dataesr/scientific-paragraphs-categorization huggingface dataset:
The samples were placed on a glass slide and mounted in the focal plane of an Olympus X50 objective. The laser spot was around 2 μm 2. Raman Scheme 1. Four-Electrode Electrochemical Cell Configurations Investigated Langmuir mappings were analyzed using WITec project 2. 08 software. UV-vis diffuse reflectance spectroscopy (UV-vis DRS) was recorded using a UV-visible-NIR spectrometer (Cary 6000, Agilent), and the preparation of the sample (pellets) was 5 mg of sample mixed with 95 mg of KBr. Fluorescence microscopy was performed using an Olympus BX3-URA fluorescence microscope with a mercury lamp as the excitation source and a Power Supply Unit U-RFL-T. The samples were excited at 360 nm, and the fluorescence images were acquired using a 420 nm filter. Interfacial electron transfer reactions at the liquid-liquid interface were investigated after the addition of an aliquot of DcMFc to the organic phase.
Scanlon -The Bernal Institute and Department of Chemical Sciences, School of Natural Sciences, University of Limerick (UL), Limerick V94 T9PX, Ireland; orcid. org/ 0000-0001-7951-7085; Email: micheal. scanlon@ul. ie Grégoire Herzog -Université de Lorraine, CNRS, LCPME, F-54000 Nancy, France; orcid. org/0000-0003-1932-9300; Email: gregoire. herzog@univ-lorraine. fr edges the Science Foundation Ireland (SFI) under Grant No. 13/SIRG/2137 and the European Research Council (ERC) through a Starting Grant (Agreement no. 716792). A. G. -Q. acknowledges funding received from an Irish Research Council (IRC) Government of Ireland Postdoctoral Fellowship Award (Grant Number GOIPD/2018/252).
Acknowledgments Funding: This work was partially supported by the  European Research Council  through the  ERC grant   681379  (SPRINT), the  European union FET  open project  ULTRAQCL  ( 665158 ), and by the  EPSRC (UK)  programme  'HyperTerahertz  ( EP/P021859/1 ). EHL acknowledges support of the  Royal Society and Wolfson Foundation.
In line with its higher REDOR dephasing at short recoupling time, the  [6]  Al component is increased in the 27 Al{ 1 H} HMQC experiment (~20% of this  [6]  Al component is found in the D-HMQC spectrum). It appears that a Lorentzian broadening is needed to account for the  [6]  Al line shape (purple component in Figure  4 ), rendering a comparison with the direct excitation spectra difficult. For Al10-SiO2-500 (Figure  4b ), we performed the simulation of the 2D dataset with the same hypothesis used above for simulating the 1D direct excitation experiments in Figure  2 , i. e. the presence of an Al1-SiO2-500 component is accounted for by including its spectra (its simulation was used to avoid additional noise). Along the 1 H dimension, we found a broad and asymmetric line shape, again approximated by a pair of Gaussian lines (H(1), H(2)).
Acknowledgements ETH Zürich ( ETH-40 17-2 ) and the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation program  under grant agreement No. 819573  are acknowledge for partial funding. Financial support from  Equipex  contracts  ANR-10-EQPX-47-01 ,  ANR-15-CE29-0022-01 , and  ANR-17-CE29-0006-01  are gratefully acknowledged. M. K. acknowledges financial support from the  Deutsche Forschungsgemeinschaft  ( KA 5221/1-1 ).
Acknowledgements Financial support from the  CNRS  and the  Agence Nationale de la Recherche  ( ANR-JCJC-2020-CDI-DEOX ) is gratefully acknowledged. D. L. thanks the  French Ministry of Higher Education and Research  for a doctoral fellowship. A. S thanks the  Tunisian Ministry of Higher Education and Research  for financial support. Sparr's photocatalysts PC4 and PC5 are available from Solvias AG. We acknowledge  Solvias AG  for generous donations. We acknowledge Kumidas for generous donation of CF2HSO2Na.
