dataesr/scientific-paragraphs-categorization huggingface dataset:
III-1. Simulation parameters All simulations were performed using the version 4. 1. 1 of SIMPSON package  (Bak et al. , 2000, p. 200 ). The powder average calculation was performed using 462 {MR, MR, MR} Euler angles relating the rotor and molecular frames. This set of angles was obtained by considering 66 {MR, MR} pairs and 7 MR angles. The {MR, MR} values were selected according to the REPULSION algorithm  (Bak and Nielsen, 1997b) , while the MR angles were regularly stepped from 0 to 360°. To accelerate the simulations, the 1 H 15 N RINEPT transfer was used, instead of the 1 H 27 Al one, because the computing time is proportional to the cube of the size of the density matrix. Furthermore, in RINEPT experiments, only CT-selective pulses are applied to the quadrupolar nuclei and hence, the contribution of STs to the signal can be disregarded.
Acknowledgments This article is dedicated to  Dr Francis Taulelle , our friend, who passed away very recently. The  Chevreul Institute  (FR 2638),  Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation, Hauts-de-France Region , and  FEDER  are acknowledged for supporting and funding partially this work. Financial support from the  IR-RMN-THC FR-3050   CNRS  for conducting the research is gratefully acknowledged. This project has received funding from the  European Union 's  Horizon 2020 research and innovation program  under grant agreement No. 731019  (EUSMI). OL acknowledges financial support from  Institut Universitaire de France (IUF)  and contract  ANR-18-CE08-0015-01  (ThinGlass). FP acknowledges financial support from I-site contract  OPE-2019-0043  ( 5400-MOFFIN ).
Analysis and Characterization of Block Copolymers Copolymer molar mass distributions were determined using size exclusion chromatography (SEC) performed with a double detector array from Viscotek (TDA 305, Malvern instruments, Worcestershire, UK). The Viscotek SEC apparatus was equipped with two mixed-columns (LT4000L, mixed low, Malvern Panalytical, Malvern, UK) with common particle size of 5 µm using THF as an eluent (1. 0 mL/min). The Viscotek system contains a refractive index detector (RI, concentration detector), and a four-capillary differential viscometer. OmniSEC software (version 10, Malvern Panalytical, Malvern, UK) was used for data analysis and acquisition. The average molar mass (M n ) and dispersity index (Ð) were calculated relative to polystyrene standards. 1 H NMR spectra were acquired with a Bruker 300 MHz spectrometer (Bruker, Wissembourg, France) using CDCl 3 or CD 2 Cl 2.
Moreover, in the model, a viscosity law is used and take into account the influence of grain size coarsening. It seems important to take the grain size into account in the viscosity law. Indeed, this impacts the diffusion paths, the solid/solid and solid/gas interfaces. This differs slightly from Manière work with Zirconia (cf. Eq. (  4 )). The modified SOVS model is implemented on a FEM (Finite Element Method) software (ABAQUS) using a user subroutine of material (UMAT) and is then validated with conventional sintering experiments. This step is required to check the validity of the law with our alumina powder, slightly different in its composition. The SOVS model is then used to simulate the microwave sintering of the alumina. A new set of parameters is identified to correlate with the relative density and the grain size obtained in microwave sintering experiments.
Implementation on ABAQUS with UMAT subroutine ABAQUS is used for the simulations with the modified SOVS model for alumina sintering. This is a commercially finite element based software. Nevertheless, the material behaviour law in Eq. (  5 ) is not a standard law. A user subroutine material (UMAT) is scripted in FORTRAN. The simulation process and the link between ABAQUS and the UMAT subroutine are described in Fig. 1. First, the input parameters (geometry, temperature profile, initial density) are defined in ABAQUS. Then the UMAT subroutine imports data from ABAQUS at the previous increment time. The relative density is calculated according to the current position of the nodes. The variables, like shear viscosity and bulk viscosity, are updated according to the time step, the temperature field, the grain size and the previous material density.
Acknowledgments This work is part of the research program of the  Dutch Research Council (NWO). This project has received funding from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation program  (Grant Agreement No. 817947 FICOMOL ). It has moreover received funding from the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Sk lodowska-Curie  grant agreements No. 886046  and  889328. We thank  Xingan Wang  for discussions and support on VUV generation, and  David Parker  for discussions on REMPI of carbon atoms and careful reading of the manuscript. We thank  Niek Janssen ,  André van Roij  and  Edwin Sweers  for expert technical support.
