@article{902, abstract = {We compare the functional spectrum of protein evolution in two separate animal lineages with respect to two hypotheses: (1) rates of divergence are distributed similarly among functional classes within both lineages, indicating that selective pressure on the proteome is largely independent of organismic-level biological requirements; and (2) rates of divergence are distributed differently among functional classes within each lineage, indicating species-specific selective regimes impact genome-wide substitutional patterns. Integrating comparative genome sequence with data from tissue-specific expressed-sequence-tag (EST) libraries and detailed database annotations, we find a functional genomic signature of rapid evolution and selective constraint shared between mammalian and nematode lineages despite their extensive morphological and ecological differences and distant common ancestry. In both phyla, we find evidence of accelerated evolution among components of molecular systems involved in coevolutionary change. In mammals, lineage-specific fast evolving genes include those involved in reproduction, immunity, and possibly, maternal-fetal conflict. Likelihood ratio tests provide evidence for positive selection in these rapidly evolving functional categories in mammals. In contrast, slowly evolving genes, in terms of amino acid or insertion/deletion (indel) change, in both phyla are involved in core molecular processes such as transcription, translation, and protein transport. Thus, strong purifying selection appears to act on the same core cellular processes in both mammalian and nematode lineages, whereas positive and/or relaxed selection acts on different biological processes in each lineage.}, author = {Castillo-Davis, Cristian I and Fyodor Kondrashov and Hartl, Daniel L and Kulathinal, Rob J}, journal = {Genome Research}, number = {5}, pages = {802 -- 811}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{The functional genomic distribution of protein divergence in two animal phyla: Coevolution, genomic conflict, and constraint}}, doi = {10.1101/gr.2195604}, volume = {14}, year = {2004}, } @article{7333, abstract = {The analysis of the complete H2/air polymer electrolyte fuel cell system shows that process air humidification is one of the biggest obstacles for a high performance portable system in the kW range. Therefore, a new concept, with passive process air humidification integrated into the stack, has been developed. Humidification in each cell makes the process independent from the number of cells and the operation mode, thus making the concept fully scalable. Without external humidification the system is simpler, smaller, and cheaper. The humidification of the process air is achieved by transfer of product water from the exhaust air, through part of the membrane, to the dry intake air. Tests have shown that cells using the concept of internal humidification and operated with dry air at 70 ° have almost the same performance as when operated with external humidification. A 42‐cell stack with this internal humidification concept was built and integrated into a portable 1 kW power generator system.}, author = {Santis, M. and Schmid, D. and Ruge, M. and Freunberger, Stefan Alexander and Büchi, F.N.}, issn = {1615-6846}, journal = {Fuel Cells}, number = {3}, pages = {214--218}, publisher = {Wiley}, title = {{Modular stack-internal air humidification concept-verification in a 1 kW stack}}, doi = {10.1002/fuce.200400028}, volume = {4}, year = {2004}, } @article{7334, abstract = {Fundamental and phenomenological models for cells, stacks, and complete systems of PEFC and SOFC are reviewed and their predictive power is assessed by comparing model simulations against experiments. Computationally efficient models suited for engineering design include the (1+1) dimensionality approach, which decouples the membrane in-plane and through-plane processes, and the volume-averaged-method (VAM) that considers only the lumped effect of pre-selected system components. The former model was shown to capture the measured lateral current density inhomogeneities in a PEFC and the latter was used for the optimization of commercial SOFC systems. State Space Modeling (SSM) was used to identify the main reaction pathways in SOFC and, in conjunction with the implementation of geometrically well-defined electrodes, has opened a new direction for the understanding of electrochemical reactions. Furthermore, SSM has advanced the understanding of the COpoisoning-induced anode impedance in PEFC. Detailed numerical models such as the Lattice Boltzmann (LB) method for transport in porous media and the full 3-D Computational Fluid Dynamics (CFD) Navier-Stokes simulations are addressed. These models contain all components of the relevant physics and they can improve the understanding of the related phenomena, a necessary condition for the development of both appropriate simplified models as well as reliable technologies. Within the LB framework, a technique for the characterization and computer-reconstruction of the porous electrode structure