dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We thank members of the LS group  Dr. S. Tardy  and  O. Patthey ; member of the RA group  E. Cerro  and Creoptix (www. creoptix. com)for technical assistance;  Prof. P. Moreau  ( University of Clermont Auvergne, FR ) for providing compounds;  Prof. R. Singh  ( Iowa State University, US ) for providing SMN2 minigenes;  Prof M. Zhang  ( Tufts University, US ) for providing the SMN2 minigene used in Drosophila and  Dr. E. C. O'Connor  ( University of Geneva, CH ) for input on the manuscript. This work was supported by the  University of Geneva  and grants from the  Swiss National Science Foundation (SNSF)  (Sinergia,  CRSI33-130016 ) to L. S. ;  Protein Kinase Research (Pro-Kinase ,  LSHB-CT-2004-503467 ) to L. S. and P. G. ; the  European Molecular Biology Organization (EMBO ,  ALTF 253-2012 ) and the  Schmidheiny Foundation  to A.
Code availability. No computer codes were developed for this study. Input scripts and software alterations used for NMR structure calculation, molecular dynamics or RNA-seq analysis are described in Supplementary Methods and are available from the corresponding authors upon request. Data availability. The NMR structure of TSL2 was deposited in the PDB (accession number 5N5C) and the BMRB (accession number 34100). Our RNA-seq data have been deposited in the Gene Expression Omnibus repository (accession code GSE94111). Additional data that support the findings of this study are available from the corresponding authors upon reasonable request.
, 2007). Numerous reports on SPAST rearrangements have been published since (see Human Gene Mutation Database website: http://www. hgmd. cf. ac. uk/ac/index. php), and the association of large deletions with reduced age at onset was again observed  (Chelban et al. , 2017). The question of how different mutational classes, which all likely act via a haploinsufficiency mechanism, could have differing clinical outcomes has not been resolved. In this study we confirm that exonic deletion of SPAST is associated with a significant reduction in age at onset of HSP, but show that this reduction is accounted for by a subset of patients in whom the deletion extends into the contiguous gene DPY30. The protein encoded by DPY30 has been implicated in endosome-to-Golgi traffic  (Xu et al. , 2009). We therefore investigated whether the DPY30 protein regulates similar endosomal trafficking steps to spastin.
Immunofluorescence microscopy Cells were fixed at room temperature in 3. 8% (v/v) formaldehyde in phosphate-buffered saline (PBS) and permeabilized in PBS containing 0. 1% (v/v) saponin (Sigma) or 0. 1% (v/v) Triton TM X-100 (Sigma). Coverslips were labelled with primary and secondary antibodies as previously described  (Connell et al. , 2009). Slides were analysed with a Zeiss LSM880 confocal microscope (100 Â NA 1. 40 oil immersion objective, 37 C), or Zeiss AxioImager Z2 Motorized Upright Microscope (63 Â NA 1. 40 oil immersion objective, room temperature, Zeiss Axiocam 506). Co-localization of immunofluorescence signals was quantified using Volocity Image Analysis Software. Images were subsequently processed using Adobe Photoshop and Illustrator and ZEN analysis software.
Cation independent M6PR trafficking assay Following a 48-h siRNA knock-down of the relevant protein, HeLa cells stably expressing GFP-GOLPH3 and CD8-ciM6PR tail were subject to ciM6PR trafficking assays as described in  Seaman (2007). Briefly, following incubation in medium containing anti-CD8 at 4 C, cells were incubated for 30 min at 37 C before fixation and processing for immunofluorescence microscopy with a Zeiss LSM880 confocal microscope as described above. Co-localization of appropriate proteins was quantified using Volocity Image Analysis Software.
The DPY30 gene deletions identified were contiguous with SPAST deletions, and almost certainly arose as part of the same mutational event in each family; 70% of SPAST copy number variants are caused by an Alu-repeat based mechanism, with the Alu-rich genomic architecture of SPAST (40% of the gene's sequence are Alu elements) making it prone to these events  (Boone et al. , 2014). Of note, DPY30 has an even higher fraction of Alu-derived sequence (51%). However, in the general population copy number variants involving DPY30 appear to be rare, with deletions having a frequency of 1 and duplications a frequency of 5 in 32 850 in non-Finnish European alleles (ExAC database)  (Lek et al. , 2016). In addition, missense variants and variants predicted to result in possible loss of function via splicing effects are also individually and collectively rare in DPY30; the most common putative splice site mutation listed in ExAC has an allele frequency of 50.
