dataesr/scientific-paragraphs-categorization huggingface dataset:
The national strategy in the fight against stroke also involves the development of epidemiological research in stroke, notably through the increased exploitation of existing information systems: PMSI-MCO (Programme de médicalisation des systèmes d'information) and SNIIR-AM (Système national inter-régime de l'assurance maladie) (action 8 of the Plan). Indeed, a number of studies have been conducted thanks to the availability and long-standing nature of medico-administrative databases. The PMSI-MCO in particular is a precious source of information for studies in epidemiology  [5]  or healthcare economics  [6]. Indeed, the PMSI is the main source of French hospitalisation data. For each patient, it gathers all of the hospital stays during the year and allows patients to be followed over time thanks to a unique data linkage number.
In this context, we can make the hypothesis that this decrease may be observable for a larger period and that its spatial distribution in France follows an heterogenic organization. We studied the number of stroke victims at the national level in France between 2008 and 2011 using PMSI-MCO medico-administrative databases, as well as the evolution of the principal characteristics of this population, notably with regard to in-hospital mortality. The analysis presents a map of in-hospital mortality, as well as an exploratory analysis of the territorial distribution of this mortality with regard to demographic and socioeconomic data. The aim of this analysis was to describe the spatial distribution of in-hospital mortality related to the socio-economic characteristics of the patients' places of residence.
Source of data and selection criteria Given the lack of long-term data in the national PMSI databases and the absence of accurate coding to distinguish between first-ever and recurrent stroke, this study analyses the characteristics of patients hospitalized for stroke rather than the in-hospital incidence. The algorithm used was the same as that used for other French studies conducted using the national PMSI database. All of the hospital stays for patients presenting with a diagnosis of stroke recorded in the national PMSI-MCO databases from 2008 to 2011, whatever their age, were included. The hospital stays were selected according to the principal diagnosis (PD) according to the following ICD10 codes: • I60, I61, I62. 9 for hemorrhagic stroke. • I63, I64, G46 for ischemic stroke. In our selection process, we chose to keep patients with a "transfer" admission, that is to say patients who stayed first in one establishment and then moved to a second establishment with a PD of stroke.
05) for the construction of each cluster. The cartographic results concerning the classification of geographic codes of the place of residence are shown in Fig. 5. For each variable, the legend presents the mean deviation, calculated overall for the geographic codes of the place of residence. The bars on the right of the vertical line represent a positive delta, while those on the left represent a negative delta. The wider the bar, the greater the mean deviation (positive or negative) is. The description of each cluster can be determined in a complementary manner from Fig. 5 , Tables  5  and 6. SAS 9. 3 software was used for all of the analyses. GIS (Geographic Information System) MapInfo 11. 0 was used for the cartography.
Discussion The list of diagnostic codes used to select patients corresponded to those used in other studies on stroke mortality, in France  [8] , and internationally  [9]. Different sensitivity and validation analyses have shown the robustness of the methodology  [10, 11]. However, following a validation study of PMSI data  [8] , our selection criteria differed slightly from those of Peretti et al. Our selection of hemorrhagic stroke was based on codes I60 and I61 and notably on code I62. 9. We did not use all I62 codes, given their lower sensitivity according to a validation study of PMSI data  [8]. Moreover, patients suffering from TIA were not included in our study given the heterogeneous nature of coding practices  [12]. According to the national PMSI databases, overall, the number of patients hospitalized for stroke increased in France from 2008 to 2011, despite a fall between 2010 and 2011.
These results indicate that primary vascular prevention is necessary throughout life and should start in childhood. At the same time, the characteristics of the hospital stay have changed. First, the mean length of hospital stay decreased and secondly, there was a clear fall in in-hospital mortality. According to a validation study conducted by the Technique de l'Information Hospitaliere (ATIH) and INSEE, the quality of recording in-hospital mortality in the PMSI database has improved. We thus focused a part of our analysis on this indicator of performance of the healthcare system, especially since this type of analysis is becoming more widespread with the growing use of medico-administrative data  [26] [27] [28]. The reduced in-hospital mortality observed for hospital stays overall corresponds to observations of a French study, which reported that the proportion of intra-hospital deaths  during the first hospital stay for stroke had fallen significantly by 0.
