Measurements of particle extinction coefficients at 1064†nm with lidar: temperature dependence of rotational Raman channels.

Aerosol intensive optical properties, including lidar ratio and particle depolarization ratio, are of vital importance for aerosol typing. However, aerosol intensive optical properties at near-infrared wavelength are less exploited by atmospheric lidar measurements, because of the comparably small backscatter cross section of Raman-scattering and a low efficiency of signal detection compared to what is commonly available at 355 nm and 532 nm. To obtain accurate optical properties of aerosols at near-infrared wavelength, we considered three factors: Raman-spectra selection, detector selection, and interference-filter optimization. Rotational Raman scattering has been chosen for Raman signal detection, because of the higher cross-section compared to vibrational Raman scattering. The optimization of the properties of the interference filter are based on a comprehensive consideration of both signal-to-noise ratio and temperature dependence of the simulated lidar signals. The interference filter that has eventually been chosen uses the central wavelength at 1056 nm and a filter bandwidth (full-width-at-half-maximum) of 6 nm. We built a 3-channel 1064-nm rotational Raman lidar. In this paper two methods are proposed to test the temperature dependence of the signal-detection unit and to evaluate the quality of the Raman signals. We performed two measurements to test the quality of the detection channel: cirrus clouds in the free troposphere and aerosols in the planetary boundary layer. Our analysis of the measured Raman signals shows a negligible temperature dependence of the Raman signals in our system. For cirrus measurements, the Raman signal profile did not show crosstalk even for the case of strong elastic backscatter from clouds, which was about 100 times larger than Rayleigh scattering in the case considered here. The cirrus-mean extinction-to-backscatter ratio (lidar ratio) was 27.8 ± 10.0 sr (1064 nm) at a height of 10.5-11.5 km above ground. For the aerosols in the planetary boundary layer, we found the mean lidar ratio of 38.9 ± 7.0 sr at a height of 1.0-3.0 km above ground.

Compact and efficient 1064†nm up-conversion atmospheric lidar.

A model was developed to simulate lidar signals and quantify the relative errors of retrieved aerosol backscattering. The results show that a 1064 nm atmospheric aerosol lidar has a small relative error, which can be attributed to the presence of a sufficient molecular signal to facilitate calibration. However, the quantum efficiency of 1064 nm photons using silicon avalanche photodiode detectors is about 2%. To improve the quantum efficiency at 1064 nm band, this study used up-conversion techniques to convert 1064-nm photons to 631-nm photons, optimizing the power of the pump laser and the operating temperature of the waveguide to enable detection at higher efficiencies, up to 18.8%. The up-conversion atmospheric lidar is designed for optimal integration and robustness with a fiber-coupled optical path and a 50 mm effective aperture telescope. This greatly improves the performance of the 1064 nm atmospheric aerosol lidar, which enables aerosol detection up to 25 km (equivalent to 8.6 km altitude) even at a single laser pulse energy of 110 µJ. Compared to silicon avalanche photodiode detectors, up-conversion single photon detectors exhibit superior performance in detecting lidar echo signals, even in the presence of strong background noise during daytime.

Improved algorithm for retrieving aerosol optical properties based on multi-wavelength Raman lidar.

Multi-wavelength Raman lidar has been widely used in profiling aerosol optical properties. The accuracy of measured aerosol optical properties largely depends on sophisticated lidar data retrieval algorithms. Commonly to retrieve aerosol optical properties of Raman lidar, the extinction-related Ångström exponent (EAE) is assumed (to be 1). This value usually generally differs from the true value (called EAE deviation) and adds uncertainty to the retrieved aerosol optical properties. Lidar-signal noise and EAE-deviation are two important error sources for retrieving aerosol optical properties. As the measurement accuracy of Raman lidar has been greatly improved in recent years, the influence of signal noise on retrieval results becomes relatively small, and the uncertainty of retrieved aerosol optical properties caused by an EAE-deviation becomes nonnegligible, especially in scenes that EAE deviation is large. In this study, an iteration retrieval algorithm is proposed to obtain more reliable EAE based on multi-wavelength Raman lidar. Results from this iteration are more precise values of aerosol optical properties. Three atmospheric scenarios where aerosol distribution and the values of EAE vary widely were simulated with a Monte Carlo method to analyze the characteristics and robustness of the iterative algorithm. The results show that the proposed iterative algorithm can eliminate the systematic errors of aerosol optical properties retrieved by traditional retrieval method. The EAEs after iteration does converge to the true value, and the accuracy of aerosol optical properties can be greatly improved, especially for the particle backscatter coefficient and lidar ratio, which has been improved by more than 10% in most cases, and even more than 30%. In addition, field observations data of a three-wavelength Raman lidar are analyzed to illustrate the necessity and reliability of the proposed iterative retrieval algorithm.

