Laser-induced dynamic alignment of the HD molecule without the Born-Oppenheimer approximation.

Laser-induced molecular alignment is well understood within the framework of the Born-Oppenheimer (BO) approximation. Without the BO approximation, however, the concept of molecular structure is lost, making it hard to precisely define alignment. In this work, we demonstrate the emergence of alignment from the first-ever non-BO quantum dynamics simulations, using the HD molecule exposed to ultrashort laser pulses as a few-body test case. We extract the degree of alignment from the non-BO wave function by means of an operator expressed in terms of pseudo-proton coordinates that mimics the BO-based definition of alignment. The only essential approximation, in addition to the semiclassical electric-dipole approximation for the matter-field interaction, is the choice of time-independent explicitly correlated Gaussian basis functions. We use a variational, electric-field-dependent basis-set construction procedure, which allows us to keep the basis-set dimension low while capturing the main effects of electric polarization on the nuclear and electronic degrees of freedom. The basis-set construction procedure is validated by comparing with virtually exact grid-based simulations for two one-dimensional model systems: laser-driven electron dynamics in a soft attractive Coulomb potential and nuclear rovibrational dynamics in a Morse potential.

Computational and photoelectron spectroscopic study of the dipole-bound anions, indole(H2O)1,2 (.).

We report our joint computational and anion photoelectron spectroscopic study of indole-water cluster anions, indole(H2O)1,2 (-). The photoelectron spectra of both cluster anions show the characteristics of dipole-bound anions, and this is confirmed by our theoretical computations. The experimentally determined vertical electron detachment (VDE) energies for indole(H2O)1 (-) and indole(H2O)2 (-) are 144 meV and 251 meV, respectively. The corresponding theoretically determined VDE values for indole(H2O)1 (-) and indole(H2O)2 (-) are 124 meV and 255 meV, respectively. The vibrational features in the photoelectron spectra of these cluster anions are assigned as the vibrations of the water molecule.

Measuring gait parameters from a single chest-worn accelerometer in healthy individuals: a validation study.

Digital health technologies (DHTs) are increasingly being adopted in clinical trials, as they enable objective evaluations of health parameters in free-living environments. Although lumbar accelerometers notably provide reliable gait parameters, embedding accelerometers in chest devices, already used for vital signs monitoring, could capture a more comprehensive picture of participants' wellbeing, while reducing the burden of multiple devices. Here we assess the validity of gait parameters measured from a chest accelerometer. Twenty healthy adults (13 females, mean ± sd age: 33.9 ± 9.1 years) instrumented with lumbar and chest accelerometers underwent in-lab and outside-lab walking tasks, while monitored with reference devices (an instrumented mat, and a 6-accelerometers set). Gait parameters were extracted from chest and lumbar accelerometers using our open-source Scikit Digital Health gait (SKDH-gait) algorithm, and compared against reference values via Bland-Altman plots, Pearson's correlation, and intraclass correlation coefficient. Mixed effects regression models were performed to investigate the effect of device, task, and their interaction. Gait parameters derived from chest and lumbar accelerometers showed no significant difference and excellent agreement across all tasks, as well as good-to-excellent agreement and strong correlation against reference values, thus supporting the deployment of a single multimodal chest device in clinical trials, to simultaneously measure gait and vital signs.Trial Registration: The study was reviewed and approved by the Advarra IRB (protocol number: Pro00043100).

Raman spectroscopy study and first-principles calculations of the interaction between nucleic acid bases and carbon nanotubes.

In this work, we have used Raman spectroscopy and quantum chemical methods (MP2 and DFT) to study the interactions between nucleic acid bases (NABs) and single-walled carbon nanotubes (SWCNT). We found that the appearance of the interaction between the nanotubes and the NABs is accompanied by a spectral shift of the high-frequency component of the SWCNT G band in the Raman spectrum to a lower frequency region. The value of this shift varies from 0.7 to 1.3 cm(-1) for the metallic nanotubes and from 2.1 to 3.2 cm(-1) for the semiconducting nanotubes. Calculations of the interaction energies between the NABs and a fragment of the zigzag(10,0) carbon nanotube performed at the MP2/6-31++G(d,p)[NABs atoms]|6-31G(d)[nanotube atoms] level of theory while accounting for the basis set superposition error during geometry optimization allowed us to order the NABs according to the increasing interaction energy value. The order is: guanine (-67.1 kJ mol(-1)) > adenine (-59.0 kJ mol(-1)) > cytosine (-50.3 kJ mol(-1)) approximately = thymine (-50.2 kJ mol(-1)) > uracil (-44.2 kJ mol(-1)). The MP2 equilibrium structures and the interaction energies were used as reference points in the evaluation of the ability of various functionals in the DFT method to predict those structures and energies. We showed that the M05, MPWB1K, and MPW1B95 density functionals are capable of correctly predicting the SWCNT-NAB geometries but not the interaction energies, while the M05-2X functional is capable of correctly predicting both the geometries and the interaction energies.

