@inproceedings{8507, abstract = {We study a Cr nearly integrable Hamiltonian system defined on 𝕋3 × ℝ3. Let and ”Σ1 be the restriction of Lebesgue measure on 𝕋3 × ℝ3 to ∑. We prove there is a perturbation , and an orbit (q(t), p(t)): ℝ → 𝕋3 × ℝ3 of the Hamiltonian equation such that .}, author = {Kaloshin, Vadim and ZHANG, KE and ZHENG, YONG}, booktitle = {XVIth International Congress on Mathematical Physics}, isbn = {9789814304627}, location = {Prague, Czech Republic}, pages = {314--322}, publisher = {World Scientific}, title = {{Almost dense orbit on energy surface}}, doi = {10.1142/9789814304634_0017}, year = {2010}, } @article{857, abstract = {The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, 3.5 × 10 9 yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.}, author = {Povolotskaya, Inna and Fyodor Kondrashov}, journal = {Nature}, number = {7300}, pages = {922 -- 926}, publisher = {Nature Publishing Group}, title = {{Sequence space and the ongoing expansion of the protein universe}}, doi = {10.1038/nature09105}, volume = {465}, year = {2010}, } @article{862, abstract = {A long-standing controversy in evolutionary biology is whether or not evolving lineages can cross valleys on the fitness landscape that correspond to low-fitness genotypes, which can eventually enable them to reach isolated fitness peaks1-9. Here we study the fitness landscapes traversed by switches between different AU and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles corresponding to GU and AC non-Watson-Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles. Substitutions leading to a Watson-Crick switch are strongly correlated, especially in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial genome. Using these data we estimate that a typical Watson-Crick switch involves crossing a fitness valley of a depth of about 10-3 or even about 10-2, with AC intermediates being slightly more deleterious than GU intermediates. This compensatory evolution must proceed through rare intermediate variants that never reach fixation. The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.}, author = {Meer, Margarita V and Kondrashov, Alexey S and Artzy-Randrup, Yael and Fyodor Kondrashov}, journal = {Nature}, number = {7286}, pages = {279 -- 282}, publisher = {Nature Publishing Group}, title = {{Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness}}, doi = {10.1038/nature08691}, volume = {464}, year = {2010}, } @article{872, abstract = {The rate of spontaneous mutation in natural populations is a fundamental parameter for many evolutionary phenomena. Because the rate of mutation is generally low, most of what is currently known about mutation has been obtained through indirect, complex and imprecise methodological approaches. However, in the past few years genome-wide sequencing of closely related individuals has made it possible to estimate the rates of mutation directly at the level of the DNA, avoiding most of the problems associated with using indirect methods. Here, we review the methods used in the past with an emphasis on next generation sequencing, which may soon make the accurate measurement of spontaneous mutation rates a matter of routine.}, author = {Fyodor Kondrashov and Kondrashov, Alexey S}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1544}, pages = {1169 -- 1176}, publisher = {Royal Society, The}, title = {{Measurements of spontaneous rates of mutations in the recent past and the near future}}, doi = {10.1098/rstb.2009.0286}, volume = {365}, year = {2010}, } @article{884, abstract = {Background: Divergence of two independently evolving sequences that originated from a common ancestor can be described by two parameters, the asymptotic level of divergence E and the rate r at which this level of divergence is approached. Constant negative selection impedes allele replacements and, therefore, is routinely assumed to decelerate sequence divergence. However, its impact on E and on r has not been formally investigated.Results: Strong selection that favors only one allele can make E arbitrarily small and r arbitrarily large. In contrast, in the case of 4 possible alleles and equal mutation rates, the lowest value of r, attained when two alleles confer equal fitnesses and the other two are strongly deleterious, is only two times lower than its value under selective neutrality.Conclusions: Constant selection can strongly constrain the level of sequence divergence, but cannot reduce substantially the rate at which this level is approached. In particular, under any constant selection the divergence of sequences that accumulated one substitution per neutral site since their origin from the common ancestor must already constitute at least one half of the asymptotic divergence at sites under such selection.Reviewers: This article was reviewed by Drs. Nicolas Galtier, Sergei Maslov, and Nick Grishin.