Water for AMW spectra was usually premixed with a carrier gas, but it was also found that water absorbed by AMP was sufficient for good cluster signals. The analysis was carried out with the help of the graphical AABS package for synchronously displaying recorded spectra and predictions  [41, 42] , which is available on the PROSPE website  [11, 12]. Fits and predictions were carried out either with ASFIT/ASROT package  [43] , also available on the PROSPE website or with the SPFIT/SPCAT package of H. M. Pickett  [44, 45]. Least-squares structural fits were performed with the program STRFIT  [30]. Quantum mechanical computations were carried out with Gaussian  [46] , CFOUR  [47] , or Firefly  [48]  packages. Dissociation energies were evaluated by correcting for BSSE using the counterpoise method  [32].
Acknowledgements We gratefully thank the  CNRS , the  Ministère de l'Enseignement Supérieur et de la Recherche  (funding for LM), the  Université Paris-Saclay , the  Ecole Polytechnique  and the  ANR  ( ANR-14-CE06-0009-01 , funding for SJ) for their support of this work. We gratefully thank  Guillaume Force  for the preparation of (S)-o-(tert-butylsulfinyl)-N-methylaniline and the corresponding attempt at the cyclization.
This means that an increase in the autocorrelated component during acquisition could be explained by refocusing of that component. Simulations, using Wolfram Mathematica™ software  (Wolfram Research Inc. , 2012) , help to further illustrate this phenomenon (see the Supplement). The chosen experimental condition for these simulations corresponds to that where an increase in spin noise is observed. Hence, the model we use presumes that SN originates from a series of small random excitation events, each of random timing, random phase, and random small flip angle. In this simple model, we neglect effects by radiation damping because the inhomogeneous broadening by the gradients exceeds the resonance linewidth, i. e. , the radiation damping rate, and Bloch equations are applicable. Therefore, spin noise contributes additively to the other Johnson-Nyquist noise sources, namely the resonance circuit, the transmission line, and the preamplifier.
Single-crystal X-ray diffraction The study of a single-crystal X-ray data collection was performed on plate single crystal with a dimensions (0. 42 x 0. 39 x 0. 018 mm) selected through an optical examination crystal of All calculations were made using the WINGX crystallographic suite of programs  [25]. The crystal structure for this compound was determined by the direct method and refined using the SHELXL and SHELXS crystallographic software package, respectively  [26, 27]. The positions of nitrogen, oxygen and carbon atoms have been identified on the subsequent Fourier difference map. The basic crystallographic parameters and some details of the the measurements structural and refinement are summarized in Table  1. The molecular structure of the studied compound was drawn and presented using ORTEP-3  [28] , DIAMOND  [29] , Mercury  [30]  and Gauss-view programs  [31].
Funding information Orphazyme A/S Communicating Editor: Robin Lachmann NPC. In a 12-month, prospective, randomised, double-blind, placebo-controlled, phase 2/3 trial (ClinicalTrials. gov identifier: NCT02612129), patients (2-18 years)   were randomised 2:1 to arimoclomol:placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times daily. The primary endpoint was change in 5-domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12 months. Fifty patients enrolled; 42 completed. At month 12, the mean progression from baseline in the 5-domain NPCCSS was 0. 76 with arimoclomol vs 2. 15 with placebo. A statistically significant treatment difference in favour of arimoclomol of À1. 40 (95% confidence interval: À2. 76, À0. 03; P =.
21, 22 he HSR is linked directly to lysosomal function and integrity, in part through HSP70-mediated augmentation of sphingolipid-degrading enzymes, stabilisation of lysosomal membranes, and protection from cell death. 20, 21, 23, 24 rimoclomol is an orally available small molecule that crosses the blood-brain barrier, as evidenced by its presence in cerebrospinal fluid of treated patients with amyotrophic lateral sclerosis. 25 Arimoclomol amplifies the natural response to cellular stress by inducing the HSR and production of HSPs to prevent protein misfolding, but also by more direct facilitation of lysosomal function. ] [28] [29]  We conducted the present trial (ClinicalTrials. gov identifier: NCT02612129) to evaluate the safety and efficacy of arimoclomol in patients with NPC. The primary endpoint was the 5-domain NPC Clinical Severity Scale (NPCCSS) score, as described by Mengel et al.
