dataesr/scientific-paragraphs-categorization huggingface dataset:
DLSPPWs: mode profile and heterointegration The DLSPPWs, in the present context, are formed by placing a polymethylmethacrylate (PMMA) ridge with a cross section of 500 nm in width by 600 nm in height as the dielectric material on top of a 65-nm thick and 3-μm wide gold strip (Fig. 1a ). This geometry provides us with full 2D confinement in the plane perpendicular to the propagation direction. The calculation of plasmonic mode properties for this geometry has been performed by a finite-element method implemented in the commercially available software COMSOL multiphysics. This geometry is one of the most popular for plasmonic waveguides due to the fact that PMMA can work as both resist and the dielectric core for the DLSPPW. It is hence quite a convenient and simple process to fabricate plasmonic devices based on DLSPPW using deep-ultraviolet (UV) lithography for those devices with larger dimensions working at telecom wavelengths  [29]  or standard E-beam lithography (EBL) for those working in the near-infrared  [30].
REVIEW ARTICLE Laser Photonics Rev. 7, No. 6 (2013)  943 NRZ data stream. A high-power erbium-doped fiber amplifier (EDFA) boosted the incoming WDM data signal, providing 24 dBm output power. A polarization controller was placed just before the hybrid chip to ensure TM-polarization conditions for the input light, as supported by plasmonic elements. The output of the hybrid waveguide, a multiwavelength data stream was then amplified by a low-noise EDFA and demultiplexed into its constituent data channels by an optical bandpass tunable filter (OBPF). Subsequently, each channel was detected by a 40-GHz 3-dB bandwidth photoreceiver followed by a 1:4 electrical demultiplexer in order to be received by a 10-Gb/s error detector for bit error rate (BER) measurements. Transmission losses of these 60-μm long DLSPP waveguide were found be to 11 dB at 1545 nm for TM-polarized light, which includes 6 dB of transmission loss, based on a cut-back measurement and 2.
By electrically controlling the upper A-MZI arm, a negative phase shift is experienced by the propagating DLSPPW mode as a result of the negative thermo-optic coefficient (TOC) of the PMMA that equals -1. 05 × 10 -4 K -1. When the induced phase shift equals π /2, the phase difference between the modes travelling through the two MZI branches equals π , and therefore the whole mode power is exported to the BAR output of the device. On the contrary, when the same current level applies only to the lower MZI plasmonic branch, the default MZI phase asymmetry is cancelled out due to the -π /2 thermo-optically induced phase shift and, consequently, the whole mode power emerges at the CROSS port of the interferometer. To evaluate the switching performance of the Siplasmonics A-MZI, first the static measurements were performed followed by dynamic as well as with four-channel WDM data measurements.
Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17,92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications.
Results Increased miR-17,92 copy number resulting from a focal 5 kb DNA copy number gain High resolution array CGH analysis revealed, amongst others, a 5 kb focal gain of the miR-17,92 locus (13q31. 3) in the MYCN amplified cell line NLF (Figure  1A ). FISH analysis showed the presence of eight copies of the locus in this tetraploid cell line (data not shown). Expression levels of the miR-17,92 cluster were measured in 19 MYCN amplified and 8 MYCN non-amplified neuroblastoma cell lines. As expected, the MYCN amplified cell lines showed significantly increased miR-17,92 levels in keeping with the previously described evidence for direct up regulation of the cluster by MYCN  [18, 19]. MiR-17,92 expression levels are not significantly higher in NLF cells as compared to the other MYCN amplified cell lines, but MYCN expression is within the lower range for NLF compared to the other MYCN amplified cell lines (Figure  1B ), in keeping with relatively lower level of MYCN amplification (Figure  S1 ).
e. E2F6, ODC1 and PPM1G)  [25, 27]. In particular, a region on chromosome 2 that is most often coamplified with MYCN as a separate amplicon (in 4/43 MYCN amplified tumors (9. 3%) and 2/24 MYCN amplified cell lines (8. 3%)) contains the bona fide oncogene ODC1 (2p25. 1), which was recently described as a critical determinant of MYCN oncogenesis  [28]. In a next step, we tested the regions of focal gain and amplification for enrichment of up regulated MYCN target genes, as available in the MYCNot database (http://medgen. ugent. be/ MYCNot). A separate analysis was performed (1) for the up regulated target genes with a validated direct interaction with MYCN (referred to as directly up regulated MYCN target genes) and (2) for all up regulated genes in the MYCNot database, meaning all indirect MYCN targets, putative direct MYCN targets (for which currently no experimental proof is available) as well as the above mentioned validated direct MYCN target genes.
Investigation of focal gains and amplicons in our sample panel revealed significant enrichment for directly up regulated MYCN target genes in high risk MYCN non-amplified (subtype 2A) and MYCN amplified (subtype 2B) tumors as well as in the cell lines. When performing this analysis for all up regulated MYCN target genes listed in the MYCNot database, significant enrichment could be seen for all tumor subtypes and cell lines (Table  1 ; Table  S3 ). Furthermore, we noticed that the regions containing direct MYCN targets in subtype 2A tumors i. e 5p15 (TERT) and 12q13. 2-q14. 1 (CDK4) are also gained or amplified in subtype 2B tumors (the indirect targets INHBE, NACA and SHMT2, also located in the 12q13. 2-q14. 1 amplicon were not found gained or amplified in the subtype 2B tumors).
Integrated genomic analysis for identification of genes down regulated by MYCN driven miRNAs and located within regions of focal genomic loss Using the MYCNot database, no enrichment of MYCN down regulated target genes could be observed in the focal deletions. This was not unexpected, since so far only a limited number of down regulated MYCN target genes have been carefully assessed and validated. Recent studies revealed that MYCN-induced miRNA activation acts as an important mechanism for indirect down regulation of gene expression following MYCN overexpression  [18, 19, 29]. We and others recently showed that DKK3 and ESR1 as well as several TGFb pathway components were down regulated as a result of increased levels of miRNAs encoded by the miR-17,92 cluster in neuroblastoma  [12, 30, 31].
Further investigation of a large array CGH data set of neuroblastomas confirmed several previously reported rare recurrent amplicons. These regions contain bona fide up regulated MYCN target genes such as ODC1, TERT, CDK4 and MDM2 (Figure  3 )  [23, 25, 26, 28]. Using the MYCNot database, we found enrichment of both directly and indirectly up regulated MYCN target genes in the focal DNA copy number gains. Encouraged by these findings, we also explored the genes that were targeted by focal deletions. Using an integrated genomics approach by combining DNA copy number data, mRNA and miRNA gene expression data as well as miRNA seed information, we selected 38 candidate genes for down regulation by MYCN activated miRNAs. Using a MYCN and miR-17,92 inducible cell line model system, we identified two new genes regulated by components of the MYCN regulated miR-17,92 cluster, i.
Array Comparative Genomic Hybridization (array CGH) and data analysis Samples were profiled on a custom designed 44K (156 samples), 60K (66 samples) or 180K (1 sample) array (Agilent Technologies) enriched for critical regions in neuroblastoma (1p, 2p, 3p, 11q, 17), cancer gene census genes  [68] , non-coding sequences (miRNAs and transcribed ultra-conserved regions) and all genes from the Neuroblastoma Gene Server (NBGS) database  [69]. The latter database contains curated lists of differentially expressed genes retrieved from all major published high-throughput neuroblastoma gene expression profiling studies. Validation experiments were performed on the commercially available 1M array (Agilent Technologies). The array designs are based on the hg18 genome build. Utilizing random prime labeling (BioPrime ArrayCGH Genomic Labeling System, Invitrogen), 400 ng (44K/180K), 200 ng (60K) or 1 mg (1M for validation purposes) of tumor and control DNA was labeled with Cy3 and Cy5 dyes (Perkin Elmer), respectively.
Further processing was then performed according to the manufacturer's instructions (Agilent Technologies). Fluorescence intensities were measured using an Agilent scanner (G2505C, Agilent Technologies). Data were extracted using the Feature Extraction v10. 1. 1. 1 software program (Agilent Technologies) and further processed with arrayCGHbase (http://medgen. ugent. be/arraycghbase) [70]. Array CGH profiles were further processed using the ''no waves''  [71]  and the circular binary segmentation (CBS) algorithm  [72]  that splits the genomic data into contiguous regions of equal copy number, and uses permutation to define copy number abnormalities at a defined significance level. The statistical environment R (version 2. 10. 0) was used to identify the location of all possible amplifications, homozygous deletions and recurrent focal gains and losses, whereas gene information was extracted using BioMart  [73]  and then used to determine the genes residing within these regions.
The miRBase database was used to extract the chromosomal locations of the miRNAs and to identify in which regions these reside. The following criteria were used to select copy number alterations (CNA) inferred by DNA copy number analysis for further validation and study: (a) homozygous deletion (log2 (CBS value) ,22. 0), (b) amplification (log2 (CBS value). 2. 0), (c) focal recurrent loss and (d) focal recurrent gain. We defined focal losses and gains for (c) and (d) as alterations ,2 Mb involving at least 2 non-overlapping contiguously altered oligos (log2 (CBS value) ,20. 3 and. 1. 0, respectively). Since we aimed to find genes important in neuroblastoma biology we looked for recurrent alterations defined by their occurrence in at least 2 samples. Chromosomal regions that are homozygously deleted or amplified (.
MYCN oncogene targets (MYCNot) database To summarize the current knowledge on MYCN downstream cascades, a thorough literature search was performed to track down all hitherto identified MYCN downstream genes. We grouped all the information and assembled and annotated the individual genes into the 'MYCN oncogene targets' (MYCNot) database (http://medgen. ugent. be/MYCNot). Most of the genes listed in the database have been identified as putative MYCN target genes through one or more differential expression screens without any other evidence suggesting that they are directly regulated by MYCN alone or by both MYCN and other transcription factors that work in a co-ordinated manner. Currently, 1041 up and down regulated MYCN mRNA targets are included in this database.
DNA copy number levels were measured relative to human genomic DNA (Roche Diagnostics) and normalized to the internal reference genes, BMCA (ID 14) and SDC4 (ID 15). mRNA expression levels were measured and normalized to at least 2 internal reference genes, TBP (ID 8098), YWHAZ (ID 8100), B2M (ID 2) and UBC (ID 8099). Primer sequences are available in RTPrimerDB (http:// www. rtprimerdb. org) [74] , ie hsa-miR26a-2 (ID 8243), hsa-miR-766 (ID 8250), RGS5 (ID 8244), TCF4 (ID 8245), ITK (ID 8246), INSR (ID 8247), TERT (ID 8248), SEPT6 (ID 8249) CDKN2A (ID 8251), NF1 (ID 8252), DIAPH2 (ID 8254), IGSF6 (ID 8255), THRAP3 (ID 8257), A2BP1 (ID 8258), MYCN (ID 11), RGS5 (ID 8261expression) and RNF11 (ID 8592-expression). Copy number and mRNA data analysis as well as error propagation was done using qbase PLUS software 1.
Expression analysis of neuroblastoma cellular model systems and cell lines SHEP-TET21N-MYC cells were cultured in RPMI (Invitrogen) supplemented with 10% fetal calf serum and treated with 1 mg/ml tetracycline (Sigma-Aldrich) to switch off MYCN expression (as reported in  [32] ). Publically available expression data from tetracycline treated and untreated SHEP-TET21N-MYC cells  [32]  were downloaded from the ArrayExpress website (accession number E-MEXP-2340) and validated for selected markers using qPCR. SHEP-TR-miR-17,92 cells were cultured in RPMI (Invitrogen) supplemented with 10% fetal calf serum and treated with 2 mg/ml tetracycline (Sigma-Aldrich) to induce miR-17,92 expression as reported in  [18]. Expression data from the tetracycline treated and untreated miR-17,92 inducible neuroblastoma SHEP cell line system were analysed using Affymetrix GeneChip Human Gene 1.
Sequencing Sequence analysis of the coding exons and flanking intronic sequences of RGS5 and the tyrosine kinase domain of ITK was performed on genomic DNA. NF1 (using emetin treated material  [78] ) and the tyrosine kinase domain of INSR were sequenced on the cDNA level. PCR products were subjected to unidirectional sequencing using BigDye Terminator V1. 1/V3. 1 Cycle Sequencing chemistry using an ABI3730XL sequencer (Applied Biosystems). Electropherograms were analyzed using Seqscape v2. 5 software (Applied Biosystems). Primer info is summarized in Table  S7.
ugent. be/nl/onderzoek/financiering/bof/GOA;grant number  01G01910 ), the FOD (http://www. health. belgium. be/eportal;grant number:  NKP_29_014 ) and the  IWT  (grant number:  SBO60848 ). This work was also funded by the  department of Pathology, Medical School, University of Valencia , Valencia, Spain:  RD06/0020/0102  and  PI10/0015  ( ISCIII & ERDF );  396/2009  (FAECC). The research leading to these results has received funding from the  European Union 's  Seventh Framework Programme  ( FP7/2007-2013)  under grant agreement nu259348 (ASSET). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Experimental Crystal data  Hydrogen-bond geometry (A ˚, ). D-HÁ Á ÁA D -H HÁ Á ÁA D Á Á ÁA D -HÁ Á ÁA C20-H20Á Á ÁO2 i 0. 93 2. 53 3. 1949 (19) 129 Symmetry code: (i) Àx þ 1; Ày þ 2; Àz þ 1. Data collection: APEX2  (Bruker, 2009) ; cell refinement: APEX2 and SAINT-Plus  (Bruker, 2009) ; data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97  (Sheldrick, 2008) ; program(s) used to refine structure: SHELXL97  (Sheldrick, 2008) ; molecular graphics: ORTEP-3 for Windows  (Farrugia, 2012) ; software used to prepare material for publication: PLATON  (Spek, 2009)  and publCIF  (Westrip, 2010). Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT6928).
Computing details Data collection: APEX2  (Bruker, 2009) ; cell refinement: APEX2 and SAINT-Plus  (Bruker, 2009) ; data reduction: SAINT-Plus  (Bruker, 2009) ; program(s) used to solve structure: SHELXS97  (Sheldrick, 2008) ; program(s) used to refine structure: SHELXL97  (Sheldrick, 2008) ; molecular graphics: ORTEP-3 for Windows  (Farrugia, 2012) ; software used to prepare material for publication: PLATON  (Spek, 2009)  and publCIF  (Westrip, 2010). Special details Geometry. All s. u. 's (except the s. u. in the dihedral angle between two l. s. planes) are estimated using the full covariance matrix. The cell s. u. 's are taken into account individually in the estimation of s. u. 's in distances, angles and torsion angles; correlations between s. u. 's in cell parameters are only used when they are defined by crystal symmetry.
Data The mortality and population data used have been described elsewhere. 19 Briefly, we selected six EU countries-Denmark, England and Wales, France (excluding the overseas departments), the Netherlands, Scotland and Sweden-after assessing the comparability of EU circulatory disease mortality data. 8 Data on deaths by age, sex, COB and underlying cause of death were acquired. The mortality data were provided for variable time periods, in some countries being centred on the 3-to 5-year period around the last census year (table  1 ). Data were extracted using ICD-9 and/or ICD-10 codes (an exception being Denmark which used ICD-8 and ICD-10): total circulatory disease ICD-9 390-459, ICD-10: I00-I99; ischaemic heart disease (IHD) ICD-9 410-414, ICD-10 I20-I25 and cerebrovascular disease ICD-9 430-438, ICD-10 I60-I69.
Study limitations Here, we consider the quality of the underlying data and the potential impact of selection bias. The data from Denmark and the Netherlands were based on linked population and death registers, where the denominator is exact. For England and Wales, France, Scotland and Sweden, this is not the case. Such data may be more prone to bias arising from COB misclassification, leading to numerator-denominator bias. 13 Also, incomplete COB registration may underestimate the level of mortality. To reduce this risk, we examined mortality for broad geographical categories. Moreover, the data include different time periods. Although important declines in circulatory mortality have been achieved over time, our results may possibly reflect different risks than the current ones. We used birth country as a proxy for ethnicity although COB tends to be less valuable in younger age groups.
COB criteria also fail to distinguish between different ethnic groups coming from the same birth country. Recent work from the Scottish Health and Ethnicity Linkage Study  24, 25  shows that circulatory disease outcomes by ethnic group tend to be similar to those in COB analyses, although differences seem to be greater with ethnic group. We could not assess the completeness of COB coding on death certificates but the absence of such information would underestimate the size of the numerator. In the event of misclassification of COB, i. e. where the wrong COB was recorded, we would expect a reduction in the strength of our associations. The general lack of information on individual-level characteristics (such as education) in the data prevented us from examining the effects of these factors on COB and mortality.
Acknowledgements This article is a product of collaboration between Work Packages 5 and 6 of the  MEHO  project. We thank  Dr Irina Stirbu  for compiling the mortality data sets for Denmark, England and Wales and the  Netherlands. This work has benefitted from numerous discussions within the MEHO collaboration and we acknowledge the  MEHO  project leaders,  Marc Bruijnzeels ,  Semiha Denktas  and  Marleen Foets  ( Erasmus Medical Centre, the Netherlands ), and the leaders of other  MEHO Work Packages  and their teams:  Laura Cacciani ,  Emanuela Forcella ,  Aldo Rosano  ( Agenzia di SanitaPubblica della Regiona Lazio, Italy );  Allan Krasnik  and  Signe Nielsen  ( University of Copenhagen, Denmark );  Oliver Razum ,  Jacob Spallek  and  Anna Reeske  ( University of Bielefeld, Germany );  Alexander Kramer  and  Manas Akmatov  ( University of Bielefeld, Germany );  Kvetoslava Rimarova  ( University of Slovenia ) and  Dineke Zeegers  (European Public Health Association).
Sequencing of the enoA gene locus YP_enoA5 and YP_enoA6 used for amplification of an approximately 400-bp segment of the enoA gene were previously published by Pannekoek and colleagues  [15]. PCR reactions were performed in a final volume of 25 ml. The mix contained 2 ml of DNA template, 2. 5 ml of 106 PCR reaction buffer, 1. 25 U of HotStarTaq DNA Polymerase (Qiagen, France), 100 mM of each deoxynucleotide triphosphate and 0. 5 mM of each primer. The conditions used for amplification were 95uC for 1 min, 45 cycles of 94uC for 30 s, 48uC for 1 min, 72uC for 1 min and 30 s, 72uC for 10 min (final extension). PCR-amplified segments of enoA were sequenced by Eurofins MWG Operon (Nantes, France). Sequence alignments were conducted using the Bionumerics software package version 4. 6 (Applied-Maths, Belgium).
Alignment (Figure  S1 ) and phylogenetic analysis (Figure  1 ) revealed that this sequence was specific to ACP and could be a convenient target for their unambiguous identification by real-time PCR. The specificity of the newly developed enoA-based real-time PCR assay (enoA-rtPCR) was tested with genomic DNA extracts of several bacterial and fungal species. Neither the DNA samples from non-chlamydial species (n = 22), nor the DNA samples from C. psittaci (n = 9), C. abortus (n = 4), C. pecorum (n = 6), C. felis (n = 1), C. caviae (n = 2) and newly described atypical chicken (ACC) isolates included in this study (n = 6) gave rise to a measurable signal. As expected, all DNA extracts from French (n = 2), German (n = 2) and Italian (n = 9) ACP isolates (Table  1 ) were successfully amplified (data not shown).
, 2004; Smith et al. , 2011). They depend on the quality and uncertainties of the underlying information, but also on the methods used to deal with missing information. In addition, studies estimating primary aerosol emissions are very time demanding and are not conducted on a regular basis. As a result a considerable time lag, as long as 5 to 10 yr, often exists between a given target period and the moment the inventory is produced. Biomass burning emissions of SO 2 and primary aerosols, black carbon (BC) and organic carbon (OC) among others, are usually estimated as the product of burned area, areal fuel loads, combustion completeness and emission factors. A commonly used inventory is the Global Fire Emissions Database  (GFED, van der Werf et al. , 2006 , 2010)  that uses burned areas product from MODIS.
Observations The daily total AOD over land and ocean and the fine mode AOD over ocean only are assimilated. Both of these AOD products are at 550 nm. The data is extracted from the ICARE Data and Services Centre (http://www. icare. univ-lille1. fr) where the aerosol products from multiple sensors are generated and/or archived. Data from the MODIS instrument onboard the Terra satellite are used, specifically, the daily level 3 aerosol products (MOD08) from collection 5. 1. These level 3 data are averaged on a 1 • × 1 • grid (MOD08 D3). Only the daily product is included in our assimilation procedure and thus the time of the measurement within the day is not considered. We apply an additional quality check besides those already included in the production of level 3 AOD MODIS product. In the original processing, the level 3 AOD data are weighted by the quality of each individual retrieval in order to prevent poor retrievals from affecting the calculated statistics  (Remer et al.
No smoothing is done to remove potential discontinuities across regional boundaries resulting from the combination of different inventories at the regional scale  (Lamarque et al. , 2010). In the present work only the fossil fuel and industrial emissions of BC, OC and SO 2 for the year 2000 will be considered. We have updated the original biomass burning inventory GFEDv2 (van der  Werf et al. , 2006)  used in L10 with the more recent version 3 (van der  Werf et al. , 2010). This later version uses improved satellite data and several modifications to the modelling framework were done, such as explicitly accounting for deforestation and forest degradation and partitioning fire emissions into different categories. This dataset provides daily emissions of SO 2 , BC and OC with a resolution of 0.