@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{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{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{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{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{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{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{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}, }