These studies showed an increase in stroke prevalence associated with a fall in mortality in high-income developed countries, like France. However, we do not have such a smallscale spatial analysis of stroke-related mortality in France. Our work therefore showed the interest of associating medical data with socio-economic data from the national census, which is available at the post-code level. Concerning in-hospital mortality, this association could be used for other diseases and in other countries, depending on the availability of databases and the scale of analysis they allow. Two major results came out of this study. The map of standardized mortality rates allowed us first of all to illustrate the territorial disparities at the national level, and notably by identifying areas of high mortality from the north-east to the south-west of the country, along the "low population density diagonal".
2 %). The results obtained with variables relative to access to the healthcare system were less satisfactory: these variables were time to reach a stroke unit or a hospital emergency unit, in minutes for each geographic code. Standardization of mortality rates on a small scale, according to the geographic code of the patient's place of residence, revealed local clusters of high mortality, notably in Brittany. This analysis of local situations, which is more detailed than analyses at the departmental level, highlighted territorial disparities, but cannot replace the results of even smaller scale analyses, at the level INSEE codes for communes, for example. We intend to continue our work using SNIIRAM data, which will allow us to break away from the use of aggregated population data to calculate incidences or comparative indices of mortality.
These variables are treated independently in the classification, which allowed us to contextualize certain high mortality rates. Despite the adjustment for age, areas marked by high mortality were also those with the oldest population. The classification showed that the demographic structure was not the only factor of the socio-territorial organization to affect mortality. Indeed, apart from the age of the population, disparities in mortality also followed the territorial distribution of socio-professional categories. It thus appears that social difficulties and problems linked to the ageing of the population are associated with higher stroke-related mortality than is the case in certain rural or peri-urban areas. The interest of the AHC is justified by the difficulty of linking the healthcare results of a large population with their socio-economic conditions as there are as yet no indicators of this type at the individual level in French medico-administrative databases.
Acknowledgements This work has been published in the frame of the LABEX  ANR-10-LABX-0034_Medalis  and received financial support from the  French government  managed by the  Agence Nationale de la Recherche  under  Programme d'investissement d'avenir. This work was also supported by the  Centre National de la Recherche Scientifique (CNRS) , the  Université de Strasbourg (Unistra)  and the  French Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche  ( Pierre Regenass fellowship ). Dr André Mann  is kindly acknowledged for his comments on the manuscript. We are grateful to  Barbara Schaeffer  and  Justine Viéville  for NMR experiments and  Patrick Wehrung  for MS analyses ( Service Commun d'Analyse, Unistra ).
acKnOWleDgMenTs The authors thank the "Ligue Contre le Cancer/Comité du Nord, " the "Fondation ARC (Association pour la Recherche sur le Cancer), " the Région Nord-Pas de Calais (Cancer Regional Program), the University of Lille and the "Centre National de la Recherche Scientifique, " the "Institut National de la Santé et de la Recherche Médicale" for their financial support. The authors are also grateful to the "SIte de Recherche Intégré sur le Cancer" (SIRIC) ONCOLille. The authors also appreciated the help of Dr. Christian Slomianny and Mrs. Elodie Richard of the CCMIC platform (BICeL Campus Lille 1). We thank Dr. Sophie Groux-Degroote (University Lille 1, UGSF), a fluent English speaker, for the final reading of our manuscript.
UDE therefore presented an interesting object of present study. In the present work, we generated tens of thousands of randomly truncated UDE constructs. Following selection of key best hits, we performed melting and gel filtration studies to evaluate the folded character of the constructs. We analyzed the secondary structural organitazion of these constructs in a comparions with full-length UDE by VUVCD. Quantitative analysis of CD data by SELCON3 program and neural network enabled us to designate new potentially domain boundaries.
The minimum at 222 nm is due to the nπ* transition of the carbonyl group of peptide, while the parallel and perpendicular excitation of the peptide ππ* transition is responsible for the other minimum at 208 nm and the positive peak at 192 nm (8,23). Additional negative band at around 170 nm and a positive shoulder at 175 nm were found specific to α-helical structures by former VUVCD measurements (20,21). Though these characteristics imply exclusive α-helix content for the intact protein, the intensity of the CD spectrum is reduced by about a factor of two as compared with purely α-helical structures, which suggests that a considerable portion of the sequence forms different secondary structures or remains unordered. Quantitative evaluation of the spectral data was performed by the SELCON3 program with the VUVCD spectra of 31 reference proteins over the wavelength region of 160-260 nm (24,25).
