dataesr/scientific-paragraphs-categorization huggingface dataset:
Size differences between nelsoni and caudacutus males (14. 9 -19. 2 g versus 19 -24 g, respectively) may thus place nelsoni at a substantial competitive disadvantage when competing with caudacutus males to secure mates in sympatric marshes. Admixed females are thus Table  4  Parameter estimates for the best fitting clines for 5 morphological traits using the package HZAR. For each trait, we present the best model, cline center (c), cline width (w), and AICc more likely to backcross with caudacutus males leading to asymmetries. This is particularly true in sites toward the southern portion of the hybrid zone, where caudacutus males outnumber nelsoni males by approximately 4:1  [67]. Cline estimates for weight coupled with a peak in weight variance near the center of the zone provide supportive evidence that size is an important factor in shaping zone dynamics in this system.
Geographic transect and sample collection For this study, we used a previously published phenotypic and microsatellite genotypic dataset collected from the caudacutus-nelsoni hybrid zone  [42] , along with new DNA sequence data from two mitochondrial, 2 Z-lined, and one autosomal marker. The sampling design captured the extent of genetic and phenotypic variation across the hybrid zone, via 34 tidal marshes sampled along a linear, coastal transect from Lubec, Maine (44°4 9′22 N, 66°59′20 W) to Madison, Connecticut (41°15′ 46 N, 72°33′00 W; Fig. 1 ; Table  1 ) during the 2012 and 2013 breeding seasons (June -August). The marshes sampled for this study represent a gradient of tidal marsh habitat types (including coastal, bay, and upriver marshes) and exhibited a range of variation in salinity, vegetation structure, isolation, and tidal amplitude  [48].
Within the hybrid zone, marshes were sampled approximately every 10 km; allopatric marshes were also sampled north and south of the hybrid zone (Fig. 1 ). We sampled 290 sparrows and collected a suite of morphological measurements from 254 of them  [50]. Due to inadequate sample sizes (n = 2) in two of the sampled locations, we used data from 286 individuals from 32 sites for all analyses (Table  1 ; Fig. 1 ). Of these individuals, 37 sparrows were sampled from putatively pure nelsoni populations (n = 4 marshes), 52 individuals were sampled from putatively pure caudacutus populations (n = 6 marshes), and 197 individuals were sampled from sympatric populations (n = 22 marshes). Because this was the first extensive sampling and genetic evaluation of the hybrid zone, we initially defined all marshes outside of the currently hypothesized overlap zone of Hodgman et al.
Analysis of molecular markers The genotypic dataset consisted of 24 microsatellite loci, including 12 putatively neutral, anonymous microsatellite loci  [85] [86] [87]  and 12 diagnostic microsatellites developed specifically to differentiate caudacutus, nelsoni, and hybrids  [52]. Information on these markers and PCR amplification conditions can be found in Walsh et al. [42]. Owing to elevated divergence in the diagnostic marker panel relative to the anonymous microsatellites (F ST = 0. 4667 and F ST = 0. 15, respectively;  [52] ), we considered these two marker sets separately for some analyses and interpretation. We also amplified each individual at two mitochondrial genes [1100 bp of NADH dehydrogenase subunit 2 (ND2); 356 bp of NADH dehydrogenase subunit 3 (ND3)], two z-linked genes [183 bp of solute carrier family 45, member 2 (SLC45A2), 724 bp of solute carrier family 30 (SLC30A5)], and one autosomal marker [900 bp of recombination activating gene 1 (RAG1); Primer information for these markers can be found in Additional file 6: Table  S1 ].
Population structure For each site, we characterized genetic diversity using standard population genetic metrics. Specifically, we calculated unbiased estimates of expected and observed heterozygosities and tested for deviations from Hardy-Weinberg equilibrium in GENEPOP V4  [88]. We also calculated genetic diversity metrics, including F IS , number of alleles, and allelic richness in FSTAT  [89]. To quantify patterns of admixture for each site, we estimated a hybrid index (proportion of caudacutus alleles in an individual) and interspecific heterozygosity (proportion of an individuals' genome with alleles inherited from both parental populations) for all individuals using the R package introgress  [90, 91]. To identify markers under selection, we performed selection tests for all loci using an F ST outlier approach  [92]  in the program LOSI-TAN  [93].
