dataesr/scientific-paragraphs-categorization huggingface dataset:
Model parameters For the segmentation of the the training region D 1 within the inpainting domain D we use the activecontour MATLAB function by which the Chan-Vese algorithm can be called. For this we fixed the maximum number of iterations to maxiter= 1000 and use the default value as a tolerance on the relative error between iterates as a stopping criterion. We use the default values for the parameters µ and ν in  (2). The subsequent labelling phase was performed by means of the standard MATLAB kmeans function after specifying a total of K = 35 labels to assign. The labelling was iteratively repeated 5 times to avoid misclassification. Once the detection of the inpainting domain is completed, in order to provide a good initialisation to the exemplar-based model we use the TV inpainting model (  4 ) with (  6 ) with the value λ = 1000 and a maximum number of iterations equal to maxiter2= 1000 with a stopping criterion on the relative error between iterates depending on a default tolerance.
Finally, we followed  [35]  for the implementation of the exemplarbased inpainting model: for this we specified 12 propagation of iterations and tested different size of the patches. In order to avoid memory shortage, we restricted to patches of the size 5 × 5, 7 × 7 and 9 × 9. The numerical tests were performed here on a standard MacBook Pro (Retina, 13-inch, Early 2015), 2,9 GHz Intel Core i5, 8 GB 1867 MHz DDR3 using MATLAB 2016b.
Preprocessing and parameters As we just saw, such a complex restoration process necessitates significant user decisions. In fact the mask containing the sub-domain to be restored must be drawn by the user as well as the edges along which Neumann boundary conditions should be applied and the sub-domain edges where the drift-field should be put to zero. For our experiments we used the discretisation proposed in  [26]. Then the linear system was solved using the MATLAB UMFPACK V5. 4. 0 LU solver. It took 8. 61 seconds to numerically obtain the final result of Figure  10  and 6. 10 seconds for the final result of Figure  9. For the inpainting step of Figure  11 , we used the implementation of the exemplar-based inpainting algorithm from [39] [4] with the nlmedians method, 9 × 9 patches, two scales and 3 iterations.
Discussion and future work We proposed in this section a method to restore covered up parts of a manuscript using infrared information. For the illuminations from the primer that we worked on, the results are mostly satisfying, especially when the added pigments do not appear [4] The code is freely available at IPOL: https://doi. org/10. 5201/ipol. 2015. 136 on the infrared or when the addition doesn't have too much texture. This method necessitates some patient work for the mask creation and is heavily dependent on the infrared wavelength. Moreover it hasn't been tested on other illuminated manuscripts. Future work should address these difficulties and test the method on a larger dataset. For the mask creation phase, a semi-supervised segmentation step could be inserted. In this work, we have only used the visible image and a single infrared image.
Acknowledgements Luca Calatroni  acknowledges the support of  Fondation Mathémathique Jacques Hadamard (FMJH). Simone Parisotto  acknowledges the  UK Engineering and Physical Sciences Research Council (EPSRC)  grant  EP/L016516/1  for the  University of Cambridge Centre for Doctoral Training , the  Cambridge Centre for Analysis. Carola-Bibiane Schöenlieb  acknowledges support from the  Engineering and Physical Sciences Research Council (EPSRC)  ' EP/K009745/1 ', the  Leverhulme Trust  project 'Breaking the non-convexity barrier', the  EPSRC  grant ' EP/M00483X/1 ', the  EP-SRC centre  ' EP/N014588/1 ', the  Alan Turing Institute  ' TU/B/000071 ',  CHiPS  ( Horizon 2020 RISE  project grant), the  Isaac Newton Institute , and the  Cantab Capital Institute for the Mathematics of Information.