We performed detailed analysis of UDE deletion mutants on secondery structure content used the data of vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy (19-21). Quantitative evaluation of VUVCD data by SELCON 3 (24-27) and neural network algorithm (28) determined the number and location of α-helical segments in the fragments and total length UDE. Data confirm the mainly α-helical content for the full-length protein, which is preserved in the truncated constructs, also for the compact C-terminal end of UDE. Comparison of secondary structure partition of the N-terminal duplicated domains it is evident that the previously determined boundaries of conserved motifs do not correspond exactly to the predicted arrangement of α-helical segments. α-helical structure has a significant role in DNA binding motifs such as helix-turn-helix (29), leucine zipper/coiled-coil (30) and zinc finger motifs (31).
After washing steps with PBS-Tween buffer, the membranes were incubated in 50 ml of PBS-Tween containing 10 µl streptavidin Alexa Fluor 488 and 50 µl Alexa Fluor 532 rabbit anti-mouse IgG for 1h at 4°C. After 3X15 minutes washing with PBS-Tween buffer and 5 minutes with destilled water, the membranes were scanned with a Typhoon 9400 fluorescence scanner for hexahistidine tag and biotin acceptor peptide signal intensities respectively. Signals were quantified from digitised images using Visual Grid software and data exported to Microsoft Excel for analysis.
Thermofluor A thermofluor assay was used to monitor the thermal stability of purified UDE truncated constructs. The reaction mix contained 0,25 mg/ml or 0,5 mg/ml or1 mg/ml of purified UDE fragments, 1 μl of 40x diluted SyproOrange dye, and 25 mM Tris ⁄ HCl, 150 mM KCl, and 1 mM EDTA (pH 7. 5) in 25 μl final volume. The mix was put into a 96 well plate and analysed with a Stratagene Mx3000P real-time PCR Thermal Cycler operated by mxpro software. This system contains a heating device for accurate temperature control set at 25°C to 99 o C at a ramp rate of 0,5°C /min.
Vel: elution volume, Mapp: apparent molecular weight, Mcalc: calculated molecular weight based on column calibration. Data of thermostability analysis by Thermofluor. Tm: melting point of the given protein. (B) Decomposition of the CD spectra of UDE and its selected fragments using six secondary structure components; regular/distorted α-helix (rH/dH), regular/distorted β-strand (rS/dS), turn (T), and unordered structure (U). Upper panel: CD spectrum of UDE as measured and as fitted using the six components (24-26). Spectra of the components are also plotted with magnitudes proportional to their ratios in the full protein. Lower Panel: Difference spectra corresponding to UDE-NA2 and NG3-NA3 together with the fittings based on the spectra of the six basic components. in its nine truncated fragments as determined from the CD spectra and the amino-acid sequence using a neural network algorithm (27-28).
X-ray Crystal Structure Description To obtain the crystal data and refinement parameters of (2Z)-3-hydroxy-3-(pyridin-2-yl)-1-(thiophen-2-yl)prop-2-en-1-one, it was subjected to X-ray diffraction intensity measurement. Single crystal data and refinement parameters are given in Table  1. CCDC 1481979 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www. ccdc. cam. ac. uk/conts/retrieving. html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc. cam. ac. uk).
X-ray Crystal Structure Description To obtain the crystal data and refinement parameters of (2Z)-3-hydroxy-3-(pyridin-2-yl)-1-(thiophen-2-yl)prop-2-en-1-one, it was subjected to X-ray diffraction intensity measurement. Single crystal data and refinement parameters are given in Table  1. CCDC 1481979 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www. ccdc. cam. ac. uk/conts/retrieving. html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc. cam. ac. uk). The molecular conformation of the compound is characterized by two degree-of-freedom, which are the O2-C3-C4-C5 and O1-C1-C8-N1 torsion angles, denoted hereafter as τ1 and τ2, respectively (Figure  1 ). The molecular conformation of the compound is characterized by two degree-of-freedom, which are the O2-C3-C4-C5 and O1-C1-C8-N1 torsion angles, denoted hereafter as τ1 and τ2, respectively (Figure  1 ).