}, author = {Kondrashov, Alexey S and Povolotskaya, Inna and Ivankov, Dmitry N and Fyodor Kondrashov}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Rate of sequence divergence under constant selection}}, doi = {10.1186/1745-6150-5-5}, volume = {5}, year = {2010}, } @article{89, abstract = {We demonstrate the operation of a device that can produce chitosan nanoparticles in a tunable size range from 50-300 nm with small size dispersion. A piezoelectric oscillator operated at megahertz frequencies is used to aerosolize a solution containing dissolved chitosan. The solvent is then evaporated from the aerosolized droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The nanoparticle size is controlled both by the concentration of the dissolved polymer and by the size of the aerosol droplets that are created. Our device can be used with any polymer or polymer/therapeutic combination that can be prepared in a homogeneous solution and vaporized.}, author = {Wright, Ian and Higginbotham, Andrew P and Baker, Shenda and Donnelly, Tom}, journal = {ACS Applied Materials and Interfaces}, number = {8}, pages = {2360 -- 2364}, publisher = {American Chemical Society}, title = {{Generation of nanoparticles of controlled size using ultrasonic piezoelectric oscillators in solution}}, doi = {10.1021/am100375w}, volume = {2}, year = {2010}, } @article{891, abstract = {Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications.}, author = {Innan, Hideki and Fyodor Kondrashov}, journal = {Nature Reviews Genetics}, number = {2}, pages = {97 -- 108}, publisher = {Nature Publishing Group}, title = {{The evolution of gene duplications: Classifying and distinguishing between models}}, doi = {10.1038/nrg2689}, volume = {11}, year = {2010}, } @article{1721, author = {Anna Kicheva and Briscoe, James}, journal = {PLoS Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Limbs made to measure}}, doi = {10.1371/journal.pbio.1000421}, volume = {8}, year = {2010}, } @article{1722, abstract = {Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues. An example is Sonic hedgehog (Shh), which acts in several developing vertebrate tissues, including the central nervous system, to provide positional information during embryonic patterning. Here we address how Shh signalling assigns the positional identities of distinct neuronal subtype progenitors throughout the ventral neural tube. Assays of intracellular signal transduction and gene expression indicate that the duration as well as level of signalling is critical for morphogen interpretation. Progenitors of the ventral neuronal subtypes are established sequentially, with progressively more ventral identities requiring correspondingly higher levels and longer periods of Shh signalling. Moreover, cells remain sensitive to changes in Shh signalling for an extended time, reverting to antecedent identities if signalling levels fall below a threshold. Thus, the duration of signalling is important not only for the assignment but also for the refinement and maintenance of positional identity. Together the data suggest a dynamic model for ventral neural tube patterning in which positional information corresponds to the time integral of Shh signalling. This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling.}, author = {Dessaud, Éric and Ribes, Vanessa and Balaskas, Nikolaos and Yang, Linlin and Pierani, Alessandra and Anna Kicheva and Novitch, Bennett and Briscoe, James and Sasai, Noriaki}, journal = {PLoS Biology}, number = {6}, publisher = {Public Library of Science}, title = {{Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog}}, doi = {10.1371/journal.pbio.1000382}, volume = {8}, year = {2010}, } @article{1752, abstract = {The epitaxial growth of germanium on silicon leads to the self-assembly of SiGe nanocrystals by a process that allows the size, composition and position of the nanocrystals to be controlled. This level of control, combined with an inherent compatibility with silicon technology, could prove useful in nanoelectronic applications. Here, we report the confinement of holes in quantum-dot devices made by directly contacting individual SiGe nanocrystals with aluminium electrodes, and the production of hybrid superconductor- semiconductor devices, such as resonant supercurrent transistors, when the quantum dot is strongly coupled to the electrodes. Charge transport measurements on weakly coupled quantum dots reveal discrete energy spectra, with the confined hole states displaying anisotropic gyromagnetic factors and strong spin-orbit coupling with pronounced dependences on gate voltage and magnetic field.