0003 (ExAC database)  (Lek et al. , 2016). For this reason, we consider it unlikely that polymorphisms in DPY30 will make a substantial contribution to influencing age at onset in patients with spastin-HSP not caused by exon deletions. In addition, in view of the relatively small effect of DPY30 depletion (which is almost complete by immunoblotting) versus spastin depletion on endosomal tubulation and M6PR traffic, we consider it unlikely that haploinsufficiency of DPY30 could itself cause HSP. Knockout of Dpy30 in mice causes embryonic lethality, and so it is again unlikely that recessive DPY30 mutations cause HSP  (Bertero et al. , 2015). Variability in age at onset of neurogenetic diseases is often ascribed to effects of genetic background, i. e. the effects a gene or genes that modify the function of the disease gene.
T. R. was supported by research grant  DFG GRK2162/1  of the  Deutsche Forschungsgemeinschaft. The study was also supported by the  European Union  within the 7th  European Community Framework Program for Research and Technological Development through funding for the NEUROMICS network  ( F5-2012-305121  to L. S. and A. D. ), the  E-Rare Network NEUROLIPID  ( 01GM 1408B  to R. S. and  ANR-13-RARE-0003-02  to G. S. ), and a  Marie Curie International Outgoing Fellowship (grant   PIOF-GA-2012-326681  to R. S. and L. S. ). This work was further supported by the  US National Institutes of Health (NIH)  (grant  5R01NS072248  to R. S. ), the  German HSP-Selbsthilfegruppe e. V. (grant to R. S. and L. S. ), and grants to C. B. : Project Grant from  Tom Wahlig Stiftung  (project  20 ), grant from the  Stiftung fu ¨r Pathobiochemie und Molekulare Diagnostik.
51, NIH, USA, https://imagej. nih. gov/ij/), developed at the National Institutes of Health, or for the most part using the intrinsic software (Image Lab 5. 0, Bio-Rad, Hertfordshire, UK) of the Chemi Doc MP imager. Image Lab 5. 0 software was set at auto-exposure to generate a signal across the blot that was both linear and that did not reach signal saturation. Western blot quantitation was normalized to either GAPDH values and/or total lane protein. The mean signal density for quantitation of control samples was set at 100% of the protein signal.
Statistics For quantitation of protein bands on Western blots, or gene expression changes for qRT-PCR, statistical comparison between data means was performed with either an ANOVA with Dunnett's multiple comparison test or a Student's t-test using GraphPad Prism software (version 7. 03, GraphPad Software Inc. , San Diego, CA, USA), with results expressed graphically as means ± SEMs. Differences between protein expression and patient age was determined using a non-parametric ANOVA (Kruskal-Wallis test). A Spearman rank-order correlation coefficient was used to assess the relationship between age or sex and protein expression. Statistical significance was set at a p value of <0. 05.
We are grateful to the following funding sources that supported this research: W. L. L. and L. L. N. were supported by University of Nottingham International Travelling Fellowships. A. M. E. was a recipient of a postdoctoral fellowship from the Basque Government. L. J. was supported by a Wellcome Trust Biomedical Summer Scholarship. A. -C. R. was supported by an European Erasmus award to work with W. G. C. L. F. C. was funded by Spanish MINECO (SAF2013-48586-R) and the Basque Government (IT616/13).
Funding: We are grateful to the following funding sources that supported this research: W. L. L. and L. L. N. were supported by University of Nottingham International Travelling Fellowships. A. M. E. was a recipient of a postdoctoral fellowship from the Basque Government. L. J. was supported by a Wellcome Trust Biomedical Summer Scholarship. A. -C. R. was supported by an European Erasmus award to work with W. G. C. L. F. C. was funded by Spanish MINECO (SAF2013-48586-R) and the Basque Government (IT616/13).
Microwave AFM Measurements The microwave measurement protocol established to monitor the impact of each element of the nanochips development is illustrated in Figure  4. Microwave spectrum acquisition is obtained by point-to-point recording of data from each area of interest. Each sample analysis is preceded and followed by an analysis of the SiO 2 reference substrate. Having a homogeneous structure, in thickness and component, allows us to check that no drift appeared during the measurement phase on the samples or to take it into account if necessary. Thus, to ensure the reproducibility of the measurements, nine measuring points are made on each specific area as described in Figure  4. Twenty-resonance frequency spectra are implemented to determine which one will obtain the best sensitivity and stability.