Statistical analyses. Children were excluded from the analyses if information on both night-waking and inattention/hyperactivity was missing for more than one time point, resulting in a sample size of 1342 children (71% of the children included at birth). Amongst them, missing data for the covariates represented only 2. 0% of the total data, thus simple imputation were performed (i. e. mean value for continuous variables and the modal value for categorical ones). To optimize the analysis of repeated measures in a context of co-evolving outcomes, Nagin's method for group-based trajectory modeling  24  (PROC TRAJ procedure, SAS 9. 4 SAS institute INC, Cary, NC, USA ® ) was used to compute joint trajectories of night-waking and inattention/hyperactivity from age 2 to 5-6. This method allowed us to identify within our population distinctive developmental trajectories for both outcomes.
Acknowledgements Collaborators: We thank the EDEN mother-child cohort study group ( I. Annesi-Maesano ,  J. Y. Bernard ,  J. Botton ,  M. A. Charles ,  P. Dargent-Molina ,  B. de Lauzon-Guillain ,  P. Ducimetière ,  M. de Agostini ,  B. Foliguet ,  A. Forhan ,  X. Fritel ,  A. Germa ,  V. Goua ,  R. Hankard ,  B. Heude ,  M. Kaminski ,  B. Larroque ,  N. Lelong ,  J. Lepeule ,  G. Magnin ,  L. Marchand ,  C. Nabet ,  F. Pierre ,  R. Slama ,  M. J. Saurel-Cubizolles ,  M. Schweitzer , O. Thiebaugeorges). We thank all funding sources for the EDEN study:  Foundation for Medical Research  (FRM, n°  ARS-3. 29 ), National Agency for Research (ANR , n°  03-BLAN-0359-01 , n°  06-SEST-03501 , n°  06-SEST-03502 ),  National Institute For Research In Public Health (IRESP: TGIR cohorte santé 2008 program ),  French Ministry of Health  (DGS, n°  CV05000146 ),  French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A)  and  Human Nutrition National Research Programs  (n°  4NU06G ),  Paris-Sud University, Nestlé ,  French National Institute for Population Health Surveillance (InVS , n°  05-PCTT2043 ),  French National Institute for Health Education (INPES , n°  007/05 DAS ), the  European Union   FP7  programs,  Diabetes National Research Program ,  Mutuelle Générale de l'Education Nationale complementary health insurance (MGEN) ,  French  national agency for food security, French speaking association for the study of diabetes and metabolism (ALFEDIAM).
5 mL/kg  [24]. Sedation was provided with remifentanyl infusion at 0. 1-2 mcg/kg/min. Neonates were continuously monitored with amplitude-integrated EEG and anticonvulsant drugs were used as necessary. All patients had an indwelling arterial line and arterial blood gases values were used to evaluate the respiratory status and calculate the oxygenation index (OI = FiO 2 x mean airway pressure/PaO 2 ) and the PaO 2 /FiO 2 ratio. Basic clinical data were real time registered in our electronic NICU database. The study protocol was approved by the local ethical committee of the South Paris University Hospitals (n. PP13-046) and parental consent was obtained upon NICU admission. Fifteen patients were eligible; four were excluded because of blood-staining and one because he died at 50h of life (that is, before completing WBH treatment) from multi-organ failure secondary to perinatal asphyxia.
Measurements To precipitate surfactant, BAL supernatant was ultracentrifuged (100000g; 4˚C;1h), and diluted with 5 mM Tris buffer, containing 150 mM NaCl (5mM; pH7) (Sigma-Aldrich, Germany), to a PC concentration of 8 mg/mL. We did not pool the material of different patients to take the biological variations into account. PC and cholesterol were assayed in triplicate using previously published enzymatic methods (Spinreact, St. Esteve de Bas, Girona, Spain)  [29, 30]. After surfactant precipitation, we obtained 50 μg of PC for each sample. Biophysical activity was evaluated applying 150 nL of surfactant suspension (8 mg/mL) in CBS at a frequency of 20 cycles/min. CBS mimics the cyclic changes in alveolar volume during breathing Table  1. Basic characteristics of all enrolled neonates. Data are expressed as mean (standard deviation) or numbers (%).