}, author = {Georgios Katsaros and Spathis, Panayotis N and Stoffel, Mathieu and Fournel, Frank and Mongillo, Massimo and Bouchiat, Vincent and Lefloch, François and Rastelli, Armando and Schmidt, Oliver G and De Franceschi, Silvano}, journal = {Nature Nanotechnology}, number = {6}, pages = {458 -- 464}, publisher = {Nature Publishing Group}, title = {{Hybrid superconductor-semiconductor devices made from self-assembled SiGe nanocrystals on silicon}}, doi = {10.1038/nnano.2010.84}, volume = {5}, year = {2010}, } @article{1753, abstract = {We investigate electronic transport in n-i-n GaN nanowires with and without AlN double barriers. The nanowires are grown by catalyst-free, plasma-assisted molecular beam epitaxy enabling abrupt GaN/AlN interfaces as well as longitudinal n-type doping modulation. At low temperature, transport in n-i-n GaN nanowires is dominated by the Coulomb blockade effect. Carriers are confined in the undoped middle region, forming single or multiple islands with a characteristic length of ∌100 nm. The incorporation of two AlN tunnel barriers causes confinement to occur within the GaN dot in between. In the case of a 6 nm thick dot and 2 nm thick barriers, we observe characteristic signatures of Coulomb-blockaded transport in single quantum dots with discrete energy states. For thinner dots and barriers, Coulomb-blockade effects do not play a significant role while the onset of resonant tunneling via the confined quantum levels is accompanied by a negative differential resistance surviving up to ∌150 K.}, author = {Songmuang, Rudeeson and Georgios Katsaros and Monroy, Eva and Spathis, Panayotis N and Bougerol, Catherine and Mongillo, Massimo and De Franceschi, Silvano}, journal = {Nano Letters}, number = {9}, pages = {3545 -- 3550}, publisher = {American Chemical Society}, title = {{Quantum transport in GaN/AlN double-barrier heterostructure nanowires}}, doi = {10.1021/nl1017578}, volume = {10}, year = {2010}, } @article{1772, abstract = {We present the realization of a cavity quantum electrodynamics setup in which photons of strongly different lifetimes are engineered in different harmonic modes of the same cavity. We achieve this in a superconducting transmission line resonator with superconducting qubits coupled to the different modes. One cavity mode is strongly coupled to a detection line for qubit state readout, while a second long lifetime mode is used for photon storage and coherent quantum operations. We demonstrate sideband-based measurement of photon coherence, generation of n photon Fock states and the scaling of the sideband Rabi frequency with √n using a scheme that may be extended to realize sideband-based two-qubit logic gates.}, author = {Leek, Peter J and Baur, Matthias P and Johannes Fink and Bianchetti, R and Steffen, L. Kraig and Filipp, Stefan and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {10}, publisher = {American Physical Society}, title = {{Cavity quantum electrodynamics with separate photon storage and qubit readout modes}}, doi = {10.1103/PhysRevLett.104.100504}, volume = {104}, year = {2010}, } @article{1773, abstract = {The quantum properties of electromagnetic, mechanical or other harmonic oscillators can be revealed by investigating their strong coherent coupling to a single quantum two level system in an approach known as cavity quantum electrodynamics (QED). At temperatures much lower than the characteristic energy level spacing the observation of vacuum Rabi oscillations or mode splittings with one or a few quanta asserts the quantum nature of the oscillator. Here, we study how the classical response of a cavity QED system emerges from the quantum one when its thermal occupation-or effective temperature-is raised gradually over 5 orders of magnitude. In this way we explore in detail the continuous quantum-to-classical crossover and demonstrate how to extract effective cavity field temperatures from both spectroscopic and time-resolved vacuum Rabi measurements.}, author = {Johannes Fink and Steffen, L. Kraig and Studer, Peter and Bishop, Lev S and Baur, Matthias P and Bianchetti, R and Bozyigit, Deniz and Lang, C and Filipp, Stefan and Leek, Peter J and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Quantum-to-classical transition in cavity quantum electrodynamics}}, doi = {10.1103/PhysRevLett.105.163601}, volume = {105}, year = {2010}, } @article{1774, abstract = {A number of superconducting qubits, such as the transmon or the phase qubit, have an energy level structure with small anharmonicity. This allows for convenient access of higher excited states with similar frequencies. However, special care has to be taken to avoid unwanted higher-level populations when using short control pulses. Here we demonstrate the preparation of arbitrary three level superposition states using optimal control techniques in a transmon. Performing dispersive readout, we extract the populations of all three levels of the qutrit and study the coherence of its excited states. Finally we demonstrate full quantum state tomography of the prepared qutrit states and evaluate the fidelities of a set of states, finding on average 95%.