dataesr/scientific-paragraphs-categorization huggingface dataset:
However, both of these hypotheses cannot account for stimulus dependent variability. Alternatively, we suppose that this property is better apprehended at the population scale. Going back to the encoding paradigm described in the first section (Figure  3 ), an alternative hypothesis would be that the over-dispersion arise from a stimulus-dependent degree of network convergence (within MT or from V1). Such a scheme could result from a center-surround connectivity profile in the direction domain: more excitatory input for a stimulus close to the preferred direction of the recipient cell. This study calls for an extension over a wider range of experimental observations. First, we would like to extend this work to more datasets with more trials to explore if our predictions are still valid, both for teasing out sources of variability but also to evaluate population decoding.
Materials and Methods In our analyses, we used three different data sets from neurophysiological recordings. LGN data set This data set  [79]  contains the spiking responses of  72  LGN neurons in the anesthetized mouse to drifting grating (square wave (n=24) and sinusoidal (n=48)). Many of these neurons are already contained in the data set published in  [80]. Contrarily to the two other data sets, it is an openly available data set. V1 data set Experiments were conducted at the INT on two adult male rhesus macaque monkeys (Macaca mulatta). Experimental protocols have been approved by the Marseille Ethical Committee in Neuroscience (approval #A10/01/13, official national registration #71-French Ministry of Research). All procedures complied with the French and European regulations for animal research, as well as the guidelines from the.
Acknowledgments WT, FC and LP were supported by  EC FP7-269921 , " BrainScaleS ", GB by  FACETS ITN project (EU funding , grant number  237955 ), a ' Marie-Curie Initial Training Network ' and PW was supported by  F32-EY019833  from the  NIH. We wish to thank  Philippe Foundation  for a travel grant support to F. C. The authors are indebted to  T. Movshon  and his laboratory for giving the opportunity to F. C. to perform MT experiments at  CNS/NYU.
Statistics All data are presented as mean 6 S. E. M. The criterion for statistical significance was set at a 5 0. 05, unless noted otherwise. Statistical analyses were conducted using either GraphPad Prism 6. 0 for windows (GraphPad Software, La Jolla, CA), or MATLAB (Mathworks, Natick, MA). Social Recognition Memory Task. For assessment of drug effects on social exploration, the dependent measure was the time(s) spent investigating a juvenile stimulus animal during an initial exposure, and data were analyzed using an independent samples t test. Within the memory experiments, the dependent measure was a recognition index, defined as IT/(IT 1 RT) Â 100, where IT is defined as the investigation time during the information trial, and RT is the investigation time during the retention trial. Outliers were identified using Pierce's criterion  (Ross, 2003)  and removed.
The data were subsequently analyzed by a one-way analysis of variance (ANOVA), followed where appropriate by Fisher's protected t post hoc tests. Object Recognition Task. Data were collected as time(s) spent actively exploring the familiar (F) or novel (N) object during RT. Recognition memory data are presented as a recognition index, defined as follows: [(N 2 F)/(N 1 F)] Â 100. Animals with low level Vortioxetine on Scopolamine-Induced Cognitive Impairment of object exploration (novel 1 familiar ,5 seconds) were excluded from the data analysis. Outliers were identified using Pierce's criterion  (Ross, 2003)  and removed. The data were subsequently analyzed by a one-way ANOVA, followed where appropriate by Fisher's protected t post hoc tests. Visual Signal Detection Task. The dependent variables were as follows: 1) percent hits 5 (number of correct responses on signal trials/ the number of signal trials completed) Â 100; 2) percent correct rejections 5 (number of correct responses on blank trials/the number of blank trials completed) Â 100; 3) response latency 5 total time elapsed from when the levers were extended to when a lever press occurred/the number of trials completed (these data were collapsed across signal and blank trials); and 4) response omissions 5 total number of trials where no response occurred (these data were collapsed across signal and blank trials).
A two-factor repeated measures ANOVA was applied with signal intensity and treatment condition as factors for percentage of hits. The F-values reported in text for this dependent measure relate to the treatment Â stimulus intensity interaction effects. A one-way repeated measures ANOVA was used to assess the effect of treatment condition on percent correct rejections, response latency, or trial omissions. A significant ANOVA model was followed by a Fisher's protected t post hoc test. Drug Exposure Experiments. Scopolamine or vortioxetine plasma concentrations are expressed as nM and mM, respectively, whereas brain concentrations are expressed as either nmol/kg or mmol/kg. The brain to plasma ratio was calculated by dividing the brain concentration by plasma concentration. Data were analyzed using independent samples t tests.