What is needed is an additional step in the pathway where promising therapies which demonstrate efficacy in a number of single centre studies are then tested more rigorously on a multi-site platform. Multi-PART (Multicentre Preclinical Animal Research Team, http:// www. dcn. ed. ac. uk/multipart/) is such a platform, set up with funding from EU FP7 for ischaemic stroke. However, the structure of the platform could easily be adapted for multisite studies for any CNS disease. The key objective of Multi-PART was "to implement and establish a platform for international multicentre preclinical stroke trials using the repertoire of randomised clinical trial design and the complexities of a multicentre, multimodel paradigm". This was made possible by the experience within the Multi-PART team of scientists and clinicians with expertise in a range of stroke models and outcome measures, regulation and ethics of in vivo research, precision, reproducibility & external validity in animal research, design and running of clinical trials, statistics, database and web site management, good laboratory practice (GLP), and standard operating procedures (SOPs), development & costing structures etc.
Coordination would need a Trial Steering Committee and central database for management of randomisation and data storage. Outcomes would need central adjudication of imaging (e. g. MRI, histology for lesion volume, microbleeds) and videos (behavioural & functional testing). Studies can utilise advanced trial techniques such as adaptive design, randomisation, and statistical analysis, and the concept extended to designing observational and characterisation studies across multiple laboratories. Key differences exist between preclinical and clinical RCTs, many of which could be ameliorated by adopting specific design elements in preclinical RCTs. Since patients are very heterogeneous, a variety of SVD models would be needed. Preclinical RCTs may need to incorporate both positive and neutral control comparator groups.
ACKNOWLEDGEMENTS A summary of the workshop proceedings consisting of short lectures and outcomes of discussion groups were provided by a writing group comprised of  Joanna Wardlaw ,  Karen Horsburgh ,  Rhian Touyz ,  Ken Smith ,  Anne Joutel ,  Roxana Carare ,  Maiken Nedergaard ,  Zameel Cader ,  Lisa Saksida ,  Malcolm Macleod ,  Mhairi Macrae ,  Andy Lockhart ,  Philip Bath ,  Terence Quinn ,  Colin Smith ,  Atticus Hainsworth ,  Tracy Farr ,  Lorraine Work ,  Seth Love ,  Steve Williams ,  Michael O'Sullivan ,  Rajesh Kalaria ,  Anna Williams ,  Cheryl Hawkes ,  Stuart Allan ,  Patrick Kehoe ,  Catherine Hall ,  Jason Berwick ,  Christopher McCabe ,  Colin Smith ,  Tom Van Agtmael ,  Hugh Markus. The administrative support of  Margaret Kinninmont  at the  BHF Cardiovascular Centre , Glasgow is gratefully appreciated.
The SNAP-tagged receptor was then extracted from the cell using suitable detergents and the non-purified material was analysed by SDS-PAGE. The SNAP-mGlu 5 -Δ856 receptor migrated predominantly as dimers (apparent molecular weight 180-200 kDa) under non-reducing conditions and as a monomer (apparent molecular weight 90-100 kDa) under reducing conditions (Supplementary Fig. 3 ). Although both monomeric and dimeric receptor could be visualized on an SDS-PAGE gel, we based our analysis on the gel mobility shifts of the monomeric species formed under reducing conditions (plus DTT) since small changes in molecular weight were more obvious. The data show a small decrease in molecular weight of the monomeric receptor when each of the N-glycosylation sites N1-N5 were mutated (Fig. 2B ), suggesting they are involved in glycosylation of the WT receptor.
