dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We thank the  Phelan-McDermid Syndrome International Registry  from the  Phelan-McDermid Syndrome Foundation  for the comparison data on SHANK3 mutations. AK receives research support from  AMO Pharma  and consults to  Ovid Therapeutics ,  Coronis Neurosciences , LabCorp, sema4, and  Takeda. EBK has received funding from  Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Yamo ,  Acadia ,  Ionis ,  Ultragenyx , and  Lumos Pharmaceuticals  to consult on trial design or development strategies and/or conduct clinical studies in fragile X syndrome or other neurologic, neurodevelopmental, or neurodegenerative disorders; from  Vtesse/Sucampo/Mallinckrodt Pharmaceuticals  to conduct clinical trials in Niemann-Pick disease type C; and from  Asuragen Inc.
01% in PBS-NDS 3% for 30 minutes at room temperature before being incubated with the following primary antibodies (diluted in 1:1000): β3-tubulin (ab78078, Abcam) plus TFEB (Thermo Fisher Scientific, PA1-31552) overnight at 4°C. Cells were then washed 3 times with PBS 1× for 5 minutes each time before an incubation with donkey Alexa-conjugated antibodies (1:400, Invitrogen) in PBS. Cells were finally stained with DAPI solution (Invitrogen) at 10 μM for 8 minutes before long washes. Coverslips were mounted onto slides using mounting solution (Dako), and image acquisitions were made on a wide-field Zeiss Imager M2 and a CCD Camera Hamamatsu C10600 using Explora Nova MorphoStrider software. The dendritic length was measured using a segmentation analysis with the simple neurite tracer plugin of ImageJ (NIH).
mRNA extraction and qPCR Nigral samples were homogenized in Tri-reagent (Euromedex), and RNA was isolated using a standard chloroform/isopropanol protocol  (62). RNA was processed and analyzed following an adaptation of published methods  (63). cDNA was synthesized from 2 μg of total RNA using RevertAid Premium Reverse Transcriptase and primed with oligo-dT primers and random primers (Fermentas). qPCR was performed using a LightCycler 480 Real-Time PCR System (Roche Diagnostics). qPCR reactions were done in duplicate for each sample, using transcript-specific primers, cDNA (4 ng), and LightCycler 480 SYBR Green Master (Roche Diagnotstics) in a final volume of 10 μl. The PCR data were exported and analyzed in an informatics tool (Gene Expression Analysis Software Environment) developed at the NeuroCentre Magendie.
Sections were scanned in an Epson expression 10000XL high-resolution scanner, and images were used in ImageJ open source software to compare the gray level in the putamen. TH-positive SNpc cells were counted by stereology, blind with regard to the experimental condition using a Leica DM6000B motorized microscope coupled with the Mercator software (Explora Nova). The SN was delineated for each slide, and probes for stereological counting were applied to the map obtained. Each TH-positive cell with its nucleus included in the probe was counted. The optical fractionator method was finally used to estimate the total number of TH-positive cells in the SNpc of each mouse hemisphere. In addition, we measured the Nissl cell count and the surface of TH occupied in SN to fully characterize the pattern of dopaminergic cell loss in the SN.
The surface is an additional quantification method that we use in tissue sections. For these analyses, a specific staining process was used to keep all tissues together in the same solution during the staining process, counterstained with 0. 1% cresyl violet solution. Then, high-resolution whole color slide images were first acquired with the 3D Histech Panoramic Scanner at the 20× magnification, with 5 layers in extended mode. Each image was opened in the off-line MERCATOR PRO 7. 12. 3 software (Explora Nova), and the mapping of all regions of interest was made. Brightness and contrast rules were applied to the RGB pictures to optimize details without any saturation of the image. The color thresholding tool was then used to select the threshold corresponding to the brown color revealed by the DAB staining.
