Well-Tempered Metadynamics Simulations Predict the Structural and Dynamic Properties of a Chiral 24-Atom Macrocycle in Solution

Inspired by therapeutic potential, the molecular engineering of macrocycles is garnering increased interest. Exercising control with design, however, is challenging due to the dynamic behavior that these molecules must demonstrate in order to be bioactive. Herein, the value of metadynamics simulations is demonstrated: the free-energy surfaces calculated reveal folded and flattened accessible conformations of a 24-atom macrocycle separated by barriers of c.a. 6 kT under experimentally relevant conditions. Simulations reveal that the dominant conformer is folded-an observation consistent with a solid-state structure determined by X-ray crystallography and a network of rOes established by 1H NMR. Simulations suggest that the macrocycle exists as a rapidly interconverting pair of enantiomeric, folded structures. Experimentally, 1H NMR shows a single species at room temperature. However, at lower temperature, the interconversion rate between these enantiomers becomes markedly slower, resulting in the decoalescence of enantiotopic methylene protons into diastereotopic, distinguishable resonances due to the persistence of conformational chirality. The emergence of conformational chirality provides critical experimental support for the simulations, revealing the dynamic nature of the scaffold-a trait deemed critical for oral bioactivity

Breakdown of scale-invariance in the coarsening of phase-separating binary fluids

We present evidence, based on lattice Boltzmann simulations, to show that the coarsening of the domains in phase separating binary fluids is not a scale-invariant process. Moreover we emphasise that the pathway by which phase separation occurs depends strongly on the relation between diffusive and hydrodynamic time scales.Comment: 4 pages, Latex, 4 eps Figures included. (higher quality Figures can be obtained from [email protected]

Short contacts between chains enhancing luminescence quantum yields and carrier mobilities in conjugated copolymers

Abstract: Efficient conjugated polymer optoelectronic devices benefit from concomitantly high luminescence and high charge carrier mobility. This is difficult to achieve, as interchain interactions, which are needed to ensure efficient charge transport, tend also to reduce radiative recombination and lead to solid-state quenching effects. Many studies detail strategies for reducing these interactions to increase luminescence, or modifying chain packing motifs to improve percolation charge transport; however achieving these properties together has proved elusive. Here, we show that properly designed amorphous donor-alt-acceptor conjugated polymers can circumvent this problem; combining a tuneable energy gap, fast radiative recombination rates and luminescence quantum efficiencies >15% with high carrier mobilities exceeding 2.4 cm2/Vs. We use photoluminescence from exciton states pinned to close-crossing points to study the interplay between mobility and luminescence. These materials show promise towards realising advanced optoelectronic devices based on conjugated polymers, including electrically-driven polymer lasers

Evolution of white matter damage in amyotrophic lateral sclerosis

Objective To characterize disease evolution in amyotrophic lateral sclerosis using an event‐based model designed to extract temporal information from cross‐sectional data. Conventional methods for understanding mechanisms of rapidly progressive neurodegenerative disorders are limited by the subjectivity inherent in the selection of a limited range of measurements, and the need to acquire longitudinal data. Methods The event‐based model characterizes a disease as a series of events, each comprising a significant change in subject state. The model was applied to data from 154 patients and 128 healthy controls selected from five independent diffusion MRI datasets acquired in four different imaging laboratories between 1999 and 2016. The biomarkers modeled were mean fractional anisotropy values of white matter tracts implicated in amyotrophic lateral sclerosis. The cerebral portion of the corticospinal tract was divided into three segments. Results Application of the model to the pooled datasets revealed that the corticospinal tracts were involved before other white matter tracts. Distal corticospinal tract segments were involved earlier than more proximal (i.e., cephalad) segments. In addition, the model revealed early ordering of fractional anisotropy change in the corpus callosum and subsequently in long association fibers. Interpretation These findings represent data‐driven evidence for early involvement of the corticospinal tracts and body of the corpus callosum in keeping with conventional approaches to image analysis, while providing new evidence to inform directional degeneration of the corticospinal tracts. This data‐driven model provides new insight into the dynamics of neuronal damage in amyotrophic lateral sclerosis