Graphs were analysed using GraphPad Prism version 7. 0 (GraphPad software, San Diego, CA). Functional concentration response data were fitted to a four parameters equation. The pEC 50 values are expressed as the mean ± SEM. Detergent-solubilized receptor binding and thermostability measurements. After 48 h of transfection, HEK293 cells were incubated one hour at room temperature with the NAM [ 3 H] MPEP at 80 nM (≈five times the K D ) in a buffer containing 25 mM HEPES pH 7. 4 and 400 mM NaCl. Membranes were then solubilized with 0. 83% (w/v) MNG3, 0. 042% (w/v) CHS for 1 h at 4 °C. Solubilized receptors (SNAP-mGlu 5 -∆856) were then incubated for 30 minutes at various temperatures ranging from 4 to 40 °C. The samples were then chilled at 4 °C for 5 min and the detergent solubilized ligand binding experiment performed as previously reported  22.
N-linked glycosylation site mutagenesis. N-linked glycosylation sites (NX (S/T)) were first predicted (Protter software) then mutated by a single substitution of the N residues to D making six distinct constructs: N88D (N1), N210D (N2), N378D (N3), N382D (N4), N445D (N5), and N734D (N6). These mutations were furthermore made in combination to generate the N89D/N210D/N445D (N1N2N5) and N89D/N210D/ N378D/N382D/N445D (N1-5) constructs. All constructs were confirmed by sequencing (Eurofins Genomics). SNAP-mGlu 5 -∆856 mutants were expressed in the HEK293 cell line and labelled using SNAP-Red as described within previous section. Proteins were then extracted from membranes using 0. 83% (w/v) MNG3/ 0. 083% (w/v) CHS with mild shaking for 45 min at 4 °C. The solution was then centrifuged at 12,000 g for 30 min at 4 °C to eliminate the cells debris.
Statistical analysis. Dunnett's test as part of one-way ANOVA was used for multiple comparisons with a defined reference level. All graphs were analysed using GraphPad Prism version 7. 0 (GraphPad software, San Diego, CA). Statistical significance was set as one, two, three and four stars to indicate P < 0. 05, P < 0. 01, P < 0. 001 and P < 0. 0001, respectively.
Acknowledgements The authors would like to acknowledge  Laurent Prézeau ,  Julie Kniazeff ,  Philippe Rondard  and  Cyril Goudet  for helpful discussion and  Chris Tate  for a critical reading of the manuscript. We are grateful to  Eric Trinquet  ( Cisbio, France ) for providing us the SNAP tag full-length mGlu 5 expression plasmid, as well as to Arpege and FFP platforms at the IGF. Karine Rottier  was supported by  FRM  " ingenieur de Recherche" program  and  Chady Nasrallah  is supported by  ATIP grant  ( 2014-2016 ) and the  University of Montpellier ,  Postodocotral scientist program  ( 2016-2018 ). Joan Font  and  Amadeu Llebaria  acknowledge  MINECO  ( PCIN-2013-017 C03-01  and  CTQ2014-57020-R ), the  Catalan Government  ( 2014SGR109  and  2014CTP0002 ) and to  ERANET Neuron project 'LIGHTPAIN'for support.
1c-f ) and is observed when residues R297 and D413 -located at the interface between the transmembrane and cytoplasmic domain of CNGA1 channels (Fig. 1a )are mutated. Therefore, the altered gating of mutant channels R297A/C, D413A/C could be caused by defects of the coupling between the binding of cGMP and channel opening. Residues R297 and D413 could be key players of the involved signal transduction mechanisms. The double mutant channel D413C_R297C can be locked in the open state. R297 is highly conserved in all known CNG channels, whereas D413 is conserved in all CNGs with the exception of CNGA4, a subunit that fails to form functional channels when expressed in a heterologous system (Fig. 2A , Supplementary Table  1 )  33. Analysis of the Cryo-EM structure of TAX-4 channel captured in the open state (PDB ID:5H3O) located R297 in the intracellular portion of S5 (Fig.
