dataesr/scientific-paragraphs-categorization huggingface dataset:
Simultaneous 8-channel EEG recordings were conducted via Ag/AgCl ring-electrode (impedance <5kOhms) using the EEG Front-End (EEG-FE) from Texas Instruments (Texas Instruments, Inc. ) that is based on ADS1299. To reduce the cost of the NIRS montage, we used only four symmetricallyplaced 770nm/850nm dual LED sources inserted through EEG ring-electrodes for each hemisphere in the lateral, Eyes-open block-averaged resting-state simultaneous NIRS and EEG recordings  [27]  were conducted during tDCS where we analyzed only the anodal tDCS data (30sec steady state stimulation). EEG from four symmetrically-placed ringelectrodes were interpolated with spherical splines to estimate the EEG at F3 and F4 sites (virtual electrode) using EEGLAB 'eeg_interp()' function  [44]. For analysis of simultaneously acquired EEG and HbO2 waveforms at F3 and F4 sites, we developed a method for the assessment of neurovascular coupling at the site of anodal tDCS.
Therefore, analog arterial pressure data from the operating room hemodynamic monitor was acquired along with NIRS in this current study which is currently being analysed to elucidate the mechanisms. Furthermore, the frequently observed initial dip in HbO2 at the beginning of anodal tDCS  [43]  may primarily be related to a fast local increase in total hemoglobin concentration due to vasodilation where the magnitude of the initial dip may reflect the temporal interplay of monophasic oxy-, deoxy-, and total haemoglobin signals, as elucidated by Sirotin et al. [55]. We postulated in our prior works  [28] ,  [43]  that this initial dip which corresponded with an increase in the log-transformed mean-power of EEG within 0. 5Hz-11. 25Hz frequency band may be a biomarker of cerebral microvessel functionality (and NVC).
ACKNOWLEDGMENT Dr. A. Dutta  would like to thank  Prof. M. A. Nitsche  for the discussions on the application of non-invasive brain stimulation techniques towards this work. The development of the EEG instrumentation (EEG-tDCS healthy study) and the  NIRS-EEG  system integration (NIRS/EEG stroke study) were performed under  Dr. A. Dutta  at the NeuroPhys4NeuroRehab team of  INRIA , France where the technical help received from - R. Sehgal ,  G. Aggarwal , and  A. Jacob  -is gratefully acknowledged. The help received from the  Neuro Rehab Services LLP, India  and the  Institute of Neurosciences Kolkata, India  in conducting the preliminary NIRS/EEG stroke study is also gratefully acknowledged.
When the optic vesicle of a control tailbud was transplanted into an enucleated morphant embryo, it nevertheless reached a normal size. In contrast, Yap-MO optic vesicles grafted in a control host generated smaller eyes, which is in accordance with Yap knockdown effects being eye autonomous. (G-J) TUNEL (G, H; stage 33/34) or EdU incorporation (I, J; 3-hr pulse at stage 40) assays analyzed on retinal sections from tadpoles injected as in (E). Arrows point to TUNEL-positive cells in higher magnifications of the area delineated with dotted line (G). The number of analyzed retinas is indicated in each bar. Data are represented as mean ± SEM. Scale bar = 1 mm in (E) and 40 μm in other panels. DOI: 10. 7554/eLife. 08488. 003 The following figure supplements are available for figure  1 :  Finally, to address whether the reduced eye size was due to abnormal embryonic morphogenesis or to post-embryonic growth defects, we adapted in Xenopus the use of photo-cleavable Morpholinos (photo-MO).
Yap knockdown impedes retinal stem cell proliferative activity To investigate the cause of eye size reduction in Yap morphant tadpoles, we determined the level of proliferation within the CMZ. Yap-MO-injected tadpoles harbored a significantly decreased number of EdU + cells compared to a control situation (Figure  2D, E ). The same was true when Yap knockdown was conditionally induced from late embryogenesis (Figure  3 -figure supplement 1). The difference in EdU-labeling between control and Yap morphant tadpoles was even more pronounced at the tip of the CMZ where stem cells reside and Yap expression is the strongest (Figure  2E ). We thus reasoned that Yap knockdown might decrease the number of proliferative cells in the CMZ as a consequence of stem cell depletion. Using in situ hybridization, we examined the expression of several retinal stem and progenitor cell markers (Figure  2F  and data not shown).
