dataesr/scientific-paragraphs-categorization huggingface dataset:
The CHARMM27 force field was used for the tRNA  (Foloppe and MacKerell 2000)  and the TIP3 model for water  (Jorgensen et al. 1983). For the protonated form of adenine, we used a force field specifically developed in this work. Calculations were done with the NAMD program  (Phillips et al. 2005). Ten nanoseconds of molecular dynamics were performed at constant room temperature and pressure. To model residue A 1 of tRNA in the crystalline environment, the symmetric units were constructed according to the crystallographic symmetry operators. Nucleotides within a 24 Å sphere around nucleotide A 1 were retained for simulations. The rest of the system preparation was identical to the setup used for the simulations of tRNA in solvent.
2007) , where the tRNA was treated as a single dielectric medium with a dielectric constant of 2; solvent was treated as another medium with a dielectric constant of 80, the experimental value for bulk water. The boundary between the two dielectric media was defined as the tRNA molecular surface, computed with a 1. 6 Å radius probe sphere. For the potential calculation, the system was discretized using a cubic grid with a 68 Å edge and a spacing of 0. 4 Å. The Poisson-Boltzmann equation was solved with Coulombic boundary conditions, using the CHARMM program  (Brooks et al. 2009 ). We used an ionic strength corresponding to a 0. 15 M concentration of monovalent ions. The proton binding constant of A1 is related to ΔΔG by the relationship: pKa tRNA = pKa adenine + 1 2. 303 kT DDG A1(0) A1(+) , where pKa tRNA and pKa adenine are the pK a values of the titrating group in the tRNA and in the reference molecule, adenine, respectively.
ACKNOWLEDGMENTS We thank the staff of the macromolecular crystallography beamlines  PX1  and  PX2  at the  SOLEIL synchrotron (Saclay, France ) for expert assistance during data collection. This work was supported by grants from the  Centre National de la Recherche Scientifique  and by  Ecole polytechnique  to  Unité Mixte de Recherche  no. 7654. A. M. was a recipient of a Gaspard Monge PhD fellowship from  Ecole polytechnique. Received June 10, 2016; accepted January 26, 2017.
These essentially encode the logical relation in the target type theory, similar to the approach we took in Section 4. 1 (Consistency of CC  ). Recent work by  Nuyts et al. [2017]  develops a theory that internalizes parametricity, including the important concept of identity extension, and gives a thorough comparison of the literature. By building a target language based on one of these systems, it's possible that we could eliminate the rule [≡-Cont] as an axiom and instead derive it internally. Verified Compilation. CertiCoq is a mechanically verified optimizing compiler currently under development  [Anand et al. 2017]. It compiles Coq's Gallina to CompCert's Clight. As mentioned in Section 1, CertiCoq is not a type-preserving compiler: it erases types before CPS conversion, optimizations, and closure conversion.
ACKNOWLEDGMENTS We gratefully acknowledge the valuable feedback provided by  Greg Morrisett ,  Karl Crary , and the anonymous reviewers. Part of this work was done at Inria Paris in Fall 2017, while Amal Ahmed was a Visiting Professor and  William J. Bowman  held an internship. This material is based upon work supported by the  National Science Foundation  under grants  CCF-1422133  and  CCF-1453796 , and a  Northeastern University Scholars' Independent Research Fellowship. This work was, in part, supported by the  European Research Council  under  ERC Starting Grant   SECOMP (715753 ). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the  National Science Foundation.
Results Overall, 801 patients were included in our study; their basic biometric and specific perioperative anaesthesia related data was collected by study nurses. Patients receiving supplemental regional anaesthesia techniques were excluded. After thorough screening, 615 complete datasets were included for final analysis (Table  1 ). Overall cohort data exhibit except of TIVA vs balanced anaesthesia no differences in dichotomized data. Detailed evaluation of the main cohort data (+NMBA/-NMBA) indicate differences in distribution within the respective t-test an chi-square tests (Table  1 ).
Limitations Anyhow, our study has some limitations. The cohort design has no active randomization displaying daily routine and were only single centre collected. Hence our statements can merely partially generalized. Although the complete dataset has a homogenous distribution, the two main subcohorts (+NMBA/-NMBA) within our study population exhibited statistic significant differences. Nevertheless, in general these differences were small and statistic significance was mostly attributable to the large study population rather than clinical relevance. Despite that, a cohort bias cannot be completely excluded. NMM was standardized and verified by our study nurses before extubation. Nevertheless this method has a potential bias. Additionally we applied an uncalibrated semiquantitative NMM which can exhibit a greater bias rather than a calibrated device.