Hydrophobic interactions between residues in the upper portion of S5 and in the P-helix have a major role in a way reminiscent of what occurs in the Slo2. 1 channels  4, 41, 42  and in the Ca 2+ -activated potassium channels KCa3. 1  3. Secondly, we have introduced exogenous cysteines in distant domains of CNGA1 so to identify key events underlying gating. The analysis of three double mutants reveals these key events: (1) when residues in position   S1. (C) Mapping CNGA1 residues on TAX-4 structure (PDB ID: 5H3O) shows the location of mutated residues in S6 and the P-helix. (D) Collected data of the effect of 2. 5 mM MTSET i in the open (red) and closed (black) state in the S6 transmembrane domain and in the C-linker. (E) left: current recordings obtained in the absence (red) and in the presence of 1 mM cGMP (black) at ± 60 mV for mutant channels F380C_L356C.
, Foster City, CA, USA), 2-6 days after RNA injection, at room temperature (20-24 °C)  30. The perfusion system allowed a complete solution change in less than 0. 1 seconds  10, 27. Macroscopic and single-channel current recordings were obtained with borosilicate glass pipettes which had resistances of 2-5 MOhm in symmetrical standard solution. The standard solution on both sides of the membrane consisted of (in mM) 110 NaCl, 10 Hepes and 0. 2 EDTA (pH 7. 4). Solutions were buffered with tetramethylammonium hydroxide at the desired pH. When the cation X + was used as the charge carrier, NaCl in the standard solution on both sides of the membrane patch was replaced by an equimolar amount of the cation X +. We used Clampex version 10. 0 for data acquisition. Recordings to perform noise analysis were low-pass filtered at 10 kHz.
All other macroscopic current recordings were low-pass filtered between 1 to 10 kHz. Data analysis. Single-channel currents (i) were estimated from patches containing only one channel and fitting normalized all-point histograms with two-component Gaussian functions. Data in this manuscript are presented as mean ± SEM (V-I relationships), dot-plots (with means ± SEM) or box-and-whisker when data sets need to be statistically compared. n indicates the number of patches. Data analysis and figures were made with Clampfit version 10. 1 (Molecular Devices, Sunnyvale, CA, USA) and Sigmaplot 12. 5 (Systat Software, Chicago, IL, USA). We excluded data when we lost the patch during the experiments, when the level of expression was too low and we could not distinguish the noise from random channel openings, from electrical noise due to an unstable patch and/or from spurious electrical noise.
Acknowledgements We acknowledge the financial support of the  NEUROSCAFFOLDS  Project n. 604263. A. M. 's work was supported by a  Long Term EMBO Fellowship  ( ALTF 1427-2014 ) and  Marie Curie Action  ( LTFCOFUND2013 ,  GA-2013-609409 ). We thank  S. Onesti  for supervising the sequence alignment analysis. We thank  F. Romagnoli  and  M. Lough  for checking the English.
research; L. K. analyzed data; Lthe paper. S. F. is supported by the  Gatsby Charitable Foundation , the  Simons Foundation , the  Schwartz Foundation , the  Kavli Foundation , and the  National Science Foundation NeuroNex Program  Award  DBI-1707398. L. K. was supported by Grants  ANR-10-LABX-0087 ,  ANR-10-IDEX-0001-02  and  ERC grant PrediSpike ,  ERC -312227.
Digitized data were analyzed off-line using pClamp10. 6 (Molecular Devices, United States) and Neuromatic package within IGOR Pro 6. 0 environment (Wavemetrics, United States). The identity of interneurons was first assessed by analyzing the firing properties of neurons recorded in current-clamp mode as previously described  (Orduz et al. , 2015). Briefly, we used a depolarizing pulse of 800 ms to measure the instantaneous discharge frequency (F initial ), the frequency at 200 ms (F 200 ), the frequency at the end of the pulse (F final, ) and the total frequency (F total ). We calculated both early and late accommodations. The membrane input resistance R m of neurons was calculated from a -200 pA hyperpolarized 800 ms step. The spike threshold, the first and second action potential amplitudes, and their corresponding durations were extracted from a 200 pA depolarizing pulse of 80 ms to calculate the amplitude reduction and duration increase.