Quantitative real-time PCR Reverse transcription was performed using the iScript cDNA Synthesis Kit (BioRad). qPCR reactions were performed in triplicate using SsoFast EvaGreen Supermix (BioRad) on a C1000 thermal cycler (CFX96 real-time system, BioRad). Results were normalized against the expression of reference genes ODC and RPL8 using CFX Manager software (BioRad). PCR primer sequences are listed in Supplementary file 1.
Nanostring The nCounter Analysis System (NanoString Technologies, Seattle, WA, United States) was used according to the manufacturer's instructions with 1000 ng of total RNA to profile 15 cell cycle genes for which we designed custom CodeSets (see Supplementary file 3). The readouts represent counts of individual fluorescent barcodes and provide a sensitive measurement of the selected RNA expression levels in the sample. The Nanostring data were analyzed using the nSolver Analysis Software 2. Background subtraction was performed by substracting the average plus two times the standard deviation of the 8 negative internal controls. Data were normalized as a geometric mean, against the internal positive control spikes and afterwards against three housekeeping genes (see Supplementary file 3).
Microscopy Fluorescence and brightfield images were captured with an ApoTome-equiped Axio Imager. M2 microscope and processed using AxioVision REL 7. 8 software (Zeiss, Oberkochen, Germany) or with a LSM 700 confocal microscope using ZEN software (Zeiss). Confocal pictures represent a merged zstack of 15 slices (1 μm each).
Quantification and statistical analyses For quantifications of labeled cells by manual cell counting in the CMZ, 6 to 10 sections per retina and a minimum of 3 retinas were analyzed. Dissected eye area, Hoechst/PCNA labeling surface or in situ hybridization staining intensity in the CMZ were measured using Adobe Photoshop CS4 software. All experiments were performed at least in duplicate. Shown in figures are results from one representative experiment unless specified. Statistical analyses were performed by Student's t-test. Statistical significance is: *p < 0. 05; **p < 0. 01; ***p < 0. 001; n. s. not significant. C de Medeiros and E Henry for animal care. We are indebted to K Marheineke for helpful discussions and grateful to X-J Yang for insightful comments on the manuscript. This research was supported by grants to MP from the ANR, Idex Paris-Saclay, Retina France, CNRS, Universit é Paris-Sud, and grants to KH from Cluster of Excellence and DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain.
Study participants and periods of study The participants were pregnant women who had sought prenatal care at public health care units administered by the Brazilian National Health Care System. Individual face-to-face interviews were carried out to collect neighbourhood and individual-level primary data between October 2008 and December 2009  [26, 28]. The baseline study was conducted at the antenatal care units during the first trimester of pregnancy and the follow-up data was collected at 30 days postpartum and related to the last 6 months of pregnancy at women's houses.
Individual covariates Individual maternal socioeconomic and demographic characteristics included marital status (married, living with a partner; has a partner, not living with him; single without a partner), number of children (1 child; 2 children; 3 or more children), years of schooling (0-4; 5-8; 9 or more years), family monthly income (<1 Brazilian Minimal Wage (BMW. One BMW was US$ 178. 00 at the time of data collection); 1 or more BMW), occupational context (no paid workwomen with no paid work, housewives or unemployed women; paid workemployed women with paid work), age  (13-19; 20-30 ; more than 30 years) and ethnicity. The latter variable was assessed through the self-reported skin colour method as proposed by the Brazilian Institute of Geography and Statistics. Participants were asked to describe their skin colour using the following options: white, brown and black  [41].
They were compared with "stable healthy behaviour" and "stable risk behaviour", respectively. Unordered logit models were used to estimate the distribution probabilities of each of the response categories. Fixed-and random parameter estimates for the twolevel ordered logit models were calculated by marginal quasi-likelihood (MQL) procedures with first-order Taylor series expansion, RIGLS (restricted iterative generalized least squares) estimation method, as implemented within MLWIN software version 2. 24. The results of multilevel analyses are presented as odds ratios (ORs) with 95 % confidence intervals (95 % CI). In these analyses, variables that presented P ≤ 0. 10 in bivariate analysis were considered for multivariate analysis. Four models were tested for each outcome. The association between neighbourhood social capital and neighbourhood socioeconomic status (social class) and the health-related behaviours outcomes was tested in Model 1.
Study design, setting and participants We undertook an observational study in a population-based cohort of HIV-infected patients residing in Barcelona aged 18 years and older. The study spanned the period between 2001 and 30 th of June 2013 (the end of follow up). Patients first diagnosed with HIV at the AIDS stage (less than 200 CD4 cells/μl and become ill with an opportunistic infection) were not included in the study  [18]. The aim was to assess the impact of the risk factors on HIV-related or a non-HIV-related outcome before AIDS was present. The cases were reported to the surveillance system of the Public Health Agency of Barcelona between 2001 and 2012. Reporting of new cases of HIV infection was voluntary between 2001 and 2009, but became mandatory for physicians from 2010. From then on the Barcelona HIV surveillance system became an active system that collects data provided by doctors, hospital discharges, the sexually transmitted infections registry, and mortality databases regarding patients diagnosed with HIV/AIDS.