was developed using advanced pattern recognition algorithms. In CFD modeling, 3-D simulations were used to investigate SOFC with internal methane steam reforming and have exemplified the significance of porous and novel fractal channel distributors for the fuel and oxidant delivery, as well as for the cooling of PEFC. As importantly, the novel concept has been put forth of functionally designed, fractal-shaped fuel cells, showing promise of significant performance improvements over the conventional rectangular shaped units. Thermo-economic modeling for the optimization of PEFC is finally addressed. }, author = {Mantzaras, John and Freunberger, Stefan Alexander and Büchi, Felix N. and Roos, Markus and Brandstätter, Wilhelm and Prestat, Michel and Gauckler, Ludwig J. and Andreaus, Bernhard and Hajbolouri, Faegheh and Senn, Stephan M. and Poulikakos, Dimos and Chaniotis, Andreas K. and Larrain, Diego and Autissier, Nordahl and Maréchal, François}, issn = {0009-4293}, journal = {CHIMIA International Journal for Chemistry}, number = {12}, pages = {857--868}, publisher = {Swiss Chemical Society}, title = {{Fuel cell modeling and simulations}}, doi = {10.2533/000942904777677029}, volume = {58}, year = {2004}, } @article{7706, abstract = {The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.}, author = {Brunet, Anne and Sweeney, Lora Beatrice Jaeger and Sturgill, J Fitzhugh and Chua, Katrin and Greer, Paul and Lin, Yingxi and Tran, Hien and Ross, Sarah and Mostoslavsky, Raul and Cohen, Haim and Hu, Linda and Chen, Hwei-Ling and Jedrychowski, Mark and Gygi, Steven and Sinclair, David and Alt, Frederick and Greenberg, Michael}, issn = {0036-8075}, journal = {Science}, number = {5666}, pages = {2011--2015}, publisher = {American Association for the Advancement of Science}, title = {{Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase}}, doi = {10.1126/science.1094637}, volume = {303}, year = {2004}, } @article{1963, abstract = {The mechanism coupling electron transfer and proton pumping in respiratory complex I (NADH-ubiquinone oxidoreductase) has not been established, but it has been suggested that it involves conformational changes. Here, the influence of substrates on the conformation of purified complex I from Escherichia coli was studied by cross-linking and electron microscopy. When a zero-length cross-linking reagent was used, the presence of NAD(P)H, in contrast to that of NAD+, prevented the formation of cross-links between the hydrophilic subunits of the complex, including NuoB, NuoI, and NuoCD. Comparisons using different cross-linkers suggested that NuoB, which is likely to coordinate the key iron-sulfur cluster N2, is the most mobile subunit. The presence of NAD(P)H led also to enhanced proteolysis of subunit NuoG. These data indicate that upon NAD(P)H binding, the peripheral arm of the complex adopts a more open conformation, with increased distances between subunits. Single particle analysis showed the nature of this conformational change. The enzyme retains its L-shape in the presence of NADH, but exhibits a significantly more open or expanded structure both in the peripheral arm and, unexpectedly, in the membrane domain also.}, author = {Mamedova, Aygun A and Holt, Peter J and Carroll, Joe D and Leonid Sazanov}, journal = {Journal of Biological Chemistry}, number = {22}, pages = {23830 -- 23836}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Substrate-induced conformational change in bacterial complex I}}, doi = {10.1074/jbc.M401539200}, volume = {279}, year = {2004}, } @article{13434, abstract = {Thin films of ionically doped gelatin have been color-patterned with submicrometer precision using the wet-stamping technique. Inorganic salts are delivered onto the gelatin surface from an agarose stamp, and diffuse into the gelatine layer, producting deeply colored precipitates. Reaction fronts originating from different features of the stamp cease within < 1 μm of each other, leaving sharp, transparent regions in between.}, author = {Campbell, C. J. and Fialkowski, M. and Klajn, Rafal and Bensemann, I. T. and Grzybowski, B. A.}, issn = {1521-4095}, journal = {Advanced Materials}, keywords = {Mechanical Engineering, Mechanics of Materials, General Materials Science}, number = {21}, pages = {1912--1917}, publisher = {Wiley}, title = {{Color micro- and nanopatterning with counter-propagating reaction-diffusion fronts}}, doi = {10.1002/adma.200400383}, volume = {16}, year = {2004}, } @article{13435, abstract = {Micropatterning of surfaces with several chemicals at different spatial locations usually requires multiple stamping and registration steps. Here, we describe an experimental method based on reaction–diffusion phenomena that allows for simultaneous micropatterning of a substrate with several coloured chemicals. In this method, called wet stamping (WETS), aqueous solutions of two or more inorganic salts are delivered onto a film of dry, ionically doped gelatin from an agarose stamp patterned in bas relief. Once in conformal contact, these salts diffuse into the gelatin, where they react to give deeply coloured precipitates. Separation of colours in the plane of the surface is the consequence of the differences in the diffusion coefficients, the solubility products, and the amounts of different salts delivered from the stamp, and is faithfully reproduced by a theoretical model based on a system of reaction–diffusion partial differential equations. The multicolour micropatterns are useful as non-binary optical elements, and could potentially form the basis of new applications in microseparations and in controlled delivery.