dataesr/scientific-paragraphs-categorization huggingface dataset:
Toxicity studies against human cells Toxicity data against human cells is important information for the identification of a novel family of antibiotic drug candidates. Initially developed for anticancer activity, complexes 1 -4 (and ligands L6 -L9) were tested against human ovarian adenocarcinoma (A2780), cisplatinresistant variant of A2780 (A2780cisR) and normal human prostate epithelial (PNT2) cell lines. Half-maximal inhibitory concentrations (IC 50 ) were determined using a 24 h MTT assay with 48 h recovery period. The IC 50 values are shown in table 2 and the IC 50 graphs for ligands L6 -L9 and complexes 1 -4 against PNT2, A2780, and A2780cisR can be found in the Supporting Information (Figs. S37 -S38 ). Complexes 1, 2 and 3 are moderately cytotoxic against the tested cell lines and showed 2 -3x higher IC 50 values towards normal prostate cells in comparison to cancer cells.
Materials and methods Hydrated metallic chlorides were purchased from Precious Metals Online. All other chemicals were purchased from Sigma-Aldrich (UK). Non-dried solvents were purchased from Fischer Scientific and used as received. Dichloromethane, tetrahydrofuran and toluene were dried over molecular sieves (3 Å). All compounds were prepared under a purified dinitrogen atmosphere using standard Schlenk and vacuum line techniques, unless otherwise specified. pH* was adjusted using EDT direction non-glass pocket pH meter with an ISFET silicon chip pH sensor. pH* values (pH readings without correction for the effect of deuterium) of NMR samples were adjusted using KOD solutions in D 2 O. All NMR spectra were recorded on a 400 MHz Bruker Spectrospin spectrometer using 5 mm NMR tubes. Data processing was carried out using TOPSPIN 4.
All data was processed through GraphPad Prism 8. M. tuberculosis was assessed by addition of OD 600 adjusted culture (OD 600 =0. 001) to experimental wells containing serially diluted complexes 1-4 (as previously described). Plates were incubated for 168 h at 37 • C, before 5 µL of each experimental well was plated onto Middlebrook 7H11 agar with OADC. These agar plates were incubated at 37 • C for 312 h. The drug containing 96-well plates were also additionally incubated for a further 240 h at 37 • C, after which resazurin (0. 0025%) was added and plates were incubated at 37 • C for a final 24 h. Minimum inhibitory concentrations were determined by conversion of resazurin to resorufin. Minimum bactericidal concentrations were determined by the lowest concentration in which no growth was visibly seen on the solid agar plates.
Acknowledgements N. P. E. B. acknowledges the support of the  Royal Society (University Research  Fellowship No. UF150295  to N. P. E. B. ), the  University of Bradford , and the  Academy of Medical Sciences/the Wellcome Trust/the Government Department of Business , Energy and Industrial Strategy/ the  British Heart Foundation   Springboard Award  ( SBF003\1170  to N. P. E. B. ). J. A. G. C. is grateful to the  Academy of Medical Sciences, Global Challenges Research Fund, Birmingham Women's and Children's Hospital Charity Research Foundation and Give A Child Health Fund  for their continued support of the  Mycobacterial Research Group at Aston University. This research was funded by the  Academy of Medical Sciences/the British Heart Foundation/the Government Department of Business, Energy and Industrial Strategy/Global Challenges Research Fund /the  Wellcome Trust Springboard Award  [ SBF003\1088 ].
Principle The principle of our method is the automation of the volume/height reading at equivalence. Our work has allowed us to set up a semi-automatic approach. This approach consisted in setting up at: Step 1: We proceeded to set up the experimental equipment to proceed with the titration of a solution. In this experiment, it is the titration of water by the solution of EDTA to 0. 01 N with as initial volume 10 ml (V0 = 10 ml). This experimentation allowed us to acquire the video of experimentation. Step 2: We proceeded to the decomposition of this video of experimentation in several sequential images illustrated in example by the following images (see Figure  2 ). Step 3: These sequential images allowed us to build an image database. For Frame 1 we made several height measurements and calculated the average height as shown in Table  1.
For Frame 2 we made several height measurements and calculated the average height as shown in Table  2. For the Frame 1200 we made several height measurements and calculated the average height as shown in Table  3. From the above, we have constituted an acquisition database with the 3030 frames. This database is illustrated by Table  4. Step 4: We measure the height of each image. If the color of the titrated solution remains unchanged, we continue to measure a new height. However, if the color of the titrated solution changes state then we are at the equivalence point. This leads us to record the height of the titrated solution. By analogy this semi-automatically determined height allows us to determine the volume at the equivalence point. Step 5: We deduce the concentration of the titrated solution.