Over 133 CYP2D6 variant star (*) alleles have been characterised (excluding sub-variants) amongst world populations of different ancestral origins and such information is available from the PharmVar database and the Human CYP450 allele nomenclature database (https://www. pharmvar. org/) (Taylor et al. , 2020). Historically, four different CYP2D6 phenotypes have been recognised: ultra-rapid metabolisers (UM), extensive metabolisers (EM), intermediate metabolisers (IM) and poor metabolisers (PM), even though the polyallelic nature of CYP2D6 has been recognised particularly in Caucasian populations (i. e. from 0 to 13 copies of the gene) and associated with prevalence of PM (approx. 8%). In contrast, Asian populations are known to have low prevalence of PM (1%) and high prevalence of IM (between 35 and 55%) compared with Caucasian populations (less than 2%)  (Yang et al.
This allele rarely occurs in African populations and it has been hypothesised to be the likely outcome of the introgression of a Neanderthal genetic variant in Caucasians since Neanderthals have been shown to be PMs  (Ingelman-Sundberg et al. , 2014; Steffens et al. , 2019; Viviani et al. , 2020). Relationships between CYP2D6 genotypes and phenotypes across world populations have been recently investigated for the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines with the most comprehensive available dataset so far (>60,000 subjects, 173 reports) which provides a quantitative tool for the prediction of CYP2D6 phenotype from genotype based on activity score  (Gaedigk et al. , 2017). CYP2D6 is expressed in the human liver (2-4% of total hepatic CYP) as well as in the brain, where it plays important physiological functions with regards to endogenous and xenobiotic metabolism  (Taylor et al.
, 2014). From this body of evidence, investigating human variability in the metabolism and PK of CYP2D6 probe substrates can provide quantitative insights to integrate inter-phenotypic differences in the risk assessment process  (Yang et al. , 2017; Zhou, 2009). In the early 2000s, relevant meta-analyses have been performed for markers of acute (Cmax) and chronic exposure (AUC and clearances) and demonstrated large inter-individual kinetic differences across CYP2D6 substrates as well as exponential relationships (R 2 > 0. 80) between phenotypes (EMs, PMs) and the extent of CYP2D6 metabolism for major and minor substrates of CYP2D6 isoform (10-100% metabolism in EMs)  (Chiba et al. , 2012; Dorne, 2010; Dorne et al. , 2002). However, the database, available at the time, was mostly limited to Caucasian populations and since then a large amount of PK data covering a wide range of CYP2D6 substrates and phenotypes in Caucasian and Asian populations have been published.
Extensive literature searches Probe substrates for CYP2D6 and oral human PK studies reporting markers of acute (maximum plasma concentration (Cmax) and chronic exposure (area-under the plasma concentration curve (AUC) or clearance)) in phenotyped individuals (EMs, IMs, PMs) from a range of world populations from different geographical ancestry were identified through two large extensive literature searches (ELS) and were performed by two independent reviewers (January 1989 to July 31st 2020) using online databases (PubMed and Scopus). These ELS were supplemented with available PK historical databases further supporting the identification of CYP2D6 probe substrates using 1. In vitro metabolism studies identifying CYP2D6-in EMs 2. Urinary excretion profiles reflecting in vivo metabolism expressed as the fraction metabolised by CYP2D6 in EMs (Southampton University and NOMIRACLE databases)  (Dorne et al.
, 2002; Løkke, 2010). Primary screening of the literature was carried out on titles and abstracts, after removal of duplicates and the following exclusion criteria were applied to studies reporting: 1. PK data for non-phenotyped human individuals or animal species, 2. In vitro data, 3. Population modelling including Physiologically-based modelling, 4. PK studies on unhealthy individuals, 5. PK studies on substrates metabolised by other CYP isoforms than CYP2D6, 6. Human PK studies using analytical methods with low sensitivity and specificity (radioimmunoassay). 7. Studies dealing with pharmacodynamic data only or therapeutic drug development.
