@article{8465, abstract = {We demonstrate that conformational exchange processes in proteins on microsecond-to-millisecond time scales can be detected and quantified by solid-state NMR spectroscopy. We show two independent approaches that measure the effect of conformational exchange on transverse relaxation parameters, namely Carr–Purcell–Meiboom–Gill relaxation-dispersion experiments and measurement of differential multiple-quantum coherence decay. Long coherence lifetimes, as required for these experiments, are achieved by the use of highly deuterated samples and fast magic-angle spinning. The usefulness of the approaches is demonstrated by application to microcrystalline ubiquitin. We detect a conformational exchange process in a region of the protein for which dynamics have also been observed in solution. Interestingly, quantitative analysis of the data reveals that the exchange process is more than 1 order of magnitude slower than in solution, and this points to the impact of the crystalline environment on free energy barriers.}, author = {Tollinger, Martin and Sivertsen, Astrid C. and Meier, Beat H. and Ernst, Matthias and Schanda, Paul}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {36}, pages = {14800--14807}, publisher = {American Chemical Society}, title = {{Site-resolved measurement of microsecond-to-millisecond conformational-exchange processes in proteins by solid-state NMR spectroscopy}}, doi = {10.1021/ja303591y}, volume = {134}, year = {2012}, } @article{8466, abstract = {Recent advances in NMR spectroscopy and the availability of high magnetic field strengths now offer the possibility to record real-time 3D NMR spectra of short-lived protein states, e.g., states that become transiently populated during protein folding. Here we present a strategy for obtaining sequential NMR assignments as well as atom-resolved information on structural and dynamic features within a folding intermediate of the amyloidogenic protein β2-microglobulin that has a half-lifetime of only 20 min.}, author = {Rennella, Enrico and Cutuil, Thomas and Schanda, Paul and Ayala, Isabel and Forge, Vincent and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {8066--8069}, publisher = {American Chemical Society}, title = {{Real-time NMR characterization of structure and dynamics in a transiently populated protein folding intermediate}}, doi = {10.1021/ja302598j}, volume = {134}, year = {2012}, } @article{8467, abstract = {Partial deuteration is a powerful tool to increase coherence life times and spectral resolution in proton solid-state NMR. The J coupling to deuterium needs, however, to be decoupled to maintain the good resolution in the (usually indirect) 13C dimension(s). We present a simple and reversible way to expand a commercial 1.3 mm HCN MAS probe with a 2H channel with sufficient field strength for J-decoupling of deuterium, namely 2–3 kHz. The coil is placed at the outside of the stator and requires no significant modifications to the probe. The performance and the realizable gains in sensitivity and resolution are demonstrated using perdeuterated ubiquitin, with selectively CHD2-labeled methyl groups.}, author = {Huber, Matthias and With, Oliver and Schanda, Paul and Verel, René and Ernst, Matthias and Meier, Beat H.}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, pages = {76--80}, publisher = {Elsevier}, title = {{A supplementary coil for 2H decoupling with commercial HCN MAS probes}}, doi = {10.1016/j.jmr.2011.10.010}, volume = {214}, year = {2012}, } @article{8502, abstract = {The famous ergodic hypothesis suggests that for a typical Hamiltonian on a typical energy surface nearly all trajectories are dense. KAM theory disproves it. Ehrenfest (The Conceptual Foundations of the Statistical Approach in Mechanics. Ithaca, NY: Cornell University Press, 1959) and Birkhoff (Collected Math Papers. Vol 2, New York: Dover, pp 462–465, 1968) stated the quasi-ergodic hypothesis claiming that a typical Hamiltonian on a typical energy surface has a dense orbit. This question is wide open. Herman (Proceedings of the International Congress of Mathematicians, Vol II (Berlin, 1998). Doc Math 1998, Extra Vol II, Berlin: Int Math Union, pp 797–808, 1998) proposed to look for an example of a Hamiltonian near H0(I)=⟨I,I⟩2 with a dense orbit on the unit energy surface. In this paper we construct a Hamiltonian H0(I)+εH1(θ,I,ε) which has an orbit dense in a set of maximal Hausdorff dimension equal to 5 on the unit energy surface.