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•New ozone transitions of the rotational and hot ν2-ν2 band observed in the range 0.9–6 THz.•13,466 line positions in FIR / MW ozone spectra theoretically modeled with experimental ...accuracy.•Significant deviations in high J,Ka line positions versus spectroscopic databases were evidenced.•Accurate ab initio intensity calculations in a good agreement with the Synchrotron ozone spectra.•Absorption near 100 cm−1 and above appears to be quite sensitive to the temperature conditions.
Ozone is one of the important molecules in terms of the impact on the atmospheric chemistry, climate changes, bio- and eco-systems and human health. It has a strong absorption in the microwave, terahertz and far-infrared spectral ranges where a large part of the Earth’s outgoing longwave radiation to space is located. In this work, the observations, and analyses of the ozone high-resolution spectra in the THz range recorded using the Synchrotron light source of the SOLEIL CNRS equipment are reported for the first time. Thanks to the exceptional brightness of the Synchrotron radiation and to the signal/noise ratio, it was possible to observe many more ozone transitions of the cold rotational band and the hot ν2-ν2 band in the range 0.9–6 THz compared to the previous works. In addition, we have carried out new measurements and assignments for the ν2 band. The simultaneous fit of the rotational band GS-GS, the hot band ν2-ν2 and the FIR ν2 band yielded an overall weighted standard deviation of 0.68 for 13,466 line positions within the experimental accuracy. This includes all previously available MW (with the best uncertainty 0.1 – 10 kHz), FIR data and the original SOLEIL measurements that provided experimental accuracy of 0.00005 – 0.0001 cm−1 for the best lines. Significant deviations in new experimental spectra compared to available spectroscopic databases were evidenced, particularly for the line positions and energy levels at high J, Ka rotational quantum numbers that are the most pronounced in the 4.5 – 6 THz range. Accurate ab initio calculations of line intensities combined with empirically fitted line positions were used to create new linelists that permit theoretical modelling of the transmittance in a good agreement with the Synchrotron spectra in the entire range of observations for various pressures and optical paths. The region near 100 cm−1 and above appears to be more sensitive to the temperature conditions that should be considered in atmospheric observation for the currently operational and future ground based and space missions.
To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, ...and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy‐seven (45.5%) individuals carried a known (CYP2B6★6,★11,★15, or ★18) or new loss/diminished‐function alleles. Resequencing defined two new loss‐of‐function alleles: allele ★27 (marked by 593T>C M198T), that results in 85% decrease in enzyme activity and allele ★28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 μg h/ml for individuals homozygous for a loss/diminished‐function allele, 58.6 μg h/ml for carriers, and 43.7 μg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11–110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.
Clinical Pharmacology & Therapeutics (2007) 81, 557–566. doi:10.1038/sj.clpt.6100072; published online 18 January 2007
Besides CYP2B6, other polymorphic enzymes contribute to efavirenz (EFV) interindividual variability. This study was aimed at quantifying the impact of multiple alleles on EFV disposition. Plasma ...samples from 169 human immunodeficiency virus (HIV) patients characterized for CYP2B6, CYP2A6, and CYP3A4/5 allelic diversity were used to build up a population pharmacokinetic model using NONMEM (non‐linear mixed effects modeling), the aim being to seek a general approach combining genetic and demographic covariates. Average clearance (CL) was 11.3 l/h with a 65% interindividual variability that was explained largely by CYP2B6 genetic variation (31%). CYP2A6 and CYP3A4 had a prominent influence on CL, mostly when CYP2B6 was impaired. Pharmacogenetics fully accounted for ethnicity, leaving body weight as the only significant demographic factor influencing CL. Square roots of the numbers of functional alleles best described the influence of each gene, without interaction. Functional genetic variations in both principal and accessory metabolic pathways demonstrate a joint impact on EFV disposition. Therefore, dosage adjustment in accordance with the type of polymorphism (CYP2B6, CYP2A6, or CYP3A4) is required in order to maintain EFV within the therapeutic target levels.
