dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical Analysis. Statistical data analysis was carried out using the STATA software (version 13. 0, STATACORP LP, College Station, TX, USA). Qualitative variables were described in percentages, and quantitative variables were described by mean with standard deviation or by median with interquartile range. Intragroup serial comparisons of categorical variables at baseline and month 3 were carried out using the Wilcoxon signed-rank test. Intragroup serial comparisons of continuous variables at baseline and followup were carried out using the Exact McNemar signification probability test. Intergroup serial comparisons were carried out using Mann-Whitney test for categorical variables and Pearson's chi-square for continuous variables. Cohen's kappa coefficient was used to measure the interuser agreement for qualitative items on OCTA at baseline and follow-up.
Patients selection The study was designed as an observational clinical study, with the following inclusion criteria: at least one missing tooth to restore on dental implant, good oral hygiene, no inflammation and a minimum age of 18 years. Patients with general diseases which could influence the healing process, pregnant or feeding women, as well as those for whom implants required additional soft tissue augmentation were excluded. The study was performed in accordance with the Helsinki Declaration of 1975, as revised in 2000. All patients included in this study provided informed written consent for their data to be used for research purposes. We did not seek ethical approval as this was a purely observational study based on routine examination, check-up appointments and patients' medical notes and such studies are exempt from ethical approval under Polish Law.
5 mm. The selected emergence profile was concave and featured a chamfer-margin design (Fig. 1 ). After being scanned, all abutments were digitally designed using the Atlantis™ 3D Editor software (Dentsply Implants, Mölndal, Sweden) and then milled out of titanium (Atlantis™ Titanium or Atlantis™ Gold Hue, Dentsply Implants, Mölndal, Sweden). After central production the abutments were mounted into implants with an insertion guide. A silicone impression at the abutment level were taken according to the authors' own procedure described previously  [12]. Subsequently, temporary crowns made of composite material (Luxatemp, DMG, Hamburg, Germany) were provisionally cemented in place with Freegenol Temporary Pack cement (GC Dental Products Corp. Toriimatsu-cha, Japan). The definitive crowns, made of monolithic zirconia (Prettau®, ZirkonZahn, Brunico, Italy), were cemented in place at the final appointment with OliSemi Cem (Olident, Krakow, Poland).
This requirement reduces the combinatorial background and recovers the resonant structure of the squark decay. Furthermore, the masses of the two jets are required to be approximately equal, and the jets must evince substructure consistent with at least four non-top quarks. These conditions help to suppress the immense background of light-quark jets produced by the strong interaction, referred to as quantum chromodynamics (QCD) multijet events, which is estimated from data with a novel technique. The background from top quark-antiquark (tt) events is also significant; its contribution is estimated from simulation. The tt events in control regions are used in the estimation of the selection efficiency, jet mass scale, and jet mass resolution. The motivation for this search comes from natural SUSY, but the analysis aims more broadly for new phenomena in general.
To reduce the effect of pileup interactions, we ignore any charged hadrons not associated with the primary vertex in this clustering procedure. The primary vertex is chosen to be the vertex with the largest quadratic sum of the p T values of AK4 jets clustered from tracks assigned to the vertex and the p T corresponding to the negative vector-p T sum of these AK4 jets. The CA12 jet energies are corrected to compensate for the combined response function of the CMS calorimeters and the presence of neutral hadrons from pileup, with calibrations designed for AK8 jets  [40]. The data are corrected with an additional scale factor to account for the residual difference in the detector response between simulation and data. Miscorrections that result from the application of AK8 calibrations to the CA12 jets are measured and are accounted for in the final results, together with their uncertainties.
Sequencing data were subjected to quality control and further analysis using an in-house pipeline as previously described. 43 lignment of Fastq sequence files with the human genome reference (GRCh37/hg19) used BWA (0. 6. 1-r104),  44  with variant calling performed using Freebayes  45  and variant annotation using Alamut Batch (Interactive Biosoftware) softwares. VCF files were then converted into Excel format to enable manual variant filtration and prioritization. Only coding nonsynonymous and splicing variants (55 bp from exon-intron boundary) were retained for further analysis. Common sequence variants were then filtered out based on their minor-allele frequency (MAF) to exclude all variants with MAF R 0. 01 in the dbSNP build 141, ExAC, Exome Variant Server, and 1000 Genomes databases.
