@article{17781, abstract = {We have discovered an extended Lyα plume (UDF 5225) associated with a compact source at redshift z ≈ 5.4 in slitless spectroscopic data from the Grism ACS Program for Extragalactic Science (GRAPES) project. The spatial extent of the emission is about 6 × 1.5 kpc (1'' × 0farcs25). Combining our grism data and the broadband images from the Hubble Ultra Deep Field (UDF) images, we find a Lyα line flux of ~2.2 × 10^-17 ergs cm^-2 s^-1 and surface brightness ~7 × 10^-17ergs cm^-2 s-1 arcsec^-2. The UDF images show diffuse continuum emission associated with UDF 5225, including three embedded knots. The morphology of UDF 5225 is highly suggestive of a galaxy in assembly. It is possible that the prominent Lyα emission from this object is due to an active nucleus, and that we are seeing the simultaneous growth through accretion of a galaxy and its central black hole. Follow-up observations at higher spectral resolution could test this hypothesis.}, author = {Rhoads, James E. and Panagia, Nino and Windhorst, Rogier A. and Malhotra, Sangeeta and Pirzkal, Norbert and Xu, Chun and Strolger, Louis Gregory and Bergeron, Louis E. and Daddi, Emanuele and Ferguson, Harry and Gardner, Jonathan P. and Gronwall, Caryl and Haiman, Zoltán and Koekemoer, Anton and Kummel, Martin and Moustakas, Leonidas A. and Pasquali, Anna and Riess, Adam and di Serego Alighieri, Sperello and Stiavelli, Massimo and Tsvetanov, Zlatan and Vernet, Joel and Walsh, Jeremy and Yan, Haojing}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {582--586}, publisher = {American Astronomical Society}, title = {{A redshift z≈ 5.4 Lyα emitting galaxy with linear morphology in the GRAPES/Hubble Ultra Deep Field}}, doi = {10.1086/427622}, volume = {621}, year = {2005}, } @article{17786, abstract = {The first stars and black holes that formed in the Universe are likely too faint for a direct detection. However, by ionizing most of the intergalactic medium (IGM), they left an indirect clue that reveals their existence. We discuss currently available observational constraints on the reionization history of IGM, and the extent to which accreting black holes (BHs) and stars can help account for these observations. We argue, based on the combined statistics of Lyman α and β absorption in quasar spectra, that the IGM contains a significant amount of neutral hydrogen with nHI/nH ≳0.1. On the other hand, we argue, based on the lack of a strong evolution in the observed abundance of Lyman α emitting galaxies beyond z ∼5.5, that the mean neutral hydrogen fraction cannot exceed nHI/nH ≈0.3 at the same redshift. We conclude that the IGM is experiencing rapid ionization at redshift z ∼6. We find that quasar BHs, including faint ones that are individually below the detection thresholds of existing optical and X-ray surveys, are unlikely to drive the evolution of the neutral fraction around this epoch, because they would over-produce the present-day soft X-ray background. On the other hand, the seeds of the z ∼6 quasar BHs likely appeared at much earlier epochs (z ∼20), and produced hard ionizing radiation by accretion. These early BHs are promising candidates to account for the high redshift (z ∼15) ionization implied by the recent cosmic microwave anisotropy data from WMAP. Using a model for the growth of BHs by accretion and mergers in a hierarchical cosmology, we suggest that the early growth of quasars must include a super-Eddington growth phase, and that, although not yet optically identified, the FIRST radio survey may have already detected several thousand > 10^8 M⊙ BHs at z > 6.}, author = {Haiman, Zoltán}, issn = {0375-9687}, journal = {Progress of Theoretical Physics Supplement}, pages = {86--104}, publisher = {Oxford University Press}, title = {{Finding the first generation of stars and black holes}}, doi = {10.1143/ptps.158.86}, volume = {158}, year = {2005}, } @article{8028, abstract = {Transmission of signals within the brain is essential for cognitive function, but it is not clear how neural circuits support reliable and accurate signal propagation over a sufficiently large dynamic range. Two modes of propagation have been studied: synfire chains, in which synchronous activity travels through feedforward layers of a neuronal network, and the propagation of fluctuations in firing rate across these layers. In both cases, a sufficient amount of noise, which was added to previous