This list was further filtered to exclude proteins often found abundant in MS analyses and therefore less likely to be specific partners of Eml1, such as histones and RNA-processing proteins. Nuclear proteins associated with nucleic acids (e. g. transcription factors), and extracellular matrix proteins were also excluded since Eml1 is found primarily in the cytoplasmic compartment. A new list of 176 proteins was obtained after filtering (Supplementary Table  S2 ). Gene ontology (GO) analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) Functional Annotation Tool 38 (https://david. ncifcrf. gov/home. jsp) (Fig. 3a-c , also see Supplementary Table  S2 ). The most represented biological processes were cell cycle, cell division and transport (Fig.
3a ). Concerning cellular component, proteins were classified mainly as cytoplasmic, as expected based on our exclusion criteria. Among these, many proteins were found in the cytoskeleton and membrane categories (Fig. 3b ). Molecular function classification identified the majority of proteins as having protein binding activity, and nucleotide, ATP and MT binding were well represented (Fig. 3c ). The 176 list was then analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) Functional Protein Association Network 39 (string-db. org) based on known and predicted protein-protein interactions (Fig. 4 ). The software was able to connect the majority of items, with only a small percentage of disconnected nodes. A large network of highly interacting nodes was revealed (grey box in Fig.
5j ). However, the apico-basal height of HeCo (pro)metaphase APs was reduced compared to WT (Fig. 5k ), leading to a distorted cell shape, with cells being flatter. This data fits the 2D measurements showing increased en face single plane areas of HeCo (pro)metaphase APs. To assess the impact on overall tissue morphology of increased horizontal area occupied by (pro)metaphase cell somata, we evaluated cell density in WT and HeCo VLs. Indeed, when integrated in a tissue cells adapt to the presence of other cells around them that exert pushing forces proportionate to their density  30. Due to INM, AP nuclei are only visible at the VL when they are in the G2-M transition, during mitosis, and during M-G1 transition. We thus counted the number of nuclei that were visible in the same en face z-stack where the area of (pro) metaphase cells was measured (Fig.
Confocal images were acquired with a 0. 17 µm or 0. 3 µm z-stack depth. Images were analyzed using Image J (Fiji) to obtain the whole z-stack data set and for γ-tubulin and Arl13b quantification. At least two ROIs of 120 × 35 µm were quantified per embryo. The Imaris software was used for single-cell 3D reconstruction and spindle length measurement. Single (pro)metaphase cells were recognized from DNA shape and centrosome position and cropped from whole-section images to isolate them. Z-stacks of cropped single cells were reconstructed in 3D by applying voxel depth, and pole-to-pole distance was measured. Pull-down. E13. 5 timed-pregnant Swiss mice (Janvier Labs, France) were sacrificed by cervical dislocation. Embryos were dissected and both brain hemispheres collected in L-15 medium, and explants immediately frozen in liquid nitrogen and ground into a powder.
Peptides extracted from each band were analyzed by nano Liquid Chromatography (LC)-MS/MS using an Ultimate 3000 system (Dionex S. A. ) coupled to an LTQ-Orbitrap XL mass spectrometer (Thermo Scientific). Data-dependent acquisition was performed in the positive ion mode. Survey MS scans were acquired in the 475-1200 m/z range for each sample, with the resolution set to a value of 60 000. Each scan was recalibrated in real time by co-injecting an internal standard from ambient air into the C-trap ('lock mass option'). The 5 most intense ions per survey scan were selected for CID fragmentation and the resulting fragments were analyzed in the linear trap (LTQ). Target ions already selected for MS/MS were dynamically excluded for 180 s. Data were acquired using the Xcalibur software and the resulting spectra analyzed via the MascotTM Software (Thermo Scientific).
1] [72]  , version 3. 0. The mass spectrometry proteomics data were deposited to the ProteomeXchange Consortium via the PRIDE  73  partner repository with the dataset identifier PXD006837. Protein lists were analyzed using the DAVID Functional Annotation Tool  38  (https://david. ncifcrf. gov/home. jsp) for Gene Ontology generation, and STRING Functional Protein Association Network 39 (string-db. org) to reveal interactions between proteins. See also Supplementary Information for more details on MS data analysis. En face immunohistochemistry. Following the protocol adapted from ref. 44  , mouse embryonic brains were fixed in 4% w/v PFA (Sigma-Aldrich, France). Cortical explants were dissected and incubated 15 min at RT in PBST 1% (PBS 1X containing 1% Triton X-100 v/v and 0. 02% sodium azide).
