dataesr/scientific-paragraphs-categorization huggingface dataset:
This equation is a variation of Morrison equation (Equation  1 ) and is used for tight binding ligands or when K d values are similar in magnitude to the concentration of enzyme used, in which case substantial amounts of both enzyme (E) and ligand (X) are consumed in forming the EX complex as the titration progresses. All data fitting was done using Origin software (OriginLab, Northampton, MA). (2) In Equation  2 , E obs represents the fluorescence emission difference at each ligand concentration, X, E max is the maximum emission change at saturating ligand concentrations, [E] is the enzyme concentration, and K d the dissociation constant for the ligand bound to the enzyme.
Diffraction data processing, structure determination and refinement X-ray diffraction data were collected at Diamond Light Source and subsequently integrated and scaled using the program XDS  31. Initial phases were obtained from a single SAD data set (S1) collected at the selenium edge. Selenium sites were located using Phenix AutoSol 32 yielding an electron density map that could be auto traced using Phenix AutoBuild  33. The resulting model was completed through iterative rounds of rebuilding in COOT  34  and refinement in Phenix  35. All subsequent structures were solved by molecular replacement in PHASER  36  using this initial SeMet derived structure as the template. Structure validation with MOLPROBITY 37 was integrated as part of the iterative rebuild and refinement procedure.
KMO-kynurenine modeling NAMD software  38  was used to perform all molecular dynamics (MD) simulations of the kynurenine-KMO complex. Topology and parameters files for substrate and FAD were obtained using Antechamber program 39 using AM1-BCC charges  40. The complex model was then immersed in a periodic water box (TIP3) and neutralized by adding Na + ions. Several cycles of minimizations (steepest descent, 10 000 steps) and MD simulations (50K, 20 ps) were performed to equilibrate the model (backbone protein atoms were kept fixed). Then MD simulations were performed (310 K, 1 ns) at a time step of 2 ps, with the protein backbone restrained on the X-ray structure conformation. Individual snapshots were extracted and minimized to assess the KMO-kynurenine interactions. Dissociation constant (K D ) for the human KMO-UPF 648 complex could not be determined by fluorescence emission due to low KMO expression yield.
MRI Acquisition Images were acquired on a 3-T Siemens Trio MRI scanner at Ghent University (Siemens Medical Systems, Erlangen, Germany) with an eight-channel radiofrequency head coil. A high-resolution anatomical image was collected using a T1-weighted 3-D MPRAGE sequence. All images were 256 × 256 × 176 with voxel size = 0. 9 × 0. 9 × 0. 9 mm 3. The data were acquired with either one of two sets of pulse sequence parameters: repetition time = 1550 msec, echo time = 2. 39 msec, flip angle = 9°, inversion time = 900 msec, pixel frequency = 180 Hz; or repetition time = 2530 msec, echo time = 2. 58 msec, flip angle = 7°, inversion time = 1100 msec, pixel frequency = 190 Hz. Most (n = 54) were acquired with the first set. The proportion of each parameter set was the same (85% to 15%) in the LLD and RLD groups.
These ROIs were chosen for several reasons. POp and PTr approximate Broca's area. PT has prominent anatomic asymmetries and is an area of language function. The insula has been found to have an interaction between anatomy and language function  (Keller et al. , 2011). HG was chosen because of known anatomical asymmetry  (Dorsaint-Pierre et al. , 2006; Penhune, Cismaru, Dorsaint-Pierre, Petitto, & Zatorre, 2003; Penhune, Zatorre, MacDonald, & Evans, 1996; Rademacher, Caviness, Steinmetz, & Galaburda, 1993). Performing an anatomical ROI analysis also provides a means through which the FreeSurfer ROI results can be compared with those of other studies as well as with the exploratory analysis.
The resulting ALA and PLA are shown in yellow outline in Figure  2. Because this is an exploratory analysis, the boundaries for these areas were selected to be rather large so as to reduce the chance of missing clusters. The ALA and PLA are larger and different than the anatomical ROIs above so that the exploratory analysis might allow the data to define new ROIs that are not necessarily defined by landmarks visible to an anatomist. A cluster analysis using the whole hemisphere was also performed to search for any clusters that might be outside of traditional language areas.