models from an external source, had to be included to support stable propagation. Sparse, randomly connected networks of spiking model neurons can generate chaotic patterns of activity. We investigate whether this activity, which is a more realistic noise source, is sufficient to allow for signal transmission. We find that, for rate-coded signals but not for synfire chains, such networks support robust and accurate signal reproduction through up to six layers if appropriate adjustments are made in synaptic strengths. We investigate the factors affecting transmission and show that multiple signals can propagate simultaneously along different pathways. Using this feature, we show how different types of logic gates can arise within the architecture of the random network through the strengthening of specific synapses.}, author = {Vogels, Tim P and Abbott, L. F.}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {46}, pages = {10786--10795}, publisher = {Society for Neuroscience}, title = {{Signal propagation and logic gating in networks of integrate-and-fire neurons}}, doi = {10.1523/jneurosci.3508-05.2005}, volume = {25}, year = {2005}, } @article{8029, abstract = {Neural network modeling is often concerned with stimulus-driven responses, but most of the activity in the brain is internally generated. Here, we review network models of internally generated activity, focusing on three types of network dynamics: (a) sustained responses to transient stimuli, which provide a model of working memory; (b) oscillatory network activity; and (c) chaotic activity, which models complex patterns of background spiking in cortical and other circuits. We also review propagation of stimulus-driven activity through spontaneously active networks. Exploring these aspects of neural network dynamics is critical for understanding how neural circuits produce cognitive function.}, author = {Vogels, Tim P and Rajan, Kanaka and Abbott, L.F.}, issn = {0147-006X}, journal = {Annual Review of Neuroscience}, number = {1}, pages = {357--376}, publisher = {Annual Reviews}, title = {{Neural network dynamics}}, doi = {10.1146/annurev.neuro.28.061604.135637}, volume = {28}, year = {2005}, } @article{843, abstract = {The impact of an amino acid replacement on the organism's fitness can vary from lethal to selectively neutral and even, in rare cases, beneficial. Substantial data are available on either pathogenic or acceptable replacements. However, the whole distribution of coefficients of selection against individual replacements is not known for any organism. To ascertain this distribution for human proteins, we combined data on pathogenic missense mutations, on human non-synonymous SNPs and on human-chimpanzee divergence of orthologous proteins. Fractions of amino acid replacements which reduce fitness by >10-2, 10-2-10-4, 10-4-10-5 and <10-5 are 25, 49, 14 and 12%, respectively. On average, the strength of selection against a replacement is substantially higher when chemically dissimilar amino acids are involved, and the Grantham's index of a replacement explains 35% of variance in the average logarithm of selection coefficients associated with different replacements. Still, the impact of a replacement depends on its context within the protein more than on its own nature. Reciprocal replacements are often associated with rather different selection coefficients, in particular, replacements of non-polar amino acids with polar ones are typically much more deleterious than replacements in the opposite direction. However, differences between evolutionary fluxes of reciprocal replacements are only weakly correlated with the differences between the corresponding selection coefficients.}, author = {Yampolsky, Lev Y and Fyodor Kondrashov and Kondrashov, Alexey S}, journal = {Human Molecular Genetics}, number = {21}, pages = {3191 -- 3201}, publisher = {Oxford University Press}, title = {{Distribution of the strength of selection against amino acid replacements in human proteins}}, doi = {10.1093/hmg/ddi350}, volume = {14}, year = {2005}, } @article{8491, abstract = {Fast multidimensional NMR with a time resolution of a few seconds provides a new tool for high throughput screening and site-resolved real-time studies of kinetic molecular processes by NMR. Recently we have demonstrated the feasibility to record protein 1H–15N correlation spectra in a few seconds of acquisition time using a new