Numerical simulation model of an optical filter using an optical vortex.

Vortex beam has the potential to significantly improve the performance of lidar (light detection and ranging) and optical communication applications in which low signal-to-noise ratio (SNR) limits the detection/transmission range. The vortex beam method allows for spatially separating the coherent light (laser signal) from the incoherent light (the background radiation and multiple-scattered light) of the received signal. This paper presents results of a simulation model in which the optical vortex acts as an optical filter. We present instrument parameters that describe the filtering effect, e.g., the form of the vortex phase modulation function, the topological charge of the vortex and the focal length of a virtual Fresnel lens that is used for optical filtering. Preliminary experimental results show that the background radiation within the spectral filter bandwidth can be suppressed by as much as 95%. At the same time, we retain 97% of the coherent laser signal. Our simulation model will be used in future design of lidar instruments and optical communication systems in which the optical vortex method is used for optical filtering of the detected signals.

Polarization Raman lidar for atmospheric correction during remote sensing satellite calibration: instrument and test measurements.

A compact polarization Raman lidar has been designed and constructed for using it for atmospheric correction measurements during satellite optical sensor calibration in areas with high altitude and extremely low aerosol loading. The parameters of this lidar, such as laser wavelength, telescope diameter and interference filter bandwidth, were simulated and optimized for the best observation performance. The instrument has low weight, is small in size, and requires air cooling instead of commonly used water-cooling of the laser. Thus, the instrument is suitable for autonomous operation in remote sites. The lidar prototype was installed in Lijiang (26°43' N, 100°01' E), China, a potential observation site for calibrations of optical sensors of satellites. This observation site has been shown to be an appropriate place for remote sensing and satellite calibration activities with low aerosol loading, thin air and a comparably high proportion of cloud-free days. A field campaign carried out between November 2019 and April 2020 allowed for thoroughly testing the instruments. The results of test observations show that complete overlap between emitted laser beam and field-of-view of the receiver unit is achieved at relatively low heights above ground. The measurement accuracy is comparably high. Thus, this instrument is suitable for operating in areas with relatively clean atmospheric conditions.

Simultaneous measurement of COVID-19 treatment drugs (nirmatrelvir and ritonavir) in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

PAXLOVID™ (Co-packaging of Nirmatrelvir with Ritonavir) has been approved for the treatment of Coronavirus Disease 2019 (COVID-19). The goal of the experiment was to create an accurate and straightforward analytical method using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to simultaneously quantify nirmatrelvir and ritonavir in rat plasma, and to investigate the pharmacokinetic profiles of these drugs in rats. After protein precipitation using acetonitrile, nirmatrelvir, ritonavir, and the internal standard (IS) lopinavir were separated using ultra performance liquid chromatography (UPLC). This separation was achieved with a mobile phase composed of acetonitrile and an aqueous solution of 0.1% formic acid, using a reversed-phase column with a binary gradient elution. Using multiple reaction monitoring (MRM) technology, the analytes were detected in the positive electrospray ionization mode. Favorable linearity was observed in the calibration range of 2.0-10000 ng/mL for nirmatrelvir and 1.0-5000 ng/mL for ritonavir, respectively, within plasma samples. The lower limits of quantification (LLOQ) attained were 2.0 ng/mL for nirmatrelvir and 1.0 ng/mL for ritonavir, respectively. Both drugs demonstrated inter-day and intra-day precision below 15%, with accuracies ranging from -7.6% to 13.2%. Analytes were extracted with recoveries higher than 90.7% and without significant matrix effects. Likewise, the stability was found to meet the requirements of the analytical method under different conditions. This UPLC-MS/MS method, characterized by enabling accurate and precise quantification of nirmatrelvir and ritonavir in plasma, was effectively utilized for in vivo pharmacokinetic studies in rats.