Extensive washing was performed in PBST 1% and PBS 1X before mounting the explants. Fluorescently stained sections were imaged as previously described. Confocal images were acquired with a 0. 2 µm z-stack depth for a total depth of 9-10 µm (Olympus FV10i microscope and TCS Leica SP5-II). At least two randomly-chosen ROIs were imaged for each hemisphere. Images were analyzed using Image J (Fiji) to obtain the whole z-stack data set and the cell counter and measuring plugins for quantification. Cell counting and single metaphase cell area measurements were performed in the same ROIs (100 × 100 µm) and on the first layer of cells starting from the VL. Areas were measured on the z-stack corresponding to the largest diameter of metaphase cells. For cell volume and height measurements, individual (pro)metaphase cells were recognized from DNA shape and centrosome position, and cropped for manual segmentation.
Acknowledgements We thank  Michel Kielar ,  Laurence Goutebroze ,  Richard Belvindrah ,  Marika Nosten-Bertrand ,  Delfina Romero  and  Melissa Stouffer  for helpful advice. We thank  Richard Bayliss  and  Andrew Fry  for the gift of the EML1-N-ter construct and for helpful discussions on Eml1 structure and function. We thank  Melissa Stouffer  for help with in situ hybridizations,  Veronique Marthiens  for advice on en face imaging,  N. Heintz  and  A. Andrieux  for supplying plasmids, and  C. Metin  for certain antibodies. We thank the IFM animal house and imaging facilities. We thank the  Ile-de-France region  for support of imaging and animal house facilities and the  FRC Rotary. We thank the IFM animal house experimentation and imaging platforms and the  CNRS-TAAM  for HeCo mouse mutant housing.
FF, SB and AU were associated with the  BioPsy Labex  project and the  Ecole des Neurosciences de Paris Ile-de-France (ENP)  network. We thank the  French Agence National de la Recherche  ( ANR-13-BSV4-0008-01 ),  Inserm ,  CNRS ,  UPMC ,  Fondation Bettencourt Schueller, Fédération pour la Recherche sur le cerveau (FRC) , the  European Union  ( EU-HEALTH-2013 ,  DESIRE ,  No 60253) , the  JTC 2015 Neurodevelopmental Disorders  and the  ANR  (for  NEURON8-Full-815-006 STEM-MCD ) for grant support to FF, the  French Ministry of Research, Fondation pour la Recherche Médicale  for PhD funding to SB, the  Ecole des Neurosciences de Paris  for PhD funding, and the  Company of Biologists  for a travel grant to AU.
Data selection for the present study: Q-bursts for sprite events in Spain For the present study, 4 kHz-sampled ELF data in the SR band from West Greenwich, Rhode Island (RI), USA (41. 6 N,-71. 7 W) are used along with video camera observations of sprites from the Ebro Delta in northeastern Spain (42. 94 N, 0. 14 E). A map of the observational stations showing the Great Circle Distance (GCP) between them is shown in Fig. 1. The ELF system in RI consists of two induction coil magnetic field sensors horizontally orientated along the geographical East-West and North-South direction and one vertical electric field sensor. Both the magnetic and electric field sensors have a flat band pass within the frequency range 1-100 Hz. We use only vertical electric field ELF data for the present work. The Sprites are recorded at 25 interlaced images per second by Watec 902H type cameras with light-sensitive 1/2 inch charge coupled device (CCD) sensors with 12mm F0.
8 lenses (31 angle of view) and UFO-Capture event detection software  (van der Velde et al. , 2014). The peak currents of the sprite producing lightning data are provided by the LINET (LIghtning NETwork) very low frequency and low frequency (1-200 kHz) time-of-arrival network  (Betz et al. , 2004). The data from the World Wide Lightning Location Network (WWLLN) are also used to identify the parent strokes for the sprites and their average VLF energy  (Hutchins et al. , 2012). All the data are time stamped in UT using GPS synchronization. Initially, 35 sprite events were selected spread over 8 days from the years 2011-2013. Out of the 8 days, 6 days of ELF data were available from RI. 21 possible ELF events were identified from the ELF time series data that could have possible correlation with the causative Q-burst lightning near the Ebro Delta.
So, the aliasing in modal frequency is important at a much lower level of CSD and thus should be taken into consideration in SR data sanitation. A simple arithmetic calculation supports the above discussion. We have 144 segments, 5 s long, to make a 12-min block. Suppose for simplicity that the mean frequency in the 143 segments was f o and all of those segments are 1 CSD. But in a single 5 s block with a 16 CSD event, the transient source was drastically displaced from the background source location and its mean frequency was shifted to f o þ Δf. Then the overall mean frequency for the full 12 min block would be (when normalized to total energy received ¼ The long-standing working hypothesis for this aliasing is that the transients represent the mesoscale lightning "tail" in the diurnal variation, with the background signal coming primarily from the earlier lateafternoon convective activity (of ordinary thunderstorms).