Data collection for CYP2D6-phenotyped populations Data collection was performed for available human PK studies for CYP2D6 probe substrates reporting markers of acute and chronic exposure (Cmax, AUC, clearance) in EMs, IMs, PMs and UMs from populations of different geographical ancestry. The selected human PK studies were imported into an EndNote database and a second screening was performed on each full text article to evaluate the methodological quality including design, analysis and reporting of the study. Each PK study reporting markers of oral acute and chronic exposure were then computed into a MS-Excel database for each phenotype and subgroups of the population. Data from individual PK studies reporting phenotypes were also harmonised to perform meta-analyses for each phenotype i. e.
Software References from the ELS were computed in EndNote (X8) files. All statistical analyses and graphical display of the data were performed using R (version 3. 5) while the Bayesian modelling was implemented within Jags (4. 2. 0)  (Plummer, 2003). All R codes applied for the metaanalyses are available open source  (Darney et al. , 2019; Wiecek et al. , 2019). Meta-regressions between the fraction of dose metabolised by CYP2D6 in EMs and inter-phenotypic differences for each PK parameter (AUC, CL, Cmax) were generated in the Benchmark dose modelling tool of the European Food Safety Authority (EFSA) (https://shiny-efsa. opena nalytics. eu/app/bmd).
Extensive literature searches and data collection Results from the extensive literature searches are illustrated in a prisma diagram (Fig. 1 ) for which a total of 3654 records were identified in the first screening and a total of 130 papers were included in the database. All individual datasets are presented the supplementary material as an excel spreadsheet and are published on EFSA Knowledge Junction under DOI XXX. Overall, results highlight that most PK studies were available for phenoptyped adult Caucasian and Asian populations and meta-analyses were performed for these populations. Very few studies were available for the PK of CYP2D6 substrates in Caucasian IMs (7 studies, 6 substrates) and for PM Asian individuals (3 studies, 3 substrates) which is consistent with the very low prevalence of both phenotype in these populations (1%).
In addition, PK data for phenotyped individuals in other human sub-populations from Caucasian or Asian origin (i. e. elderly, children, neonates) were very scarce and did not allow to perform a meta-analysis. Consequently, meta-analysis for Caucasian IMs and Asian PMs were not performed due to insufficient number of individuals. For all remaining subpopulations, bayesian meta-analyses were performed using data from 80 studies (AUC) and 29 CYP2D6 substrates in Caucasian healthy adult EMs and 46 studies for 21 CYP2D6 substrates in Caucasian PMs respectively. For Asian populations, the meta-analyses were performed using data for 58 studies and 21 substrates in EMs and 31 studies and 18 substrates in IMs respectively.
Inter-phenotypic differences in CYP2D6 between Caucasian and Asian populations The polymorphic CYP2D6 isoform is expressed in the human brain and liver. The isoform is involved in xenobiotic metabolism including over 25% of known pharmaceuticals, a wide range of chemicals relevant to food safety and a growing number of emerging designer drugs of public health concern. In addition, there is growing evidence that CYP2D6 plays a role in the metabolism of endogenous compounds, such as neurotransmitters. From the 133 star alleles known to date, four major broad human phenotypes have been classified using activity scores (UMs, EMs, IMs and PMs) and their frequencies vary considerably across world populations. Here, inter-phenotypic differences in CYP2D6 metabolism for Caucasian and Asian populations have been quantified by means of extensive literature searches and Bayesian meta-analyses from a large database reporting PK data for minor and major CYP2D6 substrates on markers of chronic oral exposure (AUC and clearance) and acute (Cmax) exposure.