}, author = {Kaloshin, Vadim and Saprykina, Maria}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {643--697}, publisher = {Springer Nature}, title = {{An example of a nearly integrable Hamiltonian system with a trajectory dense in a set of maximal Hausdorff dimension}}, doi = {10.1007/s00220-012-1532-x}, volume = {315}, year = {2012}, } @article{8503, abstract = {We prove there are finitely many isometry classes of planar central configurations (also called relative equilibria) in the Newtonian 5-body problem, except perhaps if the 5-tuple of positive masses belongs to a given codimension 2 subvariety of the mass space.}, author = {Albouy, Alain and Kaloshin, Vadim}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {1}, pages = {535--588}, publisher = {Princeton University Press}, title = {{Finiteness of central configurations of five bodies in the plane}}, doi = {10.4007/annals.2012.176.1.10}, volume = {176}, year = {2012}, } @article{8504, abstract = {In this paper we present a surprising example of a Cr unimodal map of an interval f:I→I whose number of periodic points Pn(f)=∣{x∈I:fnx=x}∣ grows faster than any ahead given sequence along a subsequence nk=3k. This example also shows that ‘non-flatness’ of critical points is necessary for the Martens–de Melo–van Strien theorem [M. Martens, W. de Melo and S. van Strien. Julia–Fatou–Sullivan theory for real one-dimensional dynamics. Acta Math.168(3–4) (1992), 273–318] to hold.}, author = {Kaloshin, Vadim and KOZLOVSKI, O. S.}, issn = {0143-3857}, journal = {Ergodic Theory and Dynamical Systems}, keywords = {Applied Mathematics, General Mathematics}, number = {1}, pages = {159--165}, publisher = {Cambridge University Press}, title = {{A Cr unimodal map with an arbitrary fast growth of the number of periodic points}}, doi = {10.1017/s0143385710000817}, volume = {32}, year = {2012}, } @article{858, abstract = {ackground: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.Results: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.Conclusions: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.Reviewers: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers' Comments section.}, author = {Povolotskaya, Inna and Fyodor Kondrashov and Ledda, Alice and Vlasov, Peter K}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Stop codons in bacteria are not selectively equivalent}}, doi = {10.1186/1745-6150-7-30}, volume = {7}, year = {2012}, } @article{887, abstract = {A subject of extensive study in evolutionary theory has been the issue of how neutral, redundant copies can be maintained in the genome for long periods of time. Concurrently, examples of adaptive gene duplications to various environmental conditions in different species have been described. At this point, it is too early to tell whether or not a substantial fraction of gene copies have initially achieved fixation by positive selection for increased dosage. Nevertheless, enough examples have accumulated in the literature that such a possibility should be considered. Here, I review the recent examples of adaptive gene duplications and make an attempt to draw generalizations on what types of genes may be particularly prone to be selected for under certain environmental conditions. The identification of copy-number variation in ecological field studies of species adapting to stressful or novel environmental conditions may improve our understanding of gene duplications as a mechanism of adaptation and its relevance to the long-term persistence of gene duplications.}, author = {Fyodor Kondrashov}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1749}, pages = {5048 -- 5057}, publisher = {Royal Society, The}, title = {{Gene duplication as a mechanism of genomic adaptation to a changing environment}}, doi = {10.1098/rspb.2012.1108}, volume = {279}, year = {2012}, } @article{900, abstract = {The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.}, author = {Breen, Michael S and Kemena, Carsten and Vlasov, Peter K and Notredame, Cédric and Fyodor Kondrashov}, journal = {Nature}, number = {7421}, pages = {535 -- 538}, publisher = {Nature Publishing Group}, title = {{Epistasis as the primary factor in molecular evolution}}, doi = {10.1038/nature11510}, volume = {490}, year = {2012}, } @article{171, abstract = {For given non-zero integers a, b, q we investigate the density of solutions (x, y) ∈ ℤ2 to the binary cubic congruence ax2 + by3 ≡ 0 mod q, and use it to establish the Manin conjecture for a singular del Pezzo surface of degree 2 defined over ℚ.