dataesr/scientific-paragraphs-categorization huggingface dataset:
67) 0 0 3,775 (45. 85) Estonia 31 (100) 0 0 106 (100) De novo replication Austria 48 (100) 0 0 183 (65. 03) Czech Republic 32 (71. 88) 0 0 22 (100) Finland 15 (100) 0 0 94 (8. 51) France 55 (100) 0 0 123 (100) Germany 174 (99. 43) 31 64 380 (66. 84) Greece 16 (100) 0 0 53 (100) Italy-South 156 (96. 79) 32 24 63 (100) Netherlands 229 (100) 45 23 380 (27. 11) Poland 52 (98. 08) 0 0 93 (100) Spain 10 (100) 0 0 328 (41. 46) UK 155 (100) 28 55 199 (65. 83) USA ** 671 (100) 349 272 2,830 (41. 31) Japan 458 (100) 213 240 421 (100) Total replication 3,135 (98. 72) 698 678 9,050 (50. 08) * All AN cases from discovery dataset were females.
, 2003). Another key area involved in the emotional processing network is the ACC. This area has extensive connections with subcortical structures, e. g. , amygdala  (Amaral and Price, 1984). Observing the above mentioned literature and considering the neural network involved in emotional processing, we investigated whether educational attainment, i. e. , the level of education, modulates the neural response associated with emotional perception. To test this hypothesis we used a part of the data in The Netherlands Study of Depression and Anxiety (NESDA 1  ). NESDA is a multicenter, longitudinal study investigating cognitive and emotional processing in affective and anxiety disorders  (Penninx et al. , 2008; Demenescu et al. , 2011; van Tol et al. , 2011 van Tol et al. , , 2012)). The present study is an exploratory one in the sense that it is not part of the original aim of the NESDA.
PARTICIPANTS For this retrospective analysis, data of participants were selected from the functional magnetic resonance imaging (fMRI) part of the multicenter longitudinal cohort study NESDA. A detailed description of the fMRI NESDA study including participants and selection criteria is presented elsewhere  (Demenescu et al. , 2011; van Tol et al. , 2011 van Tol et al. , , 2012))   Beck et al. , 1988). Participants were scanned in three main centers from Netherlands: University Medical Center of Groningen (UMCG), Academic Medical Center (AMC) Amsterdam, and Leiden University Medical Center (LUMC). All participants were native Dutch speakers. Out of the 58 healthy participants included in the main NESDA study  (Demenescu et al. , 2011) , we discharged two participants due to head movement >3 mm, and one because of dropout from the educational system after 5 years.
5 s, and having an interstimulus (black screen) interval of 0. 5 to 1. 5 s. Images were projected onto a translucent screen at the end of the scanner bed, visible via a mirror placed at a distance of 11 cm from the participants' face. The distance between the mirror and the screen was 64 cm and the images covered roughly 18 degrees of the visual field. During the presentation of facial expression participants were instructed to indicate the gender of face. To control for brain activation associated with the pressing of a button, during the showing of scrambled faces, the participants were asked to press the right-or lefthand button corresponding to respective arrows displayed on the screen. The responses and reaction times (RT) were also recorded. In the scanning session, the paradigm was presented using E-Prime software (Psychological Software Tools, Pittsburgh, PA, USA).
5 ms, matrix size: 256 × 256, voxel size 1 × 1 × 1 mm, 170 slices). Functional imaging data were preprocessed and analyzed using the statistical parametric mapping software package (SPM5) implemented in Matlab 6. 5 (The MathWorks Inc. ). A detailed description of the preprocessing was previously presented  (Demenescu et al. , 2011). The preprocessing included slice-time correction, realignment, coregistration of the T1 image to the mean EPI, spatial normalization of the EPI images to the standard Montreal Neurological Institute T1-template, and spatial smoothing using an 8 mm FWHM Gaussian kernel. Subject movement greater than 3 mm in any direction resulted in exclusion of the data from further analyses. The significant hemodynamic changes for each condition were analyzed using the general linear model (GLM,  Friston et al.
Facial expressions were defined as within subject factor, and group as between subjects factor. Scan sites were defined as nuisance factors. The ROI analyses were conducted employing ACC, insula, fusiform, and mPFC masks defined with WFU PickAtlas using and initial threshold of p < 0. 001 uncorrected and p < 0. 05 FWE SVC for the ROI area. Outside these regions of interest the FWE correction was applied. Analyses of demographic and behavioral data were conducted using SPSS 18. The RT to emotional facial expressions was calculated as the difference between non-scrambled and scrambled faces. Table  1  displays the mean and standard deviation of the RT. Independent two sample t tests were conducted testing for an effect of group on RT, age, BAI and MADRS score, whereas testing for group effect on gender and handedness was conducted using the Chi-squared test or the corresponding Fisher's Exact test if the frequency of observed values in one cell was less than the expected one.