The computed kinetic parameters resulted in the largest open source database, quantifying inter-phenotypic differences for the kinetics of CYP2D6 probe substrates in Caucasian and Asian populations, to date. The database is available in supplementary material (CYPD6 DB) and EFSA knowledge junction (DOI to added). The hierarchical Bayesian model provided a means to quantify the impact of sample sizes and heterogeneity within studies, as well as inter-study and intersubstrate variability. Inter-phenotypic differences between EMs and PMs in Caucasian populations were shown to be larger compared to those in Asian populations. Indeed, the two main phenotypes in Asian populations are EMs and IMs since PMs have very low frequencies (<1%) and consequently, data were very scarce for the later. Overall, inter-individual variability after oral exposure for major CYP2D6 substrates was also larger in Caucasian EMs compared to that in Asian EMs (CV ≥ 50% vs 40%).
The derivation of chemical-specific adjustment factors quantifying CYP2D6-related variability for each phenotype and the whole population is feasible for specific compounds but would require the estimation of fm CYP2D6 in EMs as a basis to estimate inter-phenotypic differences. When data for the estimation of fm CYP2D6 in EMs are not available, assumptions can be formulated using expert judgement and knowledge on the ADME properties of the compound under assessment and these should be documented transparently using a weight of evidence (WoE) approach  (EFSA Scientific Committee et al. , 2017a). The database described here has also shown that major CYP2D6 substrates have high clearances which depends on CYP2D6 metabolism, liver blood flow and plasma protein binding as highlighted previously  (Dorne et al.
Acknowledgements This work was supported by the  European Food Safety Authority (EFSA)  under Contract numbers: [ OC/EFSA/SCER/2014/06 ]:  Witold Wiecek  and  Billy Amzal , and [ GP/EFSA/SCER/2015/01 ]:  Keyvin Darney ,  Leonie Lautz  and  Emanuela Testai. Views  expressed in this paper are the authors only and do not represent the views of the European Food safety Authority.
Acknowledgements We gratefully acknowledge the  University of Ferrara  ( Bando Giovani Ricercatori 2019 ) for financial support (AB). The  Chinese Scholarship Scheme and University of St Andrews  are thanked for a CSC Scholarship (S. Q. ). Aix-Marseille University ,  CNRS , and  ANR  ( Agence Nationale de la Recherche)  ( AMPLI  project  ANR-18-CE07-0036 ) are also gratefully acknowledged for funding (TD, XL and CB).
The COSMO approach was originally developed by Klamt and coworkers  [12] [13] [14]  : they proposed the COSMO-RS model (COnductor -like Sreening MOdel for Real Solvent »), which is a predictive excess Gibbs free energy model. Lin and Sandler  [15]  proposed the COSMO-SAC (COnductoRlike Sreening MOdel -Segment Activity Coefficient) model , which includes the Staverman-Guggenheim combinatorial term and is expressed in terms of activity coefficient of segments rather than chemical potentials. Several versions of COSMO-SAC were then proposed  [15] [16] [17] [18] [19] [20]. Another version of the COSMO model called as COSMO-RS(ol) and based on COSMO-RS was developed by Gmehling and coworkers  [21, 22]. Pye et al. [23]  also proposed their own version of COSMO-RS and implemented it into the ADF software.
(8) The parameter w is a universal scaling factor and is equal to 0. 27027. In Eq. (  8 ) ! , ! are the dispersion energy of components 1 and 2, calculated as a sum of atomic contributions as ! = ] ^U_@,> ∑ ! ," `" "X , > , (9) where , is the number of atoms on molecule i, `" is the number of atoms of type j on molecule i, and ! ," the atomic contribution for atom of type j. In this work, we propose a generalization of Eq. (  7 ) for multicomponent mixtures, given by , = 2+ ∑ ". " "a. ( 10 ) where " = Y Z T! + ! " Wb ! ! " \. In this study, the dispersion parameter for the F atom has been modified for better predictions of refrigerant + alkane VLE data. The corresponding model is then denoted as m-COSMO-SAC dsp. A fortran code of the m-COSMO-SAC-dsp, which only requires the cosmo files inputs, has been developed at ENSTA Paris and integrated into the ThermProp®  [29]  and Simulis thermodynamics®  [30]  softwares.