In vortioxetine time course experiments, the peak vortioxetine level was determined empirically, and the elimination of vortioxetine from the plasma and blood was modeled using a one-phase exponential decay regression model. Statistical analysis of microdialysis experiments was performed, as reported previously  (Pehrson et al. , 2013). For the acute dosing study, the raw ACh concentrations were normalized to the average basal ACh concentrations observed in the vehicle group. Subsequently, the area under the curve for each individual animal's normalized extracellular ACh concentration was calculated using the trapezoid method for fractions 4-9 (0-150 minutes on Fig. 4 ), which constituted the entirety of vortioxetine's apparent time course on extracellular ACh concentrations. Area under the curve data from the vehicle and vortioxetine groups were compared using unpaired two-tailed independent samples t tests.
This analytical method was preferred for its simplicity; however, similar significance values were observed using a more traditional two-factor ANOVA of normalized extracellular ACh concentrations, including data from all dialysate fractions. For the subchronic dosing study, the basal extracellular ACh concentration was defined for each animal by taking the average of all dialysate fractions collected. These basal values were normalized to the average basal concentration for the vehicle animals and compared using a two-tailed independent samples t test.
Stimuli The stimuli consisted of 275 colored photographs of human faces from various ethnic groups, 216 colored photographs of sedan-like cars, 211 colored photographs of complete animals (mammals, birds, reptiles, fish, amphibia, insects), and 183 photographs of various vehicles (cars, motocycles, bikes, trucks, buses, boats, planes) selected from a large photolibrary database (Corel) or downloaded from the Internet (for cars). Examples of stimuli are presented in Figure  1. For all photographs the resolution was 512 3 512 pixels covering 18 3 188 of visual angle at a viewing distance of 2. 04 m. For all categories the scenes contained small (covering less than one third of the scene), medium (covering half of the scene), and large (covering more than half of the scene) objects in equivalent proportions.
Apparatus The stimuli were displayed by means of three projectors (Optoma HD83) fixed on the ceiling, and connected to a PC computer (Dell). Participants were seated 2. 04 meters from a hemispheric rigid light gray (68 cd/m2) screen covering 908 eccentricity on each side of the central fixation (see Figure  2 ). The presentation software (Vision 180) was written by the laboratory engineer in C#. Eye movements were recorded by means of the iViewXTM HED eye tracker from SensoMotoric Instruments (Teltow, Germany) with a scene camera. The video based eye tracker is head-mounted, and uses  infrared reflection to provide an eye-in-head signal at a sampling rate of 50 Hz and accuracy about 18. The scene camera mounted on the head was positioned so that its field of view was coincident with the observer's line of sight.
Calibration was performed using a five-point grid. Calibration was performed two times in order to verify the stability. Only if the eye tracker classified the calibration as ''good'' (a green light) were the recording trials initiated. Following calibration, the eye tracker creates a cursor, indicating eye-in-head position that is merged with the video from the scene camera. The video records were analyzed using the software BeGaze from SensoMotoric Instruments (Teltow, Germany). We recorded the latency of the first saccade (from the onset of the photographs). As the scene camera covers 408 and the hemispheric screen covers 1808, we could only record the direction of the saccade (left/right). Before the experiment, participants were presented with a central white square (408 3 408) containing five calibration points.
Results Anovas using the software Systat 8. 0 were conducted on accuracy and on the latency of the first saccade (for correct saccades). One participant in the human face target group was discarded because accuracy was at chance level at all eccentricities. The within-subject factors were eccentricity  (108, 208, 408, 608, and 808 ) and the distractor (e. g. , vehicles vs. animals for faces as targets). The between-subject factors were the eye recorded (left/right) and the target (face, animal, vehicle). Outliers were eliminated using the Tukey's outlier filter  (Tukey, 1977). This method considers observation X to be an outlier if X , (Q1 -1. 5 IQR) or X. (Q3 þ 1. 5 IQR) where Q1 is the lower quartile, Q3 the upper quartile, and IQR ¼ (Q3 -Q1) is the interquartile range. Accuracy is presented in Figure  3a  for faces, Figure  3b  for animals and Figure  3c  for vehicles.