Cell cycle analysis Six-day-old DG primary neurospheres were exposed to 1 nM METH for 24 h or 72 h (Fig. 2A ), dissociated and fixed in 70% ethanol for 20 min at 4ºC. Also, to exclude dead cells, DG cells were incubated with 2 µg/ml propidium iodide (Sigma-Aldrich). Data were analyzed using the flowJo software.
, 2011)  Herein, we also explored for the first time the impact of METH on the cell cycle of DG stem cells. It was possible to observe a delay in the transition from G0/G1 to the S phase, an increase of cell population in the quiescence state (phase G0), and a downregulation of cyclin E protein, which forms a complex with cyclin-dependent kinase 2 (Cdk2) being involved in the progression through the G1 phase and initiation of DNA replication in the S phase  (Mazumder et al. , 2004). Accordingly, to confirm that METH delays cell cycle progression, the doubling time for cell division was assessed and we observed that DG cells undergo two cell divisions in 24 h (data not shown). On the other hand, METH did not induce any alterations in both cyclin D1 and cyclin A protein levels, which lead us to conclude that METH specifically impairs G1-to-S transition.
Acknowledgements The authors wish to thank  Dr. Sandrine Humbert  for the helpful comments on the manuscript and to  Dr. Isabel Nunes  for the technical assistance in cell cycle experiments. This work was supported by Projects  PTDC/SAU-FCF/098685/2008 ,  PTDC/SAU-NEU/101783/2008 ,  PTDC/SAU-NEU/104415/2008  ( COMPETE  and  FEDER  funds),  GAPI  Project  04/09 ,  Pest-C/SAU/UI3282 , Project  APS911  from  Faculty of Medicine, University of Coimbra, Portugal  and fellowship  SFRH/BD/63773/2009  from  FCT , Portugal, co-financed by QREN. Nuno Milhazes  and  Fernanda Borges  were responsible for methamphetamine synthesis. Carlos Fontes-Ribeiro  provided administrative support. Fabienne Agasse  and  Ana Paula Silva  designed the experiments, analyzed the data, reviewed the article and provided administrative and financial supports.
, 2007; Foo, 2013) , which cannot be efficiently conducted at low temperatures, thereby compromising both protein and mRNA quality. Using cold jet-mediated isolation of astrocytes, followed by microarray analysis, we identified nearly 400 mRNAs significantly regulated in astrocytes when co-cultured with neurons. The resulting database confirms the validity of the used cold jet method for separation of astrocytes and neurons, and represents an important gene source toward understanding of neuron-glia communication.
MICROARRAY ANALYSIS Agilent whole rat genome 4x 44K chips were used. cDNA synthesis and labeling for microarray hybridization were performed according to the manufacturers' instructions. Briefly, oligo dT primers were used and Cy3 and Cy5 labeling was done using the Agilent two-color RNA Spike-In Kit. 0. 5 μg of Cy5 and Cy3-labeled cRNA targets were hydrolyzed and mixed for 30 min. Arrays were hybridized with Cy5 and Cy3 solution for 18 h at 60 • C in a rotating hybridization chamber, using 1× hybridization solution (Agilent technologies). Subsequently, arrays were washed, spun dry and scanned using an Agilent scanner. and standard deviation (SD) of the M values of all probes was calculated, and only mRNAs with M values equal or higher to the mean + 2× SD, or equal or lower to the mean -2× SD were selected, (2) M values had to fulfill our criteria on both replicate arrays, (3) for mRNAs that were represented on the microarray with multiple probes, data were checked for consistency, and probes were only included in the analysis when replicate sequences gave comparable results, (4) mRNAs upregulated in the CC-CJ with AA-CJ comparison could represent left-over neuronal RNA when also strongly downregulated in the CC with CC-CJ comparison.
Therefore, mRNAs upregulated in the CC-CJ with AA-CJ comparison where only included when downregulation in the CC with CC-CJ comparison was less than the mean -2× SD. To assess consistency between technical and biological replicate samples, as well as between replicate probes, non-parametric correlations (using Spearman's rho) within nonnormalized red or green fluorescence samples were calculated. For technical/biological replicate samples, correlations were only performed on regulated probes as indicated by the cold jet-astrocyte alone arrays. Thereafter, data were analyzed by TopGo  (Alexa et al. , 2006 ) using the R project for statistical computing. Overrepresented biological processes were identified by scoring statistical significance of predefined annotated groups based on the gene ontology (GO) database.