This latter was connected to a current controller that in turn was commanded by a pulser device that creates programmable TTL pulses from a software (Prizmatix Pulser/Pulser PC Software, Prizmatix Ltd. , Israel). Mice were photostimulated according to a 3 h protocol composed by 36 light trains of 30 s delivered at 10 Hz [10 ms on/90 ms off pulses; ∼3-4 mW per pulse, a power estimated from measurements in continuous wave (CW) mode] and separated by a resting period of 4. 5 min. Considering that our duty cycle is 10%, we estimated that the total energy applied during a 30 s photostimulation train is equivalent to 9-12 mJ. Prior to the surgery, the power at the tip of each mini-optic fiber was systematically measured with an optical power meter (PM100D coupled with sensor S120C, Thorlabs, United States) by connecting it to the LED system operating in CW mode (maximum output power at the 200 µm mini-optic fiber tip: ∼4.
Statistics All data were expressed in mean ± SEM. A level of p < 0. 05 was used to designate significant differences. Two group comparisons were performed using the non-parametric Mann-Whitney Test. Multiple comparisons were done with the non-parametric Kruskal-Wallis Test followed by a Dunn's multiple comparison test. Statistics and plotting were performed using GraphPad Prism 5. 00 (GraphPad Software Inc. , United States).
FUNDING This work was supported by  Fondation pour la Recherche Médicale  («Equipe FRM DEQ20150331681»),  Agence Nationale de la Recherche  ( ANR-14-CE13-0023-02 ),  Fondation ARSEP  and subaward agreement from the university of Connecticut with funds provided by the grant  N • RG-1612-26501  from  National Multiple Sclerosis Society (NMSS). FO was recipient of FRM and ARSEP post-doctoral fellowships and is supported by the  Chilean National Fund for Scientific and Technological Development (FONDECYT , INICIACION # 11160616 ). MCA is a CNRS investigator.
Experimental Procedure First, the rMT of each participant was assessed using TMS. TMS (biphasic) pulses were delivered using a 70 mm figure-8-coil connected to a Magstim Rapid 2 (Magstim Co. , United Kingdom) and MEPs were registered using the software LabChart 7 (ADInstruments, Oxford, United Kingdom) at a sampling frequency of 10 kHz, applying a bandpass filter between 20 and 2500 Hz. Participants' MEPs were recorded from the FDI and the ADM of the right, dominant hand, using Ag/AgCl surface electrodes (6 mm diameter), with the ground electrode placed on the participants' wrist. The left hand area (M1) was found by eliciting visible twitches on the contralateral hand muscles and the hot spot for the FDI was assessed by measuring the rMT, indexed as the lowest intensity of stimulation able to elicit MEPs of >50 µV peak-to-peak amplitude on five out of 10 consecutive pulses  (Rossini et al.
Participants responded by abducting the right index finger to press the space bar of the keyboard placed vertically next to their arm, with the keys facing the right hand. They were asked to keep the muscles relaxed before and after each response. Throughout each session (about 2 h), subjects were seated on a comfortable chair at a distance of 57 cm from the computer screen, with their chin on a chinrest. The task was presented on a 22 Samsung 2233RZ LCD monitor running at 120 Hz on a Windows 7 machine running Matlab 7. 2 and Psychtoolbox 2. 0 experimentation presentation software.
Participants Participants were healthy volunteers who were enrolled in the study after we obtained informed written consent. They were all students of the University Claude Bernard of Lyon, were recruited through web advertising, and were paid for their participation. None of the participants had a history of neurologic or psychiatric disorders, and the vision of all participants was normal or corrected to normal. We had no prior beliefs or pilot data to estimate a realistic effect size. We recruited 20 participants for Experiment 1 because this number reflects the average sample size in similar PPS studies. Once results were obtained, a power analysis (paired-samples t test, Cohen's d = 0. 6, α =. 05, one-tailed) indicated a minimum of 19 participants to reach a power of. 8 (the effect size from Experiment 1 was computed as if reflecting a between-participants design, and thus, this power analysis revealed itself to be conservative).