Correction function in the Lidar equation and the solution techniques for CO2 Lidar date reduction

For lidar systems with long laser pulses the unusual behavior of the near-range signals causes serious difficulties and large errors in reduction. The commonly used lidar equation is no longer applicable since the convolution of the laser pulse with the atmospheric parameter distributions should be taken into account. It is important to give more insight into this problem and find the solution techniques. Starting from the original equation, a general form is suggested for the single scattering lidar equation where a correction function Cr is introduced. The correction Function Cr(R) derived from the original equation indicates the departure from the normal lidar equation. Examples of Cr(R) for a coaxial CO2 lidar system are presented. The Differential Absorption Lidar (DIAL) errors caused by the differences of Cr(R) for H2O measurements are plotted against height

A Comparison of Spectroscopic versus Imaging Techniques for Detecting Close Companions to Kepler Objects of Interest

(Abbreviated) Kepler planet candidates require both spectroscopic and imaging follow-up observations to rule out false positives and detect blended stars. [...] In this paper, we examine a sample of 11 Kepler host stars with companions detected by two techniques -- near-infrared adaptive optics and/or optical speckle interferometry imaging, and a new spectroscopic deblending method. We compare the companion Teff and flux ratios (F_B/F_A, where A is the primary and B is the companion) derived from each technique, and find no cases where both companion parameters agree within 1sigma errors. In 3/11 cases the companion Teff values agree within 1sigma errors, and in 2/11 cases the companion F_B/F_A values agree within 1sigma errors. Examining each Kepler system individually considering multiple avenues (isochrone mapping, contrast curves, probability of being bound), we suggest two cases for which the techniques most likely agree in their companion detections (detect the same companion star). Overall, our results support the advantage the spectroscopic deblending technique has for finding very close-in companions ($\theta \lesssim$0.02-0.05") that are not easily detectable with imaging. However, we also specifically show how high-contrast AO and speckle imaging observations detect companions at larger separations ($\theta \geq$0.02-0.05") that are missed by the spectroscopic technique, provide additional information for characterizing the companion and its potential contamination (e.g., PA, separation, $\Delta$m), and cover a wider range of primary star effective temperatures. The investigation presented here illustrates the utility of combining the two techniques to reveal higher-order multiples in known planet-hosting systems.Comment: Accepted to AJ. 40 pages, 12 figure

Toxicometabolomics of the new psychoactive substances α-PBP and α-PEP studied in HepaRG cell incubates by means of untargeted metabolomics revealed unexpected amino acid adducts

Toxicometabolomics, essentially applying metabolomics to toxicology of endogenous compounds such as drugs of abuse or new psychoactive substances (NPS), can be investigated by using different in vitro models and dedicated metabolomics techniques to enhance the number of relevant findings. The present study aimed to study the toxicometabolomics of the two NPS α-pyrrolidinobutiophenone (1-phenyl-2-(pyrrolidin-1-yl)butan-1-one, α-PBP) and α-pyrrolidinoheptaphenone (1-phenyl-2-(pyrrolidin-1-yl)heptan-1-one, α-PEP, PV8) in HepaRG cell line incubates. Evaluation was performed using reversed-phase and normal-phase liquid chromatography coupled with high-resolution mass spectrometry in positive and negative ionization mode, respectively, to analyze cells and cell media. Statistical evaluation was performed using one-way ANOVA, principal component discriminant function analysis, as well as hierarchical clustering. In general, the analysis of cells did not mainly reveal any features, but the parent compounds of the drugs of abuse. For α-PBP an increase in N-methylnicotinamide was found, which may indicate hepatotoxic potential of the substance. After analysis of cell media, significant features led to the identification of several metabolites of both compounds. Amino acid adducts with glycine and alanine were found, and these have not been described in any study before and are likely to appear in vivo. Additionally, significant changes in the metabolism of cholesterol were revealed after incubation with α-PEP. In summary, the application of metabolomics techniques after HepaRG cells exposure to NPS did not lead to an increased number of identified drug metabolites compared to previously published studies, but gave a wider perspective on the physiological effect of the investigated compounds on human liver cells

Differential Influence of Levodopa on Reward-Based Learning in Parkinson's Disease

The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson's disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the “overdose hypothesis” which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients’ actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks

Comparison of reversed-phase, hydrophilic interaction, and porous graphitic carbon chromatography columns for an untargeted toxicometabolomics study in pooled human liver microsomes, rat urine, and rat plasma