Results and Discussion The semi-automatic technique implemented in the Matlab software allowed us to measure the different heights of the titrated solution. When we visually observe that there is a change in color of the titrated solution, our approach measures with precision the height. We are therefore at the turn. This height determined at the turn represents the equivalent height ( e h ). This height is expressed in pixels. By observing our experiment representing the titration of water by the EDTA solution at 0. 01 N, we have the following explanation: In the initial state, we have the Initial Volume named V 0 = 10 ml corresponding to the initial volume of the solution containing the titrated species. According to Table  4 , representing the acquisition database, we have Frame 1 corresponding to the initial state of our data.
Genome-wide database analyses have revealed a significant number of bacteria and unicellular eukaryotes that do not require molybdenum, while all multicellular eukaryotes are dependent on Mo  [12]. In addition, mainly anaerobic archaea and some bacteria are Mo-independent but instead require tungsten (W) for their growth  [13]. In the periodic table of elements, W lies directly below Mo and features chemical properties similar to Mo. The biosynthesis of Moco is highly conserved in all organisms, and it is divided into three to four general steps according to the stable biosynthetic intermediates that can be isolated [9] (Figure  1 ): a significant number of bacteria and unicellular eukaryotes that do not require molybdenum, while all multicellular eukaryotes are dependent on Mo  [12]. In addition, mainly anaerobic archaea and some bacteria are Mo-independent but instead require tungsten (W) for their growth  [13].
Funding: This work was supported by the  DFG  under Germany's Excellence Strategies-EXC  314/2 EXC 2008/1  (UniSysCat) (S. L. ): Funded by the  Deutsche Forschungsgemeinschaft (DFG, German Research Foundation ) under Germany's Excellence Strategy-EXC 2008-390540038-UniSysCat. We thank the  Aix-Marseille Université  for supporting S. L. with a visiting professor position ( FIR EC 2018 ). Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable. Acknowledgments: This work was supported by the DFG under Germany's Excellence Strategies-EXC 314/2 EXC 2008/1 (UniSysCat) (S. L. ): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC 2008-390540038-UniSysCat. We thank the Aix-Marseille Université for supporting S. L. with a visiting professor position (FIR EC 2018). K. T. was supported by the Einstein Foundation Berlin (Einstein center of catalysis) and the BIG-NSE and the University of Potsdam.
The challenge here was to know how much the inter-and/or intra-variability of raw apples impacts cooked purees? How VIS-NIR spectral data were affected due to the physical and chemical changes considering the experimental design of 'one apple to one puree'? The potential of predicting the quality traits of the final cooked purees using the VIS-NIR spectra of intact raw apples was also investigated. Accordingly, VIS-NIR spectroscopy and reference data determination were performed on 120 individual apples of 4 varieties and their corresponding individual processed purees, in order to reach three aims: i) investigating the inter-and intra-variability of both, the individual apples and corresponding purees; ii) exploring the spectral correlations and variations before and after each apple processing; and iii) predicting the textural properties and biochemical composition of cooked purees from the VIS-NIR spectra of individual raw apples using direct modelling methods.
Nondestructive characterization of individual apples The color of all apple skins (un-blushed and blushed sides) was determined three times using a CE-400 chromameter (Minolta, Osaka, Japan), and expressed in the CIE 1976 L* a* b* color space (illuminant D65, 0 • view angle, illumination area diameter 8 mm). VIS-NIR spectra of raw apples were acquired using two multipurpose analyzer spectrometers (Bruker Optics®, Wissembourg, France) at 23 • C, which provide diffuse reflectance measurements at wavelength from 500 to 780 nm (VIS) and 780-2500 nm (NIR), with a spectral resolution of 2 nm. For each spectrum, 32 scans were recorded and averaged. The spectral acquisition and instrument adjustments were controlled by OPUS software Version 5. 0 (Bruker Optics®). For each apple, VIS-NIR spectra were collected on the blushed and un-blushed sides through a 18 mm diameter area of infrared light.