| Randomisation and masking Patients enrolled in the trial were stratified by use of miglustat at baseline. An interactive response technology system assigned treatment to each patient via a randomisation list. Patients in both strata were randomised 2:1 to receive arimoclomol or placebo. Given the ultra-rare condition, and expected rate of progression, sample size and trial duration were primarily informed by feasibility and not by a formal sample size calculation. Up to 52 patients with NPC were planned to be randomised, to have at least 40 evaluable patients' data at the 12 months landmark visit. To ensure blinding, all investigational products and their packaging (arimoclomol 16 mg, 31 mg, and 62 mg capsules, and placebo capsules) were indistinguishable in terms of composition, texture, appearance, solubility, smell, and flavour.
Arimoclomol was manufactured by Juniper Pharma (Nottingham, UK). During the 12-month treatment phase, efficacy assessments for the primary endpoint, the 5-domain NPCCSS scores, and for the non-disease specific Clinical Global Impression-Improvement scale (CGI-I) scores were performed at baseline and after 3, 6, 9, and 12 months of treatment; all other efficacy and biomarker assessments were performed at baseline and after 6 and 12 months of treatment. An independent Data Safety Monitoring Board (DSMB), consisting of three experts who had access to unblinded data, reviewed safety data four times during the blinded phase. For patients in either treatment group with rapid disease progression, an "early escape clause" could be invoked if a particular set of criteria were met (assessed by the investigator and approved by the sponsor).
| Statistical analysis No formal statistical calculation was used to determine sample size. Efficacy endpoints were analysed in the full analysis set, which included all patients who were randomised and started study treatment (excluding the PK analysis single dose of arimoclomol [see Supplementary Materials]). All dosed patients were included in the analysis of efficacy; patients were included until and including the assessment at which rescue medication was initiated. The safety set comprised the same patients as the full analysis set. Data for continuous outcomes including the primary endpoint were analysed under an efficacy (de jure) estimand with a mixed model for repeated measures (MMRM), with main effects factors for treatment, visit, miglustat stratum, and the corresponding baseline value and the interaction term between visit and treatment.
Baseline disease severity scores were chosen as a covariate in the primary analysis to account for anticipated differences between individuals and treatment arms with regards to severity and to allow the analysis of change from baseline to mirror that of absolute values. Missing data were not imputed for the primary endpoint analysis but were imputed for sensitivity analyses. Sensitivity analyses were performed both under the primary estimand and under a de facto "treatment policy" estimand. The primary MMRM model was applied on the prespecified subgroup levels with enough patients to substantiate a formal analysis. See Supplementary Materials for additional analyses. All statistical analyses were performed using SAS software version 9. 3 (SAS Institute Inc. , Cary, North Carolina). All hypothesis testing was carried out using a 5% (twosided) significance level.
The overall impact of arimoclomol on disease-relevant biomarkers was in line with preclinical data in NPC1 knockout mice showing central nervous system target engagement of arimoclomol, through heat shock response activation in the brain and effects on relevant disease pathology. 21 verall, the effect on biomarkers supports the mechanism of action of arimoclomol in NPC that involves an amplification of the heat shock response, augmentation of lysosomal function and a reduction in accumulating lipid burden. Arimoclomol was well tolerated. The majority of TEAEs were assessed by the investigators to be related to NPC rather than the investigational product. The most common event of vomiting occurred in a similar proportion of patients in both treatment groups (arimoclomol: 8/34, 23. 5%; placebo: 4/16, 25.
5-domain NPCCSS (defined as the time until the patient worsened by 2 points vs baseline); proportion of patients worsening on 5-domain NPCCSS at 6 and 12 months by 2 points on the 5-domain NPCCSS; and change in 17-domain NPCCSS (excluding hearing domains) at 12 months. Additional secondary endpoints included: change from baseline in Scale for Assessment and Rating of Ataxia (SARA) score at 6 and 12 months; change in the nine-hole peg test (9-HPT) result at 6 and 12 months; change in health-related quality of life (HRQoL) as measured by the 5-dimension 3-level EuroQol questionnaire, youth version (EQ-5D-3L Y) proxy at 6 and 12 months; change in individual 5-domain NPCCSS scores at month 12; and NPC clinical database (NPC-cdb) score changes from baseline at trial time points. The NPC-cdb score aims to reflect clinical status; an increase in score indicates a reduction in the patient's abilities.