Retained variants were evaluated and prioritized based on their predicted impact at the protein level and predicted pathogenicity scores using a number of in silico softwares: Human Splicing Finder, SIFT, PolyPhen-2, Mutation Taster, Combined Annotation Dependent Depletion (CADD) score, and Multivariate Analysis of Protein Polymorphism (MAPP). Conservation across species was studied using PhastCons, PhyloP, and the BLOSUM62 matrix within BLAST. The American Journal of Human Genetics 102, 956-972, May 3, 2018 957.
Sanger Sequencing Prioritized variants in C11orf70 were further confirmed in the probands and segregated within other family members by Sanger sequencing. Primers flanking the exon harboring the mutations were designed using the NCBI Primer-BLAST tool with genomic sequence amplification performed using standard PCR conditions and annealing temperatures based on the primer Tm temperature. Primers are listed in Table  S1. Analysis of the sequencing data used SnapGene software (GSL Biotech).
Air-Liquid Interface (ALI) Culture BMI1 transformed normal human bronchial epithelial cells (BMI1 NHBE) were cultured at air liquid interface on collagencoated transwell inserts (passage 7) for 4 weeks as previously described. 46, 47 antitative RT-PCR Total RNA was extracted using Trizol Reagent (QIAGEN). cDNA was produced using Omniscript RT kit (QIAGEN). Real-time qPCR reactions were done in triplicate using the CFX96 touch real-time PCR system and iQ SYBR green Supermix and data analysis using Bio-Rad CFX Manager 3. 1 software (Bio-Rad Labs). Primers used for qPCR in human and Paramecium cells are listed in Table  S1.
Paramecium Gene Silencing We identified the Paramecium C11orf70 ortholog as GSPATG00011350001 (GenBank: XM_001443078. 1) using public databases CILDB and ParameciumDB. A 561 bp long DNA segment corresponding to the N terminus of the gene was cloned in L4440 plasmid between the two convergent T7 promotors. 51 Possible RNAi off-target effects were assessed using the ParameciumDB RNAi off-target tool. E. coli HT115 bacteria (lacking RNAase III activity) were transformed with this silencing vector and grown in Lysogeny broth (LB) medium. Paramecia (Paramecium tetraurelia d4-2 strain) were fed with the transformed bacteria over 3 days as previously described. 52 The RNAi experiment was repeated several times to ensure reproducibility of the results (n > 10). RNAi of the ND7 gene,  53  which affects trichocyst exocytosis without affecting cilia motility, was used as a negative control.
Paramecium Cilia Function Tests Paramecium velocity was tested using 3-5 paramecia per test transferred into a drop of conditioned BHB solution and tracked for 10 s every 0. 3 s to assess the swimming pattern under dark field microscopy, using MetaVue software. ImageJ software was used for image analysis and measurement of the swimming velocity. 56 or Paramecium cilia beating analysis, knockdown cells were adhered to a slide covered with Cell-TakTM (BD Bioscience) after silencing for 72 hr as previously described. 57 Cilia beating was recorded using a 633 oil immersion lens on an upright DM60 Leica microscope the same as for the nasal epithelia cells, at 500 frames per second at 37 C. The CiliaFA plugin in ImageJ was used for assessment of cilia beat frequency in Paramecium. 58.
Phylogenetic Comparisons The presence or absence of C11orf70 orthologs was determined by searches of selected organism genomes (at the genus level) using BLASTp at NCBI with the Chlamydomonas ortholog protein FBB5 sequence (GenBank: XP_001694050) as query. Apparent hits were confirmed only if they also gave FBB5 as the top hit in a reciprocal BLAST search. This procedure was also used to establish the presence or absence of two ODA subunits (HCgamma and IC2), two IDA subunits (I1HCalpha and IC140), two IFTA subunits (IFT122 and IFT140), four IFTB subunits (IFT46, IFT52, IFT88, and IFT172), ODA-DC2, and ODA16. Retention of additional IFT subunits by selected organisms was taken from van Dam et al. 61.