Sections were then mounted on gelatinized slides, dehydrated, counter-stained if necessary, and cover-slipped until further analysis. LB509-positive dots in SN were counted by stereology, blind with regard to the experimental condition using a Leica DM6000B motorized microscope coupled with the Mercator software (Explora Nova). The SN was delineated for each slide, and probes for stereological counting were applied to the map obtained (size of probes was 60 × 80 μm) and transform as object after counting. The optical fractionator method was finally used to estimate the total number of LB509-positive dots per μm² in the SN of each mouse. LB509 immunostaining-positive surface in the striatum and phosphorylated α-syn immunostaining-positive surface quantification in the SN and the striatum were performed as previously  (27).
Statistics Statistical analyses were performed with GraphPad Prism 6. 0 (GraphPad Software Inc. ). For rat experiments, comparisons among means were performed by using 1-way ANOVA followed, if appropriate, by a pairwise comparison between means by Tukey post hoc analysis. For in vivo mice experiments, comparisons among means were performed by using 2-way ANOVA followed, if appropriate, by a pairwise comparison between means by Tukey post hoc analysis. For in vitro experiments, comparisons among means were performed by using nonparametric 2-tailed t test or 1-way ANOVA followed, if appropriate, by a pairwise comparison between means by Tukey post hoc analysis. All values are expressed as the mean ± SEM. Each dot in the scatter plot represents 1 individual. In all analyses, statistical significance was set at P < 0.
Acknowledgments The authors thank  Nathalie Biendon  and  Leslie-Ann Largitte  for her technical assistance. This work was supported by  Fondation de France  Grant number  00066525  (BD). The help of the  Bordeaux Imaging Center -part of the national infrastructure France BioImaging , granted by  ANR-10INBS-04-0  -is acknowledged. Animal experiments were performed at the  Animal Facilities of the University of Bordeaux , supported by the  Région Nouvelle-Aquitaine. We also thank  Thierry Leste-Lasserre  and the genomic platform of  Magendie Institute  for mRNA extraction and qPCR analysis. The samples were obtained from the  Brain Bank GIE Neu-roCEB  (BRIF number  0033-00011 ), funded by  France Alzheimer, France Parkinson ,  ARSEP , and  Connaître les Syndromes Cérébelleux , to which we express our gratitude.
MLA is a recipient of a  MSER fellowship (France). MB was supported by grants from  Ministère de l'Enseignement Supérieur et de la Recherche fellowship  and the  France Parkinson Foundation. The  LABEX Brain , the  University of Bordeaux , and the  Centre National de la Recherche Scientifique  provided infrastructural support. Address correspondence to:  Benjamin Dehay ,  CNRS UMR 5293 ,  Institute of Neurodegenerative Diseases, University of Bordeaux, Centre Broca Nouvelle-Aquitaine ,  146  rue  Léo Saignat ,  33076  Bordeaux, France. Phone:  33. 0. 5. 33. 51. 47. 95 ;Email: benjamin. dehay@u-bordeaux. fr. MB's present address is:  Albert Einstein College of Medicine. Department of Developmental and Molecular Biology, Bronx, New York 10461, USA.
The sections were mounted on Pioloformcoated copper grids, stained 30 min in 2% uranyl acetate and 4 min in Reynolds' lead citrate  [78]  and examined at 100 kV using a JEOL JEM-1400 Plus transmission electron microscope. Micrographs were recorded with a JEOL Matataki CMOS camera using the TEM Centre for JEM1400 Plus software.
Identification of opsins The protein sequence of Drosophila Rh1 was used as a query to search the Parhyale embryonic and head transcriptomes and the Parhyale genome by BLAST  [37, 47, 48]. The best matches were confirmed to be opsins based on BLAST searches on the NCBI Gen-Bank database and their predicted transmembrane structure (performed on PRALINE  [79] ). The PhOpsin1 and PhOpsin2 sequences thus identified were deposited in the GenBank/EMBL nucleotide sequence database (accession numbers MK541893 and MK541894, respectively). The protein sequences of PhOpsin1 and PhOpsin2 were aligned with a set of 57 r-opsins from arthropods (and additional sequences from outgroups) which had been used previously to reconstruct the pancrustacean opsin phylogeny  [49]  (see Additional file 1 for complete list of sequence accession numbers).