We compared mortality among Spanish-born and immigrants (11. 5/1000 py; CI: 9. 7-13. 4/ 1000 py vs. 2. 4/1000 py; 1. 6 py-3. 3/1000 py, respectively). We observed a lower mortality rate for each cause of death in the group of immigrants, when compared to the group of Spanishborn people (Table  2 ). Moreover, we found that immigrants did not suffer from non-HIVrelated causes of death such as other infections, cancer or liver disease (data not shown). The proportion of people, older than 49 years of age, living with HIV, was three times higher in the Spanish-born group than in the immigrant group (12. 1% vs. 4. 3%, respectively). In addition, we analysed CD4 counts at HIV diagnosis. We found that mortality rates were higher in patients with CD4 count 200 cells/μL for main causes of death (Table  2 ).
Limitations The main limitation of our study was that outcome identification required using secondary data sources. The municipal registry and death registry used only captured deaths in the city of Barcelona. We could not identify deaths which occurred outside of the Catalonia region. Despite this, we have found a slightly higher proportion of deaths (5. 8%) than a) a Swiss cohort with patients starting HAART during 2005-2009 (5. 1%)  [27] , b) a collaborative cohort composed of HIV-1-infected patients following HAART between 1996 and 2006 from 13 cohorts of Europe and North America (4. 8%)  [31] , and c) Spanish cohorts of the AIDS Research Network from 1997 to 2010 (3. 6%)  [17]. General population of the municipal registry show a migratory movement surrounding 3% between 2009 and 2013.
1% of the subjects with CD4 known values) should have started HAART shortly after knowing their HIV diagnosis. However, they did not in fact initiate HAART because the criteria suggested by guidelines in 2002 was to start with CD4 counts < 200 cells/μL and in 2009 was to start with CD4 counts < 350 cells/μL  [66, 67]. Further, our database did not include data about HAART regimen and adherence. These variables would have helped us to better understand patient histories.
Acknowledgments Members of the Barcelona HIV/AIDS working group:  Sonia Gil ,  Eva Masdeu ,  Pere Simón ,  Miriam Ros ,  Roser Clos ,  Pilar Gorrindo  ( Agència de Salut Pública de Barcelona );  Maria G Mateo ,  María M Gutiérrez  ( Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona );  Vicenç Falcó ,  Martí Vall ,  Pere Armengol ,  Maider Aranda  ( Hospital Vall de Hebrón. Universitat Autònoma de Barcelona );  Teresa Carbonell  ( Hospital Universitari del Mar );  Christian Manzardo ,  Felipe García ,  José L Blanco ,  Esteban Martínez ,  Josep Mallolas  ( Hospital Clinic-IDIBAPS. University of Barcelona );  Marianna Vitaloni  ( Center for Regenerative Medicine in Barcelona, Spain). This study would not have been possible without the collaboration of all data managers, for this reason we thank specially to  Maika Rodríguez Sanz  and  Carme Serrano.
As a result, an observer is used to estimate the inductor current. Using a suitable filter the effect of disturbances on the response of the system will be decreased. The simulations were carried out using MATLAB Simulink. This paper is organized as follows: After the introduction, the global model of the plant is described in section(2), theoretical analysis of the controller, RLS estimator and Kalman filter descriptions are reported in sections (3), (  4 ) and (  5 ) respectively. Simulation results and discussion are presented in section  (6)  followed by the conclusion in the final section.
CMR acquisitions In addition to the conventional axial and coronal SSFP data used for anatomical characterization of the aortic arch, through-plane phase contrast (PC) images of the proximal aorta were acquired for each subject in a single axial view at the level of the bifurcation of the pulmonary trunk, perpendicular to both the ascending and descending aorta to simultaneously measure flow. Acquisition planes were positioned 2 to 4 cm above the aortic junction to ensure optimal imaging quality  [19]  and to avoid distortion due to aortic valve motion. The study population included two sub-groups: Group 1 included 36 subjects (43 ± 15 years, 15 females) with CMR exam on a 1. 5 T scanner (Signa HDx, GEMS, Waukesha, WI, USA) at the George Pompidou European Hospital in Paris, France, and Group 2 included 35 subjects (47 ± 15 years, 14 females) with CMR exam performed on a 3.