DISCUSSION This study tested the surprising finding of  Keller et al. (2011)  that only the volume of the insula differs between healthy LLD and RLD participants (language dominance based on asymmetry in the fMRI BOLD signals during a silent WG task). We made use of the MRI scans collected by  Van der Haegen et al. (2011) , augmented with 19 scans collected later (footnote 2). In addition, we made use of the FreeSurfer software, which allowed us to run exploratory analyses with a greater precision. Our results replicate Keller et al. for all regions tested by them. Only the size of the insula differed significantly between LLD and RLD participants. No significant differences were found for Broca's area or the PT, although the leftward asymmetry tended to be smaller for RLD participants than for LLD participants, which is intuitively more acceptable than the reverse trends reported by  Keller et al.
Correlations between fMRI and Behavioral Measures In line with the absence of a clear reversal of the overall anatomical asymmetry in RLD participants (Figure  1 ), most of the LIs in the anatomically defined ROIs were uncorrelated with functional asymmetries. This was true both for asymmetries based on fMRI BOLD signals  (WG and LDT)  and on behavioral data (DL, VHFP, and VHFW). Only insula showed correlations with the functional asymmetries (DL and WG). The STG cluster correlated with VHFP but, surprisingly, not with DL. The anatomical asymmetries in the vOT cluster correlated with DL and LDT, in line with the proposal that this area plays a central role in the integration of phonological and orthographic word information as mentioned above. The finding that anatomical vOT asymmetries are correlated with the ear advantage in DL is particularly noteworthy, as it is in line with the hypothesis that the orthography of a word helps the processing of spoken words in literate individuals  (Ziegler & Ferrand, 1988).
Acknowledgments Support for this research was provided in part by the  National Institutes of Health  ( R01NS052585-03 ), the  National Institute on Aging  ( 5R01AG029411 ,  5R01AG022381-08 ), the  National Institute of Neurological Disorders and Stroke  ( 1R01NS069696-01A1 ), the  National Center for Research Resources  ( P41-RR14075 ,  R01 RR16594-01A1 , the  NCRR   BIRN Morphometric  Project  BIRN002 , and  Functional Imaging Biomedical Informatics Research Network (FBIRN)   U24 RR021382 ), and the  National Institute for Biomedical Imaging and Bioengineering  ( R01 EB001550 ,  R01 EB006758 ,  1K25 EB013649-01 ). The scanning was made possible by an  Odysseus Grant  paid by the  Government of Flanders  to M. B.
Evolving Classification Systems With the increasing use of touch sensitive screens, there is a growing demand for handwritten gesture recognition systems. Two strategies exist for building a handwritten gesture recognition system: using a writer independent training set or a writer dependent one. The first require a lot of different writers to gather a heterogeneous training database to build a system independent of the user. This approach has limited performances, in particular if in the end user writes his gestures differently from the training users, his gestures won't be recognized well. The second strategy only uses data samples from the final user to train the system. This allows better performance, since the system is designed for a specific user, but requires him to spend a lot of time writing training gestures.
ACKNOWLEDGMENTS We thank  P. Scheiffele ,  H. Betz ,  O. Schluter ,  S. Okabe ,  N. Brose ,  C. Dotti , and  A. Triller  for the generous gifts of reagents and animals. We thank  C. Breillat ,  A. Frouin ,  D. Bouchet , and  N. Retailleau  for cell culture;  P. Gonzales  and  R. Sterling  for technical assistance;  A. Gautreau  and  F. Coussen  for help with biochemistry; and  M. Heine ,  X. Fournet , and  I. Gauthereau  for experimental contributions. We thank  C. Poujol  and  P. Legros  at the  Bordeaux Imaging Center  for help with FRAP experiments and image analysis, the  Genomic Transcriptomic Facility of Bordeaux  for DNA sequencing, and the  Proteomics Platform of the Bordeaux Center for Functional Genomics  for peptide analysis. The research leading to these results was funded by the  European Union 's  Seventh Framework Program  under grant agreement 232942  Nano-Dyn-Syn , the  Centre National de la Recherche Scientifique , the  Agence Nationale pour la Recherche  (grants Neuroligation, Synapse-2Dt, and ChemTraffic), a  Marie Curie Intra-European Fellowship  (neuroCHEMbiotools), the  Conseil Regional Aquitaine , and the  Fondation pour la Recherche Medicale.
Electrophysiological Data Acquisition & Analysis During the behavioral bilateral lexical decision task, continuous electroencephalogram (EEG) was recorded from 128 AgCl carbon-fiber coated electrodes using an Electric Geodesic Sensor NetH (GSN200; Electrical Geodesic Inc. , Oregon). The EEG was digitized at 500 Hz, band-width filtered at 0. 01-200 Hz, with the vertex electrode (Cz) serving as an on-line recording reference; and impedances were kept below 50 kV. Data were offline recalculated to the average reference and filtered between 1-30 Hz.