Neuron-enriched mRNAs are expected downregulated in coculture by cold jet, while being absent or low expressed in astrocytes. To determine the efficiency of the cold jet in removing these neuron-enriched mRNAs, their fluorescence levels in CC and CC-CJ was taken and the level in astrocytes substracted. The data indicated that the cold jet effectively removed approximately 90% of neuronal RNA (Figure  2B ).
Transcript levels were measured using qPCR for a selected group of astrocyte-expressed mRNAs that according to microarray were neuron-responsive (in MA exp 1 and MA exp 2). The ratio between expression in CC-CJ vs. AA-CJ was calculated and plotted on a Log2 scale, e. g. , expression of EGR1 was 3. 7-fold higher in CC-CJ then in AA-CJ. Data represents the mean and SD of four samples. the transcription factor Egr1 in astrocytes when co-cultured with neurons (Figure  4 ).
Immunoreactivity was visualized using a Vectastain ABC Elite kit (PK-6100, Vector Laboratories), followed by incubation in 0. 2% 3,39-diaminobenzidine, 0. 5% ammonium nickel sulphate, 0. 003% H 2 O 2 in 0. 05 M TRIS buffer (pH 7. 6). Flatmounted retinas were mounted on slides, dehydrated in graded ethanol, cleared in xylene and coverslipped. The number and the distribution of melanopsin-positive ganglion cells were determined using the software package Mercator running on ExploraNova technology.
(B) In the second light schedule, mice were exposed to 3 successive 12L/12D cycle with decreases of light intensity (1000, 300 lux and 100 lux; n = 12 for control and for STZ-diabetic mice). At 1000 lux, controls and STZ-diabetic animals are entrained with a normal phase angle of activity and with variability around the onset of activity similar to controls (left panel). When the light intensity is decreased (300 and 100 lux), STZdiabetic animals began their locomotor activity earlier than controls with increased onset variability for STZ-diabetic mice at 300 lux (p#0. 001). Data are presented as means 6 SEM, ** p#0. 01 and *** p#0. 001 compared with control. doi:10. 1371/journal. pone. 0101584. g003 assesses entrainment of locomotor activity at different stages during the development of diabetic retinopathy from the injection of STZ up to 10 weeks post-injection.
Data Analysis We measured the subjective estimates of tilt and translation perception during fore-aft translational and pitch tilt stimuli (TTS) and during lateral translation and centrifugation (VRC). Fore-aft translation gain was defined as the ratio of the perceived amplitude of translation over the actual sled translation. Lateral translation gain was defined as the ratio of the perceived amplitude of translation over the combined translation and centripetal acceleration. Pitch tilt gain was defined as the ratio of the perceived amplitude of tilt over the actual chair tilt. Roll tilt gain was defined as the ratio of the perceived amplitude of tilt over the GIA tilt during centrifugation. Differential perceptions gain were calculated as the difference between the lateral translation gain and the dynamic roll tilt gain, and as the difference between the fore-aft translation gain and the dynamic pitch tilt gain.
Nonlinear least squares sinusoidal curve fits were used to describe the modulation of the joystick responses as a function of the sinusoidal-varying linear acceleration stimulus using a custom Matlab script (MathWorks, Inc. ). The curve fits were used to determine the phase relative to tilt or translation position, with positive leading and negative lagging  [24]. Phases for tilt motion were also corrected for 180u differences that occur depending on whether the axis of rotation is above or below the head. These response parameters and the verbal reports were analyzed with repeated measures multiple analysis of variance using a commercial statistics program (SPSS, IBM). Using an alpha error of 0. 05 as the decision rule, the null hypothesis that there is no difference across mission day (pre-flight, R+0/1, R+2, R+4, and R+8 days), and stimulus frequency (0.
0ST Array kit. After fragmenting and end labeling, the cDNA were hybridized to Mouse Gene Gene-1_0-st-v1 Array's (Affymetrix) for 16 h at 45°C according to the manufacturer's instructions. The arrays were then washed and stained on the Fluidics station 450 using the hybridization, wash and stain kits and scanned on the GeneChip Scanner 3000. Analyses of microarray data were performed using the Genespring GX software package (Agilent Technologies). The p values were corrected for multiple testing using the Benjamini-Hochberg correction and a corrected p value threshold of 0. 05, together with a fold cutoff of Ͼ2 was used to select differentially expressed genes. qPCR validation. For validation of the differentially expressed genes, quantitative PCR (qPCR) was performed. E12. 5 and E14. 5 Robo1 ϩ/ϩ and Robo1 Ϫ/Ϫ (n ϭ 3, both groups) mouse embryos were dissected and RNA extraction were performed as described above.