Acknowledgments We cordially thank  Robert Holzworth  for providing the WWLLN lightning locations and average VLF energy data for this study. We also thank  Oscar van der Velde  and  Serge Soula  for providing us with optical images of the sprites detected from the  Ebro Delta in northeastern Spain  and  Mariusz Neska  for the provision of the Belsk data. The work is partially supported by the  USIEF-India Fulbright-Nehru ,  UGC Raman post-doctoral fellowship  programs and by the generous support from the  Grainger Foundation, USA. The contribution of J ozsef B or was supported by the  J anos Bolyai Research Scholarship of the Hungarian Academy of Sciences  ( BO/00651/13/10h ). The work of J ozsef B or and Gabriella S atori was supported by the  National Research, Development and Innovation Office, Hungary-NKFIH ,  K115836.
The work of Joan Montany a was supported by research grants from the  Spanish Ministry of Economy and Competitiveness  and the  European Regional Development Fund :  ESP2013-48032-C5-3-R , and  ESP2015-69909-C5-5-R. The analysis of the datais partially supported by  DST-FIST fund reference Ref. SR/FST/PSI-191/2014 ,  Government of India. This investigation was initiated by  Vadim Mushtak  (deceased), and its findings are dedicated to his memory.
The MYT1L gene is constrained for missense and protein truncating variants Protein truncating variants (PTV) in developmentally crucial genes should occur less frequently than predicted in individuals without developmental disorders. The expected frequency of PTV in human genes has been reported in the ExAC database based upon parameters such as mutation rates for given nucleotide bases  [21]. We identified only a single loss of function variant in MYT1L in the ExAC database (accessed March 2017)  [21]. This is compared to an expected number of 33 loss of function variants, giving a probability of loss of function intolerance score of 1. 0 (a probability of loss of function intolerance score>0. 9 indicates intolerance to loss of function). In addition, 205 missense variants were reported, compared to an expected 402.
The phenotype of MYT1L variant carriers resembles that of 2p25. 3 microdeletion patients To examine the hypothesis that haploinsufficiency for MYT1L drives the 2p25. 3 deletion syndrome, we compared the phenotype of 2p25. 3 deletion carriers with those of MYT1L single nucleotide variant (SNV) carriers. The phenotypes associated with deletion of 2p25. 3 were defined by a literature review  [10, 11, 12, 13, and 14]  and we report an unpublished case (patient 10 in Table  1 ). The smallest region of overlap contains PXDN and MYT1L. No PXDN SNVs were identified in the DDD exome dataset. Using Fischer's exact test there was no significant difference between the proportions of deletion or SNV patients with the following phenotypes: intellectual disability, gross motor delay, speech delay, autism, overweight/obese or hyperphagia.
All variants found to be medically relevant and returnable were validated by Sanger sequencing in an independent CLIA laboratory (Emory Genetics Laboratory) before being returned to participants, although these validated variant results are not CLIA-compliant as the input DNA was originally isolated in a research laboratory. Ethics approval and consent to participate: Review boards at Western (20130675) and the University of Alabama at Birmingham (X130201001) approved and monitored this study. Consent for publication: A parent or legal guardian was required to give consent to participate in the study and inclusion of their data for publication, and assent was obtained from those children who were capable.
In silico assessment of MYT1L expression pattern in human brain The expression pattern of MYT1L in adult brain was examined using the Allen brain atlas (microarray data using Agilent 8x60K cDNA chip)  [23]. Expression data (Z score normalized) were downloaded for 6 adult brains (donor id 9861, 10021, 12876, 14380, 15496 and 15697) for the frontal cortex, hippocampus, basal ganglia and hypothalamus (at least 3 regions from each anatomical site). Expression levels were compared between each anatomical site using Mann-Whitney U-tests. The expression pattern of MYT1L in developing human brain was examined using the brainspan atlas. Microarray data (Z score normalized) was downloaded from 2 donor brains at 15-16 post conception weeks (pcw) (donor id 12840 and 14751) and 2 donor brains at 21 pcw (donor id 12566 and 12690) for the paraventricular nucleus, anterior hypothalamic nucleus, lateral hypothalamic area, dorsomedial hypothalamic area, venteromedial hypothalamic area, posterior hypothalamic nucleus and medial mammillary nucleus.