Most of the opsins in that dataset have known spectral sensitivities, helping to characterise the spectral properties of different opsin subfamilies. The protein sequences were aligned using the online tool MAFFT  [80]  using default parameters (scoring matrix BLOSUM62, gap opening penalty 1. 53, strategy L-INS-i). The alignment was trimmed with TRIMAL  [81]  and AliView  [82]  to remove positions with multiple gaps (threshold value 0. 11) and poorly aligned N-and C-terminal regions, respectively. The trimmed protein alignment contained 450 aligned residues (see Additional file 2 for trimmed sequence alignment). Based on this alignment, we reconstructed the opsin phylogeny using maximum likelihood implemented in IQ-TREE  [83] , using the best substitution model selected by the software. Branch support values were estimated from 1000 bootstrap replicates.
Image acquisition and analysis For live imaging, transgenic embryos were mounted in a drop of 1% low melting agarose in filtered artificial seawater on the surface of a 35-mm glass bottom dish (Ibidi μ-Dish) with the eye facing the glass surface. Confocal images were obtained on a Zeiss LSM780 laser scanning confocal microscope. For live imaging, we used a Zeiss C-Apochromat 40x NA 1. 2 water immersion objective, while immunostained samples were imaged using Zeiss Plan-Apochromat 40x NA 1. 3 oil, Plan-Apochromat 63x NA 1. 4 oil and LD LCI Plan-Apochromat 25x NA 0. 8 objectives. Image data were handled using Fiji  [92] ; the Enhance Local Contrast (CLAHE) plugin was used to enhance contrast. The confocal images shown in Figs. 4b, c, 5a, c , and 6a, d were deconvolved using the Fiji plugin Decon-volutionLab2  [93] ; point spread function was calculated theoretically by the PSF generator plugin  [94].
Acknowledgements We thank  Ben Hunt  and  Ezio Rosato  for access to their unpublished Parhyale head transcriptome;  Nick Roberts  and  Mathias Wernet  for discussions on polarisation vision and behavioural assays;  Carsten Wolff  and  Pierre Godement  for advice on vibratome sectioning;  François Lapraz  for guidance on reconstructing the opsin phylogeny;  Caren Norden  for the Tol2Kit plasmids,  Jana Fuhrmann  for support on unpublished aspects of this project;  Nikos Konstantinides ,  Carsten Wolff  for numerous discussions; and  Claude Desplan ,  Mathilde Paris ,  Chiara Sinigaglia ,  Cagri Cevrim  and  Marco Grillo  for comments on the manuscript.
Introduction Current approaches to gene therapy for patients with Parkinson's disease are based on two alternative, but potentially complementary, strategies. First, interference with the degenerative process affecting the dopamine neurons in the midbrain through the supply of neurotrophic factors, such as glial cell line-derived neurotrophic factor or neurturin, an approach previously pursued by Ceregene  (Bartus et al. , 2015; Warren Olanow et al. , 2015) , and now continued in an ongoing adeno-associated viral vector (AAV) glial cell line-derived neurotrophic factor trial led by investigators at the National Institute of Neurological Disorders and Stroke (NINDS) (https://clinicaltrials. gov/ct2/show/ NCT01621581?term=gdnf&rank=1). Second, restoration of dopamine function in the denervated striatum can be accomplished through delivery of the three enzymes needed for the production of dopamine, i.