We used the admixture model and assumed correlated allele frequencies  [95]. We determined the most likely number of population clusters (K) using the ΔK method of Evanno et al. [96] ; STRUCTURE output was visualized using the program STRUCTURE HARVESTER  [97]. Lastly, we tested for linkage disequilibrium using GENEPOP. Pvalues for multiple comparisons were adjusted with the Bonferroni correction.
Patterns of differential introgression: genomic clines We used the R-package introgress to estimate genomic clines for each locus using a multinomial regression to estimate individual clines for each locus along an admixture gradient (represented by the hybrid index, calculated as the proportion of caudacutus alleles in an individual in introgress). Calculating hybrid index requires a priori definition of pure individuals of each parental species. In doing so, we took a conservative approach to minimize the potential for including introgressed individuals in our parental samples; we defined pure individuals as those sampled from allopatric populations >115 km north and south of the currently recognized overlap zone (Fig. 1 ;  [42] ). To identify loci that displayed deviations from neutral expectations, we compared the likelihoods of the regression models to a null model of neutral introgression.
This approach compares the mean hybrid index over all loci to a hybrid index for a focal locus. The logit-logistic model estimates two parameters: u gives the relative difference in cline position (positive values indicate a shift of the cline toward caudacutus and negative values indicate a shift toward nelsoni) and v gives the relative difference in slope (values greater than one indicate a more abrupt slope and stronger selection whereas values less than one indicate a more gradual slope and weaker selection compared to the multilocus average). Perfect concordance between a focal locus and the mean hybrid index would result in u = 0 and v =1. Thus, the expectation for equal introgression over all loci lies on the diagonal. We fit the parameters u and v using the function "mle2" in the R package bblme.
Patterns of differential introgression: geographic clines To evaluate the distribution of caudacutus and nelsoni alleles across the transect, we used the Metropolis-Hastings Markov chain Monte Carlo algorithm employed in the R package HZAR [100, 101] to fit a series of geographic cline models to allele frequencies for each genetic marker and a suite of morphological traits. We reduced the variation observed in the 24-microsatellite loci to a two-allele system using species-specific compound alleles  [29, 102, 103]. Using this approach, each allele was assigned to a species group based on its coordinates on the first axis of a multiple correspondence analysis (MCA), conducted using the CA package in R. We ran fifteen separate models for each genetic marker, all of which estimated cline center (distance from sampling location 1, c) and width (1/maximum slope, w).
Acknowledgements We thank  T. P. Hodgman  of  Maine Department of Inland Fisheries and Wildlife, N. S. Pau of Parker River National Wildlife Refuge ,  K. M. O'Brien  of  Rachel Carson National Wildlife Refuge, E. King of United States Fish and Wildlife Service ,  P. Hunt  of  New Hampshire Audubon ,  K. Raposa  of  Narragansett Bay National Estuarine Research Reserve ,  C. Weidman  of  Waquoit Bay National Estuarine Research Reserve , and  K. E. Iaquinto  of  Monomoy National Wildlife Refuge  for their advice and help in facilitating sampling efforts. K. Ruskin ,  C. Elphick ,  C. Field , and  G. Mittlehauser  provided sample collection assistance. We thank the  Maine Department of Inland Fisheries and Wildlife , the  Trustees of Reservations , the  Essex County Greenbelt association , and the  Nature Conservancy  for allowing sample collection in protected marshes.
Results In the final sample of patients' records included and discussed (N = 290), non-medical characteristics were mentioned in 32. 8% (n = 95) of the cases. These characteristics corresponded to demographics in 22. 8% (n = 66) of the cases, psychological data in 11. 7% (n = 34), and relational data in 6. 2% (n = 18). The patient's age and his/her "likeability" were the most frequently mentioned characteristics. In 17. 9% of the cases discussed, the final decision was deferred: this outcome was positively associated with the patients' non-medical characteristics and with uncertainty about the outcome of the therapeutic options available.
Methods Data including physicians' verbal statements and a pre-defined set of characteristics describing the context of the MDT meeting and the cases under discussion were collected using a nonparticipant observational approach during MDT meetings conducted at a single comprehensive cancer centre in France. Physicians' verbatim statements were then coded systematically before being analysed using quantitative methods. The study protocol, including the consent procedure, was approved by the Institutional Review Board of the French National Health and Medical Research National Institute (INSERM) (approval number 14-144). Application was made by mail to the Institution's legal and managerial departments, which sent their approval by return mail. The four MDT leaders were asked whether they agreed to having their meetings observed for the purpose of this study.