SWNT-DNA and SWNT-polyC hybrids: AFM study and computer modeling.

Hybrids of carbon single-walled nanotubes (SWNT) with fragmented single or double-stranded DNA (fss- or fds-DNA) or polyC were studied by Atom Force Microscopy (AFM) and computer modeling. It was found that fragments of the polymer wrap in several layers around the nanotube, forming a strand-like spindle. In contrast to the fss-DNA, the fds-DNA also forms compact structures near the tube surface due to the formation of self-assembly structures consisting of a few DNA fragments. The hybrids of SWNT with wrapped single-, double- or triple strands of the biopolymer were simulated, and it was shown that such structures are stable. To explain the reason of multi-layer polymeric coating of the nanotube surface, the energy of the intermolecular interactions between different components of polyC was calculated at the MP2/6-31++G** level as well as the interaction energy in the SWNT-cytosine complex.

Structure and conformation of N4-hydroxycytosine and N4-hydroxy-5-fluorocytosine. A theoretical ab initio study.

Optimal molecular geometries and molecular energies were obtained for N4-hydroxycytosine and its 5-fluoro congener with the use of the theoretical ab initio quantum mechanical calculations within the Self Consistent Field method corrected for the electron correlation effects by the second-order Many Body Perturbation Theory (SCF + MBPT(2)). The 6-31G Gaussian basis set was employed. Several tautomeric and rotameric forms were considered. For N4-hydroxycytosine and N4-hydroxy-5-fluorocytosine the imino tautomer (in the conformation syn relatively to the N3-nitrogen atom) appeared to be the most stable form. The imino tautomer of N4-hydroxy-cytosine in the anti rotameric form is by 12.8 kJ mol-1 less stable than the imino-syn form. The 5-fluoro substituent raises the energy difference between the syn and anti rotamers up to 38.5 kJ mol-1. The potential energy barrier for the syn-anti rotation in the imino form of N4-hydroxycytosine is estimated to be about 180 kJ/mol. The results presented in this paper suggest that the syn-imino and anti-imino forms can be treated as two structural isomers that do not interconvert at temperatures relevant to biochemical conditions. The theoretical results also show that the amino tautomeric forms do not compete with the imino forms in the gas-phase and in non-polar and weakly-polar environment. In a polar environment (e.g., in aqueous solutions), however, one may expect an increased population of the amino forms. Qualitatively, the results of the present study agree well with the available experimental and theoretical data for N4-hydroxycytosine and some of its derivatives. The implications of the present study are discussed in relation to the molecular mechanisms of mutagenesis caused by NH2OH and of enzyme (thymidylate synthase) inhibition by N4-hydroxydeoxycytidine monophosphate.

The role of hydration in the hydrolysis of pyrophosphate. A Monte Carlo simulation with polarizable-type interaction potentials.