Time to worsening is summarised as 25% Kaplan-Meier estimates, and then analysed using a log-rank test stratified by miglustat use. Abbreviations: 9-HPT, nine-hole peg test; CGI-I, Clinical Global Impression-Improvement scale; CI, confidence interval; EQ-5D-3L Y, 5-dimension, 3-level EuroQol questionnaire, youth version; IQR, interquartile range; LS, least-squares; NA, not applicable; NC, not calculated; NPC, Niemann-Pick disease type C; NPC-cdb, NPC clinical database; NPCCSS, Niemann-Pick disease type C Clinical Severity Scale; SARA, Scale for Assessment and Rating of Ataxia.
DATA AVAILABILITY STATEMENT The trial protocol and Statistical Analysis Plans will become publicly available. Study information will be posted on https://clinicaltrials. gov/ct2/show/NCT02612129. The data that support the findings of this trial are available from Orphazyme but restrictions apply to the availability of these data, which were used under licence for the current trial, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Orphazyme.
Time to worsening is summarised as 25% Kaplan-Meier estimates, and then analysed using a log-rank test stratified by miglustat use. Abbreviations: 9-HPT, nine-hole peg test; CGI-I, Clinical Global Impression-Improvement scale; CI, confidence interval; EQ-5D-3L Y, 5-dimension, 3-level EuroQol questionnaire, youth version; IQR, interquartile range; LS, least-squares; NA, not applicable; NC, not calculated; NPC, Niemann-Pick disease type C; NPC-cdb, NPC clinical database; NPCCSS, Niemann-Pick disease type C Clinical Severity Scale; SARA, Scale for Assessment and Rating of Ataxia. 5/16 (31. 3%) patients in the placebo group; 2 patients in the arimoclomol group discontinued due to serious TEAEs. One patient in the arimoclomol group died, assessed as related to NPC progression.
05 V and 0. 90 V in electrolytic solution. The deposited platinum load was about 250 ng cm -2 ; and the platinum domains dispersed on PANI film were about 100 -200 nm in diameter. Those modified electrodes are denoted as Au/PANI/Pt. The spongy-like structure of PANI allows a homogeneously deposition of platinum nanoparticles. The results indicate a good dispersion of Pt nanoparticles and absence of Pt clusters with significant size which can lead to the appearance of characteristics of the bulk metal in the voltammograms. All results obtained with PANI electrodes had current values normalized by the geometric area. Some Δm data were averaged with the Origin program in order to reduce the noise when low mass variations are involved.
f. Figure  S5  in the Supporting Information file. Differently from the situation just discussed, those experiments were performed in base electrolyte, and results in q/E and Δm/E remain nearly unaffected by the presence of Pt and the response is dominated by the volumetric processes. Following this reasoning, we now discuss the electro-oxidation of HCOOH on PANIcovered platinum electrode. Figure  7  shows the time-invariant voltammetric and nanogravimetric responses for Pt/PANI electrodes before and after addition of HCOOH, results on bare Pt is also given for comparison. Data for the platinum electrode were already presented in Figure  3 , and the results presented here are for a restricted potential window. The narrower potential region is necessary to allow the comparison with the Pt/PANI electrode, whose structure can be damaged at high potentials, as already discussed.
Results in base electrolyte,   As in the case of the Au/PANI/Pt + HCOOH system, Table  1 , oscillations E/t and Δm/t are in-phase, evidencing that the charge compensation within the polymer matrix governs the mass variation. There is apparently no spectroscopic data for the oxidation of formic acid on Pt/PANI, to confirm that the formation of COad is suppressed as the case of methanol,  18  but the unambiguous increase in the activity is a hint that this process could be inhibited, if not suppressed. Indeed, the already mentioned decrease in the onset potential for the oxidation of HCOOH and the high ratio between the oxidation peaks in backward and forward scans suggest the tolerance of PANI-modified catalysts for the formation of CO. The, previously unreported, occurrence of potential oscillations in the electro-oxidation of formic acid on Pt/PANI modified arises an interesting question.