Data collection 2. 3. 1. Dataset characteristics. During the observation period, 48 MDT meetings on cases of the four types listed above took place at the institution, corresponding to 532 complete patients' case records. The meetings were held every week in the morning (lymphoid haematology), evening (metastatic breast and digestive cancer) and at lunchtime (myeloid haematology). These consecutive meetings were systematically attended by the main researcher (LR) from March to May 2014 at the institution in question. To reduce the risk of Hawthorn effect, the participants at MDT meetings were informed that the main aim of the study was: "to study medical decision-making in oncology", without giving any details which might have influenced what the participants said. In order to minimize this risk, the observer attempted to behave as discreetly as possible and to avoid interacting with the participants during the meetings.
Two observation grids, one for noting the characteristics of the MDT meetings and the other for noting the case-record characteristics, were drawn up, based on the literature  [16, 17] ; they were gradually adapted during a previous pilot observation period which focused on six MDT meetings and at workshops in which a stepwise process of discussion was used between the researchers involved (LR, CJR and TA). The purpose of these grids was to focus our observations of the meetings on a set of specific variables which seemed to be relevant to the aims of our study, and were used to ensure that the outcome variables would be collected systematically. Data collection at MDT meetings:The observation grid was initially designed in the form of a set of themes, closed questions and pre-coded items corresponding to the duration of the meeting, the number of doctors present, the number of doctors discussing the cases, the number of cases discussed, and the number of cases removed from the agenda.
The task of collecting the other information of interest was also simplified by the standardised presentation of the clinical cases and the fact that the observer had become familiar during the pilot study with cancer patients' medical characteristics. 2. 3. 2. Coding process. MDT data: Data collected on the observation grid did not need to be transformed for the statistical analysis. They were fed directly into the computer for processing. Case data: from physicians' verbatim statements to quantitative analysis: In order to obtain a quantitative assessment of the physicians' verbatim statements, the content of the variables included in the observation grid was coded by the authors with a view to drawing up a closed thematic grid for the statistical analysis of the results of the observations.
Limitations of the study Several limitations of our study are worth discussing. First, the reason why these MDT meetings were not tape-recorded was to reduce the possibility of self-censorship by the physicians, and the non-numerical data were therefore directly observed and collected. After an initial feasibility study, it was decided to systematise the data collection procedure by drawing up an observation grid and to triangulate the coding procedures. Secondly, the present MDT meetings were specific to very severe forms of cancer on which fewer evidence based guidelines are available than in most other contexts. This was done on purpose to select contexts with nonstandard cases. Our results showing that in one third of the cases, non-medical characteristics were mentioned in the context of collective medical decision-making at cancer MDT meetings cannot be extended to more standard cases of cancer.
Acknowledgments The authors would like to thank the four MDT meetings leaders,  Anthony Gonçalvez ,  Norbert Vey ,  Reda Bouabdallah  and  Jean-Luc Raoul , and all the meeting participants who contributed to the study by allowing us to observe their meetings. We also wish to thank  Vincent Amodru ,  Najoua Guelmani  and  Jessica Blanc  for their technical expertise.
The Virtual Town The virtual town was developed and created by the LMC unit. It consisted of virtual urban environments built with LMC software EditoMem [based on3DVIA Virtools Dev 5. 0 software (3dVIA Virtools)] allowing us to create virtual environments inspired by photos of Paris and game scenarios. These urban environments have been previously used in healthy individuals and patients to assess episodic, spatial, retrospective, and prospective memories as well as working memory [e. g. , Ref. (19) (20) (21) (22) (23) ]. In the present virtual town, the main elements were located so that they could be easily detected (i. e. , in front of the subjects, in a corner of a street, or quite salient on the side of the road). Patients had to navigate as pedestrians in a virtual 3D town, using a joystick (simulation software: Simulamem), along several avenues and roads (see Figures  1A, B ).
Ciliopathies represent a significant disease burden Ciliopathies are typically autosomal recessive disorders, so their incidence is expected to increase with a higher inbreeding coefficient. We have recently devised a method to calculate the minimum burden of disease using the carrier frequency of founder mutations among a large cohort of patients with Mendelian diseases who serve as controls for mutations unrelated to their underlying illness  [18]. Using this approach, we show that ciliopathies are among the most common autosomal recessive diseases in Arabia, with a minimum disease burden of 0. 0004207 or 1 per 2376. (Additional file 6: Table  S5  lists the breakdown of this burden per ciliopathy syndrome. ) Of note, this is clearly an underestimate, since it does not account for non-founder mutations, and even for founder mutations there are a few observed in this study for which no carrier frequency could be estimated due to their absence in our database.
