Influence of Dielectric Environment upon Isotope Effects onGlycoside Heterolysis: Computational Evaluation and AtomicHessian Analysis

Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. Implicit solvent calculations with molecule-shaped cavities show that the equilibrium isotope effect (EIE) for heterolysis of the glycosidic bonds in 5′-methylthioadenosine and in 2-(p-nitrophenoxy)tetrahydropyran, both in water, are very sensitive in the range 2 ≤ ε ≤ 10 to the relative permittivity of the continuum surrounding the oxacarbenium ion. However, different implementations of nominally the same PCM method can lead to opposite trends being predicted for the same molecule. Computational modeling of the influence of the inhomogeneous effective dielectric surrounding a substrate within the protein environment of an enzymic reaction requires an explicit treatment. The EIE (KH/KD) for transfer of cyclopentyl, cyclohexyl, tetrahydrofuranyl and tetrahydropyranyl cations from water to cyclohexane is predicted by B3LYP/6-31+G(d) calculations with implicit solvation and confirmed by B3LYP/6-31+G(d)/OPLS-AA calculations with averaging over many explicit solvation configurations. Atomic Hessian analysis, whereby the full Hessian is reduced to the elements belonging to a single atom at the site of isotopic substitution, reveals a remarkable result for both implicit and explicit solvation: the influence of the solvent environment on these EIEs is essentially captured completely by only a 3 × 3 block of the Hessian, although these values must correctly reflect the influence of the whole environment. QM/MM simulation with ensemble averaging has an important role to play in assisting the meaningful interpretation of observed isotope effects for chemical reactions both in solution and catalyzed by enzymes

Adapting the International System of Units to the twenty-first century

We review the proposal of the International Committee for Weights and Measures (Comité International des Poids et Mesures, CIPM), currently being considered by the General Conference on Weights and Measures (Conférences Générales des Poids et Mesures, CGPM), to revise the International System of Units (Le Système International d’Unitès, SI). The proposal includes new definitions for four of the seven base units of the SI, and a new form of words to present the definitions of all the units. The objective of the proposed changes is to adopt definitions referenced to constants of nature, taken in the widest sense, so that the definitions may be based on what are believed to be true invariants. In particular, whereas in the current SI the kilogram, ampere, kelvin and mole are linked to exact numerical values of the mass of the international prototype of the kilogram, the magnetic constant (permeability of vacuum), the triple-point temperature of water and the molar mass of carbon-12, respectively, in the new SI these units are linked to exact numerical values of the Planck constant, the elementary charge, the Boltzmann constant and the Avogadro constant, respectively. The new wording used expresses the definitions in a simple and unambiguous manner without the need for the distinction between base and derived units. The importance of relations among the fundamental constants to the definitions, and the importance of establishing a mise en pratique for the realization of each definition, are also discussed

Critical evaluation of anharmonicity and configurational averaging in QM/MM modelling of equilibrium isotope effects

Anharmonic effects upon vibrational frequencies and isotopic partition function ratios are modelled computationally by means of quantum mechanics/molecular mechanics (QM/MM) methods for two systems. First, the methyl cation in explicit water is considered using a B3LYP/6-31+G(d)/TIP3P method in order to check the previous prediction of an inverse equilibrium isotope effect (EIE) KH3/KD3 for transfer from vacuum to water at 298 K. A full QM/MM treatment including Lennard-Jones interactions predicts significantly inverse contributions from both internal (0.843 0.001) and external (0.894 0.001) modes of the solute. This treatment yields a much larger harmonic EIE (0.753 0.002, averaged over 928 independent solvent configurations) than is obtained either by projecting out the translational and rotational contributions (0.853) or by treating the solvent by a point-charge representation (0.9360 0.0006, harmonic; 0.9366 0.0006, anharmonic). The contribution of anharmonicity to the EIE affects the value only in the 3rd significant figure. Second, anharmonicity is investigated by means of QM/MM potential-energy scans along 12 normal modes for internal and external vibrations of methyl cation in water and for three modes (one stretching and two bending) for the Ha atom at the carbenium-ion centre in cyclopentyl, cyclohexyl, tetrahydrofuranyl and tetrahydropyranyl cations in explicit water and cyclohexane solvents, as obtained by means of atomic Hessian analysi

Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection

HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments' influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies

Measurement of the resonant and CP components in B¯0→J/ψπ+π− decays

The resonant structure of the reaction B¯0→J/ψπ+π− is studied using data from 3  fb−1 of integrated luminosity collected by the LHCb experiment, one third at 7 TeV center-of-mass energy and the remainder at 8 TeV. The invariant mass of the π+π− pair and three decay angular distributions are used to determine the fractions of the resonant and nonresonant components. Six interfering π+π− states, ρ(770), f0(500), f2(1270), ρ(1450), ω(782) and ρ(1700), are required to give a good description of invariant mass spectra and decay angular distributions. The positive and negative charge parity fractions of each of the resonant final states are determined. The f0(980) meson is not seen and the upper limit on its presence, compared with the observed f0(500) rate, is inconsistent with a model where these scalar mesons are formed from two quarks and two antiquarks (tetraquarks) at the eight standard deviation level. In the qq¯ model, the absolute value of the mixing angle between the f0(980) and the f0(500) scalar mesons is limited to be less than 17° at 90% confidence level.National Science Foundation (U.S.)United States. Dept. of Energ

Measurement of the forward W boson cross-section in pp collisions at √s = 7 TeV

A measurement of the inclusive W → μν production cross-section using data from pp collisions at a centre-of-mass energy of √s=7 TeV is presented. The analysis is based on an integrated luminosity of about 1.0 fb[superscript −1] recorded with the LHCb detector. Results are reported for muons with a transverse momentum greater than 20 [GeV over c] and pseudorapidity between 2.0 and 4.5. The W [superscript +] and W [superscript −] production cross-sections are measured to be σW[superscript +]→μ[superscript +]ν=861.0±2.0±11.2±14.7pb, σW[superscript −]→μ[superscript −] [bar over ν] = 675.8±1.9±8.8±11.6pb, where the first uncertainty is statistical, the second is systematic and the third is due to the luminosity determination. Cross-section ratios and differential distributions as functions of the muon pseudorapidity are also presented. The ratio of W [superscript +] to W [superscript −] cross-sections in the same fiducial kinematic region is determined to be σW [superscript +] → μ [superscript +] ν [over σW [superscript −] → μ [superscript −] [bar over ν]] = 1.274±0.005±0.009, where the uncertainties are statistical and systematic, respectively. Results are in good agreement with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics.National Science Foundation (U.S.

Measurement of the Z+b-jet cross-section in pp collisions at √s = 7 TeV in the forward region

The associated production of a Z boson or an off-shell photon γ * with a bottom quark in the forward region is studied using proton-proton collisions at a centre-of-mass energy of 7 TeV. The Z bosons are reconstructed in the [Z over γ] * → μ [superscript +] μ [superscript −] final state from muons with a transverse momentum larger than 20 GeV, while two transverse momentum thresholds are considered for jets (10 GeV and 20 GeV). Both muons and jets are reconstructed in the pseudorapidity range 2.0 < η < 4.5. The results are based on data corresponding to 1.0 fb [superscript −1] recorded in 2011 with the LHCb detector. The measurement of the Z+b-jet cross-section is normalized to the Z+jet cross-section. The measured cross-sections are 0.1 σ( [Z over γ] *(μ[superscript+] μ[superscript −]) + b-jet) = 295 ± 60 (stat) ± 51 (syst) ± 10 (lumi) fb for p [subscript T] (jet) > 10 GeV, and 0.2 σ( [Z over γ]*(μ[superscript +] μ[superscript −]) + b-jet)=128±36 (stat) ±22 (syst) ±5 (lumi) fb for p [subscript T](jet) > 20 GeV.National Science Foundation (U.S.

Observation of Overlapping Spin-1 and Spin-3 D¯0K− Resonances at Mass 2.86 GeV/c2

The resonant substructure of B_{s}^{0}→D[over ¯]^{0}K^{-}π^{+} decays is studied using a data sample corresponding to an integrated luminosity of 3.0  fb^{-1} of pp collision data recorded by the LHCb detector. An excess at m(D[over ¯]^{0}K^{-})≈2.86  GeV/c^{2} is found to be an admixture of spin-1 and spin-3 resonances. Therefore, the D_{sJ}^{*}(2860)^{-} state previously observed in inclusive e^{+}e^{-}→D[over ¯]^{0}K^{-}X and pp→D[over ¯]^{0}K^{-}X processes consists of at least two particles. This is the first observation of a heavy flavored spin-3 resonance, and the first time that any spin-3 particle has been seen to be produced in B decays. The masses and widths of the new states and of the D_{s2}^{*}(2573)^{-} meson are measured, giving the most precise determinations to date.National Science Foundation (U.S.)United States. Dept. of Energ