}, author = {Klajn, Rafal and Fialkowski, Marcin and Bensemann, Igor T. and Bitner, Agnieszka and Campbell, C. J. and Bishop, Kyle and Smoukov, Stoyan and Grzybowski, Bartosz A.}, issn = {1476-4660}, journal = {Nature Materials}, keywords = {Mechanical Engineering, Mechanics of Materials, Condensed Matter Physics, General Materials Science, General Chemistry}, pages = {729--735}, publisher = {Springer Nature}, title = {{Multicolour micropatterning of thin films of dry gels}}, doi = {10.1038/nmat1231}, volume = {3}, year = {2004}, } @article{1456, abstract = {We study the space of L2 harmonic forms on complete manifolds with metrics of fibred boundary or fibred cusp type. These metrics generalize the geometric structures at infinity of several different well-known classes of metrics, including asymptotically locally Euclidean manifolds, the (known types of) gravitational instantons, and also Poincaré metrics on ℚ-rank 1 ends of locally symmetric spaces and on the complements of smooth divisors in Kähler manifolds. The answer in all cases is given in terms of intersection cohomology of a stratified compactification of the manifold. The L2 signature formula implied by our result is closely related to the one proved by Dai and more generally by Vaillant and identifies Dai's τ-invariant directly in terms of intersection cohomology of differing perversities. This work is also closely related to a recent paper of Carron and the forthcoming paper of Cheeger and Dai. We apply our results to a number of examples, gravitational instantons among them, arising in predictions about L2 harmonic forms in duality theories in string theory.}, author = {Tamas Hausel and Hunsicker, Eugénie and Mazzeo, Rafe R}, journal = {Duke Mathematical Journal}, number = {3}, pages = {485 -- 548}, publisher = {Duke University Press}, title = {{Hodge cohomology of gravitational instantons}}, doi = {10.1215/S0012-7094-04-12233-X}, volume = {122}, year = {2004}, } @article{1464, abstract = {The moduli space of stable vector bundles on a Riemann surface is smooth when the rank and degree are coprime, and is diffeomorphic to the space of unitary connections of central constant curvature. A classic result of Newstead and Atiyah and Bott asserts that its rational cohomology ring is generated by the universal classes, that is, by the Kunneth components of the Chern classes of the universal bundle. This paper studies the larger, non-compact moduli space of Higgs bundles, as introduced by Hitchin and Simpson, with values in the canonical bundle K. This is diffeomorphic to the space of all connections of central constant curvature, whether unitary or not. The main result of the paper is that, in the rank 2 case, the rational cohomology ring of this space is again generated by universal classes. The spaces of Higgs bundles with values in K(n) for n > 0 turn out to be essential to the story. Indeed, we show that their direct limit has the homotopy type of the classifying space of the gauge group, and hence has cohomology generated by universal classes. 2000 Mathematics Subject Classification 14H60 (primary), 14D20, 14H81, 32Q55, 58D27 (secondary). }, author = {Tamas Hausel and Thaddeus, Michael}, journal = {Proceedings of the London Mathematical Society}, number = {3}, pages = {632 -- 658}, publisher = {Oxford University Press}, title = {{Generators for the cohomology ring of the moduli space of rank 2 higgs bundles}}, doi = {10.1112/S0024611503014618}, volume = {88}, year = {2004}, } @article{6155, abstract = {The genome of the nematode Caenorhabditis elegans encodes seven soluble guanylate cyclases (sGCs) [1]. In mammals, sGCs function as α/β heterodimers activated by gaseous ligands binding to a haem prosthetic group 2, 3. The principal activator is nitric oxide, which acts through sGCs to regulate diverse cellular events. In C. elegans the function of sGCs is mysterious: the worm genome does not appear to encode nitric oxide synthase, and all C. elegans sGC subunits are more closely related to mammalian β than α subunits [1]. Here, we show that two of the seven C. elegans sGCs, GCY-35 and GCY-36, promote aggregation behavior. gcy-35 and gcy-36 are expressed in a small number of neurons. These include the body cavity neurons AQR, PQR, and URX, which are directly exposed to the blood equivalent of C. elegans and regulate aggregation behavior [4]. We show that GCY-35 and GCY-36 act as α-like and β-like sGC subunits and that their function in the URX sensory neurons is sufficient for strong nematode aggregation. Neither GCY-35 nor GCY-36 is absolutely required for C. elegans to aggregate. Instead, these molecules may transduce one of several pathways that induce C. elegans to aggregate or may modulate aggregation by responding to cues in C. elegans body fluid.