Optical and fluorescent images were collected using a Leica Microsystems light microscope (DM5000B). Images were reconstructed and digitized with Photoshop CS4 software (Adobe Systems). Statistics. Statistical analyses were performed by GraphPad 3 (Graph-Pad Software). All data are reported as mean number and SEM. The statistical significance between group means was tested by one-way ANOVA, followed by Bonferroni's post hoc test (for multiplecomparison tests). Significance was set at p Յ 0. 05.
Rho-GAP Function with RAICHU Probes-The pRAICHU probes for Cdc42, RhoA, and Rac1 were generously provided by M. Matsuda  (15). COS-7 cells plated in 96 wells were transfected with the different probes and stimulated with 100 nM phorbol 12-myristate 13-acetate (PMA) over 10 min to activate Rho-GTPases. Fluorescence intensity at 480 nm (CFP) and 530 nm (YFP) were measured using a Safire II fluorimeter (TECAN, Lyon, France) after CFP stimulation at 430 nm. FRET efficiency was then determined by measuring the sensitized emission of the acceptor as previously described  (16). Data were expressed as the mean Ϯ S. E. and statistical tests performed using the Student's t test. FRET intensity was calculated as follows: FRET ϭ YFP ex430 Ϫ (CFP ex430 ϫ (YFP co /CFP fco )) Ϫ ((YFP fyo /CFP fyo ) ϫ YFP ex515 ), where YFP ex430 is YFP excited by CFP at 430 nm; CFP ex430 is CFP excited at 430 nm; YFP co /CFP fco is fluorescence values for transfected CFP alone and excited at 430 nm; YFP fyo /CFP fyo is fluorescence values for transfected YFP alone and excited at 430 nm; and YFP ex515 is YFP excited at 515 nm.
Data were expressed as the mean Ϯ S. E. and statistical tests performed using the Student's t test. FRET Intensity Measurement and FRET Image Acquisition-FRET image acquisition in neurons transfected with pRAICHU probes was performed using a LSM-Meta 510 Zeiss confocal microscope (Carl Zeiss S. A. S. , Le Pecq, France). CFP excitation was performed at 405 nm, and image fluorescence emission signals were collected from 415 nm to 580 nm. A fluorescence spectrum was thus generated from images acquired every 10 nm (see Fig. 3B ). Ratio of images obtained at 525 nm and 480 nm provided FRET images. Calculation of FRET efficiency was obtained by dividing spectral values of individual dendritic spines obtained at 525 nm and 480 nm (Fig.
2, D and E). Electrophysiology-Mouse hippocampal cultures were continuously perfused with the following external medium (mM): NaCl (140), MgCl 2 (2), CaCl 2 (2), KCl (3), HEPES  (10) , D-glucose  (10) , tetrodotoxin (0. 0003), bicucullin (0. 01), pH 7. 4 and osmolarity of 330 mOsm. The transfected neurons were selected on the basis of their fluorescence (YFP) and recorded at room temperature using the whole-cell configuration of the patch-clamp technique. The recording pipettes had a resistance of 3-5 MOhms when filled with the following medium (mM) KCl (140), HEPES  (10) , D-glucose  (10) , pH 7. 2 and osmolarity of 300 mOsm. Miniature EPSCs (mEPCs) were recorded at Ϫ65 mV membrane potential through an Axopatch 200B amplifier (Axon Instruments, Union City, CA), filtered at 1 kHz and then digitized at 3 kHz using Axotape software (Axon Instruments).
Currents were analyzed using the pClamp 9 software (Axon Instruments). All the detected events were re-examined and accepted or rejected on the basis of visual examination. Once more than 100 events had been collected from a neuron, the average frequency and amplitude of the events were measured on the total duration of the sample. Data obtained from the indicated number (n) of cells were expressed as the mean Ϯ S. E. and analyzed using the statistical Student's t test. Immunofluorescence Staining and Analysis-Cells were fixed for 20 min in 4% paraformaldehyde buffered in phosphate-buffered saline (PBS) followed by three washes in PBS. They were then permeabilized in PBS supplemented with 2% BSA and 0. 1% Triton X-100 and incubated for 1 h at room temperature with appropriate primary antibodies in the same buffer.