The exchange of energy in biochemical reactions involves, in a majority of cases, the hydrolysis of phosphoanhydrides (P-O-P). This discovery has lead to a long discussion about the origin of the high energy of such bonds, and to a proposal that hydration plays a major role in the energetics of the hydrolysis. This idea was supported by recent ab initio quantum mechanical calculations (Saint-Martin et al. (1991) Biochim. Biophys. Acta 1080, 205-214) that predicted the hydrolysis of pyrophosphate is exothermic in the gas phase. This exothermicity can account for only a half of the total energy release that one measures in aqueous solutions. Here we address the problem of hydration of the reactants and products of the pyrophosphate hydrolysis by means of Monte Carlo simulations, employing polarizable potentials whose parameters are fitted to energy surfaces computed at the SCF/6-31G** level of the theory. The present results show that the hydration enthalpies of the reactants and products contribute significantly to the total energy output of the pyrophosphate hydrolysis. The study predicts that both, the orthophosphate and the pyrophosphate, have hydration spheres with the water molecules acting as proton acceptors in the P-OH ... O(water) hydrogen bonds. These water molecules weakly repel the water molecules in the further hydration spheres. The perturbation of the structure of the solvent caused by the presence of the solute molecules is short ranged: after ca. 5 A from the P atoms, the energy and the structure of water correspond to bulk water. Due mainly to nonadditive effects, the molecular structure of the hydrated pyrophosphate is quite different from two fused structures of the hydrated orthophosphates. The hydration sphere of pyrophosphate is very loose and has a limited effect on the water network, whereas for orthophosphate it has a well developed shell structure. Hence, upon hydration there will be both a gain in hydration enthalpy and a gain in entropy because of distortion of the water molecular network.

Ab initio calculations of the pyrophosphate hydrolysis reaction.

Ab initio quantum mechanical calculations were used to study the hydrolysis reaction H4P2O7 + H2O in equilibrium with 2H3PO4, as well as some molecular properties of the reactants and products. SCF calculations with several basis sets ranging from minimal to extended with polarization functions were used to look at the basis dependency of the reaction enthalpies and optimized geometries. Although the minimal basis sets yield erratic predictions of the enthalpy, when a more extended basis (3-21G*) was used for the geometry optimization, and the total energies of the reactants and products were computed with this and larger basis sets, we obtained more consistent predictions of the structural properties of the P-O-P bridge and of the heat of the hydrolysis reaction (delta E = -7.39 kcal/mol at the SCF/6-31G** level). A comparison is made with previous estimates performed with smaller basis sets and without taking into account the electron correlation effects, which are calculated in the present work. The inclusion of the zero point energy calculated using the harmonic approximation, and of the electronic correlation energy determined at the MBPT(2) level, raised the computed heat of the reaction to -3.83 kcal/mol, and when an estimate for the thermal energy was added, the value obtained was of -3.38 kcal/mol. In conclusion, we found that the hydrolysis of pyrophosphate should be exothermic in the gas phase. The implications of this result in relation to some recent theories about enzyme catalysis are discussed.

Theoretical and matrix-isolation experimental studies on 2-thiocytosine and 5-fluoro-2-thiocytosine.

2-Thiocytosine (s2Cyt) and 5-fluoro-2-thiocytosine (f5s2Cyt) were studied by means of IR spectroscopy under different environmental conditions: isolated in low-temperature inert gas matrices, associated in thin amorphous and polycrystalline films. The compounds isolated in matrices were only very slightly influenced by the environment. From the analysis of the IR spectra of both compounds it appears that they exist in inert gas matrices only in the amino-thiol tautomeric form. Strong environmental effects were observed for s2Cyt and f5s2Cyt deposited in the form of thin polycrystalline films. Contrary to matrices, in polycrystalline films the amino-thione form dominates for both s2Cyt and f5s2Cyt. The experimental findings are in agreement with the ab initio quantum mechanical calculations of the relative total energies of the tautomeric forms. Those energies were calculated using the Self Consistent Field method corrected for electron correlation effects with the use of the second-order many-body perturbation theory (SCF+MBPT(2)). The theoretical calculations show that the amino-thiol tautomeric form is more stable than the amino-thione form by 38 kJ mol-1 and 48 kJ mol-1 for s2Cyt and f5s2Cyt, respectively. Both molecules, s2Cyt and f5s2Cyt, may also appear in the uracil-like imino-thione tautomeric form, which is predicted to be only 8 kJ mol-1 less stable than the amino-thione form. A new method of the preparation of f5s2Cyt is reported.

Crystal structures of 5-fluoro-dUrd and its 2 and/or 4-thio analogues: models of substituted dUMP pyrimidine ring interacting with thymidylate synthase.