Functional Characterization of C11orf70 in Chlamydomonas Genomic sequences for Chlamydomonas C11orf70 ortholog FBB5 (Cre12. g556300; GenBank: XM_001693998. 1) and intron/exon boundaries were based on genome assembly annotation version 5. 5 and obtained from the Phytozome server. Alignments with FBB5 protein (GenBank: XP_001694050) orthologs were generated with MEGA version 6. 64  The expression vector pDIC2linkerHA was created by replacing the Chlamydomonas PsaD promoter and 5 0 UTR in pGenDlinkerHA  19  with the promoter and 5 0 UTR of the Chlamydomonas ODA-IC2 gene. 65 The resulting expression vector retains a unique EcoRI site between the IC2 ATG start codon and sequences that encode three copies of an HA epitope tag. Two overlapping gBlocks Gene Fragments (Integrated DNA Technologies) of 464 and 458 bp were used to insert FBB5 coding sequences at this EcoRI site.
Results Targeted Next Generation Sequencing Identifies C11orf70 Mutations in Individuals with PCD A targeted next-generation sequencing gene panel was used for mutational analysis in a cohort of affected individuals with PCD. As previously described, the panel contains all the currently known genes which, when mutated, cause PCD in addition to a set of other candidate genes predicted to play a role in cilia motility, based upon collaborative information derived from past PCD genetic mutation screening projects and a number of ciliate organism genome and proteome projects. 31 Screening of 161 unrelated individuals with a confirmed or presumed diagnosis of PCD revealed variants in a previously uncharacterized candidate gene, C11orf70 (GenBank: NM_032930. 2, NP_116319), in two unrelated case subjects where PCD diagnosis had been confirmed by a number of diagnostic clinical testing modalities.
42 irst, we identified a homozygous C11orf70 missense variant (GenBank: NM_032930. 2; c. 776A>G [p. His259Arg]) in one of two affected siblings in a Pakistani consanguineous family where the parents are first cousins. Sanger sequencing confirmed the homozygous status of this mutation in the affected individual and in their affected sibling as well as the carrier status of both parents and an unaffected sibling (Figure  1A ). This variant is found only once in the ExAC control exome database in a heterozygous carrier from the South Asian population, showing an overall allele frequency in unaffected controls of 8. 242eÀ06. It is absent from the EVS, 1000G, and dbSNP control databases. Phylogenetic analysis revealed that the His259 amino acid is a highly conserved residue, located within the DUF4498 domain of C11orf70 (Figures  1B  and S1 ).
Using PolyPhen-2 software, this mutation is predicted to be damaging, with a score of 0. 997 (sensitivity: 0. 27; specificity: 0. 98). It is also predicted to have a damaging effect on the protein using the SIFT tool. MutationTaster predicts it to be a disease-causing mutation and it has a CADD score of 23. 9 (CADD score of R20 indicates a variant is among the top 1% of deleterious variants in the genome). Second, we identified two compound heterozygous C11orf70 stop-gain (nonsense) variants in an affected child from an Indian non-consanguineous family (GenBank: NM_032930. 2; c. 154C>T [p. Gln52*] inherited from the father and GenBank: NM_032930. 2; c. 361C>T [p. Arg121*] inherited from the mother) (Figure  1A ). Sanger sequencing  confirmed the mutations in the affected individual's DNA and the carrier status of the parents.
In the ExAC database, the p. Gln52* mutation (rs767760877) is found in two heterozygote carriers from the South Asian population with a total allele frequency of 1. 653eÀ05 and the p. Arg121* mutation (rs561237622) is found only once in a heterozygote carrier from the South Asian population with a total allele frequency of 8. 254eÀ06. Both stop-gain variants are also located within the C11orf70 DUF4498 domain (Figure  1B ) and are expected to cause a major deleterious effect on the protein. Their respective CADD scores are 36 (c. 154C>T [p. Gln52*]) and 39 (c. 361C>T [p. Arg121*]).
These data are shown in Figure  S2 , with representative images shown in Figure  2A. The composition of the cilia in the respiratory epithelial cell samples in these affected individuals was also examined by immunofluorescence (IF) analysis compared to control subjects. Respiratory epithelial cells were double-labeled with antibodies directed against the axoneme (acetylated alpha-tubulin) and markers of the outer dynein and inner dynein arms. This showed a significantly reduced level (absence) of staining for the established diagnostic outer dynein arm marker DNAH5 (Figure  2B ) and inner dynein arm marker DNALI1 (MIM: 602135) (Figure  2C ) in the affected individual's respiratory cilia compared to control samples from an unaffected healthy individual. In agreement with the TEM ultrastructure results, immunofluorescent staining with markers of other cilia structures including the radial spokes (RSPH4A [MIM: 612647] antibody  71  ) and nexin-dynein regulatory complexes (GAS8 [MIM; 605178] antibody  72  ) did not display altered distribution in the cilia (data not shown).