SOFAST-HMQC experiment (Schanda and Brutscher (2005) J. Am. Chem. Soc. 127, 8014). Here, we investigate in detail the performance of SOFAST-HMQC to record 1H–15N and 1H−13C correlation spectra of proteins of different size and at different magnetic field strengths. Compared to standard 1H–15N correlation experiments SOFAST-HMQC provides a significant gain in sensitivity, especially for fast repetition rates. Guidelines are provided on how to set up SOFAST-HMQC experiments for a given protein sample. In addition, an alternative pulse scheme, IPAP-SOFAST-HMQC is presented that allows application on NMR spectrometers equipped with cryogenic probes, and fast measurement of one-bond 1H–13C and 1H–15N scalar and residual dipolar coupling constants.}, author = {Schanda, Paul and Kupče, Ēriks and Brutscher, Bernhard}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, keywords = {Spectroscopy, Biochemistry}, number = {4}, pages = {199--211}, publisher = {Springer Nature}, title = {{SOFAST-HMQC experiments for recording two-dimensional deteronuclear correlation spectra of proteins within a few seconds}}, doi = {10.1007/s10858-005-4425-x}, volume = {33}, year = {2005}, } @article{8492, abstract = {We demonstrate for different protein samples that 2D 1H−15N correlation NMR spectra can be recorded in a few seconds of acquisition time using a new band-selective optimized flip-angle short-transient heteronuclear multiple quantum coherence experiment. This has enabled us to measure fast hydrogen−deuterium exchange rate constants along the backbone of a small globular protein fragment by real-time 2D NMR.}, author = {Schanda, Paul and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {22}, pages = {8014--8015}, publisher = {American Chemical Society}, title = {{Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on the time scale of seconds}}, doi = {10.1021/ja051306e}, volume = {127}, year = {2005}, } @article{8516, abstract = {The purpose of this paper is to construct examples of diffusion for E-Hamiltonian perturbations of completely integrable Hamiltonian systems in 2d-dimensional phase space, with d large. In the first part of the paper, simple and explicit examples are constructed illustrating absence of ‘long-time’ stability for size E Hamiltonian perturbations of quasi-convex integrable systems already when the dimension 2d of phase space becomes as large as log 1/E . We first produce the example in Gevrey class and then a real analytic one, with some additional work. In the second part, we consider again E-Hamiltonian perturbations of completely integrable Hamiltonian system in 2d-dimensional space with E-small but not too small, |E| > exp(−d), with d the number of degrees of freedom assumed large. It is shown that for a class of analytic time-periodic perturbations, there exist linearly diffusing trajectories. The underlying idea for both examples is similar and consists in coupling a fixed degree of freedom with a large number of them. The procedure and analytical details are however significantly different. As mentioned, the construction in Part I is totally elementary while Part II is more involved, relying in particular on the theory of normally hyperbolic invariant manifolds, methods of generating functions, Aubry–Mather theory, and Mather’s variational methods.}, author = {Bourgain, Jean and Kaloshin, Vadim}, issn = {0022-1236}, journal = {Journal of Functional Analysis}, keywords = {Analysis}, number = {1}, pages = {1--61}, publisher = {Elsevier}, title = {{On diffusion in high-dimensional Hamiltonian systems}}, doi = {10.1016/j.jfa.2004.09.006}, volume = {229}, year = {2005}, } @article{877, abstract = {Sequence analysis of protein and mitochondrially encoded tRNA genes shows that substitutions producing pathogenic effects in humans are often found in normal, healthy individuals from other species. Analysis of stability of protein and tRNA structures shows that the disease-causing effects of pathogenic mutations can be neutralized by other, compensatory substitutions that restore the structural stability of the molecule. Further study of such substitutions will, hopefully, lead to new methods for curing genetic dis- eases that may be based on the correction of molecule stability as a whole instead of reversing an individual pathogenic mutation.