Clinical Pharmacology & Therapeutics (2009); 85, 5, 485–494 doi:10.1038/clpt.2008.271
•Global analysis of many rovibrational bands of CF4.•This allows to simulate hot bands in the strongly absorbing 3μm region.•The results allow to model 92% of the atmospheric absorption of this ...greenhouse gas.•They have been used for spectroscopic database updates, including HITRAN2016.
CF4, or tetrafluoromethane, is a chemically inert and strongly absorbing greenhouse gas, mainly of anthropogenic origin. In order to monitor and reduce its atmospheric emissions and concentration, it is thus necessary to obtain an accurate model of its infrared absorption. Such models allow opacity calculations for radiative transfer atmospheric models. In the present work, we perform a global analysis (divided into two distinct fitting schemes) of 17 rovibrational bands of CF4. This gives a reliable model of many of its lower rovibrational levels and allows the calculation of the infrared absorption in the strongly absorbing ν3 region (1283 cm−1 / 7.8 μm), including the main hot band, namely ν3+ν2−ν2 as well as ν3+ν1−ν1; we could also extrapolate the ν3+ν4−ν4 absorption. This represents almost 92% of the absorption at room temperature in this spectral region. A new accurate value of the C–F bond length is evaluated to re=1.314860(21)Å. The present results have been used to update the HITRAN, GEISA and TFMeCaSDa (VAMDC) databases.
In this study, the importance of anion−π interactions in four-membered rings has been evidenced. Two kinds of rings have been found to be suitable for participation in anion−π interactions: first, in ...different salts of cyclobuten-1,2-dione derivatives and, second, in η4-cyclobutadiene complexes with transition metals.
Relying on high-resolution Fourier transform infrared (FTIR) spectra, the present work involved extensive measurements of individual line intensities and self-broadening coefficients for the ν7 band ...of 12C2H4. The measured self-broadening coefficients exhibit a dependence on both J and Ka. Compared to the corresponding information available in the latest edition of the HITRAN spectroscopic database, the measured line intensities were found to be higher by about 10% for high J lines in the P branch and lower by about 5% for high J lines of the R branch, varying between these two limits roughly linearly with the line positions. The impact of the presently measured line intensities on retrievals of atmospheric ethylene in the 949.0–952.0cm−1 microwindow was evaluated using a subset of ground-based high-resolution FTIR solar spectra recorded at the Jungfraujoch station. The use of HITRAN 2012 with line intensities modified to match the present measurements led to a systematic reduction of the measured total columns of ethylene by −4.1±0.1%.
•Extensive line intensities and self-broadening coefficients for the ν7 band of 12C2H4.•Systematic discrepancies between the measured line intensities and HITRAN 2012.•Empirical modeling of the self-broadening coefficients.•Systematic reduction of the measured total columns of atmospheric C2H4 by −4.1±0.1%.
Darunavir is a protease inhibitor that is administered with low-dose ritonavir to enhance its bioavailability. It is prescribed at standard dosage regimens of 600/100 mg twice daily in ...treatment-experienced patients and 800/100 mg once daily in naive patients. A population pharmacokinetic approach was used to characterize the pharmacokinetics of both drugs and their interaction in a cohort of unselected patients and to compare darunavir exposure expected under alternative dosage regimens.
The study population included 105 HIV-infected individuals who provided darunavir and ritonavir plasma concentrations. Firstly, a population pharmacokinetic analysis for darunavir and ritonavir was conducted, with inclusion of patients' demographic, clinical and genetic characteristics as potential covariates (NONMEM(®)). Then, the interaction between darunavir and ritonavir was studied while incorporating levels of both drugs into different inhibitory models. Finally, model-based simulations were performed to compare trough concentrations (Cmin) between the recommended dosage regimen and alternative combinations of darunavir and ritonavir.
