Exploring Ubiquinone Biosynthesis Inhibition as a Strategy for Improving Atovaquone Efficacy in Malaria.

Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8 and ubiquinone-9 (UQ-8 and UQ-9) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-concept research to better elucidate the mechanism of action of AV and improve its efficacy. Initially, UQ biosynthesis was evaluated using several radioactive precursors and chromatographic techniques. This methodology was suitable for studying the biosynthesis of both UQ homologs and its redox state. Additionally, the composition of UQ was investigated in parasites cultivated at different oxygen saturations or in the presence of AV. AV affected the redox states of both UQ-8 and UQ-9 homologs by increasing the levels of the respective reduced forms. Conversely, low-oxygen environments specifically inhibited UQ-9 biosynthesis and increased the antimalarial efficacy of AV. These findings encouraged us to investigate the biological importance and the potential of UQ biosynthesis as a drug target based on its inhibition by 4-nitrobenzoate (4-NB), a 4-hydroxybenzoate (4-HB) analog. 4-NB effectively inhibits UQ biosynthesis and enhances the effects of AV on parasitic growth and respiration rate. Although 4-NB itself exhibits poor antimalarial activity, its 50% inhibitory concentration (IC50) value increased significantly in the presence of a soluble UQ analog, p-aminobenzoic acid (pABA), or 4-HB. These results indicate the potential of AV combined with 4-NB as a novel therapy for malaria and other diseases caused by AV-sensitive pathogens.

Toward High Precision XCO2 Retrievals From TanSat Observations: Retrieval Improvement and Validation Against TCCON Measurements.

TanSat is the 1st Chinese carbon dioxide (CO2) measurement satellite, launched in 2016. In this study, the University of Leicester Full Physics (UoL-FP) algorithm is implemented for TanSat nadir mode XCO2 retrievals. We develop a spectrum correction method to reduce the retrieval errors by the online fitting of an 8th order Fourier series. The spectrum-correction model and its a priori parameters are developed by analyzing the solar calibration measurement. This correction provides a significant improvement to the O2 A band retrieval. Accordingly, we extend the previous TanSat single CO2 weak band retrieval to a combined O2 A and CO2 weak band retrieval. A Genetic Algorithm (GA) has been applied to determine the threshold values of post-screening filters. In total, 18.3% of the retrieved data is identified as high quality compared to the original measurements. The same quality control parameters have been used in a footprint independent multiple linear regression bias correction due to the strong correlation with the XCO2 retrieval error. Twenty sites of the Total Column Carbon Observing Network (TCCON) have been selected to validate our new approach for the TanSat XCO2 retrieval. We show that our new approach produces a significant improvement on the XCO2 retrieval accuracy and precision when compared to TCCON with an average bias and RMSE of -0.08 ppm and 1.47 ppm, respectively. The methods used in this study can help to improve the XCO2 retrieval from TanSat and subsequently the Level-2 data production, and hence will be applied in the TanSat operational XCO2 processing.

Infrared properties of chemical-vapor deposition polycrystalline diamond windows.

Low-resolution transmittance and reflectance spectra of high-quality chemical-vapor deposition (CVD) diamond windows were measured in the infrared in the 2.5-500-mum wavelength range (20-4000 cm(-1)). High-resolution measurements on a window with nearly parallel surfaces show well defined interference fringes at low frequencies. By standard procedures the optical constants n and k of CVD diamond were determined, for the first time to the author's knowledge, in the far-infrared region. It is shown that a window with a large wedge angle, close to 1 degrees , does not produce appreciable interference fringes. Modeling of these results confirms that interference fringes can be avoided by use of properly wedged CVD diamond windows. This result is of considerable relevance to the use of CVD diamond windows in spectroscopic applications for which fringe suppression is a major requirement.

Optical properties of contrail-induced cirrus: discussion of unusual halo phenomena.

Photographs of a 120 degrees parhelion and a 22 degrees parhelion within persistent contrails are presented. These phenomena result from hexagonal plate-shaped ice crystals oriented horizontally with diameters between 300 mum and 2 mm. From our observations and reinvestigation of previous reports, we conclude that a subset of the population in persistent contrails can consist of highly regular, oriented, hexagonal plates or columns comparable to the most regular crystals in natural cirrus clouds. This is explained by measured ambient humidities below the formation conditions of natural cirrus. The resulting strong azimuthal variability of the scattering phase function impacts the radiative transfer through persistent contrails.

Infrared spectroscopy of tropospheric trace gases: combined analysis of horizontal and vertical column abundances.

Vibration-rotation absorptions in high-resolution Fourier-transform infrared spectra from a 246-m horizontal path were used to derive local concentrations of trace gases at the Alpine observatory at the Zugspitze summit, Germany (2964 m above sea level). The analysis was performed by using the line-by-line nonlinear least-squares spectral fitting software, SFIT, based on the 1992 HITRAN line parameter compilation. (HITRAN is a high-resolution transmission molecular absorption database.) A comparison to in situ measurements shows an agreement of better than 4.3% for the species CO, CO(2), and CH(4). Using the same spectrometer and analysis software, we obtained the vertical column density of N(2)O together with an adjusted vertical volume mixing ratio distribution. This translates to a local N(2)O concentration at the altitude of Zugspitze that agrees with the horizontal path-derived value to within 1%.