}, author = {Kondrashov, Fyodor}, journal = {Biofizika}, number = {3}, pages = {389 -- 395}, publisher = {Pleiades Publishing}, title = {{The analysis of monomer sequences in protein and tRNA and the manifestation of the compensation of pathogenic deviations in their evolution}}, volume = {50}, year = {2005}, } @article{878, abstract = {Negative trade-offs are thought to be a pervasive phenomenon and to inhibit evolution at all levels. New evidence shows that at the molecular level, there may be no trade-offs preventing the emergence of an enzyme with multiple functions. }, author = {Fyodor Kondrashov}, journal = {Nature Genetics}, number = {1}, pages = {9 -- 10}, publisher = {Nature Publishing Group}, title = {{In search of the limits of evolution}}, doi = {10.1038/ng0105-9}, volume = {37}, year = {2005}, } @article{880, abstract = {Here, I describe a case of loss of the D-arm by mitochondrial cysteine tRNA in the nine-banded armadillo (Dasypus novemcinctus) convergent with mt tRNASer(AGY). Such evolution sheds light on the relationship between structure and function of tRNA molecules and its impact on the patterns of molecular evolution.}, author = {Kondrashov, Fyodor}, journal = {Biofizika}, number = {3}, pages = {396 -- 403}, publisher = {Pleiades Publishing}, title = {{The convergent evolution of the secondary structure of mitochondrial cysteine tRNA in the nine-banded armadillo Dasypus novemcinctus}}, volume = {50}, year = {2005}, } @article{882, abstract = {Some mutations in human mitochondrial tRNAs are severely pathogenic. The available computational methods have a poor record of predicting the impact of a tRNA mutation on the phenotype and fitness. Here patterns of evolution at tRNA sites that harbor pathogenic mutations and at sites that harbor phenotypically cryptic polymorphisms were compared. Mutations that are pathogenic to humans occupy more conservative sites, are only rarely fixed in closely related species, and, when located in stem structures, often disrupt Watson-Crick pairing and display signs of compensatory evolution. These observations make it possible to classify ∼90% of all known pathogenic mutations as deleterious together with only ∼30% of polymorphisms. These polymorphisms segregate at frequencies that are more than two times lower than frequencies of polymorphisms classified as benign, indicating that at least ∼30% of known polymorphisms in mitochondrial tRNAs affect fitness negatively.}, author = {Fyodor Kondrashov}, journal = {Human Molecular Genetics}, number = {16}, pages = {2415 -- 2419}, publisher = {Oxford University Press}, title = {{Prediction of pathogenic mutations in mitochondrially encoded human tRNAs}}, doi = {10.1093/hmg/ddi243}, volume = {14}, year = {2005}, } @article{893, abstract = {Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G+C)-rich (or (A+T)-rich) genomes contain more (or fewer) amino acids encoded by (G+C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day.}, author = {Jordan, Ingo K and Fyodor Kondrashov and Adzhubeǐ, Ivan A and Wolf, Yuri I and Koonin, Eugene V and Kondrashov, Alexey S and Sunyaev, Shamil R}, journal = {Nature}, number = {7026}, pages = {633 -- 638}, publisher = {Nature Publishing Group}, title = {{A universal trend of amino acid gain and loss in protein evolution}}, doi = {10.1038/nature03306}, volume = {433}, year = {2005}, } @article{9491, abstract = {Cytosine DNA methylation in vertebrates is widespread, but methylation in plants is found almost exclusively at transposable elements and repetitive DNA [1]. Within regions of methylation, methylcytosines are typically found in CG, CNG, and asymmetric contexts. CG sites are maintained by a plant homolog of mammalian Dnmt1 acting on hemi-methylated DNA after replication. Methylation of CNG and asymmetric sites appears to be maintained at each cell cycle by other mechanisms. We report a new type of DNA methylation in Arabidopsis, dense CG methylation clusters found at scattered sites throughout the genome. These clusters lack non-CG methylation and are preferentially found in genes, although they are relatively deficient toward the 5′ end. CG methylation clusters are present in lines derived from different accessions and in mutants that eliminate de novo methylation, indicating that CG methylation clusters are stably maintained at specific sites. Because 5-methylcytosine is mutagenic, the appearance of CG methylation clusters over evolutionary time predicts a genome-wide deficiency of CG dinucleotides and an excess of C(A/T)G trinucleotides within transcribed regions. This is exactly what we find, implying that CG methylation clusters have contributed profoundly to plant gene evolution. We suggest that CG methylation clusters silence cryptic promoters that arise sporadically within transcription units.