Stimuli The stimuli were exactly the same human faces and animals as those used in Experiment 1. For the achromatic version the colored photographs were converted into gray-scale images using the software XnView (free access). We also selected a set of 216 photographs of homogeneous sedan-like cars which were downloaded from the Internet and presented in colored and in gray-scale versions. Examples of stimuli are presented in Figure  1. The angular size of each scene was fixed at 18 3 188. The stimuli (faces, animals, and cars) had various sizes (small, medium, large) within the scene.
Data analyses Anovas using the software Systat 8. 0 were conducted on accuracy and on the latency of the first saccade (Mean SRT). The within subject factors were the target (cars, faces), eccentricity  (108, 208, 408, 608, and 808)  and the distractor (e. g. , cars vs. animals for faces as targets). The between-subject factor was the eye recorded (left/ right) and the version of photographs (colored/gray levels). Outliers were eliminated using the Tukey's method. Accuracy is presented in Figure  6. Mean correct saccade latencies are presented in Figure  7. The Min SRT is presented in Figure  8  for each eccentricity.
Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested to principally rely on G-protein signalling. Here, we report that for a subset of OSNs, deleting G proteins or altering their levels of signalling does not affect axonal identity. Signalling-deficient ORs or surrogate receptors that are unable to couple to Gs/Golf still provide axons with distinct identities and the anterior -posterior targeting of axons does not correlate with the levels of cAMP produced by genetic modifications. In addition, we refine the models of negative feedback by showing that ectopic ORs can be robustly expressed without suppressing endogenous gene choice.
This conclusion is based on various observations. If A-P targeting would solely rely on differences in basal cAMP levels, then OSNs with the same level of basal G-protein signalling would project to the same A-P position, irrespective of the expressed OR. Since every OR is suggested to induce different basal activities, we devised a genetic swap experiment, where we expressed different signalling-deficient ORs from the same endogenous locus, and restored activity via receptor-independent G-protein signalling. Importantly, this showed that signalling-deficient M71(RDY) and MOR23(RDY) ORs induced distinct identities and projected axons to different A-P regions on the bulb, close to the cognate WT receptor. These data show that even in the absence of effective coupling of ORs to G proteins, M71(RDY) and MOR23(RDY) ORs were still regulating A-P targeting.
In this regard, the altered axonal projections and mistargeting observed in O/E2-M71 mice, may in part be due to our observed changes in the expression of Kirrel2, Epha5 and ephrin-A5. Furthermore, we observed that M71 and M71(RDY)-caGs axons had distinct identities. It is known that even single amino acid substitutions can alter axonal identity  [6]. Importantly, M71 and M71(RDY)-caGs have completely different activity profiles, with M71(RDY)-caGs OSNs resembling activity knockouts. This suggests that the differential axonal identities of these OSNs are shaped by their neuronal activity patterns. The importance of neuronal activity for axonal identity and glomerular segregation has been previously reported. For example, blocking neuronal activity via the forced expression of Kir2. 1 leads to the erroneous innervation of multiple glomeruli by neurons expressing the same OR  [53].
Wholemount staining and imaging Wholemount X-gal staining was performed as previously described  [17]. The A-P and D-V coordinates of X-gal-stained glomeruli in wholemounts where determined using IMAGEJ software. Intrinsic fluorescence in wholemounts was acquired with an upright Zeiss LSM710 microscope. Images were collected as z-stacks followed by maximum intensity projection to a single image.
An extra 2-to-4Â magnification was achieved by a magnifying lens in the light path. The GFPþ or tdTomatoþ labelled cells were visualized under fluorescent illumination. Superimposition of the fluorescent and bright field images allowed identification of the fluorescent cells under bright field, which directed the recording pipettes. Electrophysiological recordings were controlled by an EPC-10 USB amplifier combined with PATCHMASTER software (HEKA Electronic, Germany). Perforated patch-clamp was performed on the dendritic knobs by including 260 mM nystatin in the recording pipette, which was filled with the following solution (in mM): KCl 70, KOH 53, methanesulfonic acid 30, EGTA 5, HEPES 10, sucrose 70; pH 7. 2 (KOH) and 310 mOsm. The junction potential was approximately 9 mV and was corrected in all experiments off-line.