Introduction Untargeted metabolomics studies are expected to cover a wide range of compound classes with high chemical diversity and complexity. Thus, optimizing (pre-)analytical parameters such as the analytical liquid chromatography (LC) column is crucial and the selection of the column depends primarily on the study purpose. Objectives The current investigation aimed to compare six diferent analytical columns. First, by comparing the chromatographic resolution of selected compounds. Second, on the outcome of an untargeted toxicometabolomics study using pooled human liver microsomes (pHLM), rat plasma, and rat urine as matrices. Methods Separation and analysis were performed using three diferent reversed-phase (Phenyl-Hexyl, BEH C18, and Gold C18), two hydrophilic interaction chromatography (HILIC) (ammonium-sulfonic acid and sulfobetaine), and one porous graphitic carbon (PGC) columns coupled to high-resolution mass spectrometry (HRMS). Their impact was evaluated based on the column performance and the size of feature count, amongst others. Results All three reversed-phase columns showed a similar performance, whereas the PGC column was superior to both HILIC columns at least for polar compounds. Comparing the size of feature count across all datasets, most features were detected using the Phenyl-Hexyl or sulfobetaine column. Considering the matrices, most signifcant features were detected in urine and pHLM after using the sulfobetaine and in plasma after using the ammonium-sulfonic acid column. Conclusion The results underline that the outcome of this untargeted toxicometabolomic study LC-HRMS metabolomic study was highly infuenced by the analytical column, with the Phenyl-Hexyl or sulfobetaine column being the most suitable. However, column selection may also depend on the investigated compounds as well as on the investigated matrix

Magneto-shear modes and a.c. dissipation in a two-dimensional Wigner crystal

The a.c. response of an unpinned and finite 2D Wigner crystal to electric fields at an angular frequency $\omega$ has been calculated in the dissipative limit, $\omega \tau \ll 1$, where $\tau ^{-1}$ is the scattering rate. For electrons screened by parallel electrodes, in zero magnetic field the long-wavelength excitations are a diffusive longitudinal transmission line mode and a diffusive shear mode. A magnetic field couples these modes together to form two new magneto-shear modes. The dimensionless coupling parameter $\beta =2(c_{t}/c_{l})|\sigma_{xy}/\sigma_{xx}|$ where $c_{t}$ and $c_{l}$ are the speeds of transverse and longitudinal sound in the collisionless limit and $\sigma_{xy}$ and $\sigma_{xx}$ are the tensor components of the magnetoconductivity. For $\beta \geqslant 1$, both the coupled modes contribute to the response of 2D electrons in a Corbino disk measurement of magnetoconductivity. For $\beta \gg 1$, the electron crystal rotates rigidly in a magnetic field. In general, both the amplitude and phase of the measured a.c. currents are changed by the shear modulus. In principle, both the magnetoconductivity and the shear modulus can be measured simultaneously.Comment: REVTeX, 7 pp., 4 eps figure

Abuse of nutmeg seeds: Detectable by means of liquid chromatography-mass spectrometry techniques?

Numerous case reports of intoxications with nutmeg seeds (Myristica fragrans, Houtt.) can be found in literature often following their abuse, as psychotropic effects were described after ingestions of large doses. The successful detection of the main ingredients of the nutmeg seeds essential oil elemicin, myristicin, and safrole, as well as their metabolites in human urine by gas chromatography coupled to mass spectrometry (GC-MS) was already described. The aim of this study was to investigate the detectability of the main ingredients of nutmeg seeds and their metabolites in human blood and urine samples using liquid chromatography coupled to linear ion trap mass spectrometry (LC-LIT-MSn ) and liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) after nutmeg seed abuse. Sample material of three individuals was retrospectively investigated after a systematic screening approach indicated an intoxication with nutmeg seeds as a likely cause of symptoms. Metabolic patterns in plasma and urine using GC-MS were comparable with those described in earlier publications. Investigations using hyphenated liquid chromatography techniques lead to the detection of myristicin and safrole, as well as further metabolites not described using GC-MS and revealed sulfation as an additional Phase II metabolic pathway. These results might help to detect or confirm future intoxications with nutmeg seeds by using LC-MS techniques

Effect of hyperparameters on variable selection in random forests

Random forests (RFs) are well suited for prediction modeling and variable selection in high-dimensional omics studies. The effect of hyperparameters of the RF algorithm on prediction performance and variable importance estimation have previously been investigated. However, how hyperparameters impact RF-based variable selection remains unclear. We evaluate the effects on the Vita and the Boruta variable selection procedures based on two simulation studies utilizing theoretical distributions and empirical gene expression data. We assess the ability of the procedures to select important variables (sensitivity) while controlling the false discovery rate (FDR). Our results show that the proportion of splitting candidate variables (mtry.prop) and the sample fraction (sample.fraction) for the training dataset influence the selection procedures more than the drawing strategy of the training datasets and the minimal terminal node size. A suitable setting of the RF hyperparameters depends on the correlation structure in the data. For weakly correlated predictor variables, the default value of mtry is optimal, but smaller values of sample.fraction result in larger sensitivity. In contrast, the difference in sensitivity of the optimal compared to the default value of sample.fraction is negligible for strongly correlated predictor variables, whereas smaller values than the default are better in the other settings. In conclusion, the default values of the hyperparameters will not always be suitable for identifying important variables. Thus, adequate values differ depending on whether the aim of the study is optimizing prediction performance or variable selection.Comment: 18 pages, 2 figures + 2 figures in appendix, 3 table