Mutation analysis All patients and available relatives were genotyped using the Axiom single nucleotide polymorphism (SNP) chip platform to determine the candidate autozygome as described previously  [38, 39]. In parallel, the previously described "Mendeliome assay" was applied to search for likely causal variants in previously reported ciliopathy genes  [40]. Briefly, we used highly multiplexed gene panels covering known ciliopathy disorders as annotated by the Online Mendelian Inheritance in Man (OMIM) catalog. The primers were designed using Ion AmpliSeq Designer software (Life Technologies, Carlsbad, CA, USA), synthesized and pooled into two multiplex reactions based upon PCR compatibility minimizing likelihood of primer-primer interactions. The libraries were run on an Ion Proton instrument (Thermo Fisher, Carlsbad, CA, USA).
When negative, whole exome sequencing was performed and variants were filtered essentially as described previously  [40]. When negative, autozygome-guided RT-PCR of known ciliopathy genes was attempted whenever an RNA source was available to search for cryptogenic mutations. In some cases, the causal variant was directly targeted when a founder haplotype was identified at the genotyping stage. Variants in known ciliopathy genes were considered likely causal if they were nonsense, frameshift, or canonical ± 1 or 2 splice sites, absent as homozygous in the ExAC and Saudi genome databases, and having a minor allele frequency (MAF) <0. 01 in the heterozygous state. For missense or in-frameshift variants, they had to be absent as homozygous in the ExAC and Saudi genome databases and have a MAF <0.
01 in the heterozygous state, predicted to be pathogenic and deleterious by the sorting intolerant from tolerant (SIFT) and Polyphen tools, and with a Combined Annotation Dependent Depletion (CADD) score >15. For non-canonical splice site variants, they had to be absent as homozygous in the ExAC and Saudi genome databases, have a MAF <0. 01 in the heterozygous state, and either reported in the Human Gene Mutation Database (HGMD) with confirmed abnormal splicing effect on reverse transcriptase PCR (RT-PCR), or demonstrated by us on RT-PCR to result as a minimum in (1) an aberrant band exclusive to the patient and confirmed by sequencing and/or (2) complete absence of the normal transcript in the patient despite the proper use of internal controls.
3, obtained from GeneCopoeia Inc. , Rockville, MD, USA) into a destination construct that had C-terminal strep-II/ FLAG tags for tandem affinity purification (CTAP). Human hTERT-RPE1 cells were transfected with the TXNDC15-CTAP expression construct, as described previously  [41] , and stained for the FLAG tag. To identify protein interactants of TXNDC15, the cells were lysed, and streptavidin-and FLAG-based tandem affinity purification steps were performed as described previously  [42]. Liquid chromatography-MS/MS analysis was performed using an UltiMate 3000 Nano HPLC system and a mass spectrometer (LTQ Orbitrap XL, Thermo Fisher Scientific). The results from three biological replicates were filtered on the basis of n ≥ 2 peptides in at least two replicates and absence in a negative control dataset (pull-downs of RAF1-CTAP and untransfected cells; Additional file 2: Table  S3 ).
Acknowledgements We thank the study families for their enthusiastic participation. We also thank the  Genotyping and Sequencing Core Facilities at KFSHRC  for their technical help. The Ciliopathy Working Group consists of  Ghada Abdulsalam ,  Abdullah Alashwal ,  Abdulrahman Aldeeri ,  Adnan Alhadid ,  Abdullah S. AlKharashi ,  Mariam Almureikhi ,  Zainab Babay ,  Mohammad Al-Qattan ,  Nada Alsahan ,  Sondos Alsaleh ,  Munira Alshammari ,  Hamad Alzaidan ,  Amer Ammari ,  Fahad A. Bashiri ,  Fatima Bastaki ,  Tawfeg Ben-Omran ,  Mohammad Elshaikh ,  Chantal Farra ,  Khaled Hundallah ,  Mohamed Khalil ,  Wessam Kurdi ,  Elham Mardawi ,  Charles Marques-Lourenco ,  Arif O. Khan ,  Alya Qari ,  Rifaat Rawashdeh ,  Yasser Saber ,  Nadia Saqati ,  Samira Saqati ,  Hanan Shamseldin ,  Ameen Softa , and  Maha Tulba.