Odorant mixture was prepared as a 0. 1 M solution in DMSO and kept at 2208C; final solutions at 10 25 M for each odorant were prepared before each experiment by adding Ringer. Forskolin, an activator of adenylyl cyclase, was prepared as a 10 mM stock solution in DMSO. IBMX, an inhibitor of phosphodiesterases, was prepared as a 100 mM stock solution in DMSO. Final solution containing 200 mM of IBMX and 20 mM of forskolin was prepared before each experiment by adding Ringer. Unless specified, all chemicals were from Sigma-Aldrich (St-Quentin Fallavier, France). Lyral was provided as a generous gift from International Fragrances and Flavors (Dijon, France). Data were analysed using FITMASTER (HEKA). Maximum amplitude of the response and kinetics characteristics was measured. Dose-response curves were drafted and fitted using ORIGIN software (OriginLabs).
, Minneapolis, MN). Oocytes were clamped at Ϫ60 mV (Roboocyte2 recordings) or Ϫ50 mV (manual recordings), and ASIC currents were activated by rapid changes in extracellular pH induced by microperfusion systems. HEPES was replaced by MES (5 mM) for buffer solutions at pH 5. 0. Stimulation, data acquisition, and analysis for manual recordings were performed using pCLAMP 9. 2 software (Axon Instruments, Union City, CA) or Roboocyte2ϩ software. All experiments were performed at 19 -21 °C in ND96 solution supplemented with 0. 05% fatty acid-and globulin-free bovine serum albumin (Sigma) to prevent nonspecific adsorption of the toxins to tubing and containers. Mambalgins were applied 30 s before the acid stimulation. Data analysis was performed using GraphPad Prism 4. 03 software. Data are represented as means Ϯ S.
Heat pain was assessed measuring the hind paw withdrawal latency (seconds) from a 46 °C bath using the paw-flick test, with a cutoff time at 30 s. Synthetic mambalgin-1 was i. pl. -injected (0. 34 nmol/mouse) in the left hind paw (vehicle, 0. 9% NaCl ϩ 0. 05% BSA) on carrageenan-induced heat hyperalgesia, and the paw withdrawal latency was measured during 2 h after injection. Data analysis and statistics were performed with Microcal Origin 6. 0 and GraphPad Prism 4 software. After testing the normality of data distribution with Kolmogorov-Smirnov, Shapiro-Wilk, and D'Agostino-Pearson tests, the statistical difference between two different experimental groups was analyzed by unpaired Student's t test. For data within the same experimental group, a paired Student's t test was used. Crystallization and Crystallographic Structure Determination-Crystallization experiments were carried out with lyophilized wild-type sMamb-1 and various modified toxins derived from alanine scanning, redissolved at 5 mg/ml in 50 mM sodium acetate, pH 5.
Accession Codes-The crystal structure data for the sMamb-1 wild-type and variants have been deposited at Protein Data Bank with accession codes (T23A, 5DO6; wild type P2 1 , 5DU1; and wild type P4 1 2 1 2, 5DZ5). Docking Studies-We used ZDOCK (server version 2. 3. 2f) to carry out the protein-protein docking simulations of rASIC1a to sMamb-1 crystal structures. ZDOCK performs rigid-body docking by exploring both the rotational and translational degrees of freedom of the protein structures. The homology model of the channel in the desensitized state at conditioning pH 7. 0 was used. The toxin was represented by its four crystal structures of wild-type PDB 5DU1 chains A-D. ZDOCK was used with default settings along with the filtering option. To take into account the data from alanine scanning, complex solutions from the top 2000 ZDOCK predictions were filtered using the rASIC1a-Phe-350/sMamb-1-Leu-32 pairing residues and a 6-Å distance cutoff.