The global field power maxima are thus the best representatives of a given microstate in terms of signal-tonoise ratio. As in previous studies on state-dependent information processing, we determined the scalp potential map at the global field power peak in a time window between 100 ms before to 10 ms after stimulus onset as representing the momentary functional brain state at the moment of stimulus presentation. The map at the timeframe of maximum global field power in this 110 ms temporal window was extracted and concatenated for all participants. Due to noise in the electrophysiological data caused by oculomotor artifacts, EEG data from two participants had to be rejected. Thus the results described here after correspond to the electrophysiological analyses of ten participants. All participants were concurrently submitted to a hierarchical agglomerative cluster analysis in order to identify the most dominant scalp topographies across all subjects during two phases of their menstrual cycle: the menstruation period (baseline) and the early luteal phase.
Data Analyses In order to elucidate whether lexical decision performance was dependent on the FBS maps, we calculated individuals' percent of correct responses for each condition. First, we summed for each individual, all artifact-free and correct trials for each functional brain state class separately. This sum score was used for each functional brain state class as individuals' reference to calculate percent correct responses for each word type in each visual field (i. e. , Left and Right visual field). Then, as in previous studies, we calculated an emotional word advantage index score for each one of the FBS topographies separately for each visual field These emotional word advantage index scores were subjected to an analysis of variance (ANOVA). Post-hoc simple comparisons were also performed.
Forty-six premature infants were investigated in the department of neonatology comprising the neonatal intensive care unit (NICU) of Saint-Vincent de Paul Hospital (Paris, France), an academic center with regional maternity ward. This center was a level III center (defined in France by its ability to provide mechanical ventilation). Gestational age at birth was 29-30 (n = 12), 31-32 (n = 22), 33-34 (n = 11) and 35 (n = 1) weeks of gestation, age at recording was expressed as PMW (weeks of gestational age at birth+post-natal weeks)  [53]. EEGs were performed as part of routine neurological follow-up according to the recommendations for premature infants  [34]. Written informed consent was obtained from all parents. The clinical trial was in accordance with the Ethics Code of the World Medical Association, approved by our institutional review board, INSERM's (French National Institute of Health and Medical Research) Ethics Committee, and was registered as a Clinical Research Study classified within ''methodology of reference'' under the nu 558/BB/PA/2005-12 (available on the ANR (French Research Agency) site under the nu ANR-05-NEUR-014-02).
Signals were amplified (1000 x), band pass filtered at 0. 01-97 Hz and digitized at 256 Hz, using the Deltamed Coherence EEG system. Offline analysis was made with the Coherence review program (Deltamed/Natus Paris, France) and Matlab (Mathworks, Natick MA). Auditory stimuli were presented with constant sound volume threshold via a loud-speaker placed 10 cm behind the head. Sound intensity (sound pressure level using the hearing threshold pressure of 2610 26 Pa as baseline) was measured during the entire EEG recording with a sonometer (Chauvin Arnoux, C. A 832) placed near the head. The direct current (DC) output of the sonometer was connected to a DC input of the amplifier, allowing insertion of stimulation markers in the EEG recording using threshold detection. The background noise level in the neonatal department was between 50 and 53 dB Sound Pressure Level (SPL).
Two measures were used: the total charge flux was calculated as the sum of EEG within two seconds following stimulation, while the maximum amplitude was the peak of the negative wave of the average response. All electrodes were examined versus the mean reference. Topographic mapping was performed on the mean responses for 31-34 PMW. The peak response was chosen for the time point mapped, and the value at that time point was converted into a pseudo color map using the EEGLAB software package  [56]. Total power spectrum analysis according to age and stimulus type. In order to analyze the whole spectral power separately by age, stimulus type, sleep stage and electrode, the power spectra for the two second windows immediately preceding and following each stimulus were compared using the Fast Fourier Transform (FFT) algorithm with 0.
Acknowledgments We thank  Mrs Chloe  ´Pochat and  Mr Maurice Lemeux  for recording the infants and  Nicole Monod  for her kind support. We thank  Walter Janssens  and  Yann Abe  ´guile( Deltamed/Natus France ) for technical assistance and  Dr Monika Eisermann  for her assistance in recording management. We thank  Jacques Laschet  for his assistance in graph drawing and  Pr. Alexandre Lapillonne  for his kind support.