Statistics Data analysis, plotting and statistics were conducted in SPSS version 23. Statistical tests included Bonferroni corrected paired Student's t-test when only two states or time points were compared and one-way ANOVA or two-way mixed model repeated measures ANOVA when three or more groups, states, or time points were compared. In the latter case this was followed by Levene's homogeneity test. This determined the choice of post-hoc test to either Dunnett's T3 (when Levene's fail) or Tukey's HSD. In comparisons to baseline or vehicle control group, a different from vehicle group a one-sided Dunnett t-test was used. Unless otherwise noted, data in figures are presented as the arithmetic mean plus and/or minus one standard error of the mean (SEM). Comparisons were considered significant when P-value 5 0.
, 2012). Thus, our data indicate that post-transcriptional events are limiting TH protein detection. However, further investigations are warranted to determine the exact mechanism. Lastly, we assessed the magnitude of dopamine denervation in the MPTP treated animals through stereological cell counts of the substantia nigra. Systemic MPTP treatment resulted in a loss of TH + neurons in the substantia nigra ranging from 56 to 91% with an overall average of 78% (Fig. 5F ). All lesioned groups differed significantly from the intact animals, while the MPTP treatment groups did not differ from each other. C ) Side-by-side comparison between behavioural recovery (assessed by motor score component of the disability rating scale) seen after increasing doses of peripheral L-DOPA at baseline (post MPTP, pre-AAV) (B), and the recovery observed after AAVmediated continuous L-DOPA delivery (C).
Genotyping and statistics Genomic DNA was isolated using standard procedures from whole blood or saliva samples. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) variants were genotyped using customdesigned TaqMan assays (Thermo Fisher). Assay accuracy was checked by including positive and negative controls in each experiment. APOE alleles were determined by genotyping rs429358 and rs7412. Association with AD was calculated using Fisher's exact test with statistical significance of p < 0. 05. All variants were in Hardy-Weinberg equilibrium (HWE, p > 0. 05). Power calculations were performed using Genetic Power Calculator for discrete traits (http://zzz. bwh. harvard. edu/ gpc/cc2. html). Meta-analysis for the effect of rare variants in association with AD was conducted using beta and standard error with Metafor R-package  11.
14 vs OR CEU = 3. 6, http://www. alzgene. org/), its frequency in AD cases was lower (26. 9% in ARG vs. 38% in CEU, http://www. alzgene. org/). This lower frequency is in agreement with data previously reported in other Latin American countries  21. Interestingly, it is among the lowest worldwide together with that of Mediterranean basin and Native Americans  22, 23  , which are the main contributors to Argentinian admixture. It is of note that the rare variants studied here showed MAFs similar to those reported by IGAP in Caucasians  4. Unfortunately, since there are no reports in Amerindians, we could not compare their MAFs. However, TREM2 p. R47H is almost absent in East Asians  8, 9  , suggesting that it might also be extremely rare in Native Americans. For the rest of the variants, we performed a search in ExaC database (exac.
Acknowledgements This work was supported by grants from the  International Society for Neurochemistry (ISN)  and  Alexander von Humboldt Foundation  (to M. C. D. );  Agencia Nacional de Promoción Científica y Tecnológica  ( PBIT/09 2013 ,  PICT-2015-0285  and  PICT-2016-4647  to L. M. ;  PICT-2014-1537  to M. C. D. );  GENMED Labex  and  JPND  PERADES grant; and  JPND   EADB grant  ( German Federal Ministry of Education and Research, BMBF :  01ED1619A ).
Extracellular multiunit activity (MUA) recordings were obtained with a linear 16-channel multi-electrode array (Neuronexus) that spanned the nRT and VB. MUA signals were amplified 10,000 times and band-pass filtered between 100 Hz and 6 kHz using the RZ5 from Tucker-Davis Technologies (TDT, SCR_006495). Position of recording array was visually checked for each recording to confirm position of electrodes in nRT and VB. We delivered electrical stimuli to the internal capsule with a pair of tungsten microelectrodes (50-100 kΩ, FHC). The stimuli were 100 μs in duration, 50 V in amplitude, and delivered once every 30 s. We then used custom MATLAB software to analyze thalamic MUA recordings. Detection of Kcnn2 mRNA in brain tissue-DS mice and WT littermate control mice (age 3-5 months) were euthanized with Fatal Plus, and nRT were microdissected in ice-cold sucrose cutting solution.