Enhanced mass spectrum was used as a survey scan to trigger information dependent acquisition of MS/MS spectra. The criteria for the data-dependent acquisition (IDA) were set for the most two intense peaks, which exhibited more than 5000 counts. The identification of compounds was performed according to their MS 2 fragmentation, using standards when available. Quantification was carried out with data acquired at 320 nm from the PDA, using gallic acid as internal standard (280 nm). 5-CQA and 6-C-glucosyl apigenin (isovitexin) were used as calibration standards to quantify hydroxycinnamic acids (caffeoylquinic acids CQA and caffeoylshikimic acids CSA) and flavones, respectively.
Acknowledgments: This work was funded by a grant from  European council (FEDER) ,  Region Guyane, Ministère de l'Enseignement Supérieure et de la Recherche ,  Centre National d'Etudes Spatiales  ( Palmazon project  " Valorisation des palmiers amazoniens de Guyane ", 2010) and  HPLC  project: "acquisition of chromatographic material". We also thank  Nicole PRIVAT  for the English correction of this manuscript.
Epi-fluorescence signals were collected during imaging. Fluorescence photons were separated from excitation photons using a dichroic mirror (Semrock FF705-Di0) and a bandpass filter (Semrock FF01-750/SP) and then separated according to their wavelength using a second dichroic mirror (Semrock FF555-Di03). Red fluorescence was further isolated using a band-pass emission filter (Semrock FF02-617/73) and detected using a multi-alkali photomultiplier (Hamamatsu R9110). Green fluorescence light was further isolated using a blocking edge short-pass emission filter (Semrock FF01-750/SP) as well as a band-pass emission filter (Semrock FF01-510/84), and detected using a multi-alkali photomultiplier (Hamamatsu R3896). Images were acquired with ScanImage software. The laser intensity was controlled using a combination of an electricallycontrolled liquid crystal variable phase retarder (LRC-200-IR1, Meadowlark Optics) and a polarizer beamsplitter (BB-050-IR1, Meadowlark Optics).
Electrophysiology Patch pipettes were pulled from borosilicate glass capillaries (outer diam. 1. 5 mm, inner diam. 0. 86 mm Harvard apparatus). Voltage and current signals were recorded using a MultiClamp 700B amplifier (Molecular Devices)), in the whole-cell recording configuration, low-pass filtered at 10 kHz, digitized at 20-40 kHz and recorded using Neuromatic (http://www. neuromatic. thinkrandom. com, written in Igor Pro). Data was analyzed using Neuromatic or pClamp (Axon Instruments) and Microsoft Excel. Membrane potentials are given without correction for the liquid junction potential.
ACKNOWLEDGMENTS We thank  Rossella Conti  and  Cecile Jouffret  for taking care of CHO cell cultures and transfections,  Nidal Bouzekri  for his help with figures preparation,  Amanda Foust  for contributing in the design and the construction of the 2P scanning imaging system and  Lyle Graham  for proof-reading the manuscript. VE acknowledges the  Agence Nationale de la Recherche  (grants  ANR-12-BSV5-0011-01 ,  ANR-12-BSV5-0011 ,  ANR-14-CE13-0016 ), the  National Institutes of Health  ( NIH 1-U01-NS090501-01 ), the  Medical Research foundation FRM  ( DVS20131228920 ) the  FRC  and the  Rotary Club through the program  " Espoir en Tête 2012 ". HZ and GS thank the  Allen Institute founders ,  Paul G. Allen  and  Jody Allen , for their vision, encouragement, and support.
The incremental prognostic value of the more complex imaging techniques needs to be further validated. The available data have to be considered and the improved workflow of echocardiographic platforms will facilitate its outspreading. 115, 116 eal-time 3DE is free of assumptions and accordingly an attractive alternative for the evaluation of LA volume. The best validation we have for the 3D approach of direct measurement of LA volume includes 92 patients with a wide range of it. Patients underwent CMR (1. 5-T) and echocardiographic imaging on the same day. 2DE images were analysed by the biplane area -length technique and 3DE images by TOMTEC LA Function software. 117 3DE-derived LAV measurements were more accurate than 2DE-based analysis, resulting in fewer patients with undetected atrial enlargement when compared with the CMR reference.