}, author = {Bianchetti, R and Filipp, Stefan and Baur, Matthias P and Johannes Fink and Lang, C and Steffen, L. Kraig and Boissonneault, Maxime and Blais, Alexandre and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Control and tomography of a three level superconducting artificial atom}}, doi = {10.1103/PhysRevLett.105.223601}, volume = {105}, year = {2010}, } @article{1800, abstract = {Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.}, author = {Busskamp, Volker and Duebel, Jens and BĂĄlya, DĂĄvid and Fradot, Mathias and Viney, Tim J and Sandra Siegert and Groner, Anna C and Cabuy, Erik and Forster, ValĂ©rie and Seeliger, Mathias W and Biel, Martin and Humphries, Peter and PĂąques, Michel and Mohand-SaĂŻd, Saddek and Trono, Didier and Deisseroth, Karl A and SĂ€hel, JosĂ© A and Picaud, Serge A and Roska, Botond M}, journal = {Science}, number = {5990}, pages = {413 -- 417}, publisher = {American Association for the Advancement of Science}, title = {{Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa}}, doi = {10.1126/science.1190897}, volume = {329}, year = {2010}, } @article{1970, abstract = {Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the α-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 Å resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-Å long amphipathic α-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 Å resolution. The L-shaped assembly consists of the α-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic α-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.}, author = {Efremov, Rouslan G and Baradaran, Rozbeh and Leonid Sazanov}, journal = {Nature}, number = {7297}, pages = {441 -- 445}, publisher = {Nature Publishing Group}, title = {{The architecture of respiratory complex I}}, doi = {10.1038/nature09066}, volume = {465}, year = {2010}, } @article{2071, abstract = {The X or Z chromosome has several characteristics that distinguish it from the autosomes, namely hemizygosity in the heterogametic sex, and a potentially different effective population size, both of which may influence the rate and nature of evolution. In particular, there may be an accelerated rate of adaptive change for X-linked compared to autosomal coding sequences, often referred to as the Faster-X effect. Empirical studies have indicated that the strength of Faster-X evolution varies among different species, and theoretical treatments have shown that demography and mating system can substantially affect the degree of Faster-X evolution. Here we integrate genomic data on Faster-X evolution from a variety of animals with the demographic factors, mating system, and sex chromosome regulatory characteristics that may influence it. Our results suggest that differences in effective population size and mechanisms of dosage compensation may influence the perceived extent of Faster-X evolution, and help to explain several clade-specific patterns that we observe.}, author = {Mank, Judith E and Beatriz Vicoso and Berlin, Sofia and Charlesworth, Brian}, journal = {Evolution}, number = {3}, pages = {663 -- 674}, publisher = {Wiley-Blackwell}, title = {{Effective population size and the Faster-X effect: Empirical results and their interpretation}}, doi = {10.1111/j.1558-5646.2009.00853.x}, volume = {64}, year = {2010}, } @phdthesis{2075, abstract = {This thesis investigates the combination of data-driven and physically based techniques for acquiring, modeling, and animating deformable materials, with a special focus on human faces. Furthermore, based on these techniques, we introduce a data-driven process for designing and fabricating materials with desired deformation behavior. Realistic simulation behavior, surface details, and appearance are still demanding tasks. Neither pure data-driven, pure procedural, nor pure physical methods are best suited for accurate synthesis of facial motion and details (both for appearance and geometry), due to the difficulties in model design, parameter estimation, and desired controllability for animators. Capturing of a small but representative amount of real data, and then synthesizing diverse on-demand examples with physically-based models and real data as input benefits from both sides: Highly realistic model behavior due to real-world data and controllability due to physically-based models. To model the face and its behavior, hybrid physically-based and data-driven approaches are elaborated. We investigate surface-based representations as well as a solid representation