In order to understand the influence on thymidylate synthase interactions with dUMP analogues of the pyrimidine ring 2- and/or 4-thio, and 5-fluoro substitutions, X-ray diffractions by crystals of 5-fluoro-dUrd and its 2- and 4-thio, and 2,4-dithio analogues were measured, the four structures solved and refined. The following conclusions were suggested by results of comparative analyses of structural parameters (bond lengths, valence angles), followed by theoretical considerations based on calculated resonance structure distributions and aromaticity indices of the uracil, thiouracil, fluorouracil and fluorothiouracil rings. The effect of 4-thio substitution of FdUMP, altering specificity of inactivation of thymidylate synthases from various sources, is probably due to weaker proton acceptor power of the 4-thio substituent and increasing acidity (enhanced proton-donor power) of the N(3)-H moiety, resulting in an impaired fitness into the network of hydrogen bonds in the enzyme active center cleft. 2,4-Dithio substitution results in (i) impaired pyrimidine ring recognition by the enzyme active center, due to the 4-thio substituent (ii) increased pyrimidine ring aromaticity in dUMP, leading to resistance of C(6) to nucleophilic attack by the enzyme active center cysteine and (iii) altered planarity of the pyrimidine ring and deflections, with respect to the ring plane, of substituents at C(2), C(4) and C(5). 5-Fluoro substitution apparently activates the pyrimidine ring towards the interaction with thymidylate synthase by producing local strain, which results in an increased reactivity as predicted by the Walsh-Bent rule.

Photochemical syn-anti isomerization reaction in N4-hydroxycytosine. An experimental matrix isolation and theoretical study.

Infrared spectra of N4-hydroxycytosine isolated in argon and nitrogen low-temperature matrixes are reported. The compound was found to adopt the syn structure of the imino-oxo tautomeric form exclusively. A photoreaction (lambda > 250 nm) converting this form into the anti isomer was observed. The reaction is reversible and leads to a photostationary point. The initial infrared spectrum and the spectrum of the photoproduct were assigned to the syn and anti isomers, respectively. This assignment is based on a close agreement between the experimental spectra and the spectra theoretically simulated at the DFT(B3LYP)/6-31++G** level of theory.

Computing the relative gas-phase populations of C60 and C70: beyond the traditional delta H(fo),298 scale.

Computations and experiments have shown that the relative heat of formation (i.e., the heat of formation per carbon atom) of C70 is lower than of C60. Moreover, various computations suggest that this is actually a general trend among fullerene cages. The relationship is particularly important for gas-phase fullerenes. Experiments have shown that C60 is typically more populated than C70 when produced in high-temperature gas-phase synthesis. It is not immediately obvious how to reconcile those two terms, or whether the relative heats of formation and the relative populations are in conflict or in agreement. This article deals with this problem, treating it as a general task of relative stabilities of gas-phase clusters of different dimensions (i.e., nonisomeric clusters) under different types of thermodynamic equilibria. The results are then applied to C60 and C70 and point out that the conventional standard pressure of 1 atm is considerably different from actual fullerene-synthesis conditions. Apparently, we should expect considerably lower cluster pressures in carbon-arc synthesis. At 1 atm, C70 is more populated than C60, but at the conditions of a saturated carbon vapor the stability order is reversed in favor of C60 so that an agreement with experiment is obtained already within the thermodynamic treatment. The pressure effects are modeled using the MNDO, AM1, PM3, and SAM1 quantum-chemical semi-empirical methods as well as the available experimental data. The computations consistently show that, if the pressure effects are considered, C60 becomes more populated than C70. Relationships of the thermodynamic treatment to more sophisticated but impractical kinetic analysis are also discussed.

Modeling of reaction steps relevant to deoxyuridylate (dUMP) enzymatic methylation and thymidylate synthase mechanism-based inhibition.