Morpholino oligonucleotide (MO) injections MO injections for sim1 were used as previously published  [45]. For the myt1la and myt1lb genes, two MOs for each gene were used to knockdown these proteins. One MO was designed to block translation and the other was designed to block splicing. The following MOs were synthesized by Gene-Tools, LCC: myt1la ATG MO, 5'-ACCTCCATCTGAATGCAGTGG TTGA; myt1la Splice MO, 5'-GGACAGCTGGAGACAAGAGAAATAA; myt1lb ATG MO, 5'-CATCTGCTACATCCACCTCCATCTG; myt1lb Splice MO, 5'-ATATTTGTGCCCTCAC CTATTTCAT; and tp53 MO, 5'-GCGCCATTGCTTTGCAAGAATTG. The Standard Control MO from Gene Tools was used as control. Solutions consisting of 4 ng/nl MO plus 0. 5% tetramethyl rhodamine dextran in dH20 were microinjected into one to four cell stage embryos. Images were acquired using a Zeiss Axioplan2 microscope fitted with an AxioCam camera using AxioVision software, or, with a Zeiss stereoscope fitted with a Canon Oneshot digital camera.
Acknowledgments We thank the families who kindly agreed to be part of this study. This study makes use of data generated by the  DECIPHER Consortium. A full list of centres who contributed to the generation of the data is available from http://decipher. sanger. ac. uk and via email from decipher@sanger. ac. uk. The research team acknowledges the support of the  National Institute for Health Research , through the  Comprehensive Clinical Research Network. We are grateful to the patients and their families who contributed to this study. We would like to thank members of the  HudsonAlpha CSER team , especially  Shirley Simmons ,  Kelly East ,  Whitley Kelley ,  Kevin Bowling ,  Susan Hiatt ,  Candice Finnila ,  David Gray ,  James Lawlor , and  Michelle Amaral , for help with sequencing data analysis.
Funding for the project was provided by the  Wellcome Trust. We declare that those who collected data and deposited it in the DECIPHER database bear no responsibility for its use and interpretation in the current work. The DDD study presents independent research commissioned by retardation". the  Health Innovation Challenge Fund  (grant number  HICF-1009-003 ), a parallel funding partnership between the  Wellcome Trust  and the  Department of Health , and the  Wellcome Trust Sanger Institute  (grant number  WT098051 ). The cell biology part of the study was funded by a grant from  BDF Newlife   SG/15-16/07  (AM). This work was supported by grants from the  US National Human Genome Research Institute  (NHGRI;  UM1HG007301 ) and the  National Cancer Institute (NCI ;  R01CA197139 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
ACKNOWLEDGMENTS This work was supported by the  Juvenile Diabetes Research foundation  (#3-SRA-2014-282-Q-R, #3-SRA-2017-415-S-B, # 3-SRA-2017-416-S-B , # 26-2008-639 , # 17-2013-426 ), the  INSERM AVENIR program , the  INSERM , the  European Research Council  (# StG-2011-281265 ), the  FRM  (# DRC20091217179 ), the  ANR/BMBF  (# 2009 GENO 105 01/01KU0906 ), the  "Investments for the Future" LABEX   SIGNALIFE  (# ANR-17-ERC2-0004-01 ,  ANR-16-CE18-0005-02 ),  Club Isatis , Mr. and  Mrs. Dorato ,  Mr. and  Mrs. Peter de Marffy-Mantuano , the Dujean family, the  Fondation Générale de Santé  and the  Foundation Schlumberger pour l'Education et la Recherche.
Instrumentation HPLC and LC-MS analyses were performed with a Shimadzu LC-10ADvp equipped with an SPDM10Avp diode-array detector (Shimadzu Europa GmbH, Duisburg, Germany). ESI-MS spectra were recorded on a Shimadzu LC-MS-2010EV system with ESI interface, Q-array-octapole-quadrupole mass analyzer, and Shimadzu LC-MS solution Workstation software for data processing. For all LC and LC-MS analysis, ultrapure water 0. 1% TFA (A) and ultrapure acetonitrile 0. 1% TFA (B) were used as solvent system. The QCM device (open source QCM) was supplied from Novaetech s. r. l. (Napoli, Italy). ATR experiment was performed on FT-IR Jasco 430 Spectrometer (JASCO Corporation, Tokyo, Japan) utilizing an ATR cell composed by ZnSe, purchased from Pike Technologies (Madison, WI, USA). Spectra were recorded on cleaned quartz crystal at 2 cm -1 of resolution with 256 accumulations, from 4000 to 700 cm -1.