Demonstration of tunable three-body interactions between superconducting qubits

Nonpairwise multi-qubit interactions present a useful resource for quantum information processors. Their implementation would facilitate more efficient quantum simulations of molecules and combinatorial optimization problems, and they could simplify error suppression and error correction schemes. Here we present a superconducting circuit architecture in which a coupling module mediates 2-local and 3-local interactions between three flux qubits by design. The system Hamiltonian is estimated via multi-qubit pulse sequences that implement Ramsey-type interferometry between all neighboring excitation manifolds in the system. The 3-local interaction is coherently tunable over several MHz via the coupler flux biases and can be turned off, which is important for applications in quantum annealing, analog quantum simulation, and gate-model quantum computation.Comment: 14 pages, 11 figure

Measurements of Flavour Dependent Fragmentation Functions in Z^0 -> qq(bar) Events

Fragmentation functions for charged particles in Z -> qq(bar) events have been measured for bottom (b), charm (c) and light (uds) quarks as well as for all flavours together. The results are based on data recorded between 1990 and 1995 using the OPAL detector at LEP. Event samples with different flavour compositions were formed using reconstructed D* mesons and secondary vertices. The \xi_p = ln(1/x_E) distributions and the position of their maxima \xi_max are also presented separately for uds, c and b quark events. The fragmentation function for b quarks is significantly softer than for uds quarks.Comment: 29 pages, LaTeX, 5 eps figures (and colour figs) included, submitted to Eur. Phys. J.

Bose-Einstein Correlations in e+e- to W+W- at 172 and 183 GeV

Bose-Einstein correlations between like-charge pions are studied in hadronic final states produced by e+e- annihilations at center-of-mass energies of 172 and 183 GeV. Three event samples are studied, each dominated by one of the processes W+W- to qqlnu, W+W- to qqqq, or (Z/g)* to qq. After demonstrating the existence of Bose-Einstein correlations in W decays, an attempt is made to determine Bose-Einstein correlations for pions originating from the same W boson and from different W bosons, as well as for pions from (Z/g)* to qq events. The following results are obtained for the individual chaoticity parameters lambda assuming a common source radius R: lambda_same = 0.63 +- 0.19 +- 0.14, lambda_diff = 0.22 +- 0.53 +- 0.14, lambda_Z = 0.47 +- 0.11 +- 0.08, R = 0.92 +- 0.09 +- 0.09. In each case, the first error is statistical and the second is systematic. At the current level of statistical precision it is not established whether Bose-Einstein correlations, between pions from different W bosons exist or not.Comment: 24 pages, LaTeX, including 6 eps figures, submitted to European Physical Journal

W+W- production and triple gauge boson couplings at LEP energies up to 183 GeV

A study of W-pair production in e+e- annihilations at Lep2 is presented, based on 877 W+W- candidates corresponding to an integrated luminosity of 57 pb-1 at sqrt(s) = 183 GeV. Assuming that the angular distributions of the W-pair production and decay, as well as their branching fractions, are described by the Standard Model, the W-pair production cross-section is measured to be 15.43 +- 0.61 (stat.) +- 0.26 (syst.) pb. Assuming lepton universality and combining with our results from lower centre-of-mass energies, the W branching fraction to hadrons is determined to be 67.9 +- 1.2 (stat.) +- 0.5 (syst.)%. The number of W-pair candidates and the angular distributions for each final state (qqlnu,qqqq,lnulnu) are used to determine the triple gauge boson couplings. After combining these values with our results from lower centre-of-mass energies we obtain D(kappa_g)=0.11+0.52-0.37, D(g^z_1)=0.01+0.13-0.12 and lambda=-0.10+0.13-0.12, where the errors include both statistical and systematic uncertainties and each coupling is determined setting the other two couplings to the Standard Model value. The fraction of W bosons produced with a longitudinal polarisation is measured to be 0.242+-0.091(stat.)+-0.023(syst.). All these measurements are consistent with the Standard Model expectations.Comment: 48 pages, LaTeX, including 13 eps or ps figures, submitted to European Physical Journal

Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays

Bose-Einstein Correlations (BEC) of three identical charged pions were studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP. The genuine three-pion correlations, corrected for the Coulomb effect, were separated from the known two-pion correlations by a new subtraction procedure. A significant genuine three-pion BEC enhancement near threshold was observed having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029 (syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041 (syst.). The Coulomb correction was found to increase the \lambda_3 value by \~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of 0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the three-pion sample purity. A relation between the two-pion and the three-pion source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal