dataesr/scientific-paragraphs-categorization huggingface dataset:
The results of this project integrate with several other efforts currently underway (e. g. the EU-H2020 PRIMAVERA project). In particular this study complements groundbreaking past initiatives in pioneering the use of HPC for climate simulations such as the UPSCALE  (Mizielinski et al. , 2014)  and the ATHENA  (Kinter III et al. , 2013)  projects. Climate SPHINX was made possible by a considerable amount of computing time provided by PRACE (the Partnership for Advanced Computing in Europe) and of data storage from EUDAT (the collaborative Pan-European infrastructure providing research data services). We were granted 20 million core hours during a single year at SuperMUC, the IBM Petascale System at the Leibniz-Rechenzentrum (LRZ) in Garching near Munich, Germany. Storage of data produced by Climate SPHINX is secured by the EUDAT Pilot Project DATA SPHINX (DATA Storage and Preservation of High resolution climate eXperiments), which provides a widely accessible archive for medium term storage to facilitate data access and discovery.
DATA SPHINX is managed by CINECA (the largest Italian computing centre) and at present hosts 140 TB of data generated by Climate SPHINX. In this paper we describe in detail the important technical aspects of this project and highlight some preliminary scientific results on the impact of increased resolution and stochastic parameterisations on climate simulations. Model configuration and tuning are presented in Section 2, while the experimental setup is described in Section 3. Section 4 is devoted to detail the technical configuration. An overview of results and concluding remarks are reported in Sections 5 and 6.
Present-day SST and SIC Given that both FSA and PDA simulations are atmosphere-only runs, a special effort has been taken to provide reliable SSTs in order to fully exploit the high resolution. For PDA, SSTs have been obtained from the daily SST and sea ice concentration (SIC) HadISST2. 1. 1, a pentad based dataset with resolution of 0. 25°x0. 25°for SSTs  (Kennedy et al. , 2016)  and 1°x 1°for SIC  (Titchner and Rayner, 2014). These are bilinearly interpolated onto the required reduced Gaussian grid for each resolution: climatologies for SST and SIC for the 1979-2008 period can be seen in the upper panels of Figure  1. A number of inconsistencies are found between the land-sea mask of IFS and of HadISST2. 1. 1: these are due to slightly different coastlines and a different representation of the lakes.
For the different coastlines, linear extrapolation from HadISST2. 1. 1 has been performed. For the interior (i. e. lakes), a methodology similar to the one used in ERA20CM dataset  (Hersbach et al. , 2015)  has been adopted: one-month lagged 2m temperatures from the ERA-Interim monthly climatology of 1979-2008 are used as SST. Where the temperature is below zero, SIC is set to one, otherwise it is left at zero. This is interpolated in time on a daily basis and in space on the needed grid to create a smoothed seasonal cycle for lakes. For all PDA simulations, well mixed greenhouse gases, stratospheric ozone and volcanic aerosol concentrations have been set according to the historical scenario of the CMIP5 protocol  (Taylor et al. , 2012).
As a last step, we must evaluate SST for points where SIC coverage has disappeared in the future scenario. The lack of information about historical SST under sea ice results in undefined SST at these points using the methodology outlined above. We define these as "bare point". For bare points, we want to make use of the model variability, but we do not want to have inconsistent SST at the boundaries (i. e. where bare points border the Step1Hadisst dataset). Initially, we perform a linear extrapolation for bare points for Step1HadISST SSTs -which gives us a measure of the average SSTs at the bare points. However, these extrapolated values are missing a realistic spatial variability. We then mask the bare points also in the SST field of the CMIP5 EC-Earth ensemble member "r8i1p1", and we subsequently linearly extrapolate new values.
The new dataset is defined as FutureHadiSST2. 1. 1. The same methodology used for the PDA simulations has been adopted also for FSA runs in order to solve the issues of the lakes and the different land sea-mask: however, in this case we must account for the estimated temperature change over land. We consider the difference between the one-month lagged 2m surface temperature from CMIP5 EC-Earth RCP8. OpenMP/Shared memory parallelisation, which has been tested without showing any significant computational benefit. An accurate scaling of the performance was performed during the first months of the simulations. However, a conservative choice has been undertaken, after considering that the walltime needed to run the simulations was not the main concern for the project success. The number of cores assigned to each experiments have been selected following the resolution of the model considered.
Data output and postprocessing In Climate SPHINX, IFS has been set up to provide output in GRIB format every 3 hours:; however, the four T1279 simulations alone sum up to about 200 TB of raw data output. Summing together the restarts files and the output of all experiments the total amount of space occupied at the peak of the project (February 2016) reached about 1 PB. In order to reduce the size of the output and to increase the data accessibility to a larger audience, automatic post-processing routines have been implemented. At the end of each simulation leg, a script aimed at post-processing is launched: the script handles both the spectral and reduced Gaussian data from IFS and extracts and converts the requested variables from the default ECMWF format to a user-friendly, CMOR-like format on regular Gaussian grid.
Results overview In this section we present a brief overview of the preliminary findings of the Climate SPHINX project. Considering that the number of aspects of climate that could be analyzed in such a large dataset is extremely dispersive, we decided to focus on a few selected features of the climate variability. In fact, larger benefits from increasing resolution and using stochastic physics are expected in terms of variability rather than in terms of mean state. More specifically, we investigate the improvements and/or deteriorations following resolution increases and including stochastic parameterisation of three different phenomena in the present-day climate (i. e. in PDA experiments): the distribution of the intensity of tropical rainfall, the tropical variability related to the Madden-Julian Oscillation and the mid-latitude variability associated with atmospheric blocking.
, 2007)  and one ensemble member for each PDA run. The results are very similar in separate subperiods, so sampling variability is small. At all resolutions, rain rates below 15 mm/day occur too often in the model data and rain rates between 25-60 mm/day occur too infrequently compared to both observational datasets. Figure  5b  shows the ratio of the frequency in each rain rate interval as a fraction of that in GPCP for each resolution. At rain rates near 30 mm/day, the simulated frequencies are between about 35-50% of the frequency in GPCP. At higher rain rates, the frequency differences between TRMM and GPCP become comparable in size to or larger than the differences between the modelled frequencies and the observational datasets. We do not know of a reason to strongly prefer one dataset over the other, so we consider the model bias to be uncertain at these rain rates.
The frequency of rain rates above 30 mm/day in the T159 and T255 models are below about 40% of that in GPCP. At T511, T799 and T1279 the relative frequency difference compared to GPCP and TRMM decreases as the rain rate increases, and becomes comparable to that in GPCP in the 60-65 mm/day interval, though still much smaller than that in TRMM. Therefore increasing the model resolution from T159 to T511 improves the simulated frequency of heavy rainfall events compared to observational datasets, with the further improvements caused by increasing the resolution to T799 or T1279 being considerably smaller. Figures  5c, d  show the same data for the stochastic PDA runs. Stochastic physics has a similar effect at all resolutions. Frequencies of rain rates between 5-15mm/day are reduced by about 10% compared to those in the deterministic models, reducing the model bias.
Moreover, a comprehensive description of the methodology adopted for the creation of the present day and future scenario SST and SIC (starting from the HadISST 2. 1. 1 dataset) has been described. A novel method aimed at estimating SST where SIC have disappeared in future climate simulations has been introduced. More importantly, Climate SPHINX post-processed outputs are freely accessible to the climate community. This has been possible thanks to an EUDAT pilot project which makes available a THREDDS server operational at CINECA from which data can be easily downloaded. Preliminary results show the importance of both resolution and stochastic perturbations on the representation of the climate variability, although different phenomena show different sensitivities. Tropical rainfall variability seems to benefit of both increased horizontal resolution and stochastic parameterisation, whereas the Madden-Julian Oscillation shows improvements only when the stochastic perturbations are added.
Data availability Post-processed data have been transferred from LRZ to CINECA via GridFTP, where they have been permanently stored. More important, free data accessibility to the climate user community is granted through a dedicated THREDDS Web Server hosted by CINECA (https://sphinx. hpc. cineca. it/thredds/sphinx. html), where it is possible to browse and directly download SPHINX data. Details on the the data accessibility and on the Climate SPHINX project itself are available on the website of the project (http://www. to. isac. cnr. it/sphinx/). The set up of this infrastructure for data sharing has been possible thanks to DATA SPHINX, an EUDAT Data Pilot project, which will allow long-term storage and sharing among a wide scientific user community of high-resolution climate model output data.
atmosphere-only simulations according respectively to CMIP5 historical and RCP8. 5 forcing. These have been run at five different horizontal 14 Geosci. Model Dev. Discuss. , doi:10. 5194/gmd-2016-115, 2016 Manuscript under review for journal Geosci. Model Dev. Published: 23 June 2016 c Author(s) 2016. CC-BY 3. 0 License. resolutions -spanning from 125 km up to 16 km -with several ensemble members. Furthermore, a smaller set of transient coupled simulations (PFC simulations, 1850-2100) at T255 ORCA1 (∼80 km for the atmosphere and about 1°for the ocean) has been run. Each deterministic experiment included in Climate SPHINX has a counterpart where the sub-grid unresolved scale has been parameterised with two different stochastic physics schemes (namely the SPPT and SKEB schemes). This makes Climate SPHINX the first climate dataset which includes a large number of ensemble members with a stochastic parameterisation at different horizontal resolution: along with other high-resolution simulation campaigns such as UPSCALE.
Acknowledgements. We acknowledge  PRACE  for awarding us access to resource SuperMUC based in Germany at the  Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (LRZ). We thank the EUDAT (European Data Infrastructure) project for awarding us a Data Pilot project and CINECA for providing resources and technical assistance for the storage and distribution of the postprocessed model output files. We thank  Peter Bechtold  and  ECMWF  for useful suggestions on the QBO tuning. PD acknowledges the funding from the  European Union 's  Horizon 2020 research and innovation programme COGNAC  under the  European Union Marie Skłodowska-Curie  grant agreement n. 654942. JvH and PD acknowledge support by the  Project of Interest NextDATA  ( MIUR PNR 2011-2013 ). HC, SJ, AS, PW and TP were supported under the  European Research Council  grant  291406   PESM.
Several of these disallowed genes are also upregulated in humans with T2DM  (Pullen and Rutter, 2013). These data indicate that the R299Q g2 mutation causes re-expression of b cell disallowed genes, with a profile reminiscent of that of T2DM. To determine whether, as in the hypothalamus, GHSR-based signaling contributed to the g2-related islet phenotype, including impaired GSIS, we evaluated glucose tolerance following GHSR antagonism. [D-Lys 3 ]-GHRP-6 normalized the insulin secretory response of R299Q g2 mice 30 min post-glucose without affecting glucose tolerance or basal insulin levels (Figures  6I,  6J,  and S5I ). The Corresponding R302Q g2 AMPK Mutation in Man Is Associated with Increased Adiposity, Reduced Basal b Cell Function, and Elevated Plasma Glucose Heterozygous human carriers of the R302Q g2 missense mutation-orthologous to R299Q in mice-have a relatively mild cardiac phenotype  (Sternick et al.
ACKNOWLEDGMENTS We thank  Sandra Stobrawa  and colleagues ( Genoway Lyon ) for generating R299Q g2 mice; families participating in the R302Q phenotyping study;  Wellcome Trust Centre for Human Genetics High-Throughput Genomics Group  (grant  090532/Z/09/Z ) for sequencing data;  Hermes Pardini  for human biochemistry;  Karen McGuire ,  Kate Thomson , and  Jessica Woodley  ( Oxford Medical Genetics Laboratories ) for R302Q genotyping;  Keith Burling  ( Core Biochemical Assay Laboratory Cambridge ) and  Tertius Hough  ( MRC, Harwell Oxford ) for murine biochemistry;  Paul Trayhurn  for comments; and  Parisa Yavari  for artwork support. This work utilized  Core Services  supported by grants  DK089503  (MNORC) and DK020572 (MDRC) of the  NIH  to the  University of Michigan. C. B. is supported by a  Diabetes UK   RD Lawrence Fellowship  ( 13/ 0004647 ).
C. F. and B. G. are supported by the  Hungarian National Brain Research Program. L. K. H. is supported by the  Wellcome Trust  ( WT098012 ) and  BBSRC  ( BB/K001418/1 ). G. A. R. was supported by a  Wellcome Trust   Senior Investigator Award  ( WT098424AIA ),  MRC   Programme Grant  ( MR/ J0003042/1 ), and a  Royal Society Wolfson Research Merit Award. A. Y. was funded by a  Wellcome Trust   Research Training Fellowship  ( 086632/Z/08/Z ) and is supported by the  UK National Institute for Health Research. A. Y. ( RE/ 08/004 ), H. W. , and H. A. acknowledge support from the  BHF Centre of Research Excellence, Oxford. This work was supported by a grant from the  MRC  to H. A. and H. W. ( MR/K019023/1 ). This paper is dedicated to the memory of the late  Professor Michael A. Cawthorne.
The details of the experimental process are described later. We first begin by using a previously developed rigorous model  21  to simulate the performance of reverse-AMOL. The model utilizes finite-element-method (FEM) (COMSOL interfaced with MATLAB) to model the photochemical reactions and light propagation that occur inside the AML. Such a model has been previously used  21, 25, 26  to elucidate the effect of the material properties, light polarization, etc. in AMOL and demonstrated to be highly successful in handling dispersive and inhomogeneous media such as the AML and solving Maxwell's equations based on user defined material properties. Details of the model specific to reverse-AMOL and relevant mathematical derivations are described in the supplementary information. 27.
Integrons are extensively targeted as a proxy for anthropogenic impact in the environment. We developed a novel high-throughput amplicon sequencing pipeline that enables characterization of thousands of integron gene cassette-associated reads, and applied it to acquire a comprehensive overview of gene cassette composition in effluents from wastewater treatment facilities across Europe. Between 38 100 and 172 995 reads persample were generated and functionally characterized by screening against nr, SEED, ARDB and β-lactamase databases. Over 75% of the reads were characterized as hypothetical, but thousands were associated with toxin-antitoxin systems, DNA repair, cell membrane function, detoxification and aminoglycoside and β-lactam resistance. Among the reads characterized as βlactamases, the carbapenemase bla OXA was dominant in most of the effluents, except for Cyprus and Israel where bla GES was also abundant.
rrc. uic. edu/dnas) and The Technion Genome Center (Haifa, Israel) (http://tgc. net. technion. ac. il/) respectively, using Illumina paired end sequencing technology on a MiSeq desktop sequencer (Illumina). Construction of a Comprehensive β-Lactamase Database. Inclusive characterization of integron-associated βlactamase genes was preceded by construction of an extensive β-lactamase database (EX-B) that integrated four clinically important publically available databases: The Lahey β-lactamase database,  40, 41  The Lactamase Engineering Database (LACED),  42  The Comprehensive Antibiotic Resistance Database (CARD)  43  and The Pasteur Institute's OXY, OKP and LEN protein variation databases (http://bigsdb. web. pasteur. fr/ perl/bigsdb/bigsdb. pl?db=pubmlst_klebsiella_seqdef_ public&page=downloadAlleles).
All of the sequences deposited into EX-B were compared using BioEdit 7. 2. 5 software and checked for nonredundant sequences; producing a database containing 1566 nonredundant β-lactamase sequences. The EX-B database is publically available for download at (http:// app. agri. gov. il/eddie/tools. html). Classification of Integron Gene Cassette Amplicons. Illumina amplicon reads were initially filtered to remove ambiguities with Mothur v1. 35. 1. 44 Subsequently, filtered contigs (see below) and amplicon sequences were compared to five different databases using the blastx  45  and Diamond  46  algorithms at an e-value cutoff of 10 -5 (preliminary analysis determined that both algorithms gave very similar results, but Diamond was significantly faster). The NCBI nonredundant (nr) protein database 472 and SEED  48  were used to acquire an overall classification of the amplicon reads and assembled contigs; the Antibiotic Resistance Genes Database (ARDB)  49  was applied to classify antibiotic resistant genes; while the EX-B database was used to comprehensively characterize βlactamases.
coli DH5α competent cells and plated on selective LB media as recommended by the manufacturer. Plasmids were then extracted from four randomly selected positive colonies, subsequently sequenced using conventional Sanger sequencing and compared to the INTEGRALL integron gene database  55  using the BLAST algorithm (SI Table  S2 ). Results from the EX-B database analyses (see below) were validated by conventional and quantitative real-time PCR analyses targeting bla OXA-2 , bla OXA-10 , and bla GES , the most abundant β-lactamase genes identified in the integron amplicon sequencing analysis. The primers and PCR conditions used for all of the above analyses are summarized in SI Table  S3. Sequence Accession Numbers. The sequences generated in this study were deposited in the European Nucleotide Archive (ENA) under accession numbers ERS1030613-ERS1030628.
■ RESULTS The novel next generation amplicon sequencing-based methodology developed here generated between 38,100 to 172,995 high quality reads per sample for the 12 European effluent and four Shafdan samples (SI Tables  S4  and S5 ). These reads were compared to different databases in order to comprehensively characterize and assess the relative abundance of integron GCassociated coding sequences in the various samples. Characterization of Integron-Associated Genes in European WWTP Effluents. Functional characterization of the GC reads in the 12 WWTP effluents was inferred by blasting sequences against the nr (SI Table  S6 ) and SEED (SI  Table  S7 ) databases. This revealed a broad array of genes with diverse putative functionality. Between 12-71% and 50-82% of the reads in all of the samples were predicted to encode for hypothetical proteins according to the nr and SEED databases, respectively.
These included between 13 and 86% hypothetical proteins that were specifically defined by the nr database as putative integron gene cassette proteins based on a previous study by Koenig et al. 56  Between 0. 47-3. 2% (nr) and 0. 84-3. 8% (SEED) of the all generated reads encoded functionally characterized proteins. These were associated with a myriad of functions including antibiotic resistance and biosynthesis, transport, membrane proteins, toxin/antitoxin systems, mobile element functions, and transcriptional regulation (Figure  2 ). Screening GC amplicons against the ARDB database showed high relative abundance of genes encoding β-lactamases, aminoglycoside acetyltransferases, aminoglycoside adenyltrasnferases and dihydrofolate reductases (Figure  3 ; SI Table  S8 ). Collectively, β-lactamase encoding genes were the dominant GC-associated antibiotic resistance elements in AT, DE1, DE2, FR, IL, PT, and UK effluents; aminoglycosides resistance mechanisms were most prominent in CY1, CY2, NO, and IT effluents; and dihydrofolate reductases were abundant in the DD3 effluents.
Due to their abundance and clinical importance, we specifically targeted β-lactamases by comparing generated GC amplicon reads to the newly compiled EX-B database described above (SI Table  S9 ). In total, 0. 009% to 1. 04% of the integron GC-associated reads in the 12 WWTP effluents were characterized as β-lactamases, which represented on average 14. 17% or 52. 59% of the characterized antibiotic resistance genes according to the nr and ARDB databases, respectively. The IT effluent GCs contained the highest relative abundance of β-lactamases, followed by the IL, CY1 and DE2 effluents (Figure  4 ). A large number of β-lactamases could not be assigned to specific gene families, and therefore an analysis based on general molecular β-lactamase classification  41  was performed (SI Table  S10  and Figure  S1 ).
Nonetheless, a myriad of functionally characterized reads were identified by nr (SI Table  S13 ) and SEED (SI Table  S14 ) database comparisons. High relative abundances of β-lactamase and glyoxalase encoding genes were detected in the dewatered sludge and effluent samples vs negligible presence of these genes in the infiltration pond and control soils. In contrast, aminoglycoside acetyltransferases were detected in amplicons from all four samples. Genes encoding toxin-antitoxin and killer proteins, associated with plasmid maintenance, were found in almost all of the samples, but toxin proteins were dominant in both infiltration pool and control soil samples; whereas killer proteins were most abundant in the effluent sample. These plasmid maintenance-associated elements were previously identified in integron gene cassettes from contaminated Suez Bay sediment.
57 The control soil contained high relative abundances of cupins and mobile elements relative to sludge and effluent samples. Cupin domains have been observed in biofilm-isolated integrons,  58  and have been found to be involved in transcriptional responses to diverse stress signals,  59  but their actual function is currently unknown. Screening the GC reads against the ARDB databases revealed β-lactam, aminoglycoside, macrolide, vancomycin, quinolone and multidrug resistance mechanisms in the various Shafdan samples (SI Table  S15 ). The β-lactamaseand aminoglycoside adenyltransferase-encoding genes were substantially more   S9  and S16 ). In contrast, the composition and the relative abundance of GC-associated βlactamase genes in the dewatered sludge were substantially different than the effluents despite that fact that these two samples were from the same sampling date.