CMR data analysis Aortic arch length was measured three-dimensionally from sagittal oblique SSFP or dark blood T1 acquisitions as described in  [7]. The 3D approach was used to take into account possible tortuosity of the aortic arch  [7]. Ascending (AA) and descending (DA) aortic lumen borders were automatically detected on the modulus images for every frame of the cardiac cycle using the ARTFUN software (INSERM 1146, UPMC, Paris, France). The only manual intervention was to select the ascending and descending aortic centres and a single point on their border. The subsequent detection of the borders for the whole cardiac cycle was fully automatic and thus highly reproducible  [21]. Aortic borders were then superimposed on CMR velocity images providing time varying AA and DA flow curves, which were used to automatically estimate TT by three different approaches (Fig.
Wavelet-based transit time (TT-WU) A new method for TT-WU estimation was developed using Matlab (Matlab 2013, The Mathworks, Natick, MA) software. First, the wavelet cross spectrum of AA and DA aortic flow waveforms was estimated (Fig. 1 ), providing a time-scale distribution of cross-spectra between signals. The main advantage of this analysis is that it enables temporal localization of signal frequencies allowing us to focus only on the systolic upslope. Whereas in Fourier-analysis signals are represented as sine wave components, in wavelet analysis, signals are represented as convolutions with a set of functions derived from the scaled and shifted versions of an initial function named "mother wavelet". Wide wavelets are shifted in time in order to detect low frequency magnitude and phase components and narrow wavelets are shifted in time in order to detect high frequency magnitude and phase components.
Acknowledgements We thank  N. Foulkes ,  S. Lemke ,  F. Loosli , and  J. L. Mateo  for critical discussion and comments on the manuscript;  J. L. Mateo  and  M. Ramialison  for help with the DNA motif analysis;  M. Gebert  for advice regarding the EMSA;  E. Leist  and  A. Saraceno  for fish husbandry; and  T. Kellner  and  L. Schertel  for technical assistance. DI received fellowships from the  Human Frontier Science Program (HFSP)  and the  Japan Society for the Promotion of Science (JSPS) ; TT received a fellowship of the  Hartmut Hoffmann Berling International Graduate School (HBIGS) in Heidelberg. The project was supported by the  Collaborative Research Center SFB 873  (J. W. ) of the  German Research Foundation (DFG).
Sanger sequencing and segregation analysis of pedigrees Pathogenic variants identified in probands were confirmed by direct Sanger sequencing. Sanger sequencing was also used to determine if the pathogenic variants were present in family members for whom genomic DNA was available. Briefly, genomic DNA was amplified using the primers and PCR conditions described for amplicon library preparation in Artuso et al. 7  Sequencing was performed on an ABI Prism 310 genetic analyser (PE Applied Biosystems) and data were analysed with Sequencher software v4. 9 (Gene Codes, Ann Arbor, USA). Genotypes of pedigrees were examined to determine if the COL4A3 and COL4A4 mutations on chromosome 2 were linked in cis or trans and to assess genotype-phenotype correlation.
3 (Interactive Biosoftware, Rouen, France). To determine if the identified sequence variants were novel or had been previously reported, we searched in the dbSNP database (http://www. ncbi. nlm. nih. gov/projects/SNP/), the Human Gene 18tation Database (http://www. hgmd. cf. ac. uk/ac/index. php)18, the Leiden Open Variation Database v2. 0 Build 35 (https://grenada. lumc. nl/LOVD2/COL4A/variants. php?select_db=COL4A3&action=search_ all&search_MutCol=%3E) and the ALPORT (COL4A5) database (http://www. arup. utah. edu/database/ALPORT/ALPORT_display. php?sort=2#alport; Last update: October 2013).
These findings contrast with the previously reported increase in PLS3 expression found during the neural differentiation of PC12 cells  22  and further support the lack of a modifier role for PLS3 in the SMA family under study. One of the main aims for SMA therapeutic research is the definition of reliable biomarkers, ideally measured in surrogate samples or cells of easy access  64, [67] [68] [69] [70] [71] [72]. SMN2 copy number has consistently shown high correlation with SMA type  13, 14  , except in discordant SMA families such as the one studied here  [15] [16] [17] [18] [19] [20] [21] 73. Mea urements of SMN transcripts and protein do not clearly distinguish between the diversity of SMA phenotypes  10, 64, [67] [68] [69] [70] [71]  , as we have confirmed here in iPSC-derived MNs. Using our dataset from iPSC-MN differentiation studies we concur that the FL/Δ7-SMN mRNA ratio is a robust parameter to distinguish control individuals with two functional SMN1 alleles and SMA patients, as described in cell cultures, foetal tissues and adult whole blood samples  10, 37, 64  , but our results also indicate that it is not suitable to differentiate wild-type from the carrier mother.