5. Microwave AFM Measurements The microwave measurement protocol established to monitor the impact of each element of the nanochips development is illustrated in Figure  4. Microwave spectrum acquisition is obtained by point-to-point recording of data from each area of interest. Each sample analysis is preceded and followed by an analysis of the SiO2 reference substrate. Having a homogeneous structure, in thickness and component, allows us to check that no drift appeared during the measurement phase on the samples or to take it into account if necessary. Thus, to ensure the reproducibility of the measurements, nine measuring points are made on each specific area as described in Figure  4. Twenty-resonance frequency spectra are implemented to determine which one will obtain the best sensitivity and stability.
Size Distribution of Gold Nanoparticles on Different Substrates The size distribution of annealed AuNPs on non-conductive and conductive substrates are shown in Figure  2C ,D and analyzed using the Public Domain ImageJ software developed by the National Institutes of Health. The results are described in Figure  5A, B. It should be noted that on glass substrates, a wide AuNPs size distribution has been observed in a range of 5 to 30 nm, with a majority of NPs of 10 nm to 30 nm range (Figure  5A ), while the size distribution of AuNPs deposited on ITO substrate is narrow in a range from 30 to 40 nm (Figure  5B ). It shows that size distribution of 10 nm AuNPs (23. 4%) on glass substrate is greater than that of.
Size Distribution of Gold Nanoparticles on Different Substrates The size distribution of annealed AuNPs on non-conductive and conductive substrates are shown in Figure  2C ,D and analyzed using the Public Domain ImageJ software developed by the National Institutes of Health. The results are described in Figure  5A, B. It should be noted that on glass substrates, a wide AuNPs size distribution has been observed in a range of 5 to 30 nm, with a majority of NPs of 10 nm to 30 nm range (Figure  5A ), while the size distribution of AuNPs deposited on ITO substrate is narrow in a range from 30 to 40 nm (Figure  5B ). It shows that size distribution of 10 nm AuNPs (23. 4%) on glass substrate is greater than that of AuNPs on ITO substrate (3. 2%). Moreover, the percentage of size distribution on glass substrate is 23.
Funding: This work has been supported by the  EIPHI Graduate School  (contract " ANR-17-EURE-0002 "), and the  French National Research Agency :  ANR-15-IDEX-03 PIA2/iSite-BFC ,  ANR-15-CE09-0002-02  grants, and  FEFER BG0005900-PARI 2016-9201AAO050S01714 Region  of  Bourgogne Franche-Comte  grants that made possible the fruitful collaboration between  ICB  and  ICD/L2N.
Statistical analysis All statistical analyses were performed using SPSS 22. 0 (SPSS, IBM). Two-tailed Student's t-test was used in transcription level analysis. One-way analysis of variance was used to investigate the difference in velocities with magnetic field increase. Size, shape factor, and number of magnetosomes in one cell were analyzed using Mann-Whitney U-test. Each experiment was repeated thrice, and all data are ±. CC-BY-NC 4. 0 International license a certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under The copyright holder for this preprint (which was not this version posted March 19, 2018. ; https://doi. org/10. 1101/284786 doi: bioRxiv preprint expressed as mean ± SD. Level of significance of the differences observed between the control and test samples were expressed as one, two, or three stars, for *P<0.
Acknowledgements This work was supported by the  National Youth Foundation of China  (Grant  NO. 31300689 ), the  National Key Research and Development Program of China  (Grant NO. 2017YFC0108501 ), and the Research Project Funded by the  Institute of Electrical Engineering, Chinese Academy of Sciences  (Grant  NO. Y650141CSA ). We greatly appreciate  Xu Tang  for TEM observation and  Junwei Du  for magnetic field measurement. We thank  Xiaoxiao Zhu ,  Pingping Wang  and  Changyou Chen  with the help of useful discussion and suggestions. We are grateful to  Ying Li  and  Xu Wang  for the plasmids of pUX19 and pUCGm. We also thank the anonymous reviewers and the editor for their valuable comments.
(D) Estimation of relative rate constants of the folding reactions. Ten independent datasets for Tox62 folding were processed independently using Kintecus. Averaged percent R squared values are 99. 4 (N), 98. 4 (C), and 98. 2 (D) when 6 principal reactions were involved in the fitting. The application of the criteria described in the methods section identified reactions other than C to N as indispensable principal reactions because they were essential to maintaining percent R-squared values higher than 98. 0, as indexed in the Kintecus fitting. The reactions D to U2 and C to D were eliminated based on the following results. By including these reactions, the rate constants of the 5 principal reactions fluctuated to increase the averaged standard deviations to 1. 184 times for D to U2 and 1.