A one-compartment model with first-order absorption adequately characterized darunavir and ritonavir pharmacokinetics. The between-subject variability in both compounds was important coefficient of variation (CV%) 34% and 47% for darunavir and ritonavir clearance, respectively. Lopinavir and ritonavir exposure (AUC) affected darunavir clearance, while body weight and darunavir AUC influenced ritonavir elimination. None of the tested genetic variants showed any influence on darunavir or ritonavir pharmacokinetics. The simulations predicted darunavir Cmin much higher than the IC50 thresholds for wild-type and protease inhibitor-resistant HIV-1 strains (55 and 550 ng/mL, respectively) under standard dosing in >98% of experienced and naive patients. Alternative regimens of darunavir/ritonavir 1200/100 or 1200/200 mg once daily also had predicted adequate Cmin (>550 ng/mL) in 84% and 93% of patients, respectively. Reduction of darunavir/ritonavir dosage to 600/50 mg twice daily led to a 23% reduction in average Cmin, still with only 3.8% of patients having concentrations below the IC50 for resistant strains.
The important variability in darunavir and ritonavir pharmacokinetics is poorly explained by clinical covariates and genetic influences. In experienced patients, treatment simplification strategies guided by drug level measurements and adherence monitoring could be proposed.
The difference between mean inspiratory and expiratory respiratory reactance (delta(rs)) measured with forced oscillation technique (FOT) at 5 Hz allows the detection of expiratory flow limitation ...(EFL) in chronic obstructive pulmonary disease (COPD) patients breathing spontaneously. This aim of this study was to evaluate whether this approach can be applied to COPD patients during noninvasive pressure support. Delta(rs) was measured in seven COPD patients subjected to nasal continuous positive airway pressure (CPAP) at 0, 4, 8 and 12 cmH2O in sitting and supine positions. Simultaneous recording of oesophageal pressure and the Mead and Whittenberger (M-W) method provided a reference for scoring each breath as flow-limited (FL), non-flow-limited (NFL) or indeterminate (I). For each patient, six consecutive breaths were analysed for each posture and CPAP level. According to M-W scoring, 47 breaths were FL, 166 NFL and 51 I. EFL scoring using FOT coincided with M-W in 94.8% of the breaths. In the four patients who were FL in at least one condition, delta(rs) was reduced with increasing CPAP. These data suggest that the forced oscillation technique may be useful in chronic obstructive pulmonary disease patients on nasal pressure support by identifying continuous positive airway pressure levels that support breathing without increasing lung volume, which in turn increase the work of breathing and reduce muscle effectiveness and efficiency.
•Calculated spectroscopic database.•Major updates of existing databases of CH4 and C2H4.•New databases built on the same model.•Planetary and atmospheric applications.
We present an important update ...of our previously existing calculated spectroscopic databases (CH4 and C2H4), as well as new databases built on the same model (CF4, SF6, GeH4, RuO4 and SiF4). Display omitted
We report the current status of our calculated spectroscopic relational databases. They contain line lists for specific molecules, that result from recently published spectroscopic analyses. The two original databases, denoted MeCaSDa (CH4) and ECaSDa (C2H4), have been greatly improved with the addition of new calculated lines. Then, five new databases, TFMeCaSDa (CF4), SHeCaSDa (SF6), GeCaSDa (GeH4), RuCaSDa (RuO4) and TFSiCasDa (SiF4) were deployed based upon the same model. These databases are developed in the framework of the international consortium VAMDC (Virtual Atomic and Molecular Data Centre, http://vamdc.org) and are also part of the Dat@OSU project (http://dataosu.obs-besancon.fr).
We present a short review on the tensorial formalism developed by the Dijon group to solve molecular spectroscopy problems. This approach, originally devoted to the rovibrational spectroscopy of ...highly symmetrical species (spherical tops) has been recently extended in several directions: quasi-spherical tops, some symmetric and asymmetric tops, and rovibronic spectroscopy of spherical tops in a degenerate electronic state. Despite its apparent complexity (heavy notations, quite complex mathematical tools), these group theoretical tensorial methods have a great advantage of flexibility: a systematic expansion of effective terms for any rovibrational/rovibronic problem up to a given order is automatically generated. Inclusion of all possible interaction terms for any polyad scheme is therefore easy. This makes such an approach suitable for many types of molecular problems, not only the most symmetric ones.
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