The code can automatically recognize the molecular structure from the. cosmo file in which the positions of atoms are stored, by determining the types of bonds. For example, the code can automatically recognize carbon atoms of type sp3, sp2, sp, OH and carboxylic groups. COSMO-SAC like models have been used with the freely available VT2005 database of. cosmo files developed by Mullins et al. [16]. For the HFO and HCFO refrigerants, the. cosmo files were created by using the Materials Studio / DMOL3 package and by following the procedure of Xiong et al. [32]  and Paricaud  [33]. In this procedure, the GGA-VWN-BP ab initio method is used with the DNP basis set. The whole procedure to generate. cosmo files has been explained in details by Paricaud  [29]. The VLE predictions with COSMO-SAC dsp and COSMO-RS are performed by assuming that the vapor phase is an ideal gas mixture.
Combination with the PR equation of state + MHV1 mixing rule The assumption that the vapor phase is an ideal gas mixture is valid for pressures below 1MPa. An equation of state must be used to compute the vapor-liquid equilibria of mixtures at high pressure and close to critical points. In this work, we consider a cubic equation of state based on the combination of the m-COSMO-SAC dsp, the Peng-Robinson (PR) equation of state (1978 version)  [34 , 35]  and the MHV1 mixing rule  [36]. This model only requires the knowledge of the experimental critical temperature, pressure and acentric factors of pure refrigerants (Tc, Pc, w) as input parameters, and is available in the ThermProp software  [29]. The PR Eos can be expressed in terms of the pressure P as = 2+ e -f - g e e + f + f e -f (12) where a and b and the covolume and cohesive energy of the mixture, T the temperature and v the molar volume.
Prediction of saturated liquid densities Following the work of Xiong et al. [32] , we propose a simple correlation to predict the saturated liquid densities of pure refrigerants, which is valid over a limited temperature range around the boiling point. The correlation relates the molecular volume with the temperature, the experimental boiling point (boiling temperature at atmospheric pressure) and the COSMO cavity volume determined by COSMO ab initio calculation (DMOL3 package in the Material Studio software). The parameters of the correlation were determined on 36 refrigerants. The molar volume of the saturated liquid (in cm 3. mol -  ) is given by e / 0 = 0. 43542158 × + : -0. 3856798 × + : + 0. 76951752 × # $  (10)  where # $ is the COSMO cavity volume in Å 3 calculated with DMOL3, and Tr = T/Teb , where Teb the experimental boiling point of the pure component.
Prediction of boiling points with COSMO-RS The COSMO-RS 2010 and the parameterization "BP_TZVP_C21_0110" + the def-TZVP database were used to predict the boiling points of some refrigerants (Eq. (  2 )). For the compounds like HFOs that were not included in the database, the. energy and. cosmo files  Reasonable predictions of the boiling points and enthalpies of vaporization are obtained (Figure  2 , Table  1 ), but deviations of more than 20K are observed for some compounds like RC318. This compound has a cycle, which may explain the large deviation. COSMO-RS tends to overestimate ∆Hvap, as the bias error is positive and close to the average absolute deviation.
Vapor pressure correlations In order to apply the asymmetric approach (vapor phase assumed to be an ideal gas mixture), it is necessary to know the vapor pressures of pure compounds. In this work the vapor pressures were calculated by using Simulis (DIPPR) correlations. For the compounds that were not included in the Simulis database (in particular the HFO and HFCO), we fitted the parameters of the Simulis /DIPPR correlation on the experimental data available in the literature. We used the correlation labeled "101" in Simulis, which is given by ln = + …/+ + † ln + + ‡+ o , ( 11 ) where T is in Kelvin and in Pa. The parameters are reported in Table  2. The Cosmotherm software that includes the COSMO-RS model also contains correlations for vapor pressures. In this work, the same vapor pressures have been used for both COSMO-RS and COSMO-SAC in most cases, for a fair comparison between both approaches.