}, author = {Tran, Robert K. and Henikoff, Jorja G. and Zilberman, Daniel and Ditt, Renata F. and Jacobsen, Steven E. and Henikoff, Steven}, issn = {1879-0445}, journal = {Current Biology}, number = {2}, pages = {154--159}, publisher = {Elsevier}, title = {{DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes}}, doi = {10.1016/j.cub.2005.01.008}, volume = {15}, year = {2005}, } @article{9514, abstract = {Background: DNA methylation occurs at preferred sites in eukaryotes. In Arabidopsis, DNA cytosine methylation is maintained by three subfamilies of methyltransferases with distinct substrate specificities and different modes of action. Targeting of cytosine methylation at selected loci has been found to sometimes involve histone H3 methylation and small interfering (si)RNAs. However, the relationship between different cytosine methylation pathways and their preferred targets is not known. Results: We used a microarray-based profiling method to explore the involvement of Arabidopsis CMT3 and DRM DNA methyltransferases, a histone H3 lysine-9 methyltransferase (KYP) and an Argonaute-related siRNA silencing component (AGO4) in methylating target loci. We found that KYP targets are also CMT3 targets, suggesting that histone methylation maintains CNG methylation genome-wide. CMT3 and KYP targets show similar proximal distributions that correspond to the overall distribution of transposable elements of all types, whereas DRM targets are distributed more distally along the chromosome. We find an inverse relationship between element size and loss of methylation in ago4 and drm mutants. Conclusion: We conclude that the targets of both DNA methylation and histone H3K9 methylation pathways are transposable elements genome-wide, irrespective of element type and position. Our findings also suggest that RNA-directed DNA methylation is required to silence isolated elements that may be too small to be maintained in a silent state by a chromatin-based mechanism alone. Thus, parallel pathways would be needed to maintain silencing of transposable elements.}, author = {Tran, Robert K. and Zilberman, Daniel and de Bustos, Cecilia and Ditt, Renata F. and Henikoff, Jorja G. and Lindroth, Anders M. and Delrow, Jeffrey and Boyle, Tom and Kwong, Samson and Bryson, Terri D. and Jacobsen, Steven E. and Henikoff, Steven}, issn = {1465-6906}, journal = {Genome Biology}, number = {11}, publisher = {Springer Nature}, title = {{Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis}}, doi = {10.1186/gb-2005-6-11-r90}, volume = {6}, year = {2005}, } @article{9529, abstract = {Eukaryotic organisms have the remarkable ability to inherit states of gene activity without altering the underlying DNA sequence. This epigenetic inheritance can persist over thousands of years, providing an alternative to genetic mutations as a substrate for natural selection. Epigenetic inheritance might be propagated by differences in DNA methylation, post-translational histone modifications, and deposition of histone variants. Mounting evidence also indicates that small interfering RNA (siRNA)-mediated mechanisms play central roles in setting up and maintaining states of gene activity. Much of the epigenetic machinery of many organisms, including Arabidopsis, appears to be directed at silencing viruses and transposable elements, with epigenetic regulation of endogenous genes being mostly derived from such processes.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {0959-437X}, journal = {Current Opinion in Genetics and Development}, number = {5}, pages = {557--562}, publisher = {Elsevier}, title = {{Epigenetic inheritance in Arabidopsis: Selective silence}}, doi = {10.1016/j.gde.2005.07.002}, volume = {15}, year = {2005}, } @inproceedings{4624, abstract = {Surveying results from [5] and [6], we motivate and introduce the theory behind formalizing rich interfaces for software and hardware components. Rich interfaces specify the protocol aspects of component interaction. Their formalization, called interface automata, permits a compiler to check the compatibility of component interaction protocols. Interface automata support incremental design and independent implementability. Incremental design means that the compatibility checking of interfaces can proceed for partial system descriptions, without knowing the interfaces of all components. Independent implementability means that compatible interfaces can be refined separately, while still maintaining compatibility.