Theoretical quantum mechanical ab initio Hartree-Fock calculations on molecular systems, modeling processes related to the specificity of thymidylate synthase inactivation are reported. We considered several steps of the methylation of the substrate dUMP and 4- or 5-mono- and 4,5-bisubstituted dUMP analogs, as well. The following reactions were modeled: the cysteine residue (Cys198 in the L.casei enzyme) nucleophilic attack on the substrate and the substrate C(5)-H proton abstraction. The substrate was modeled by the 1-methyluracil molecule and its structural analogs. The cysteine Cys198 residue was modeled by the methylmercaptane molecule. The substrate-enzyme binary complex was modeled by the 1-methyl-5,6-dihydro-6-thiomethyl-uracil (P1) molecule. The present theoretical calculations suggest that the cysteine nucleophilic attack on the substrate may result in the SH-group addition to the pyrimidine C(5)=C(6) bond in the course of a weakly exothermic reaction. The formerly presumed enolate carbanion appeared to be weakly stable or unstable and it can readily split into the thiol and pyrimidine residues. The s2-thio- (P2) and s2,4-dithio- (P3) substrate analogs should form stable thiolate anions after cysteine residue attachment to the C(6) position of the pyrimidine ring. Studies of the deformed P1 molecule interacting with a water molecule bound to the pyrimidine C(4)=O carbonyl residue allow a suggestion that this water molecule may be directly involved in the C(5)-H proton abstraction and may serve as a proton transmitter between the substrate and the proton acceptor residue, possibly located on the cofactor N10-nitrogen. Interaction of the pyrimidine C(4)=O group, or its modification, with the N5,10-methylenetetrahydrofolate N(10) nitrogen atom is suggested as an additional factor influencing the inhibition process.

Ab initio calculations of electronically excited states of cyano-substituted polyacetylene cations.

The transition energies for the lowest energy pi --> pi* electronic excitations are calculated with the complete active space self-consistent field method (CASSCF) and with the complete active space second-order perturbation theory method (CASPT2) for the linear cyano-substituted polyacetylene cations, H-Cn-CN+, n = 4-11, and NC-Cn-CN+, n = 2-10. These systems are models for an important class of interstellar species. We demonstrate the utility of the theoretical calculations in assigning the experimental spectra.

Study of combined vaccination against yellow fever and measles in infants from six to nine months.

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.

An ab initio theoretical prediction: an antiaromatic ring pi-dihydrogen bond accompanied by two secondary interactions in a "wheel with a pair of pedals" shaped complex FH . . . C4H4 . . . HF.

By the counterpoise-correlated potential energy surface method (interaction energy optimization), the structure of the pi H-bond complex FH cdots, three dots, centered FH . . . C4H4 . . . HF has been obtained at the second-order Møller-Plesset perturbation theory (MP2/aug-cc-pVDZ) level. Intermolecular interaction energy of the complex is calculated to be -7.8 kcal/mol at the coupled-cluster theory with single, double substitutions and perturbatively linked triple excitations CCSD (T)/aug-cc-pVDZ level. The optimized structure is a "wheel with a pair of pedals" shaped (1mid R:1) structure in which both HF molecules almost lie on either vertical line passing through the middle-point of the C[Double Bond]C bond on either side of the horizontal plane of the C4 ring for cyclobutadiene. In the structure, an antiaromatic ring pi-dihydrogen bond is found, in which the proton acceptor is antiaromatic 4 electron and 4 center pi bond and the donors are both acidic H atoms of HF molecules. In accompanying with the pi-dihydrogen bond, two secondary interactions are exposed. The first is a repulsive interaction between an H atom of HF and a near pair of H atoms of C4H4 ring. The second is the double pi-type H bond between two lone pairs on a F atom and a far pair of H atoms.

Rhythms of cell proliferation in the hindlimb epidermis of control and thyroxine-treated Rana pipiens tadpoles.

Labeling and mitotic index rhythms were studied in premetamorphic tadpoles under an LD 12:12 with the light phase beginning at 0800 hr. In a 72-hr experiment, control labeling and mitotic index curves showed a peak in the light and a peak in the dark with labeling index rhythms of 12.4, 17.7, and 23.6 hr and a 21.4-hr mitotic index rhythm. Thyroxine (T4) treatment resulted in a marked elevation of labeling index by 24 hr and of mitotic index by 48 hr, obscured the control bimodal pattern of peaks, and altered the rhythms. During the first 3 days of T4 treatment, a labeling index rhythm of 22 hr and a mitotic index rhythm of 37.5 hr occurred. However, additional work demonstrated that the dominant control rhythms of labeling and mitotic indices returned in the T4-treated during Days 4 and 5. The same pattern of change in labeling index occurred during Day 3 of T4 treatment when hormone administration began at different times in the diurnal phase of the light-dark cycle. The findings suggest that cell proliferation rhythms can be temporarily disturbed by an exogenous T4 stimulus without apparent reference to the phase of the circadian rhythm.