {14}, pages = {4413 -- 4420}, publisher = {ACS}, title = {{Identification of a novel subunit of respiratory complex I from Thermus thermophilus}}, doi = {10.1021/bi0600998}, volume = {45}, year = {2006}, } @article{2066, abstract = {Although the X chromosome is usually similar to the autosomes in size and cytogenetic appearance, theoretical models predict that its hemizygosity in males may cause unusual patterns of evolution. The sequencing of several genomes has indeed revealed differences between the X chromosome and the autosomes in the rates of gene divergence, patterns of gene expression and rates of gene movement between chromosomes. A better understanding of these patterns should provide valuable information on the evolution of genes located on the X chromosome. It could also suggest solutions to more general problems in molecular evolution, such as detecting selection and estimating mutational effects on fitness}, author = {Beatriz Vicoso and Charlesworth, Brian}, journal = {Nature Reviews Genetics}, number = {8}, pages = {645 -- 653}, publisher = {Nature Publishing Group}, title = {{Evolution on the X chromosome: Unusual patterns and processes}}, doi = {10.1038/nrg1914}, volume = {7}, 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{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}, }