Acknowledgments Authors are grateful to  Dr. Pascal Drevet  for his generous offer of some of the mutants and folding data used in this study. We are also grateful to  Dr. Carole Fruchart-Gaillard , who provided us with the data for the nAChR binding assay. Most of the experiments in this study were performed when A. S. visited  CEA Saclay, France  for a year, with precious support from the staff there. The manuscript was prepared with the help of various critical advice from  Dr. Andrzej Galat. A. S. is also grateful to  Prof. Nobuo Tamiya  at  Tohoku University  and  Prof. Barbara W. Low  at  Columbia University  for providing him the most valuable and fascinating opportunity to determine the crystal structure of erabutoxin b from an electron density map.
Background: Dental aberrations have been mentioned in relation to non-surgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP). However, a systematic review of dental characteristics have not been performed. The present systematic review describes the dental findings in patients with Ns-HypoPT and PHP. Methods: Studies on Ns-HypoPT and PHP reporting dental features were eligible. A systematic literature search was conducted using four bibliographic databases (Web of Science, Scopus, Pubmed, and Embase) and was limited to studies written in English. Reviews, meta-analyses and letters were excluded. Both the research and reporting of results were based on PRISMA (preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Results: Of 88 studies included, nine were cross-sectional, one was a prospective cohort study, 26 were case series, and 52 were case reports.
MATERIALS AND METHODS The systematic review was based on PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses;  Moher et al. , 2009)  and contained the PICO elements  (Participants, intervention, comparison, outcome, and study design). In collaboration with an experienced research librarian (JLS), the first author conducted the search for relevant publications in four databases, PubMed, Web of Science, Scopus, and Embase.
Quality Assessment We aimed to assess the publications according to Newcastle-Ottawa Quality Assessment Scale  (Hospital, 2014)  (NOS), Centre for Evidence-Based Medicine (CEBM)  (Medicin, 2017) , and Strength of Recommendation Taxonomy (SORT)  (Ebell et al. , 2004). Results were reported in five tables, two concerning Ns-HypoPT (Tables  2, 3 ), and another two related to PHP (Tables  4, 5 ) and one related to quality assessment (Table  6 ). Data extraction was carried out using a tailored form that had been pilot-tested. The first author carried out the data extraction. During the quality assessment, some of the findings were challenging, such as Fraser and co-workers publishing the same study in 1979  (Nikiforuk and Fraser, 1979) , and in1981  (Nikiforuk and Fraser, 1981)  and in 1982  (Fraser and Nikiforuk, 1982).
ACKNOWLEDGMENTS We acknowledge the research librarian  Janne Lytoft Simonsen  (JLS) at The  Royal Danish Library, Aarhus University, Aarhus, Denmark  for her kind help with the literature search. We also acknowledge  Virginie Laugel-Haushalter  at  Laboratoire de Génétique Médicale ,  INSERM UMRS_1112 ,  Institut de Génétique Médicale d'Alsace, FMTS, Université de Strasbourg, Strasbourg, France , who helped to gather information about the Gene Expression in tooth formation in mouse.
ALDH activity determination ALDH activity was determined using an ALDEFLUOR assay kit (Stem Cell Technologies) according to the manufacturer's protocol. Briefly, 10 6 cells were stained with bodipy-aminoacetaldehyde (BAAA) and incubated for 30 minutes at 37°C. A specific inhibitor of ALDH1, diethylamino-benzaldehyde (DEAB), was used to control background fluorescence. The stained cells were analyzed using the FACS Aria II (BD Biosciences). The data were analyzed using the Flow Jo software program.
Human inflammatory cytokine assay The amount of human proinflammatory cytokines (IL1β, tumor necrosis factor alpha, IL12-p70, IL6, IL8, and IL10) present in cell supernatants from CD44 + CD24 Neg and CD44 + CD24 Pos cells was determined using a human inflammatory cytokine kit (BD™ Cytometric Bead Array following the manufacturer's instructions. A FACScan flow cytometer (BD) was used for the data acquisition and the FCAP Array Software with BD FACSArray Bioanalyzer-BD Biosciences for the analysis.
Statistical analysis Comparisons for gene expression levels, cell growth, sphere formation, adhesion, migration, and invasion capacities were analyzed with Graph Pad Prims v5 software using nonparametric two-tailed t-test (Mann-Whitney) and two-way ANOVA with Bonferroni post-test. Significant P-value was considered as <0. 05, <0. 01, or <0. 001 as indicated in the figures.