}, author = {Cheung, Benny H.H and Arellano-Carbajal, Fausto and Rybicki, Irene and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {12}, pages = {1105--1111}, publisher = {Elsevier}, title = {{Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior}}, doi = {10.1016/j.cub.2004.06.027}, volume = {14}, year = {2004}, } @article{9454, author = {Chan, Simon W.-L. and Zilberman, Daniel and Xie, Zhixin and Johansen, Lisa K. and Carrington, James C. and Jacobsen, Steven E.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {5662}, pages = {1336}, publisher = {American Association for the Advancement of Science}, title = {{RNA silencing genes control de novo DNA methylation}}, doi = {10.1126/science.1095989}, volume = {303}, year = {2004}, } @article{9493, abstract = {In a number of organisms, transgenes containing transcribed inverted repeats (IRs) that produce hairpin RNA can trigger RNA-mediated silencing, which is associated with 21-24 nucleotide small interfering RNAs (siRNAs). In plants, IR-driven RNA silencing also causes extensive cytosine methylation of homologous DNA in both the transgene "trigger" and any other homologous DNA sequences--"targets". Endogenous genomic sequences, including transposable elements and repeated elements, are also subject to RNA-mediated silencing. The RNA silencing gene ARGONAUTE4 (AGO4) is required for maintenance of DNA methylation at several endogenous loci and for the establishment of methylation at the FWA gene. Here, we show that mutation of AGO4 substantially reduces the maintenance of DNA methylation triggered by IR transgenes, but AGO4 loss-of-function does not block the initiation of DNA methylation by IRs. AGO4 primarily affects non-CG methylation of the target sequences, while the IR trigger sequences lose methylation in all sequence contexts. Finally, we find that AGO4 and the DRM methyltransferase genes are required for maintenance of siRNAs at a subset of endogenous sequences, but AGO4 is not required for the accumulation of IR-induced siRNAs or a number of endogenous siRNAs, suggesting that AGO4 may function downstream of siRNA production.}, author = {Zilberman, Daniel and Cao, Xiaofeng and Johansen, Lisa K. and Xie, Zhixin and Carrington, James C. and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {13}, pages = {1214--1220}, publisher = {Elsevier}, title = {{Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA methylation triggered by inverted repeats}}, doi = {10.1016/j.cub.2004.06.055}, volume = {14}, year = {2004}, } @article{9511, abstract = {Recent progress in understanding the silencing of transposable elements in the model plant Arabidopsis has revealed an interplay between DNA methylation, histone methylation and small interfering RNAs. DNA and histone methylation are not always sufficient to maintain silencing, and RNA-based reinforcement can be needed to maintain as well as initiate it.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {1465-6906}, journal = {Genome Biology}, number = {12}, publisher = {Springer Nature}, title = {{Silencing of transposons in plant genomes: kick them when they're down}}, doi = {10.1186/gb-2004-5-12-249}, volume = {5}, year = {2004}, } @article{9517, abstract = {Multicellular eukaryotes produce small RNA molecules (approximately 21–24 nucleotides) of two general types, microRNA (miRNA) and short interfering RNA (siRNA). They collectively function as sequence-specific guides to silence or regulate genes, transposons, and viruses and to modify chromatin and genome structure. Formation or activity of small RNAs requires factors belonging to gene families that encode DICER (or DICER-LIKE [DCL]) and ARGONAUTE proteins and, in the case of some siRNAs, RNA-dependent RNA polymerase (RDR) proteins. Unlike many animals, plants encode multiple DCL and RDR proteins. Using a series of insertion mutants of Arabidopsis thaliana, unique functions for three DCL proteins in miRNA (DCL1), endogenous siRNA (DCL3), and viral siRNA (DCL2) biogenesis were identified. One RDR protein (RDR2) was required for all endogenous siRNAs analyzed. The loss of endogenous siRNA in dcl3 and rdr2 mutants was associated with loss of heterochromatic marks and increased transcript accumulation at some loci. Defects in siRNA-generation activity in response to turnip crinkle virus in dcl2 mutant plants correlated with increased virus susceptibility. We conclude that proliferation and diversification of DCL and RDR genes during evolution of plants contributed to specialization of small RNA-directed pathways for development, chromatin structure, and defense.}, author = {Xie, Zhixin and Johansen, Lisa K. and Gustafson, Adam M. and Kasschau, Kristin D. and Lellis, Andrew D. and Zilberman, Daniel and Jacobsen, Steven E. and Carrington, James C.