Western Blot. Samples were harvested and Western blotting performed using standard procedures, with the antibodies listed on Supplementary Table  S3. Detection and quantification of proteins was performed with an Odyssey Infrared Imaging System and application software V1 (LI-COR Biosciences). Target protein levels were normalised to the geometric mean of the values from alpha tubulin (TUBA), glucose phosphate isomerase (GPI1) and actin. A protein sample from SMA type II fibroblasts was systematically included along the samples of study and its value arbitrarily set to one in order to be used as calibrator. Flow cytometry. Cells co-expressing surface makers SSEA3 and TRA-1-81 were quantified by flow cytometry in a BD FACSCanto II with the BD FACSDiva Software (BD Biosciences). Karyotyping.
Statistical analyses. GraphPad Prism software was used for statistical analyses. Data were presented as mean ± standard error of the mean (SEM). Two-way ANOVA with Bonferroni's post hoc test was used to analyse normalised neurite number, neurite length, SMN and PLS3 expression. For the analyses of linear trends of SMN and PLS3 expression one-way ANOVA with Dunnet's and linear trend post hoc tests were employed. Kruskal-Wallis with Dunn's post hoc test was used for the analysis of the area of AChR clusters. For correlation analyses Pearson correlation coefficients were calculated. Differences were considered statistically significant when the P value was < 0. 05 (*), < 0. 01 (**), < 0. 001 (***) or < 0. 0001 (****).
Acknowledgements The authors acknowledge grant support from  Genoma España  (Project  GENAME , to E. F. T. and R. J. Y. -M. ), the 6th  EU Framework Programme (CLINIGENE , grant agreement no. 18933 , to R. J. Y. -M. ),  Royal Holloway, University of London  (to R. J. Y. -M. ),  Fundación Mutua Madrileña  (to E. F. T. ) and  Instituto de Salud Carlos III  ( FIS 11-2606 ,  FIS 08-0729 ,  FIS 05-2416 , to E. F. T. ); R. M. -H was supported by  PFIS   09-00023 , S. B. was supported by  FUNDAME  and L. A. was supported by  CIBERER. We thank  Fred Gage  for the HB9-RFP lentiviral plasmid,  Luigi Naldini  for lentiviral packaging plasmids and  Michael Sendtner  for MN culture advice.
Raw. CEL files were downloaded from the GEO website (http://www. ncbi. nlm. nih. gov/geo/) corresponding to data from 351 samples of normal human tissues, including a large series of adult somatic and germline tissues (334 samples from GSE3526), placenta (14 samples from GSE18809, GSE7434, and GSE9984), and embryonic stem cells (3 samples from GSE9440). The data were normalized together using the RMA algorithm for summarization and quantile normalization, and the expression of the Atad2 gene in each of the indicated tissues is shown as box plots. The numbers from 1 to 32 indicate the following tissues, respectively: adipose tissue, adipose omental, adipose subcutaneous, adrenal gland cortex, amygdala, bronchus, cervix, colon caecum, coronary artery, oesophagus, heart atrium, heart ventricle, kidney cortex, kidney medulla, liver, lung, mammary gland, myometrium, neuro, nipple cross section, oral mucosa, pharyngeal mucosa, pituitary gland, salivary gland, saphenous vein, skeletal muscle, stomach cardia, stomach fundus, stomach pyloric, thyroid gland, tongue main corpus and trachea.
(C) The expression levels of two groups of genes, those associated with Atad2 peaks (+) and those not associated with Atad2 peaks (2), are shown as box plots for both ChIP experiments (left panel: Exp1 and Exp2, respectively). The expression levels increase significantly with the number of Atad2 peaks (right panel: ANOVA P-values ,0. 001). The gene expression levels were determined from RNA-seq data from wild-type 46C Atad2-tag cells, treated with a scrambled siRNA (see below, D). (D) 46C Atad2-tag cells were treated with two active anti-Atad2 siRNAs and an inactive siRNA. Each RNA sample was sequenced twice, and the efficiency of Atad2 knockdown was verified by comparing Atad2 mRNA read counts from control cells and cells treated with either anti-Atad2 siRNA. The indicated fold changes correspond to the ratios of read counts of knockdown vs.