Liquid Chromatography-High-Resolution Mass Spectrometry-Based In Vitro Toxicometabolomics of the Synthetic Cathinones 4-MPD and 4-MEAP in Pooled Human Liver Microsomes

Synthetic cathinones belong to the most often seized new psychoactive substances on an international level. This study investigated the toxicometabolomics, particularly the in vitro metabolism of 2-(methylamino)-1-(4-methylphenyl)-1-pentanone (4-MPD) and 2-(ethylamino)-1-(4- methylphenyl)-1-pentanone (4-MEAP) in pooled human liver microsomes (pHLM) using untargeted metabolomics techniques. Incubations were performed with the substrates in concentrations ranging from 0, 12.5, and 25 µM. Analysis was done by means of high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS/MS) in full scan only and the obtained data was evaluated using XCMS Online and MetaboAnalyst. Significant features were putatively identified using a separate parallel reaction monitoring method. Statistical analysis was performed using Kruskal-Wallis test for prefiltering significant features and subsequent hierarchical clustering, as well as principal component analysis (PCA). Hierarchical clustering or PCA showed a distinct clustering of all concentrations with most of the features z-scores rising with the concentration of the investigated substances. Identification of significant features left many of them unidentified but revealed metabolites of both 4-MPD and 4-MEAP. Both substances formed carboxylic acids, were hydroxylated at the alkyl chain, and formed metabolites after combined hydroxylation and reduction of the cathinone oxo group. 4-MPD additionally formed a dihydroxy metabolite and a hydroxylamine. 4-MEAP was additionally found reduced at the cathinone oxo group, N-dealkylated, and formed an oxo metabolite. These findings are the first to describe the metabolic pathways of 4-MPD and to extend our knowledge about the metabolism of 4-MEAP. Findings, particularly the MS data of the metabolites, are essential for setting up metabolite-based toxicological (urine) screening procedures

Toxicokinetic studies of the four new psychoactive substances 4-chloroethcathinone, N-ethylnorpentylone, N-ethylhexedrone, and 4-fluoro-alpha-pyrrolidinohexiophenone

Purpose The presented study aimed to elucidate the toxicokinetics of the four synthetic cathinones 4-chloroethcathinone (4-CEC), N-ethylnorpentylone (N-ethylpentylone, ephylone), N-ethylhexedrone (NEH), and 4-fluoro-alpha-pyrrolidinohexiophenone (4-fluoro-alpha-pyrrolidinohexanophenone, 4-F-α-PHP, 4F-alpha-PHP, 4F-PHP). Methods First, their metabolism was studied using human urine and blood samples. Analysis of specimens was performed by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC–MS). LC-HRMS/MS was also used to analyze in vitro incubations of the new psychoactive substances using pooled human liver S9 fraction (pS9), to identify the monooxygenases involved in the initial metabolic steps, and determination of plasma concentrations after a standard addition method. Metabolic stability was tested in pooled human liver microsomes incubations analyzed by LC-ion trap MS. Results Using LC-HRMS/MS, 47 metabolites in total were found in patient samples and pS9 incubations. Using GC–MS, 4-CEC, ephylone, NEH, and five of their metabolites were detectable in urine. The following main phase I reactions were observed: carbonyl group reduction, N-deethylation, hydroxylation, lactam formation (4F-PHP), and demethylenation (ephylone). Mainly glucuronidations were observed as phase II reactions besides conjugates with the dicarboxylic acids malonic, succinic, and glutaric acid (4-CEC), sulfation, methylation (both ephylone), and N-acetylation (NEH). A broad range of monooxygenases was involved in the initial steps with exception of NEH (only CYP1A2 and CYP2C19). 4F-PHP had the shortest in vitro half-life (38 min) and highest intrinsic clearance (15.7 mL/min/kg). Plasma concentrations ranged from 0.8 to 8.5 ng/mL. Conclusions Our results are expected to help toxicologists to reliably identify these substances in case of suspected abuse and allow them a thorough risk assessment