}, author = {Timothy Browning and Baier, Stephan}, journal = {Journal fur die Reine und Angewandte Mathematik}, number = {680}, pages = {1 -- 65}, publisher = {Walter de Gruyter}, title = {{Inhomogeneous cubic congruences and rational points on del Pezzo surfaces}}, doi = {https://doi.org/10.1515/crelle.2012.039}, volume = {2013}, year = {2012}, } @article{1725, abstract = {The spatial organization of cell fates during development involves the interpretation of morphogen gradients by cellular signaling cascades and transcriptional networks. Recent studies use biophysical models, genetics, and quantitative imaging to unravel how tissue-level morphogen behavior arises from subcellular events. Moreover, data from several systems show that morphogen gradients, downstream signaling, and the activity of cell-intrinsic transcriptional networks change dynamically during pattern formation. Studies from Drosophila and now also vertebrates suggest that transcriptional network dynamics are central to the generation of gene expression patterns. Together, this leads to the view that pattern formation is an emergent behavior that results from the coordination of events occurring across molecular, cellular, and tissue scales. The development of novel approaches to study this complex process remains a challenge.}, author = {Anna Kicheva and Cohen, Michael H and Briscoe, James}, journal = {Science}, number = {6104}, pages = {210 -- 212}, publisher = {American Association for the Advancement of Science}, title = {{Developmental pattern formation: Insights from physics and biology}}, doi = {10.1126/science.1225182}, volume = {338}, year = {2012}, } @article{1756, abstract = {We report on the electronic transport properties of multiple-gate devices fabricated from undoped silicon nanowires. Understanding and control of the relevant transport mechanisms was achieved by means of local electrostatic gating and temperature-dependent measurements. The roles of the source/drain contacts and of the silicon channel could be independently evaluated and tuned. Wrap gates surrounding the silicide-silicon contact interfaces were proved to be effective in inducing a full suppression of the contact Schottky barriers, thereby enabling carrier injection down to liquid helium temperature. By independently tuning the effective Schottky barrier heights, a variety of reconfigurable device functionalities could be obtained. In particular, the same nanowire device could be configured to work as a Schottky barrier transistor, a Schottky diode, or a p-n diode with tunable polarities. This versatility was eventually exploited to realize a NAND logic gate with gain well above one.}, author = {Mongillo, Massimo and Spathis, Panayotis N and Georgios Katsaros and Gentile, Pascal and De Franceschi, Silvano}, journal = {Nano Letters}, number = {6}, pages = {3074 -- 3079}, publisher = {American Chemical Society}, title = {{Multifunctional devices and logic gates with undoped silicon nanowires}}, doi = {10.1021/nl300930m}, volume = {12}, year = {2012}, } @article{1757, abstract = {Self-assembled Ge wires with a height of only 3 unit cells and a length of up to 2 micrometers were grown on Si(001) by means of a catalyst-free method based on molecular beam epitaxy. The wires grow horizontally along either the [100] or the [010] direction. On atomically flat surfaces, they exhibit a highly uniform, triangular cross section. A simple thermodynamic model accounts for the existence of a preferential base width for longitudinal expansion, in quantitative agreement with the experimental findings. Despite the absence of intentional doping, the first transistor-type devices made from single wires show low-resistive electrical contacts and single-hole transport at sub-Kelvin temperatures. In view of their exceptionally small and self-defined cross section, these Ge wires hold promise for the realization of hole systems with exotic properties and provide a new development route for silicon-based nanoelectronics.}, author = {Zhang, Jianjun and Georgios Katsaros and Montalenti, Francesco and Scopece, Daniele and Rezaev, Roman O and Mickel, Christine H and Rellinghaus, Bernd and Miglio, Leo P and De Franceschi, Silvano and Rastelli, Armando and Schmidt, Oliver G}, journal = {Physical Review Letters}, number = {8}, publisher = {American Physical Society}, title = {{Monolithic growth of ultrathin Ge nanowires on Si(001) }}, doi = {10.1103/PhysRevLett.109.085502}, volume = {109}, year = {2012}, } @article{1758, abstract = {We studied the low-energy states of spin-1/2 quantum dots defined in InAs/InP nanowires and coupled to aluminum superconducting leads. By varying the superconducting gap Δ with a magnetic field B we investigated the transition from strong coupling Δ≪T K to weak-coupling Δ≫T K, where T K is the Kondo temperature. Below the critical field, we observe a persisting zero-bias Kondo resonance that vanishes only for low B or higher temperatures, leaving the room to more robust subgap structures at bias voltages between Δ and 2Δ. For strong and approximately symmetric tunnel couplings, a Josephson supercurrent is observed in addition to the Kondo peak. We ascribe the coexistence of a Kondo resonance and a superconducting gap to a significant density of intragap quasiparticle states, and the finite-bias subgap structures to tunneling through Shiba states. Our results, supported by numerical calculations, own relevance also in relation to tunnel-spectroscopy experiments aiming at the observation of Majorana fermions in hybrid nanostructures.