Tissue was immediately flash-frozen and then RNA was isolated using QIAGEN RNeasy kits with on-column DNase digest. Superscript First-Strand cDNA synthesis kits were used to convert RNA into cDNA. qRT-PCR experiments were performed using the following primers for mouse Kcnn2S (short transcript variant, Genbank: NM_080465. 2): F-5′ AGT GGT CTG GAG GAA GAG GA 3′ and R-5′ CAT TTG CAC GTT CTC CCG AA 3′ and mouse Kccn2L (long transcript variant, Genbank: NM_001312905. 1): F-5′ TGG TTA CAG ACT GAG ACT CTT GT 3′ and R-5′ TCC TCT TCC TCC AGA CCA CT 3′ and the mouse house-keeping gene Gapdh (Genbank: NM_001289726. 1 and Genbank: NM_008084. 3): F-5′ GGT CGG TGT GAA CGG ATT TG 3′ and R-5′ GCA ACA ATC TCC ACT TTG CC 3′. Reactions were performed using Sybr Green Master Mix (Applied Biosystems) on a 7900HT Fast Thermal Cycler (Applied Biosystems) and levels of Kcnn2 mRNA were determined using the ΔΔC T method.
QUANTIFICATION AND STATISTICAL ANALYSIS All numerical values are given as means and error bars are standard error of the mean (SEM) unless stated otherwise. Data analysis was performed with MATLAB (SCR_001622), Origin 9. 0 (Microcal Software, SCR_002815), GraphPad Prism 6 (SCR_002798), and SigmaPlot (SCR_003210). Comparison of thalamic circuit oscillations in thalamic slices-We used custom MATLAB software to detect extracellular spikes based on taking the first derivative of the MU signal and thresholding over background. Spikes were excluded if their waveform lasted 2 ms longer. An experienced user confirmed parameter settings to optimize for all recordings. Bursts were defined as three or more spikes per burst, with the max interburst interval as 1. 2 s. We quantified the number of total evoked bursts and oscillation duration recorded in the most active VB channels using on average 10-20 sweeps per recording.
ACKNOWLEDGMENTS S. R. -M. is supported by the  American Epilepsy Society  and the  Dravet Syndrome Foundation Postdoctoral Research Fellowship. B. H. is supported by the  American Epilepsy Society Postdoctoral Research Fellowship. J. T. P. is supported by  NIH/NINDS   R01NS096369 , the  DoD , the  NSF ,  Gladstone Institutes , the  Kavli Institute for Fundamental Neuroscience , the  Michael Prize , and the  Jewett Foundation. A. C. -P. and F. S. C. are supported by  NSF  Graduate Research Fellowships. S. S. H. is supported by the  ARCS Foundation  and  Weill Institute Foundation  scholarships. O. H. J. E. R. and F. E. H. are supported by  Dutch   NWO-ALW VIDI 016. 121. 346  and  ZON-MW TOPGO. L. 10. 066  and the  Erasmus MC MRace. M. -C. C. is supported by the  Belgian American Education Foundation.
Data analysis. Image analysis was performed by using ImageJ and MATLAB (Mathworks). ROIs covering individual target and non-target cell somata were manually selected in ImageJ based on both red (ReaChR-dTomato) and green (GCaMP6s) channels. The time-lapse fluorescent signal of GCaMP6s from all ROIs was exported in MATLAB. Image frames from ROIs that are affected by the photostimulation artefacts were removed in analysis. For each ROI, the relative percentage change of GCaMP6s fluorescence was computed as ΔF/F = (F -F 0 )/F 0 , where F 0 was the average raw fluorescence signal 3-0. 2 s before photostimulation started. A cell was considered activated if the average ΔF/F 1 s after the last illumination onset was significantly larger compared to that 1 s before the first illumination onset (right-tailed paired t-test with a significance level of 0.