Demographic characteristics of the participants are summarized in Table  1. The sclerosis in either left or right hippocampus in the two patient groups was corroborated by a volumetric analysis using Freesurfer software  (Fischl, 2012; Reuter et al. , 2012)  that attested an ipsilateral hippocampal volume reduction of an average of 24. 51% in the LTLE and 29. 71% in the RTLE group compared to healthy controls. Between-group comparisons confirmed the significance of these volume reductions in the atrophic hippocampus (p < 0. 05). Volumes and percentage of reduction are summarized in Table  2  (for details on the volumetric analysis, see Data Analysis). The local ethics committee approved this study and informed consent was obtained from each participant.
PROCEDURE Participants were instructed to listen attentively with closed eyes while avoiding moving, humming, or singing along. No behavioral data were collected. Stimuli were presented using E-Prime 1. 1 (Psychology Software Tools) and delivered binaurally through air pressure headphones (MR confon). Additionally, participants used earplugs to minimize noise interference. All blocks were presented in one of four pseudorandom orders, with a silent gap between blocks of 10 s (±0. 5 s) allowing the hemodynamic response to return to baseline  (Belin and Zatorre, 2003). This resulted in a total duration of the experiment of around 30 min. Blocks of the same condition were not presented more than twice in a row. At the end of the experiment, all participants filled in a debriefing questionnaire with several nine-point scales (1 = not at all, 9 = always) in which they rated their attention during listening at 7.
DATA ANALYSIS The fMRI data were analyzed using SPM8 (Wellcome Trust Centre for Neuroimaging). Preprocessing included spatial realignment and reslicing and coregistration of the anatomical T1 to the mean functional data. The first level analysis was carried out in the native space. 2010 ), we additionally compared both main effects to identify brain regions that showed an independent processing of either lyrics or melodies (i. e. , stronger adaptation for lyrics than for melodies [2 × (S M D L )] and vice versa [2 × (D M S L )]). Segmentation of the anatomical files was performed with the VBM8 toolbox  (Ashburner and Friston, 2005)  to form a normalized anatomical image and the DARTEL exported tissue types. A template with eight iterations was created in DARTEL  (Ashburner, 2007)  including all 43 subjects to improve anatomical accuracy in the normalization of the functional contrast images obtained in the first level.
, 2012) , which is documented and freely available for downloading online (http://surfer. nmr. mgh. harvard. edu/). Non-parametric tests (Kruskal-Wallis, SPSS 18. 0) were used to compare these measures between the patient and controls groups. To control global differences, intracranial volume was included in the analysis as a covariate, which was not found to be significant. The percentage of reduction of each structure was calculated for each patient group in comparison to the control group and is reported in Table  2.
We also offer free software called BMR (Braille Music Reader) which can read BMML files and facilitates the reading of musical information in Braille, by sound and in spoken form. With BMR the musician can explore the score, hide some parts or elements and access all the musical information. BMR has the same functionality to read a score as BME (a commercial product)  [6]  which can also edit a score in Braille. These different tools are necessary but not sufficient to help blind people in their musical learning. We propose some guidelines, video and pedagogical scenarios to help teachers and students in their use.
Locomotor behavior analysis Flies were crossed and maintained at 22 °C while entrained to a 12 h LD cycle. Newly eclosed adult males were placed in glass tubes containing standard food and monitored for locomotor activity using the DAM system (TriKinetics). Isolated males were kept in LD conditions for 3 days, followed by 6 days at 22 °C on DD. On day 7, the temperature was raised to 28 °C, flies were transferred to fresh tubes under red light and kept in the incubator for additional 7 days. Period, FFT and rhythmicity were estimated using ClockLab software (Actimetrics) as previously described  [12, 43].
Acknowledgments The authors would like to thank  M. P. Fernández  for invaluable help with TRP experiments. We are indebted to  E. Beckwith ,  N. Muraro  and  A. Schinder  for critical reading of the manuscript, and to members of the  Ceriani lab  for helpful discussion. We would like to specially thank  U. Heberlein  (now at  HHMI, Janelia Farm, VA ) for providing access to the GAL4 collection kept at  UCSF. We also thank  K. Scott  ( UC Berkeley, US ),  J. Dubnau  ( CSHL, US ),  J. Berni  ( Univ. of Cambridge, UK), P. Emery (Univ. of Massachusetts, US)  and the  Bloomington Stock Center for fly stocks , and the  Developmental Studies Hybridoma Bank  for antibodies. MFC, LF and NP are members of the  Argentine Research Council (CONICET). EAG and AD-C were supported by graduate fellowships from  CONICET  and  ANPCyT.