This work was supported by the  French Agency for Research (ANR)  (www. agence-nationale-recherche. fr):AK, CC,  RK ) and  ANR-09-MNPS-006   Delta-Brush  (to AK, CC, RK), the  Government of the Russian Federation  (Grant  11. G34. 31. 0075  to RK), and  Fondation pour la Recherche Me dicale  ( DEQ20110421301  to RK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
ACKNOWLEDGMENTS We warmly thank  Dr. Bernard Lakaye  of  University of Liège (Belgium) , for the gift of MCHR1-KO mice and  Dr Mounia Annour-Louet  for careful reading of the manuscript. We wish to thank  Drs Alice Guyon ,  Frédéric Brau , and  Olivier Meste  for development and validation of bioinformatics tools,  Christophe Houdayer  for collecting samples used in lasercaptured experiments,  Gabrielle Franchi  for help in in situ hybridization,  Veronique Thieffin  for animal care,  Isabelle Larre  for help with immunoassays, and  Franck Aguila  for excellent artwork. We also thank  Mauna Kea Technologies (Paris, France)  for providing access to the CellviZio system during the duration of the experiments. Funding sources: this work was funded by the  French Government (National Research Agency, ANR)  through the  "Investments for the Future "  LABEX SIGNALIFE :# ANR-11-LABX-0028-01  ( Jean-Louis Nahon ),  ANR-08-MNPS-018-01  ( Jean-Louis Nahon) , and  ANR-2010-BLAN-1415-01  ( Patrice Mollard ), the  Centre National de la Recherche Scientifique (PEPS INSB ;  Jean-Louis Nahon ); the sixth  FP EU STREPS/NEST-APES Project  no.
28594  ( Jean-Louis Nahon ), the  Fondation de la Recherche Médicale (FRM) (Jean-Louis Nahon) , the  SFR Biocampus de Montpellier  (IPAM platform). Financial support:  Gregory Conductier  was supported by postdoctoral fellowships from the  ANR-08-MNPS-018-01  and the  Centre National de la Recherche Scientifique (INSB)  and by awards from the  "Société Française de Nutrition   2011 " and the " Institut Danone 2012. ".
ml Ϫ1 ) and then incubated for 4 h at 37°C to allow the cells to adhere. The culture media was replaced with RPMI medium containing 0. 1% FBS and the drugs or control, and the dish incubated at 37°C in 5% CO 2 overnight. The degree of cells invading underneath the agarose spot was analyzed by collecting pictures under an inverted microscope Olympus IX91 using a ϫ10 objective equipped with an Andor Camera and Software, and then counting the number of cells using ImageJ software. Six representative fields of view of equal size sectors were individually counted per agarose spot, and the mean number of invading cells per field of view calculated. The values reported herein are the average of three independent dishes. The experiment was reproduced twice and gave similar results. Reverse transcription-PCR.
Pictures were taken by using a digital camera (AxioCam; Zeiss) and connected image-acquisition software (AxioVision). Dopaminergic neurons were recorded in the wholecell mode in voltage clamp and characterized as described previously by the presence of the hyperpolarization-activated cation current and lowthreshold Ca current (I T ), and using single-cell reverse transcription (RT)-PCR to reveal the presence of mRNA for the tyrosine hydroxylase as described previously  (Guyon et al. , 2006). Patch-clamp pipettes had a resistance of 3-6 M⍀ when filled with the internal solution containing the following (in mM): 120 CsCl, 5 MgCl 2 , 1 CaCl 2 , 10 EGTA, 4 Na ATP, 0. 4 Na GTP, and 10 HEPES supplemented with 15 mm phosphocreatine and 50 U/ml creatine phosphokinase (pH adjusted to 7. 3 with CsOH).
Statistical significance between groups (average data expressed as mean Ϯ SEM, n ϭ number of neurons) was tested using either the one-way ANOVA or repeated-measures one-way ANOVA test followed by a Newman-Keuls post hoc test with a threshold of significance of *p Ͻ 0. 05, **p Ͻ 0. 01, and ***p Ͻ 0. 001 using a statistical software package (SigmaStat 2. 03 from Jandel Scientific or Origin from MicroCal). Changes of extracellular solution were obtained by a fast multibarrel delivery system positioned close to the cell tested. Electrophysiological recording in Xenopus oocytes was done 2-5 d after cRNA injection. Two-electrode voltage-clamp was performed with a GeneClamp 500 amplifier interfaced to a Digidata 1200 A/D (Molecular Devices). The interface was controlled with a PC computer (Dell) running pClamp version 10.