X-ray Diffraction Analysis Xcalibur, Sapphire3, Gemini CCD plate diffractometer was used to perform X-ray analysis on the parallelepiped colourless sample. MoKα radiation (λ = 0. 71073 Å) and ω scan were employed in the data collection. Data collection, cell refinement and data reduction were carried out with CrysAlis 171 Oxford Diffraction, 2009 software. In this analysis, all the crystallographic data were collected at room temperature. The SHELXS-97 program  [40]  was used to solve the structure with direct methods. Refinements of the structure on F 2 were done using full-matrix least-squares techniques with SHELXL-2013 software  [40]. Anisotropic refinements were applied on all non-hydrogen atoms. All C-bound hydrogen atoms were inserted at their calculated positions and then refined using a riding model.
X-ray diffraction data was collected on an Oxford XCalibur CCD diffractometer (Oxford Diffraction, Abingdon, Oxfordshire, UK) using graphite-monochromated Cu Kα radiation (λ = 0. 7107 Å) at a temperature 298 K. The structure was solved by direct methods using SIR-92 (Semi-Invariants Representation)  [40]  and refined by the full-matrix method (SHELXL-2016/4) [41]. The reactions were monitored by thin layer chromatography (TLC) on aluminium plates coated with silicagel 60F254 (Merck KGaA, Darmstadt, Germany). UV radiation and iodine were used as the visualizing agents. Column chromatography was performed on silica gel (100-200 mesh, Merck KGaA).
X-ray diffraction data was collected on an Oxford XCalibur CCD diffractometer (Oxford Diffraction, Abingdon, Oxfordshire, UK) using graphite-monochromated Cu Kα radiation (λ = 0. 7107 Å) at a temperature 298 K. The structure was solved by direct methods using SIR-92 (Semi-Invariants Representation)  [40]  and refined by the full-matrix method (SHELXL-2016/4)  [41]. The reactions were monitored by thin layer chromatography (TLC) on aluminium plates coated with silica-gel 60F 254 (Merck KGaA, Darmstadt, Germany). UV radiation and iodine were used as the visualizing agents. Column chromatography was performed on silica gel (100-200 mesh, Merck KGaA).
Acknowledgments: The authors thank the financial support provided by the  University of Delhi  to  Virinder S. Parmar ,  Ashok K. Prasad ,  Brajendra K. Singh ,  Ramesh C. Kuhad  and  Rajendra K. Saxena  under the  DU-DST Purse Grant Scheme. Shashwat Malhotra  and  Divya Mathur  thank the  Council of Scientific and Industrial Research (CSIR, New Delhi, India)  and the  Science & Engineering Research Board (SERB, New Delhi, India ; project's reference no. PDF/2015/000604 ) for the grant of Research Awards.
Acknowledgements The authors thank  Dr. Josef Zapp  ( Saarland University ) for recording NMR spectra and  Michael Hoffmann  ( Helmholtz Institute for Pharmaceutical Research Saarland, HIPS ) for HRMS measurements. We are grateful to the  Helmholtz Association  (grant no. VH-NG-934 ) and the  Deutsche Forschungsgemeinschaft  (grant no. Ti756/2-1 ) for financial support.
Equipment. The analyses were performed in an air conditioned room using a UFLC system (Prominence, Shimadzu, Tokyo, Japan), which consisted of the CBM-20A controller, the DGU-20A5R degassing unit, the LC-20AD pump, the SIL-20AC thermostated autosampler, and the CTO-20AC column oven. The two last pieces of equipment are able to regulate the temperature in a large range going from 4 ∘ C to 40 ∘ C and 10 ∘ C below room temperature to 85 ∘ C, respectively. Finally, the SPD-M20A diode array detector and the LabSolutions software (Shimadzu) were used to control the system and acquire and process the data. The separation of PAHs was performed by means of the 250 mm × 4. 6 mm Kinetex-C 18 column packed with recent 5 m core-shell particles (Phenomenex, Le Pecq, France) and two other 250 mm × 4. 6 mm columns packed with 5 m fully porous particles, Supelcosil LC-PAH (Supelco, Sigma-Aldrich) and Spherisorb PAH (Alltech, Waters, Guyancourt, France).