Spectrum acquisition on individual purees VIS-NIR spectral data of processed purees were acquired using the same conditions as for apples (described in part 2. 2). Each sample was transferred into a 10 mL glass vial (5 cm height × 18 mm diameter) which was placed on the automated sample wheel of the spectrophotometer. Each puree sample was randomly measured three times on different aliquots and the averaged spectrum was calculated for data treatment and chemometrics. The mean spectra of three replicates of each puree were used for further analysis. A reference background measurement was automatically activated before each data set acquisition using an internal Spectralon reference. Finally, the 120 VIS-NIR spectra of processed purees were obtained and correspond one by one to the spectra of raw individual apples.
Statistical analyses and chemometrics After checking the normal distribution of the reference data, T-test analysis was carried out to determine the significant differences between varieties considering them two by two (Fig. 2 ) using R software (version 4. 0. 2) (R Core Team, 2019) with the package of 'ggpubr'  (Kassambara, 2020)  Spectral pre-processing and multivariate data analysis were performed with Matlab 7. 5 (Mathworks Inc. Natick, MA, USA) software using the SAISIR package  (Cordella & Bertrand, 2014). Particularly, the VIS-NIR spectra of apples and corresponding purees from 500 to 2500 nm were preprocessed with several strategies, including smoothing with a window size of 23 variables, standard normal variate (SNV) and the first derivative Savitzky-Golay transformation with the 11 gap sizes.
The two-dimensional correlation spectroscopy method (2D-COS) was used to investigate the spectral correlations between raw apples and purees  (Noda, 1993). The partial least square (PLS), support vector machine (SVM) and random forest (RF) models were built using R software (version 4. 0. 2) (R Core Team, 2019) with several packages, including 'prospectr'  (Stevens & Ramirez-Lopez, 2013) , 'pls'  (Mevik, Wehrens, & Liland, 2011) , 'kernlab'  (Karatzoglou, Smola, Hornik, & Zeileis, 2004) , 'caret'  (Kuhn, 2015)  and 'Boruta'  (Kursa & Rudnicki, 2010). The whole VIS-NIR spectra dataset included 120 spectra of individual apples (4 varieties × 10 apples × 3 weeks) and the 120 corresponding puree spectra. The dataset was split using stratified random sampling as follows: two-thirds of the spectral dataset from each variety (4 variety × 20 spectra of apples and their related cooked purees) were used for calibration and one-third of the spectral dataset (4 variety × 20 spectra of apples and their related cooked purees) for validation.
Acknowledgements This work was done within The ' Interfaces ' project, an  Agropolis Fondation  project publicly funded through the  ANR (French Research Agency)  under " Investissements d'Avenir" programme  ( ANR-10-LABX-01-001   Labex Agro , coordinated by  Agropolis Fondation). Weijie Lan  was supported by a doctoral grant from  Chinese Scholarship Council. The authors thank  Patrice Reling ,  Romain Bott ,  Barbara Gouble  ( INRAE, SQPOV unit ) for their technical help.
Physicochemical Characterization of SbL8 and SbL10 Nanoassemblies The formulations were characterized for particle size distribution (mean hydrodynamic diameter and polydispersity index) by dynamic light scattering (DLS) and zetapotential, using the Zetasizer equipment (Nano ZS90; Malvern Instruments, Malvern, UK) and measurements at a fixed angle of 90 •. Dispersion Technology Software, version 6. 12, was used to collect and analyze the data obtained. SbL8 and SbL10 dispersions were diluted in 0. 15 M NaCl solution at final concentration of 30 mM of Sb, and kept at 25 • C during the entire experiment. The particle size was also investigated using nanoparticle tracking analysis (NTA; Malvern Instruments, UK) and NTA 3. 44 software (Malvern Panalytical, Malvern, UK) to collect and analyze data.
05 M, PBS 7. 2, 5. 8 or 4. 5 in a quartz cuvette maintained at 37 • C under magnetic stirring. DPH fluorescence was then registered continuously as a function of time at excitation and emission wavelengths of 360 and 428 nm, respectively. The half-times of dissociation of the nanoassemblies were determined through non-linear regression fit according to monoexponential decay model, using the GraphPad Prism software © , Version 9, GraphPad Software, LLC (San Diego, CA, USA). Small-angle X-ray scattering (SAXS) studies were conducted in line 2 of LNLS-Brazilian Synchrotron Light Laboratory/MCT (Campinas, Sao Paulo, Brazil). This line is equipped with a monochromator (λ = 1. 54 Å), an ionization chamber, and a 300 k Pilatus detector placed at 1 m from the sample to record the intensity of the scattering.