Development of an UPLC-MS/MS method for quantitative analysis of abexinostat levels in rat plasma and application of pharmacokinetics.

Broad-spectrum histone deacetylase inhibitors (HDACi) have excellent anti-tumor effects, such as abexinostat, which was a novel oral HDACi that was widely used in clinical treatment. The purpose of this study was to establish a rapid and reliable method for the detection of abexinostat concentrations in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The mobile phase we used was acetonitrile and 0.1% formic acid, and the internal standard (IS) was givinostat. Selective reaction monitoring (SRM) was used for detection with ion transitions at m/z 397.93 → 200.19 for abexinostat and m/z 422.01 → 186.11 for givinostat, respectively. The intra-day and inter-day precision of abexinostat were less than 11.5% and the intra-day and inter-day accuracy ranged from - 10.7% to 9.7% using this method. During the analysis process, the stability of the test sample was reliable. In addition, the recovery and matrix effects of this method were within acceptable limits. Finally, the method presented in this paper enabled accurate and quick determination of abexinostat levels in rat plasma from the pharmacokinetic study following gavage at a dose of 8.0 mg/kg abexinostat.

CYP3A4 and CYP2C19 genetic polymorphisms and myricetin interaction on tofacitinib metabolism.

Tofacitinib can effectively improve the clinical symptoms of rheumatoid arthritis (RA) patients. In this current study, a recombinant human CYP2C19 and CYP3A4 system was operated to study the effects of recombinant variants on tofacitinib metabolism. Moreover, the interaction between tofacitinib and myricetin was analyzed in vitro. The levels of M9 (the main metabolite of tofacitinib) was detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The findings revealed that 11 variants showed significant changes in the levels of M9 compared to CYP3A4.1, while the other variants didn't reveal any remarkable significances. Compared with CYP2C19.1, 11 variants showed increases in the levels of M9, and 10 variants showed decreases. Additionally, it was demonstrated in vitro that the inhibition of tofacitinib by myricetin was a non-competitive type in rat liver microsomes (RLM) and human liver microsomes (HLM). However, the inhibitory mechanism was a competitive type in CYP3A4.18, and mixed type in CYP3A4.1 and .28, respectively. The data demonstrated that gene polymorphisms and myricetin had significant effects on the metabolism of tofacitinib, contributing to important clinical data for the precise use.

Inhibitory mechanism of vortioxetine on CYP450 enzymes in human and rat liver microsomes.

Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an in vitro incubation system of 200 µL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC50) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (Ki) values of 2.17 µM and 9.37 µM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its Ki values were 7.26 µM and 6.96 µM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with Ki values were 8.55 µM and 4.17 µM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (Ki = 4.41 and 100.9 µM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (Ki = 2.87 and 0.12 µM). The inhibition types of CYP2C-1 and CYP2C-3 (Ki = 39.91 and 4.23 µM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided.

An improved bound on the electron's electric dipole moment.

The imbalance of matter and antimatter in our Universe provides compelling motivation to search for undiscovered particles that violate charge-parity symmetry. Interactions with vacuum fluctuations of the fields associated with these new particles will induce an electric dipole moment of the electron (eEDM). We present the most precise measurement yet of the eEDM using electrons confined inside molecular ions, subjected to a huge intramolecular electric field, and evolving coherently for up to 3 seconds. Our result is consistent with zero and improves on the previous best upper bound by a factor of ~2.4. Our results provide constraints on broad classes of new physics above [Formula: see text] electron volts, beyond the direct reach of the current particle colliders or those likely to be available in the coming decades.