Acknowledgements We thank  Vincent de Sars  for software developing,  Coherent Inc. for the loan of the Fidelity laser. This research received support from the  ' Agence Nationale de la Recherche'  (grant  ANR-15-CE19-0001-01 , 3DHoloPAc), the  Human Frontiers Science Program  (Grant  RGP0015/2016 ), the  Fondation Bettencourt Schueller  ( Prix Coups  d' élan pour la recherché française), the  Getty Lab , the  National Institute of Health  (Grant  NIH   1UF1NS107574 -01 ) and Axa research funding. N. A. received funding from the  European Union 's  Horizon 2020 research and innovation programme  under the  Marie Skłodowska-Curie  grant agreement no. 746173. E. R. received funding from the  European Research Council   SYNERGY Grant  scheme (HELMHOLTZ,  ERC  Grant Agreement #  610110 ). IWC received funding from the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Skłodowska-Curie  grant agreement no.
Clinical and therapeutic data Clinical data already collected as part of both national programmes were de-identified, and merged in a new database. Epidemiological characteristics (sex, age at disease onset, ethnicity and country of provenience), clinical characteristics (phenotype at onset, date of conversion to NMOSD, severity at onset and last follow-up evaluated with the Expanded Disability Status Scale [EDSS]), imaging abnormalities (≥ 1 lesion on T2-weighted sequences) on the first brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) characteristics (cell count [pleiocytosis > 5 cells/mm 3 ], oligoclonal bands [OCB] and IgG index) were included. For ON, visual acuity (VA) was evaluated by the visual functional system at the last follow-up in patients experiencing any ON.
At the end of the follow-up, patients were assigned to one of the following diagnostic categories; NMOSD-like phenotype fulfilling 2015 criteria  [24] , MS-like phenotype in those fulfilling McDonald 2010 criteria  [25] , relapsing ADS in a single CNS area (i. e. relapsing ON or TM) or multiphasic acute disseminated encephalomyelitis (MADEM)  [24, 26]. Patients with short TM and ON who did not strictly fulfil NMOSD criteria were classified as optico-spinal phenotype  [24]. Acute treatment such as oral or IV CS, plasma exchange (PLEX) or IVIG was noted at the first episode. Based on treatment experience  [27] , cumulative availability of clinical data as well as first-and second-line therapy recommendations  [28] , we classified azathioprine (AZT), mycophenolate mophetil (MMF) and rituximab (RTX) as type I IS, and cyclophosphamide (CYC), methotrexate (MTX) and mitoxantrone (MiTX) as type II IS.
Funding The present study is supported by a grant from  ARSEP  foundation and a grant provided by the  French State  and handled by the  "Agence Nationale de la Recherche ", within the framework of the "Investments for the Future" programme, under the reference  ANR-10-COHO-002   Observatoire Français de la Sclérose en Plaques (OFSEP) ,  Déchaine Ton Cour , and by  Red Española de Esclerosis Múltiple (REEM) ,  Instituto de Salud Carlos III ,  Fondo Europeo  de.
, 2019) , expert-based feature engineering and increasing emphasis on surrogate tasks. Such tasks attempt to learn on abundant high-quality data an outcome that is not primarily interesting, to then exploit its correlation with the actual outcome of interest in small datasets. This can be seen as transfer learning problem  (Pan and Yang, 2009)  which, in its simplest form, is implemented by reusing predictions from a surrogate-marker model as predictors in the small dataset. Over the past years, predicting the age of a person from its brain data has crystalized as a surrogate-learning paradigm in neurology and psychiatry  (Dosenbach et al. , 2010). First results suggest that the prediction error of models trained to learn age from brain data of healthy populations provides clinically relevant information  (Cole et al.