The infection index was defined as II = (% infection rate × amastigotes/infected macrophage)/100. The IC 50 in this case is the drug concentration in which the II corresponds to 50%, using the non-treated control as 100%  [14]. Both IC 50 and CC 50 values in all experiments were calculated in GraphPad Prism ® 9. 2. 0 software through non-linear regression of log(inhibitor) vs. response (variable slope). Only results in each Hillslope was around -3 and R Square was >0. 95 were considered. Results are from a representative experiment out of at least three independent experiments.
The amplification protocol included an annealing temperature and extension of 60 • C, with melting curve construction, on the Applied Biosystems™7500 Fast Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA) and the analysis was made using the 7500 System Software. Parasite load was determined by absolute quantification based on the standard curve Ct vs. gDNA mass in pg. Results are shown as the parasite load that represents the number of Leishmania per ng of total DNA. Additionally, in the cutaneous infection model, lesion development was followed during the treatment and plot of the change in lesion size with respect to time zero was obtained as a function of time. As the lesions developed into a circular shape, the size was calculated from the means of the coronal and sagittal lesion diameters, using a universal calliper, 150 mm, Digimess (São Paulo, Brazil), every 5 days from the onset of the treatment.
Effect of pH on the Stability of SbL8 and SbL10 Nanoassemblies Previous studies led to the identification of 1:3 Sb-ligand complexes as the main species in SbL8 and SbL10 compounds  [4] , as illustrated in Figure  1. cluded an annealing temperature and extension of 60 °C, with melting curve construction, on the Applied Biosystems™7500 Fast Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA) and the analysis was made using the 7500 System Software. Parasite load was determined by absolute quantification based on the standard curve Ct vs. gDNA mass in pg. Results are shown as the parasite load that represents the number of Leishmania per ng of total DNA. Additionally, in the cutaneous infection model, lesion development was followed during the treatment and plot of the change in lesion size with respect to time zero was obtained as a function of time.
In Vitro Study of the Pharmacological Interaction between SbL10 and Milt Evidence has been obtained previously for the spontaneous incorporation of miltefosine into SbL8 micelles, through increase in the fluorescence intensity of MT-11-BDP miltefosine analog in SbL8 aqueous suspension  [5]. A similar behavior was observed with SbL10 suspension (Figure  S3 ), supporting the partitioning of Milt into the hydrophobic core of SbL10 nanoassemblies. The pharmacological interaction between SbL10 and Milt was evaluated in the axenic amastigote and intramacrophage amastigote models, after incorporation of Milt into SbL10 suspension at different ratios. Figure  4  displays the IC 50 of Milt at increasing proportion of SbL10. The data indicates an increase of the antileishmanial activity with increasing SbL10 proportions to a much higher extent in the intracellular amastigote model than in the axenic model.
Funding: This research was funded by  Conselho Nacional de Desenvolvimento Científico e Tecnológico  ( CNPq, Brazil ), grant numbers  425332/2018-7 ,  306198/2021-5  and  401390/2020-9 ,  Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil) , grant number  PPM-00372-17  and  RED-00202-22 ,  Brazilian Synchrotron Light Laboratory/MCT , grant number  SAXS1-14258 ,  Agence Nationale de la Recherche (France) , grant number  ANR-11-IDEX-0003-02 ,  Région Ile-de-France  ( DIM1Health ) and  COST Action  number  CA21111. L. R. is supported by  Ministerio de Ciencia e Innovación, Subdirección General de Redes y Centros del Investigación Cooperativa-FEDER , grant number  RD16/0027/0010/AEI/10. 13039/501100011033. F. F. was recipient of fellowships from  CNPq , " Chaire Jean d'Alembert" (IdEx Université Paris-Saclay ) and " Chaire d'Excellence DIM1Health " ( Région Ile-de-France).
CEST-linescan pulse sequence CEST data were acquired using a CEST-LS sequence developed for Paravision 6. 0. 1 starting from a standard gradient echo pulse sequence in which we deactivated the phase encoding gradient and added a CEST saturation module. Compared to the simplest implementation of the UFZ technique,  13  the CEST-LS sequence used here includes a slice selection gradient and outer-volume saturation bands (Figure  1 ), in order to limit the CEST acquisition to a given region-of-interest (ROI). The saturation module consists in saturation pulses applied on-resonance in the presence of a gradient. As a result, spins that are located along the direction of the gradient at a distance d from the isocenter will experience an irradiation at saturation offsets given by  × G sat × d, where  is the gyromagnetic ratio and G sat is the amplitude of the gradient.