}, author = {Lee, Eduardo J and Jiang, Xiaocheng and Aguado, Ramón and Georgios Katsaros and Lieber, Charles M and De Franceschi, Silvano}, journal = {Physical Review Letters}, number = {18}, publisher = {American Physical Society}, title = {{Zero-bias anomaly in a nanowire quantum dot coupled to superconductors}}, doi = {10.1103/PhysRevLett.109.186802}, volume = {109}, year = {2012}, } @article{1782, abstract = {Steering a quantum harmonic oscillator state along cyclic trajectories leads to a path-dependent geometric phase. Here we describe its experimental observation in an electronic harmonic oscillator. We use a superconducting qubit as a nonlinear probe of the phase, which is otherwise unobservable due to the linearity of the oscillator. We show that the geometric phase is, for a variety of cyclic paths, proportional to the area enclosed in the quadrature plane. At the transition to the nonadiabatic regime, we study corrections to the phase and dephasing of the qubit caused by qubit-resonator entanglement. In particular, we identify parameters for which this dephasing mechanism is negligible even in the nonadiabatic regime. The demonstrated controllability makes our system a versatile tool to study geometric phases in open quantum systems and to investigate their potential for quantum information processing.}, author = {Pechal, M and Berger, Stefan T and Abdumalikov, Abdufarrukh A and Johannes Fink and Mlynek, Jonas A and Steffen, L. Kraig and Wallraff, Andreas and Filipp, Stefan}, journal = {Physical Review Letters}, number = {17}, publisher = {American Physical Society}, title = {{Geometric phase and nonadiabatic effects in an electronic harmonic oscillator}}, doi = {10.1103/PhysRevLett.108.170401}, volume = {108}, year = {2012}, } @article{1783, abstract = {Nonlinearity and entanglement are two important properties by which physical systems can be identified as nonclassical. We study the dynamics of the resonant interaction of up to N=3 two-level systems and a single mode of the electromagnetic field sharing a single excitation dynamically. We observe coherent vacuum Rabi oscillations and their nonlinear √N speedup by tracking the populations of all qubits and the resonator in time. We use quantum state tomography to show explicitly that the dynamics generates maximally entangled states of the W class in a time limited only by the collective interaction rate. We use an entanglement witness and the 3-tangle to characterize the state whose fidelity F=78% is limited in our experiments by crosstalk arising during the simultaneous qubit manipulations which is absent in a sequential approach with F=91%.}, author = {Mlynek, Jonas A and Abdumalikov, Abdufarrukh A and Johannes Fink and Steffen, L. Kraig and Baur, Matthias P and Lang, C and Van Loo, Arjan F and Wallraff, Andreas}, journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, number = {5}, publisher = {American Physical Society}, title = {{Demonstrating W-type entanglement of Dicke states in resonant cavity quantum electrodynamics}}, doi = {10.1103/PhysRevA.86.053838}, volume = {86}, year = {2012}, } @article{1784, abstract = {A localized qubit entangled with a propagating quantum field is well suited to study nonlocal aspects of quantum mechanics and may also provide a channel to communicate between spatially separated nodes in a quantum network. Here, we report the on-demand generation and characterization of Bell-type entangled states between a superconducting qubit and propagating microwave fields composed of zero-, one-, and two-photon Fock states. Using low noise linear amplification and efficient data acquisition we extract all relevant correlations between the qubit and the photon states and demonstrate entanglement with high fidelity.