All data were produced for more than one oocyte batch and analyzed with Clampfit 10. 2 (Molecular Devices). Whole-cell patch-clamp recordings in transfected HEK293 cells used an Axopatch 200A amplifier. Cells were voltage clamped at Ϫ60 mV. Pipettes had membrane resistance of 2-5 M⍀ and were filled with a solution containing the following (in mM): 145 KCl, 10 NaCl, 1 MgCl 2 , 3 Na ATP, 0. 4 Na GTP, and HEPES 10, pH 7. 3, for HEK293 cells. The extracellular recording was the following (in mM): 145 NaCl, 4 KCl, 1 MgCl 2 , 2 CaCl 2 , and 16 HEPES, pH 7. 4 (theoretical E K ϩ ϭ Ϫ90 mV). HEK293 cells that had been successfully transfected with the Kir3. 1 and Kir3. 2 subunits were identified by their YFP fluorescence. To enhance the amplitude of the CXCL12-evoked GIRK currents, we recorded inward current through these inwardly rectifying channels (see Fig.
Solutions containing the same concentration of ligand and a null lipoparticle (lipoparticles without a receptor expressed) were used as reference samples to account for any nonspecific binding to the particle. Dopamine was used as a nonbinding negative control ligand and did not show any binding signal. For each sample, a solution of ligand and the null lipoparticle was introduced into the channel and the BSI signal was measured. The channel was rinsed and the solution containing the ligand and the CXCR4 lipoparticle was introduced into the channel and the signal measured. This procedure was repeated iteratively for increasing ligand concentrations. Data were collected with a program written in-house using LabView (National Instruments). The binding signal was calculated as the difference in phase between the null lipoparticle-ligand solution and the CXCR4 lipoparticle-ligand complex.
The background signal due to the presence of the receptor was subtracted from all measurements. This corrected binding signal was plotted versus concentration to form a saturation binding isotherm and the affinity was calculated by fitting to a square hyperbolic function using GraphPad Prism software. Tag-lite receptor-ligand binding assay. To perform the binding assay at the CXCR4 ligand binding site (see Fig. 8 ), Cisbio Bioassays provided CXCR4 terbium cryptate-labeled HEK cells and CXCR4 and GABA B d2-labeled ligands. The assay was run in 384 low-volume white plates and readings were performed on PHERAstar FS flash lamp. It was performed twice with identical results. For the competition assay with the CXCR4 ligand d2-labeled and unlabeled GABA B ligands, we used 10 l of transfected terbium-labeled CXCR4 expressing HEK cells (resuspended in Tag-lite buffer), 5 l of unlabeled GABA B ligands (baclofen, GABA, CGP 55 845, and CGP 54626) at different concentrations, and 5 l of labeled CXCL12 at 12.
Drugs were applied in the bath. Statistics. Statistical significance between groups (average data expressed as mean Ϯ SEM, n ϭ number) was tested using either the Student's t test or nonparametric Mann-Whitney test or ANOVA followed by t test. Statistical analysis was done using SigmaPlot (Jandel Science) and Origin (MicroCal) software. For BSI, data analysis and curve fitting was done with GraphPad Prism. Values of p Ͻ 0. 05 were considered significant. This study was approved by Centre National de la Recherche Scientifique and University of Nice Sophia Antipolis.
4 ). The EC 50 s (see Table  1 ) were, respectively, 1. 87 and 61. 02 nM with Hill numbers of 1. Similarly, the GABA B receptor agonists baclofen and GABA were both able to reversibly activate inward currents in a dose-dependent man-   1. The curves were fitted to sigmoid curves using MicroCal Origin software. EC 50 and a Hill number are also indicated in Table  1  (mean Ϯ SEM). ner (Fig. 4 ). They both acted in a similar concentration range (EC 50 s of 6. 9 and 7. 5 M, respectively, and Hill numbers of 1). Notice that the Hill number of the concentration-response curve for CXCL12 (1. 92) was higher than the Hill number of the concentration-response curve of the GABA B receptor agonists/antagonists, which suggests that GABA B receptor agonists/antagonists use different mechanisms of activation of CXCR4 than CXCL12.