based on FEM. To achieve realistic behavior, we propose to build light-weighted data capture devices to acquire real-world data to estimate model parameters and to employ concepts from data-driven modeling techniques and machine learning. The resulting models support simple acquisition systems, offer techniques to process and extract model parameters from real-world data, provide a compact representation of the facial geometry and its motion, and allow intuitive editing. We demonstrate applications such as capture of facial geometry and motion and real-time animation and transfer of facial details, and show that our soft tissue model can react to external forces and produce realistic deformations beyond facial expressions. Based on this model, we furthermore introduce a data-driven process for designing and fabricating materials with desired deformation behavior. The process starts with measuring deformation properties of base materials. Each material is represented as a non-linear stress-strain relationship in a finite-element model. For material design and fabrication, we introduce an optimization process that finds the best combination of base materials that meets a user’s criteria specified by example deformations. Our algorithm employs a number of strategies to prune poor solutions from the combinatorial search space. We finally demonstrate the complete process by designing and fabricating objects with complex heterogeneous materials using modern multi-material 3D printers. }, author = {Bernd Bickel}, booktitle = {Unknown}, number = {7458}, publisher = {Unknown}, title = {{Measurement-based modeling and fabrication of deformable materials for human faces}}, doi = {dx.doi.org/10.3929/ethz-a-006354908}, volume = {499}, year = {2010}, } @article{2095, abstract = {This paper describes a passive stereo system for capturing the 3D geometry of a face in a single-shot under standard light sources. The system is low-cost and easy to deploy. Results are submillimeter accurate and commensurate with those from state-ofthe-art systems based on active lighting, and the models meet the quality requirements of a demanding domain like the movie industry. Recovered models are shown for captures from both high-end cameras in a studio setting and from a consumer binocular-stereo camera, demonstrating scalability across a spectrum of camera deployments, and showing the potential for 3D face modeling to move beyond the professional arena and into the emerging consumer market in stereoscopic photography. Our primary technical contribution is a modification of standard stereo refinement methods to capture pore-scale geometry, using a qualitative approach that produces visually realistic results. The second technical contribution is a calibration method suited to face capture systems. The systemic contribution includes multiple demonstrations of system robustness and quality. These include capture in a studio setup, capture off a consumer binocular-stereo camera, scanning of faces of varying gender and ethnicity and age, capture of highly-transient facial expression, and scanning a physical mask to provide ground-truth validation.}, author = {Beeler, Thabo and Bernd Bickel and Beardsley, Paul A and Sumner, Bob and Groß, Markus S}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{High-quality single-shot capture of facial geometry}}, doi = {10.1145/1778765.1778777}, volume = {29}, year = {2010}, } @article{2096, abstract = {Point-based graphics has gained much attention as an alternative to polygon-based approaches because of its simplicity and flexibility. However, current point-based techniques do not provide a sufficient rendering quality for translucent materials such as human skin. In this paper, we propose a point-based framework with subsurface scattering of light, which is important to create the soft and semi-translucent appearance of human skin. To accurately simulate subsurface scattering in multilayered materials, we present splat-based diffusion to apply a linear combination of several Gaussian basis functions to each splat in object space. Compared to existing point-based approaches, our method offers a significantly improved visual quality in rendering human faces and provides a similar visual quality to polygon-based rendering using the texture space diffusion technique. We demonstrate the effectiveness of our approach in rendering scanned faces realistically.}, author = {Kim, Hyeonjoong and Bernd Bickel and Groß, Markus S and Choi, Soomi}, journal = {Science in China, Series F: Information Sciences}, number = {5}, pages = {911 -- 919}, publisher = {Springer}, title = {{Subsurface scattering using splat-based diffusion in point-based rendering}}, doi = {10.1007/s11432-010-0068-y}, volume = {53}, year = {2010}, }