Temperature dependence of Raman vibrational bandwidths in poly(rA) and rAMP

Isotropic and anisotropic spontaneous Raman spectra were obtained from solutions of poly(ra) and rAMP in buffer. The temperature dependence of these spectra was measured to elucidate the influence of macromolecular dynamics and solvent dynamics on the bandwidths of base vibrations in the single stranded polynucleotide poly(rA). The temperature dependence of a bandwidth depends upon the particular vibration under study. The bands can for the larger part be described by Lorentz functions. When fitted by Voigt functions, maximally 10% of each bandprofile of the adenine base vibrations can be attributed to a Gaussian component. The second moment has been determined from the spectra for the 725 cm¿1 band. From the second moment and the bandwidth, we were able to deduce that the vibrational oscillator is in the fast modulation limit. The determined timescale (perturbation correlation time 0.13 ps) eliminate perturbations connected to long range diffusion like concentration fluctuations (timescale in the order of 10 ps). The spectra were analyzed by an extensive curve fitting procedure providing accurate bandparameters (position, width and integrated intensity). The 725 cm¿1 band of adenine has a bandwidth which is dependent upon the degree of polymerization. In RAMP it is 17.6 cm¿1, in stacked (i.e. low temperature 5°C) poly(rA) it is 11.5 cm¿1. The bandwidth of the adenine vibration at 1336 cm¿1 cm¿1 has a temperature dependence which is similar to the intensity changes of the Raman and the absorption hypochromic effect as a function of temperature. The melting transition can therefore be followed by the changes in bandwidth of suitable vibrations

Subpicosecond Dynamics in Nucleotides Measured by Spontaneous Raman Spectroscopy

The band widths in Raman spectra are sensitive to dynamics active on a time scale from 0.1 to 10 ps. The band widths of nucleotide vibrations and their dependence on temperature, concentration, and structure are reported. From the experimental band widths and second moments, it is derived that the adenine vibrations at 725, 1336, 1480, and 1575 cm-1, and the uracil vibration at 787 cm-1, are in the fast modulation limit. The correlation times of the perturbations are faster than 0.4 ps. Thermal melting of the helical structure in polynucleotides results in larger band widths, due to an increase in vibrational dephasing and energy relaxation as a consequence of the increased interaction of the base moieties with the solvent molecules. The band width of the 725 cm-1 adenine vibration is dependent on the type and structure of the backbone. It is found to be perturbed by movements of the sugar-phosphate moiety relative to the base. The band width of the 1575 cm-1 adenine vibration is found to be sensitive to the base-pairing interaction. From a comparison of the band widths in polynucleotides with a different base sequence (homopolymer vs alternating purine-pyrimidine sequence), it is concluded that resonant vibrational energy transfer between the base molecules is not important as a relaxation process for the vibrational band widths of nucleotides. Several theoretical models for the interpretation of band widths are discussed. The theory does not take into account the strong hydrogen-bonding nature water and hence fails to describe the observations in nucleotide-water systems. The bands of the carbonyl stretching vibrations are inhomogeneously broadened. The carbonyl groups have a strong dipolar interaction with the polar water molecules and are therefore strongly perturbed by coupling to the heatbath via hydrogen bonds

Temperature dependence of Raman vibrational bandwidths in poly(rA) and rAMP

Isotropic and anisotropic spontaneous Raman spectra were obtained from solutions of poly(ra) and rAMP in buffer. The temperature dependence of these spectra was measured to elucidate the influence of macromolecular dynamics and solvent dynamics on the bandwidths of base vibrations in the single stranded polynucleotide poly(rA). The temperature dependence of a bandwidth depends upon the particular vibration under study. The bands can for the larger part be described by Lorentz functions. When fitted by Voigt functions, maximally 10% of each bandprofile of the adenine base vibrations can be attributed to a Gaussian component. The second moment has been determined from the spectra for the 725 cm¿1 band. From the second moment and the bandwidth, we were able to deduce that the vibrational oscillator is in the fast modulation limit. The determined timescale (perturbation correlation time 0.13 ps) eliminate perturbations connected to long range diffusion like concentration fluctuations (timescale in the order of 10 ps). The spectra were analyzed by an extensive curve fitting procedure providing accurate bandparameters (position, width and integrated intensity). The 725 cm¿1 band of adenine has a bandwidth which is dependent upon the degree of polymerization. In RAMP it is 17.6 cm¿1, in stacked (i.e. low temperature 5°C) poly(rA) it is 11.5 cm¿1. The bandwidth of the adenine vibration at 1336 cm¿1 cm¿1 has a temperature dependence which is similar to the intensity changes of the Raman and the absorption hypochromic effect as a function of temperature. The melting transition can therefore be followed by the changes in bandwidth of suitable vibrations

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362