The preferred crystal form depends strongly on the protein  sequence, but most modified toxins respond positively to streak seeding  (15)  with the tetragonal crystal form. Even if the crystal seeds deposited along the streak fail to grow, crystals of a different polymorph nucleate along the line to yield crystals suitable for x-ray data collection. The resolution to which the crystals diffract ranges from 2. 9 to 1. 5 Å. The crystal structures of two wild-type sMamb-1 polymorphs and five alanine variants have been determined (Table  3 ). Among the variants, the T23A crystal form with a higher solvent content was instrumental in obtaining a solution for the x-ray structures. No molecular replacement solution could be obtained using neither the NMR models nor using truncated crystal structures from three-finger fold toxins.
angusticeps MT7, for which crystals of various morphology were obtained but none that lead to useful x-ray data until the diiodotyrosine variant was successfully crystallized  (37). models obtained by NMR (Fig. 6 ). The ensemble of molecules obtained by x-ray crystallography gives an idea of the diversity that exists in the crystal lattice. The regions that show the greatest variation are finger III and to a lesser extent the tip of finger II. The highest r. m. s. d. on C␣ for residues 1-39 is 0. 7 Å, twice that for the best agreement with any of the NMR models. This stems from variations in the NMR ensemble that are mainly located in the lower part of finger II, a region well conserved among all the crystal structures. In addition, there are differences in the well structured disulfide-stabilized core of the polypeptide between the crystal and NMR structures (Fig.
Acknowledgments-We thank members of the Lingueglia team for discussions,  M. Lazdunski  for support,  V. Friend  for technical assistance, and  C. Chevance  for secretarial assistance. The help of the staff at the  Soleil beamline Proxima 2A  and  ESRF  beamline  Massif1 ID30A-1  and the grant of beamtime are acknowledged with gratitude, in particular to  Drs. Shepard  and Savko for assistance during data collection. We thank  G. Upert  for fruitful discussion.
* This work was supported by  CNRS ,  INSERM , and  Agence Nationale de la Recherche  Grant  ANR-13-BSV4-0009. The authors declare that they have no conflicts of interest with the contents of this article. The atomic coordinates and structure factors (codes  5DU1 ,  5DZ5 , and  5DO6 ) have been deposited in the Protein Data Bank (http.
EAG amplitudes were calculated by subtracting the solvent response. Analyses were done with Clampfit 10 software (Molecular Devices). Mating survey with or without antennae. Single pair matings were organized as follows: 1) male and female having both their antennae (positive control), 2) both male and female with no antennae, 3) male with no antennae and intact female and 4) intact male and female with no antennae. Six pairs of each of the three categories were kept with sugar water under the same conditions as the regular rearing and observed every two hours during three scotophases for mating. Egg laying was recorded after the 3 days and eggs were kept until larvae hatching, if any.
Acknowledgements We thank  Christine Merlin  ( Texas A&M, USA ) for precious advices in egg injection and  Aurélie Janvier  ( iEES-Paris, France ) for help in genotyping. This work was supported by an  INRA   grant  ( Plant Health and Environment department ) and an  INRA  fellowship to FK. We also thank the  EFOR network and TEFOR (Investissement d'avenir- ANR-II-INBS-0014 ) for promoting our model and innovative transgenesis tools.
e. the adhesion and migration processes. For that purpose, we compared adhesion capacities of two breast carcinoma cell lines (MCF-7 and MDA-MB-231) representative of two molecular subtypes of breast cancer (luminal and basal- like) to different barrier models  [7]. We used (i) well-characterized animal in vitro BBB models  [8, 9] , (ii) HUVECS, commonly found in the cancer related literature  [10] , and (iii) a new human BBB model recently developed in the laboratory  [11, 12]. To be considered as valuable, the model should display at once BBB properties closed to in vivo data and interactions with breast cancer cell lines which fit with their described propensity to form brain metastases. At the molecular level, the involvement of breast cancer glycosylation in adhesion was analyzed.
Acknowledgments The authors would like to thank  Mrs Lucie Dehouck  and  Mr Emmanuel Sevin  for technical assistance,  Mrs Marlène Mortuaire  for her technical assistance in cancer cell culture and also service  Maternité du centre hospitalier de Beuvry (Beuvry, France) , and in particular  Mr Patrick Jacson  ( Director of the Hospital Centre ),  Dr Fabienne Viala  ( Head of the Maternity Unit ) and  Mr Jean-Yves Caudrelier  (Senior Health Manager in gynecology and obstetrics), as well as the midwife team for collecting cord blood samples.