The structural specificity of the SHG signal to fibrillar collagen allows collecting non-invasively well-contrasted 3D images of the fiber organization in skin-based materials. This technique clearly evidences structural differences linked to parchment orientation, manufacturing or alteration. Our data show that the parchment alteration is associated with a decrease or loss of the SHG signal and a joint increase in the 2PEF signal. The structural organization is also strongly affected with the collagen fibers being disassembled and the formation of an amorphous and compact material providing a strong homogenous fluorescence signal. The origin of these modifications in the NLO images was identified using IR nanoscopy. Comparison of pure gelatin and collagen reference samples prepared from the same collagen batch showed that the gelatin exhibits a new band at 1738 cm -1.
Although the laser spot was large, the sharp AFM tip served as a near-field detector by locally detecting the small thermal expansion resulting from light absorption in the sample thus conferring high lateral resolution to the measurements. The resulting spatial resolution for IR mapping has been shown to be between 50 and 100 nm depending on the response of the absorbing object  23. All IR mappings and spectra were normalized to the incident power. IR mappings were acquired at a scan rate of 0. 2 Hz and averaged on 8 pulses. Local spectra were collected using a 2 cm -1 step scan and averaging each data point on 256 pulses. Furthermore, three spectra acquired at the same location were averaged. The spectral resolution was estimated as 8 cm -1 (OPO pulse width). Topographic images were acquired in contact mode with cantilevers of 0.
Acknowledgements The authors thank  Carole Aimé ,  Gervaise Mosser ,  Thibaud Coradin ,  Bertrand Lavedrine  and  Claire Teulon  for critical scientific discussion,  David Peggie  for critical reading of the manuscript and  Nadège Duqueyroix  and  Marjolaine Mourot  for providing access to the maritime map. This work was partly supported by  Agence Nationale de la Recherche  (contracts  ANR-10-INBS-04   France BioImaging  and  ANR-11-EQPX-0029 Morphoscope2 ).
Acknowledgements The  Swiss National Science Foundation  (Project  200020_152782 ), the  State Secretariat for Education, Research and Innovation (SBFI Nr. C14. 0096 ) and the  Agence National de La Recherche  (Project  ANR Blanc 13 BS07-0010-01  " UZFul-Chem ") are gratefully acknowledged for financial support. The  COST Action CM1201 has generously supported a shortterm scientific mission of Christian Simon Gloor.
Optical Setup The AMULSE laser is a GaSb-based DFB semiconductor diode in a butterfly package (nanoplus GmbH, Gerbrunn, Germany). The optical power at the output of the single mode fiber is approximately 1 mW at a current of 95 mA. A fiber-based collimator in a pigtail style (LPC-01-2004-7/125-S-1-2. 61GR-40-3A-3-1, Oz Optics, Carp, ON K0A 1L0, Canada) with a GRIN lens (2. 61-mm focal length) is connected to the output of the laser optical fiber in order to collimate the light (1-mm beam diameter). This light is directed to a home-made open-path multipass cell configured as Herriott type. The focal length of the used mirrors (2-inche diameter) is equal to 150 mm. Small (2-Watt) heaters are attached on the edge of each mirror in order to prevent condensation during balloon descent due to the low temperature of the high troposphere.
This software is also used to turn on and control the AMULSE. This system allows variation of the pressure between 0 and 1200 mbar (with fine tuning function) for a temperature range between -25 • C and +50 • C. The standard deviation of the pressure and the temperature measurement (0. 01 mbar and 0. 01 • C respectively) were held at 1 Hz during 1. 5 h. Sensors 2016, 16, 1609 7 of 14 software system. Temperature measurements are based on four PT-100 class 1/10 temperature sensors connected to a 24-bit thermometer. A thermal insulation layer covers the whole enclosure to avoid heat-flux exchange with the outside ambient atmosphere. Five electronic valves were connected to this enclosure dedicated for a pumping system (valve number 1 on the Figure  4  below) and different calibrated gas cylinders provided by the by the "Laboratoire des Sciences du Climat et de l'Environnement LSCE" (connected separately to the valves 2 to 5 (see Figure  4 )).