The only known conserved domain is a ''domain of unknown function'' (DUF4498). The phylogenetic conservation of the mutated amino acid histidine 259 across different mammalian and other ciliate species is highlighted in blue below the protein. Uniprot accession numbers are indicated; XENTR, Xenopus tropicalis; DANRE, Danio rerio; CHLRE, Chlamydomonas reinhardtii. (C) Clinical characteristics of individuals carrying biallelic C11orf70 mutations. NRD, neonatal respiratory distress; SS, situs solitus; SI, situs inversus totalis; nNO, nasal nitric oxide level (normal cutoff is >77 nL/min); HSVM, high-speed video microscopy; n. t. , not tested as subject too young; IDA, inner dynein arm; ODA, outer dynein arm.
Acknowledgments We are very grateful to the families who participated in this study and thank the  UK PCD Family Support Group  for their continued support. We thank  Ms. Dani Lee  and  Prof. Chris O'Callaghan  ( UCL Great Ormond Street Institute of Child Health ) for help with assessment of Paramecium motility and  Dr. Dale Moulding  ( GOS-ICH Confocal Microscopy Core Facility ) for experimental assistance. Funding for this study was provided by  Action Medical Research  ( GN2101 ; H. M. M. ) and  Great Ormond Street Children's Charity grant  ( V4515 ; H. M. M. ) and Leadership awards ( V1299 ,  V2217 ; H. M. M. ). M. R. F. is supported by the  British Council Newton-Mosharafa Fund  and the  Ministry of Higher Education in Egypt. We acknowledge support from the  NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London  ( Doctoral Trainee Support Award ; M.
R. F. ). Work by A. S. is independent research funded by a postdoctoral research fellowship from the  National Institute of Health Research and Health Education England. The views expressed in this publication are those of the authors and not necessarily those of the  NHS , the  National Institute of Health Research , or the  Department of Health. We would like to thank  C. Mathon  for generating plasmid constructs,  L. Shi  for the IFT46 construct,  J. Bonaventure  for his help in RNA isolation, and  C. Janke  for his generous gift of PolyE antibodies. The authors acknowledge the contribution of the  BEAT-PCD COST Action. The authors participate in the  COST Action BEAT-PCD: Better Evidence to Advance Therapeutic options for PCD network  ( BM1407 ) and this work was supported by two  BM1407   COST Action STSM Grants  awarded to M.
BiFC was successfully applied to visualize protein interactions in a range of cellular models  [5] [6] [7]. Moreover, BiFC has been particularly useful to evaluate the effect of small molecules on protein complex formation in high throughput screens (HTS)  8, 9. For efficient cell-based screening assays of PPIs by BiFC, at least two genes of interest need to be co-produced efficiently in a single cell. If complex multicomponent assemblies are studied, even more genes that encode for interactors will need to be expressed. Moreover, the individual expression levels must be ideally the same in each cell assayed in the experiment. Earlier, we had developed MultiMam 10 , a modular, plasmid-based expression system to co-produce multiple genes at defined ratios in mammalian cells, and we demonstrated its efficacy for multigene expression in transiently or stably transfected mammalian cells  11.
MultiMam relies on small synthetic progenitor DNA plasmid modules, that are assembled into a multigene expression construct containing multiple expression cassettes by a procedure called tandem recombineering (TR)  12. TR exploits sequence and ligation independent cloning for gene insertion iteratively coupled to site specific recombination by the Cre-LoxP fusion reaction  12. The unique modularity of MultiMam is optimally suited for setting up a highly efficient BiFC tool-box to assay PPIs of interest, by rapidly creating in parallel all interactor-fluorophore fusion pairs required to choose the optimal BiFC setup  13. Furthermore, we set out to make our toolbox readily adaptable to a wide range of cellular models, including cell types which are known to be recalcitrant to plasmid-based transfection.