}, author = {Eichler, Christopher and Lang, C and Johannes Fink and Govenius, J and Filipp, Stefan and Wallraff, Andreas}, journal = {Physical Review Letters}, number = {24}, publisher = {American Physical Society}, title = {{Observation of entanglement between itinerant microwave photons and a superconducting qubit}}, doi = {10.1103/PhysRevLett.109.240501}, volume = {109}, year = {2012}, } @article{1801, abstract = {Brain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of an individual adult brain region differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes in one brain region, the mouse retina. We found that each adult cell type expressed a specific set of genes, including a unique set of transcription factors, forming a 'barcode' for cell identity. Cell type transcriptomes carried enough information to categorize cells into morphological classes and types. Several genes that were specifically expressed in particular retinal circuit elements, such as inhibitory neuron types, are associated with eye diseases. The resource described here allows gene expression to be compared across adult retinal cell types, experimenting with specific transcription factors to differentiate stem or somatic cells to retinal cell types, and predicting cellular targets of newly discovered disease-associated genes.}, author = {Sandra Siegert and Cabuy, Erik and Scherf, Brigitte G and Kohler, Hubertus and Panda, Satchidananda and Le, Yunzheng and Fehling, Hans J and Gaidatzis, Dimos and Stadler, Michael B and Roska, Botond M}, journal = {Nature Neuroscience}, number = {3}, pages = {487 -- 495}, publisher = {Nature Publishing Group}, title = {{Transcriptional code and disease map for adult retinal cell types}}, doi = {10.1038/nn.3032}, volume = {15}, year = {2012}, } @article{1972, abstract = {Outer membrane protein F, a major component of the Escherichia coli outer membrane, was crystallized for the first time in lipidic mesophase of monoolein in novel space groups, P1 and H32. Due to ease of its purification and crystallization OmpF can be used as a benchmark protein for establishing membrane protein crystallization in meso, as a "membrane lyzozyme" The packing of porin trimers in the crystals of space group H32 is similar to natural outer membranes, providing the first high-resolution insight into the close to native packing of OmpF. Surprisingly, interaction between trimers is mediated exclusively by lipids, without direct protein-protein contacts. Multiple ordered lipids are observed and many of them occupy identical positions independently of the space group, identifying preferential interaction sites of lipid acyl chains. Presence of ordered aliphatic chains close to a positively charged area on the porin surface suggests a position for a lipopolysaccharide binding site on the surface of the major E. coli porins.}, author = {Efremov, Rouslan G and Leonid Sazanov}, journal = {Journal of Structural Biology}, number = {3}, pages = {311 -- 318}, publisher = {Academic Press}, title = {{Structure of Escherichia coli OmpF porin from lipidic mesophase}}, doi = {10.1016/j.jsb.2012.03.005}, volume = {178}, year = {2012}, } @misc{1976, abstract = {Complex I is a key enzyme of the respiratory chain in many organisms. This multi-protein complex with an intricate evolutionary history originated from the unification of prebuilt modules of hydrogenases and transporters. Using recently determined crystallographic structures of complex I we reanalyzed evolutionarily related complexes that couple oxidoreduction to trans-membrane ion translocation. Our analysis points to the previously unnoticed structural homology of the electron input module of formate dehydrogenlyases and subunit NuoG of complex I. We also show that all related to complex I hydrogenases likely operate via a conformation driven mechanism with structural changes generated in the conserved coupling site located at the interface of subunits NuoB/D/H. The coupling apparently originated once in evolutionary history, together with subunit NuoH joining hydrogenase and transport modules. Analysis of quinone oxidoreduction properties and the structure of complex I allows us to suggest a fully reversible coupling mechanism. Our model predicts that: 1) proton access to the ketone groups of the bound quinone is rigorously controlled by the protein, 2) the negative electric charge of the anionic ubiquinol head group is a major driving force for conformational changes.}, author = {Efremov, Rouslan G and Leonid Sazanov}, booktitle = {Biochimica et Biophysica Acta - Bioenergetics}, number = {10}, pages = {1785 -- 1795}, publisher = {Elsevier}, title = {{The coupling mechanism of respiratory complex i - A structural and evolutionary perspective}}, doi = {10.1016/j.bbabio.2012.02.015}, volume = {1817}, year = {2012}, }