As these cells were derived from a parental epithelial cell line that underwent first an EMT and then an MET,  12  we proceeded to evaluate the expression of EMT-associated protein markers, as well as that of microRNA members of the miR-200 family. Data from Western blot (Figure  2C ) and qRT-PCR (Figure  2D ) analyses indicate that the expression of both epithelial (E-cadherin and Kr19) and mesenchymal markers (Vimentin, Zeb1, Zeb2, and Twist) are slightly more robust in the CD44 + CD24 Pos cells, as compared to CD44 + CD24 Neg , as it is the relative expression of miR-200a and miR-429 (Figure  2E ). We next evaluated functional properties associated with the EMT, namely migration, invasion, and adhesion  capacities. CD44 + CD24 Pos cells were more motile, with cells migrating more than CD44 + CD24 Neg cells as assessed by "wound healing" assay (spontaneous migration) (Figure  3A ) or by directed migration toward FBS in the transwell migration assay (Figure  3B ).
Acknowledgments We would like to thank  Doctor Jinneth Acosta ,  Pathology Group ,  Faculty of Medicine ,  Universidad Nacional de Colombia , for processing and analyses of tumors. This work was supported by funding from the  Patrimonio Autónomo Fondo Nacional de Financiamiento para la Ciencia , la  Tecnología y la Innovación ,  Francisco José de Caldas , Colciencias (Contract No  RC-692-2013 ),  División de Investigación y Extensión, Bogotá , and  Faculty of Medicine ,  Universidad Nacional de Colombia , to JPV. Work in the laboratory of ALV was supported by  INCa  and  ARC  grants and the  Labellisation Program of the "Ligue contre le Cancer ".
Results represent the mean Ϯ S. D. (n ϭ 5). *, p Ͻ 0. 05; NS, not significant (Mann-Whitney-U test). B, S. aureus long-term survival in infected macrophages. RAW 264. 7 macrophages (5 ϫ 10 5 cells/ml) were infected with a m. o. i. of 20 of S. aureus strains Newman (black bar), Newman ⌬ptpA (white bar), and Newman ⌬ptpA::ptpA_Flag (gray bar), respectively, and co-incubated for 2 h at 37 °C, followed by a gentamicin/lysostaphin treatment to eliminate external bacteria. Macrophages were lysed with Triton X-100 (0. 1%) at 22 h pGt, and bacteria enumerated by plate counting. Survival rates are given in relationship to the intracellular bacterial cell numbers seen immediately after gentamicin treatment. Data represent the mean Ϯ S. D. (n ϭ 5). *, p Ͻ 0. 05; NS, not significant (Mann-Whitney-U test).
05; NS, not significant (Mann-Whitney-U test). B, S. aureus long-term survival in infected macrophages. RAW 264. 7 macrophages (5 ϫ 10 5 cells/ml) were infected with a m. o. i. of 20 of S. aureus strains Newman (black bar), Newman ⌬ptpA (white bar), and Newman ⌬ptpA::ptpA_Flag (gray bar), respectively, and co-incubated for 2 h at 37 °C, followed by a gentamicin/lysostaphin treatment to eliminate external bacteria. Macrophages were lysed with Triton X-100 (0. 1%) at 22 h pGt, and bacteria enumerated by plate counting. Survival rates are given in relationship to the intracellular bacterial cell numbers seen immediately after gentamicin treatment. Data represent the mean Ϯ S. D. (n ϭ 5). *, p Ͻ 0. 05; NS, not significant (Mann-Whitney-U test). C, in vitro growth kinetics of the S. aureus Newman/⌬ptpA/⌬ptpA::ptpA_Flag strain triplet.
*, p Ͻ 0. 05; NS, not significant (Mann-Whitney-U test). B, S. aureus long-term survival in infected macrophages. RAW 264. 7 macrophages (5 ϫ 10 5 cells/ml) were infected with a m. o. i. of 20 of S. aureus strains Newman (black bar), Newman ⌬ptpA (white bar), and Newman ⌬ptpA::ptpA_Flag (gray bar), respectively, and co-incubated for 2 h at 37 °C, followed by a gentamicin/lysostaphin treatment to eliminate external bacteria. Macrophages were lysed with Triton X-100 (0. 1%) at 22 h pGt, and bacteria enumerated by plate counting. Survival rates are given in relationship to the intracellular bacterial cell numbers seen immediately after gentamicin treatment. Data represent the mean Ϯ S. D. (n ϭ 5). *, p Ͻ 0. 05; NS, not significant (Mann-Whitney-U test). C, in vitro growth kinetics of the S. aureus Newman/⌬ptpA/⌬ptpA::ptpA_Flag strain triplet.