1a ) in plasmid modules pACEMam1 and pMCDP, respectively. In the MultiMam system, individual plasmid modules are recombined by Cre-LoxP fusion, ensuring expression of all proteins of choice in all transfected cells at defined ratios, yielding homogeneous cell populations  10. Plasmids fused by Cre were transfected into COS7 cells to test the efficiency of the different combinations in BiFC. The highest number of positive cells (i. e. cells yielding detectable fluorescent signal) and fluorescence intensities were reached when both CDK5 and p25 were tagged on their N-termini (data not shown). The CDK5-p25 interaction can cause cell death by chromosome condensation  18. To forestall widespread cell death in the transfected cell population, a mutation in the CDK5 catalytic domain (D144N) was introduced.
Discussion Here we present our MultiBacMam BiFC toolbox, a versatile new platform that integrates the advantages of BiFC with the flexible modularity of our MultiMam system and the highly efficient MultiBacMam baculovirus transduction reagent in a setup compatible with automation and HTS. The percentage of positive cells, the (lack of) toxicity of the overexpressed target proteins, and obtaining a reasonably wide assay window are critically important parameters for obtaining robust screening outcomes and key to success in assay development. The MultibacMam BiFC toolbox we present here combines numerous advantages beyond the current state-of-the-art  [31] [32] [33] [34]. Our toolbox relies on accessible synthetic plasmid DNA modules which are flexibly combined into multiple gene  expression cassettes by our TR protocol, enabling rapid identification of combinations best suited for BiFC.
Acknowledgements We thank all members of the  Thoma, Carralot and Berger groups  for their contribution and helpful discussions. We particularly thank  Eric Kitas  for peptide chemistry work and  Thomas Woltering  for outsourcing support. IBE was supported by a  Roche pRED post-doctoral fellowship. IB was supported by  European Commission   Framework Program 7 collaborative projects ComplexINC  (contract nr. 279039) and SynSignal (contract number  613879 ). This research received support from  BrisSynBio , a  BBSRC/EPSRC Research Centre  for synthetic biology at the  University of Bristol  ( BB/L01386X/1 ).
And along with these new technologies comes the need for transparent and affordable software tools as well as trained experts to process these large datasets promptly and accurately. Hyperspectral images are often described as a data cube with a spatial X-and Ydimension, and a third dimension containing information on the earth surface reflectance across the electromagnetic spectrum. This information is provided for hundreds of spectral bands in the wavelength range spanning from the visible to the mid-infrared part of the spectrum. Such data set can be linked to biochemical and biophysical vegetation properties via empirical models which can be used to: LiDAR sensors use the light emitted from a laser pulse to measure the travel time of the pulse from the source to the target and back. Using this procedure, the instrument provides information on the surface and the vegetation 3D structure at high spatial resolution  (Lim et al.
2003). The data collected is distributed in point clouds with varying density depending on the sensor specifications, flight height and velocity. The higher the point density the higher the accuracy in the products derived from it. For example, digital elevation models (DEMs) can be derived from low density point clouds (1 point per m ) while vegetation studies require higher point density (from 8 point per m onwards)  (Wu et al. 2016). The LiDAR-derived 3D structure of the terrain and the vegetation can be used as surrogates for physiographic and biophysical properties (e. g. Lenoir et al. 2016) , respectively, both being potential determinants of the distribution and spread of IAPs. For this reason, LiDAR images are very complementary to hyperspectral images when the aim is to understand the determinants of IAPs' distribution within the invaded range and subsequently model the potential spread.
The aim of this paper is to provide an open source toolbox to face the challenge of detecting, monitoring and assessing the impact of IAPs on ecosystem functioning through remote sensing, this work is based on the results and knowledge gained from an interdisciplinary BiodivERsA project (DIARS, http://diars. vgt. vito. be/). The toolbox (http://diarsproject. github. io/DIARS/HomeDIARS. html) features clear guidelines to process and analyze ground and remote sensing data to map, model and assess the impact on ecosystem functioning of IAPs. A dataset specially designed to allow computation even at small processing power as well as the "iSDM" R package (https:// cran. r-project. org/web/packages/iSDM/) to help inform the sampling of IASs as well the mapping and modelling of IASs are also provided together with the toolbox.