The systematic study included the analysis of several configurations: gold electrodes covered with a PANI film and dispersed platinum (Au/PANI/Pt); platinum electrodes covered with PANI (Pt/PANI); and bare platinum electrodes. The current and mass changes profiles for the redox processes in Au/PANI and Au/PANI/Pt modified electrodes in aqueous sulfuric acid solutions are dominated by the charge compensation processes within the film. Both the voltammetric profiles and the dynamics of charge compensation is only slightly affected by the presence of the platinum nanoparticles within the PANI film. The Au/PANI/Pt modified electrode was found to be more active than conventional platinum electrode towards the electro-oxidation of formic acid. In particular, the high reversibility in the cyclic voltammogram on the Au/PANI/Pt electrode suggests that the reaction proceeds without the formation of adsorbed carbon monoxide, COad, in agreement with previously published data with methanol.
ACKNOWLEDGMENTS GCAF acknowledges  Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil (CAPES)/PROEX  for financial support. HV (grant # 306060/2017-5 ) acknowledges  Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)  for financial support. HV (grants # 2013/16930-7  and # 2019/22183-6 ) and  RMT  (grant # 2015/26308-7 ) acknowledge  São Paulo Research Foundation (FAPESP)  for financial support. The authors acknowledge  Dr. Murilo F. Cabral  for helping with the EQCN setup. This study was partially financed by the  CAPES -Finance Code 001. The authors acknowledge CAPES/ COFECUB  project  Ch. 747-12  and Ch. 914-18. TWN acknowledge financial support from the  European Union (ERDF)  and  Région Nouvelle Aquitaine.
Samples were then immediately placed on the AFM for visualization, ensuring they did not dry at any time. For subsequent AFM investigations, the solution was exchanged with diluted PBS buffers and finally with UHQ water. Force ramps were obtained at different lateral positions by operating the AFM in the force volume (FV) mode  [30]  and analyzed with the FSAS software (https://github. com/JSotres/FSAS-ForceSpectroscopyAnalysisSoftware-MatLab). Specifically, FV measurements consisted of 64x64 force ramps obtained at a speed of 1 mmÁs À1 over an area of 2 mm Â 2 mm. Force ramps consist of successive displacements of the sample towards and away from the tip, always performed at different lateral positions when operating in the FV mode, while registering the deflection of the cantilever by monitoring a laser beam reflected at the backside of its free end with a position sensitive photodetector (PSD).
1 mLÁmin À1. When the chamber was filled, the pump was stopped and the stock solutions were left to adsorb for 1 h. Then, the chambers were rinsed for 5 min with PBS buffer, followed by 55 min stabilization under non-flow conditions. This cycle was then repeated for PBS/10, PBS/100 and UHQ water. The Q-Tools software (Q-Sense AB, Sweden) was employed for fitting data to the Voigt model (details on the fit are provided in Supplementary Material Section S1. 1).
4°a nd 2. 8°were used. SuperAdam is a monochromatic machine (k = 5. 21 Å) with a horizontal scattering plane, the reflected beam was measured over a range of detector angles to achieve the same q-range. The measured reflected intensity, I(q), was normalised by the direct beam, I 0 , to achieve the reflectivity, R(q). R(q) plots are provided as mean and standard deviation values of the reflectivities for a specific q. From the reflectivity data collected, the scattering length density, SLD(z), is calculated through data analysis in RasCAL modelling software to give the structural conformation normal to the surface. For error analysis, we used the Bayesian Markov chain Monte Carlo (MCMC) approach implemented in the refnx software  [37]. Further details on the experimental method and data analysis can be found in the Supplementary Material Section S2.
Moreover, QCM-D data supported that obtained by means of force spectroscopy investigations. Decreasing ionic strength led to an immediate swelling of both salivary pellicles and MUC5B films. After this initial swelling, an eventual coiling was observed for both systems. However, in agreement with force spectroscopy data, the eventual coiling of MUC5B films was significantly higher than for salivary pellicles, up to an extent that they eventually coiled down to a thickness only slightly larger than that observed for physiological ionic strength. In fact, this eventual coiling of MUC5B films was significantly more pronounced than that observed in force spectroscopy experiments. QCM-D revealed, because of its sensitivity to the whole films and not only to their outer layer, a structural aspect of salivary pellicles exposed to low ionic strength that could not be observed in force spectroscopy investigations.