}, author = {de Alfaro, Luca and Thomas Henzinger}, pages = {83 -- 104}, publisher = {Springer}, title = {{Interface-based design}}, doi = {10.1007/1-4020-3532-2_3}, volume = {195}, year = {2005}, } @article{4625, abstract = {Temporal logic is two-valued: formulas are interpreted as either true or false. When applied to the analysis of stochastic systems, or systems with imprecise formal models, temporal logic is therefore fragile: even small changes in the model can lead to opposite truth values for a specification. We present a generalization of the branching-time logic CTL which achieves robustness with respect to model perturbations by giving a quantitative interpretation to predicates and logical operators, and by discounting the importance of events according to how late they occur. In every state, the value of a formula is a real number in the interval [0,1], where 1 corresponds to truth and 0 to falsehood. The boolean operators and and or are replaced by min and max, the path quantifiers ∃ and ∀ determine sup and inf over all paths from a given state, and the temporal operators ⋄ and □ specify sup and inf over a given path; a new operator averages all values along a path. Furthermore, all path operators are discounted by a parameter that can be chosen to give more weight to states that are closer to the beginning of the path. We interpret the resulting logic DCTL over transition systems, Markov chains, and Markov decision processes. We present two semantics for DCTL: a path semantics, inspired by the standard interpretation of state and path formulas in CTL, and a fixpoint semantics, inspired by the μ-calculus evaluation of CTL formulas. We show that, while these semantics coincide for CTL, they differ for DCTL, and we provide model-checking algorithms for both semantics.}, author = {de Alfaro, Luca and Faella, Marco and Thomas Henzinger and Majumdar, Ritankar S and Stoelinga, Mariëlle}, journal = {Theoretical Computer Science}, number = {1}, pages = {139 -- 170}, publisher = {Elsevier}, title = {{Model checking discounted temporal properties}}, doi = {10.1016/j.tcs.2005.07.033}, volume = {345}, year = {2005}, } @inproceedings{575, abstract = {We present the first demonstration of Jozsa's "counterfactual computation", using an optical Grover's search algorithm. We put the algorithm in a superposition of 'running' and 'not-running', obtaining information even though the algorithm does not run.}, author = {Onur Hosten and Rakher, Matthew T and Barreiro, Julio T and Peters, Nicholas A and Kwiat, Paul G}, pages = {365 -- 367}, publisher = {IEEE}, title = {{Counterfactual quantum computation}}, doi = { 10.1109/QELS.2005.1548783}, volume = {1}, year = {2005}, } @article{6153, abstract = {A current challenge in neuroscience is to bridge the gaps between genes, proteins, neurons, neural circuits, and behavior in a single animal model. The nematode Caenorhabditis elegans has unique features that facilitate this synthesis. Its nervous system includes exactly 302 neurons, and their pattern of synaptic connectivity is known. With only five olfactory neurons, C. elegans can dynamically respond to dozens of attractive and repellant odors. Thermosensory neurons enable the nematode to remember its cultivation temperature and to track narrow isotherms. Polymodal sensory neurons detect a wide range of nociceptive cues and signal robust escape responses. Pairing of sensory stimuli leads to long-lived changes in behavior consistent with associative learning. Worms exhibit social behaviors and complex ultradian rhythms driven by Ca2+ oscillators with clock-like properties. Genetic analysis has identified gene products required for nervous system function and elucidated the molecular and neural bases of behaviors.}, author = {de Bono, Mario and Villu Maricq, Andres}, issn = {1545-4126}, journal = {Annual Review of Neuroscience}, pages = {451--501}, publisher = {Annual Reviews}, title = {{Neuronal substrates of complex behaviors in C. elegans}}, doi = {10.1146/annurev.neuro.27.070203.144259}, volume = {28}, year = {2005}, }