Local B 0 field homogenization was performed prior to the CEST-LS acquisitions using an automatic shimming routine. All CEST-LS acquisitions were performed with TE/TR= 3/8000 ms (with negligible T 1 or T 2 * weightings) and a saturation power of 1 T. Other parameters varied depending on the investigated region and are detailed in Table  1. Eighty repetitions (pairs of CEST-LS datasets with and without the saturation module) were acquired to increase the SNR for a total acquisition time of 21m20s. Additionally, single-voxel 1 H-NMR spectra were acquired using a LASER sequence  15  (TE/TR = 25/3000 ms, 256 averages, 8 kHz acquisition bandwidth, 1024 T A B L E 1 Parameters used for in vivo Z-spectra generated with CEST-LS. r is the ratio between the saturation gradient G sat and the acquisition gradient G acq.
CEST-LS All CEST-LS data were analyzed using in-house written MATLAB scripts (Mathworks, version 9. 7, R2019b). To obtain the Z-spectra, CEST data were processed as follows: after a zero-filling which doubled the number of FID data points (from 64 to 128), the ratio between the Fourier transform of the signal acquired with and without saturation was plotted against the saturation frequency offsets. The chemical shifts of the Z-spectrum were corrected using a cubic spline data interpolation in order to center the water peak on 0 ppm. For higher resolution Z-spectra, not covering the water peak, the chemical shift correction was performed using other known, major peaks: phosphocreatine at 2. 6 ppm in the muscle and creatine at 2 ppm in the olfactory bulb and neocortex. The in vivo Z-spectra were analyzed using a Python-based algorithm (PEAKIT)  18  able to detect, calculate heights and areas and evaluate the significance of CEST peaks.
For the skeletal muscle, only the significance of the carnosine + anserine peak was assessed while for the olfactory bulb and cortex, the areas of carnosine, homocarnosine and APT peaks were also determined. The area of the APT peak was calculated over a range of 2. 8 ppm and centered on the peak maximum, as found by PEAKIT. For the carnosine and homocarnosine peaks, the range for area calculation was automatically selected by PEAKIT. PEAKIT is freely available from https://github. com/SKMikee/PeakIt.
MRS Following removal of the residual water signal using the Hankel Lanczos singular value decomposition (HLSVD) algorithm, in vivo 1 H-NMR spectra were processed over the [0. 5-9] ppm range using LCModel 6. 2. 19 The basis set of metabolite spectra was simulated using a spin (B) (A) F I G U R E 2 (A) CEST-LS Z-spectrum obtained with B 1,sat 0. 15 T and a resolution of 0. 005 ppm. Homocarnosine, carnosine and anserine peaks are clearly visible and distinct. (B) CEST-LS Z-spectrum obtained with B 1,sat 1 T and a resolution of 0. 03 ppm. The Z-spectra in A and B were averaged over 10 and 18 repetitions, respectively. We note that in,  6  the CEST effect of carnosine was reported at 3. 1 ppm which is slightly different from our results. This is most likely due to slight differences in pH. simulation software implemented in Matlab and based on the density matrix formalism.
LC-ESI-MS/MS The calibration curves were built for each analyzed sample by using a standard addition method. The peak area ratios of analyte/IS were plotted versus the nominal concentrations of genuine carnosine, anserine and homocarnosine spiked in the sample to reach the following final concentrations: 0, 1, 2, 3, and 4 M. Weighted (1/×2) least-squares linear regressions were calculated by using the software GraphPad Prism. The calculated analyte concentration was then reported as moles per gram of wet tissue on the basis of the weight of the wet tissue and serial dilutions.
DISCUSSION AND CONCLUSIONS In this study, we demonstrate the in vivo detection of carnosine and its derivatives in rats using CEST. This was accomplished by using a custom designed fast CEST acquisition, CEST-LS, in combination with an ultra-high magnetic field (17. 2 T) imaging system. The characterization of the CEST effect was performed using the PEAKIT software,  18  which makes a local estimation of the baseline and therefore reduces the contamination from other broad CEST signals (e. g. taurine, glutamine, glutamate in the brain  22  ) improving the detection selectivity of the technique. We cannot however, completely exclude any signal contamination from other metabolites or peptides if present. The presence of carnosine and derivatives was validated in the leg with direct NMR spectroscopy in vivo but was not possible for the olfactory bulb and the neocortex.