}, issn = {1545-7885}, journal = {PLoS Biology}, number = {5}, pages = {0642--0652}, publisher = {Public Library of Science}, title = {{Genetic and functional diversification of small RNA pathways in plants}}, doi = {10.1371/journal.pbio.0020104}, volume = {2}, year = {2004}, } @article{11762, abstract = {In this paper, we describe six algorithmic problems that arise in web search engines and that are not or only partially solved: (1) Uniformly sampling of web pages; (2) modeling the web graph; (3) finding duplicate hosts; (4) finding top gainers and losers in data streams; (5) finding large dense bipartite graphs; and (6) understanding how eigenvectors partition the web.}, author = {Henzinger, Monika H}, issn = {1944-9488}, journal = {Internet Mathematics}, number = {1}, pages = {115--123}, publisher = {Internet Mathematics}, title = {{Algorithmic challenges in web search engines}}, doi = {10.1080/15427951.2004.10129079}, volume = {1}, year = {2004}, } @inproceedings{11800, abstract = {Web search engines have emerged as one of the central applications on the Internet. In fact, search has become one of the most important activities that people engage in on the the Internet. Even beyond becoming the number one source of information, a growing number of businesses are depending on web search engines for customer acquisition. The first generation of web search engines used text-only retrieval techniques. Google revolutionized the field by deploying the PageRank technology – an eigenvector-based analysis of the hyperlink structure – to analyze the web in order to produce relevant results. Moving forward, our goal is to achieve a better understanding of a page with a view towards producing even more relevant results.}, author = {Henzinger, Monika H}, booktitle = {31st International Colloquium on Automata, Languages and Programming}, issn = {1611-3349}, location = {Turku, Finland}, pages = {3}, publisher = {Springer Nature}, title = {{The past, present, and future of web search engines}}, doi = {10.1007/978-3-540-27836-8_2}, volume = {3142}, year = {2004}, } @inproceedings{11801, abstract = {Web search engines have emerged as one of the central applications on the internet. In fact, search has become one of the most important activities that people engage in on the Internet. Even beyond becoming the number one source of information, a growing number of businesses are depending on web search engines for customer acquisition. In this talk I will brief review the history of web search engines: The first generation of web search engines used text-only retrieval techniques. Google revolutionized the field by deploying the PageRank technology – an eigenvector-based analysis of the hyperlink structure- to analyze the web in order to produce relevant results. Moving forward, our goal is to achieve a better understanding of a page with a view towards producing even more relevant results. Google is powered by a large number of PCs. Using this infrastructure and striving to be as efficient as possible poses challenging systems problems but also various algorithmic challenges. I will discuss some of them in my talk.}, author = {Henzinger, Monika H}, booktitle = {2th Annual European Symposium on Algorithms}, isbn = { 3540230254}, issn = {1611-3349}, location = {Bergen, Norway}, pages = {3}, publisher = {Springer Nature}, title = {{Algorithmic aspects of web search engines}}, doi = {10.1007/978-3-540-30140-0_2}, volume = {3221}, year = {2004}, } @inproceedings{11859, abstract = {In this article we describe the approach taken by the first web search engines, discuss the state of the art, and present some of the challenges for the future.}, author = {Henzinger, Monika H}, booktitle = {SPIE Proceedings}, issn = {0277-786X}, location = {San Jose, CA, United States}, pages = {23 -- 26}, publisher = {Society of Photo-Optical Instrumentation Engineers}, title = {{The past, present, and future of web information retrieval}}, doi = {10.1117/12.537534}, volume = {5296}, year = {2004}, } @article{11877, abstract = {The World Wide Web provides a unprecedented opportunity to automatically analyze a large sample of interests and activity in the world. We discuss methods for extracting knowledge from the web by randomly sampling and analyzing hosts and pages, and by analyzing the link structure of the web and how links accumulate over time. A variety of interesting and valuable information can be extracted, such as the distribution of web pages over domains, the distribution of interest in different areas, communities related to different topics, the nature of competition in different categories of sites, and the degree of communication between different communities or countries.}, author = {Henzinger, Monika H and Lawrence, Steve}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {suppl_1}, pages = {5186--5191}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Extracting knowledge from the World Wide Web}}, doi = {10.1073/pnas.0307528100}, volume = {101}, year = {2004}, } @article{209, author = {Timothy Browning and Heath-Brown, Roger}, journal = {Inventiones Mathematicae}, number = {3}, pages = {553 -- 573}, publisher = {Unknown}, title = {{Equal sums of three powers}}, doi = {10.1007/s00222-004-0360-9}, volume = {157}, year = {2004}, }