As a result, two ab initio calculations have to be performed on the same molecule: one in vacuum and one inside the cavity. The value of 4 $$5 is contained in the. energy file while 4 )7 87 is in the. cosmo file. A geometry optimization has to be performed for each file, as the geometry of the molecule is not the same in vacuum and inside the cavity. The vaporization enthalpy is obtained from the Clapeyron equation, by neglecting the molar volume in the saturated liquid phase. The 2010 version of the def-TZVP DB database of. cosmo files developed by Klamt's group has been used with the turbomole software, which contains most of HFC and HCFC refrigerants. However, HFO and HCFO refrigerants are not included in this database. The Tmolx interface is used to generate the. cosmo and. energy files for the HFO and HFCO compounds.
High-performance liquid chromatography separations Several chromatographic systems were used for the analytical experiments (HPLC-MS) and the purification steps: System A: RP-HPLC-MS (Phenomenex Kinetex C18 column, 2. 6 μm, 2. 1 ´ 50 mm) with MeCN (+0. 1% FA) and 0. 1% aqueous formic acid (aqueous FA, pH 2. 1) as eluents [5% MeCN (0. 1 min) followed by linear gradient from 5% to 100% (5 min) of MeCN, then 100% MeCN (1. 5 min)] at a flow rate of 0. 5 mL/min. UV-visible detection was achieved at 220, 260, 645 and 680 nm (+diode array detection in the range of 220-700 nm). Low resolution ESI-MS detection in the positive/negative mode (full scan, 100-1000 a. m. u. , data type: centroid, needle voltage: 3. 0 kV, probe temperature: 350 °C, cone voltage: 75 V and scan time: 1 s). System B: semi-preparative RP-HPLC (SiliCycle SiliaChrom C18 column, 10 μm, 20 ´ 250 mm) with MeCN and aq.
0. 1 TFA (pH 1. 9) as eluents [10% MeCN (5 min), followed by a gradient of 10% to 20% MeCN (7. 5 min), then 20% to 100% MeCN (93 min)] at a flow rate of 20. 0 mL/min. Quadruple UV-visible detection was achieved at 220, 270, 645 and 700 nm. System C: RP-HPLC-fluorescence (Phenomenex Kinetex C18 column, 2. 6 μm, 2. 1 × 50 mm) with same eluents and gradient as system A. Fluorescence detection was achieved at 45 °C at the following Ex/Em channels: 650/675 nm, and 685/730 nm (sensitivity: 1, PMT Auto, filter wheel: Auto). System D: system A with UVvisible detection at 220, 260, 650 and 680 nm (+diode array detection in the range 220-800 nm). Low resolution ESI-MS detection in the positive/negative modes (full scan, 100-1000 a. m. u. , data type: centroid, needle voltage: 3. 0 kV, probe temperature: 350 °C, cone voltage: 75 V and scan time: 1 s).
Acknowledgements This work is part of the project '" Pharmacoimagerie et Agents Theranostiques ", supported by the  Université de Bourgogne  and  Conseil Régional de Bourgogne  through the  Plan d ' Actions Régional pour l'Innovation (PARI)  and the  European Union  through the  PO FEDER-FSE Bourgogne 2014/2020 programs. Financial supports from the French "Investissements d'Avenir" program , project  ISITE BFC  (contract  ANR-15-IDEX-0003 ), especially for the post-doc fellowship of  Dr. Sébastien Jenni , and  Agence Nationale de la Recherche  ( ANR ,  AAPG 2018 ,  PRCI, LuminoManufacOligo ,  ANR-18-CE07-0045 ), especially for the post-doc fellowship of  Dr. Kévin Renault  are also greatly acknowledged. GDR  CNRS "Agents d'Imagerie Moléculaire" (AIM)   2037  is also thanked for its interest in this research topic.