dataesr/scientific-paragraphs-categorization huggingface dataset:
This situation has already been reported for E10 (see the sub-chapter "Functional consequence of H1 haplotype on pathology"). Alternative 5′ UTR/alternative first exon In the literature, E0 is always described as the first exon in all MAPT transcripts. However, when analyzing different MAPT transcripts in databases such as Ensembl, it is apparent that E0 can be present or absent in the H1 haplotype; thus, it may be considered an alternative exon due to alternative promoter usage. Furthermore, E0 inclusion is less frequent in the sequences of transcripts from the reverse strand (H2 haplotype) (Fig. 3 ). Several possible initiating transcription sites may exist in E0 as described above (see the sub-chapter regarding promoters), leading to different possible lengths of E0 and of the 5′ UTR because E0 is a non-coding exon (Fig.
3 ). According to the Ensembl database, the length of E1 may also vary depending on the first exon that is included (E0/E1). Indeed, E1, a partially coding exon, is 150 or 133 nt long when initiated from E0 or E1, respectively, on the forward strand. For H2 (the reverse strand), in the absence of E0, the length of E1 is three nucleotides longer at its 5′ side (153 nt) or 17 nucleotides shorter at the ATG codon (133 nt). These variations in E1 length do not affect the sequence of the translated protein because the 5′ end is non-coding; therefore, this length variation only results in modification of the 5′ UTR of the transcript (Fig. 2 ).
Additional exons The possible insertion of additional exons, although not yet identified in the published human transcripts, is suggested by data in the Ensembl database. This possibility is the case for E8, which was first identified in bovines and then in certain species such as rhesus monkeys  [146, 147]  but has not been described in humans  [148]  (Fig. 4a ). However, according to the Ensembl database, transcripts containing E8 include all of the alternative exons except for E0, which can be included or excluded (MAPT-203 ENST00000344290, MAPT-004 ENST00000415613). Studies of different animal species have shown that E8 insertion is possible in the absence of certain alternative exons. In particular, 4 transcripts containing E8 have been identified in cows  [148]. All of these transcripts also contain E2 and E10 but lack E4A.
4b ). Other exons generated by the extension of known exons have been found in particular isoforms in Ensembl database. Exon E4A Long has been described in MAPT transcripts as another spliced form of exon 4A  [41]  (see above). E4A Long may also be the only exon in a short transcript listed in Ensembl database (MAPT-010 ENST00 000576238/ENST00000625417) (Fig. 4b ). Another example is extended E3 (E3 Ext , 5658 nt versus E3, 87 nt), which may be the first exon in the MAPT-009 transcript (ENST00000576518/ENST00000626880) (Fig. 4b ). Exon E3 Ext is composed of exons E3 and E4, the 1603 nt upstream of E3 and the entire retained intron between E3 and E4 (3903 nt) (Fig. 4b ). E3 Ext may be a partially coding exon because an ATG is located 100 nt before E4 and is spliced to exon 5, encoding a protein that lacks part of the 5′ region that contains the acidic projection domain (Fig.
Indeed, two alternative polyadenylation sites followed by a short poly(A) sequence located at a distance of approximately 4000 nt have been found in different animal species  [74, 115, 120, 156]  (Fig. 3 ). Thus, at least two transcription termination sites could be used, resulting in transcripts with short or long 3′ UTRs. Interestingly, the first polyadenylation site is located within an intronic sequence that is deleted in some transcripts from various animal species. Indeed, in some Ensemble database transcripts from mouse, rat and cow, E14 is separated from E13 by a short intronic sequence of approximately 900 nt  [148, 157]. The splicing of E13 to E14 results in extension of the C-terminus of the protein and truncation of the 3′ UTR. In humans, the short intronic region between E13 and E14 is always retained, as described in the literature  [74]  and databases such as Ensembl.
Additional data are necessary to confirm or exclude the possible existence of another promoter. Furthermore, differences exist between isoforms reported in the literature and those reported in databases, suggesting that some splicing possibilities remain to be explored. Data regarding Tau isoforms reported in the literature primarily concern the nervous system. However, Tau (transcripts/proteins) is expressed in other tissues, and its expression may play roles in some pathologies, such as cancer and IBM. Thus, increasing our understanding of the isoforms expressed in these different tissues and of the regulation of their expression, which may differ from those in the brain (for example, different promoters and polyadenylation sites) is of interest. In addition to the isoforms described in the literature, the data from databases suggest the possible existence of shortened Tau isoforms, noncoding transcripts and one transcript that may undergo NMD, thereby bringing into question the roles of these hypothetical forms.
Briefly, the cell cycle assay uses PI, a nuclear DNA stain, to identify the specific cell-cycle phase. Resting cells (at the G 0 /G 1 phase) contain two copies of each chromosome. Cycling cells synthesize chromosomal DNA (S phase), which results in increased fluorescence intensity. When all chromosomal DNA is doubled (G 2 /M phase), the cells fluoresce with twice the intensity of the initial population. Data for the determination of cell viability, apoptotic rate, and cell cycle were collected using a Attune cytometer (Life Technologies, Rockville, MD, http:// www. lifetech. com) and were analyzed using Attune software.
These experiments were conducted in triplicate and repeated on three separate occasions. The presence and concentration of each of the aforementioned mediators were evaluated using the MasterPlex QT 1. 0 system (MiraiBio, Alameda, CA, http://www. miraibio. com) and analyzed using Luminex-100 software version 1. 7 (Luminex, Austin, TX, http://www. luminexcorp. com). A five-parameter regression formula was used to calculate concentrations of the respective mediators using standard curves for each mediator assessed  [22]. The data were analyzed using either a five-or a four-parameter logistic or spline curve-fitting method as recommended by the manufacturer. The type of curve-fitting method for each mediator was chosen with respect to the lowest residual variance (,5%).
Data collection One of the ultimate goals of the ICHOM efforts is to provide a single set of standard data that can be compared across health care systems, countries, and patient populations. A reference guide including sample questionnaires and a data dictionary designed for each standard set created by the ICHOM is an integral part of implementing the measurement process, and will facilitate standardization of data collection. The guide is free and is available on the ICHOM website (www. ichom. org/medical-conditions/ advanced-prostate-cancer).
Conclusions The distribution of brain injury into no, mild/moderate, or severe injury did not differ among the groups neither for the overall cUS score nor for MRI. There was less severe brain injury in the experimental group as assessed by central reading of cerebral ultrasound, which is in line with the reduction of cerebral hypoxia in the experimental group of the SafeBoosC II trial, but MRI conducted at TEA in 64% of the infants did not support this finding. The problems in acquiring cUS and MRI data of good quality might be addressed by dedicated training. cUS as well as MRI images at TEA were often missing. Central, blinded readers of cUS achieved high interobserver agreement for severe brain injury. Large randomized clinical trials should be performed to evaluate the effect of the burden of cerebral hypoxia on brain injury in extremely preterm infants.
Study Design and Population One-hundred and sixty-six extremely preterm infants from eight European countries were included (1 June 2012 to 31 December 2013)  (5). The infants were randomized to either the experimental group or the control group. Infants in the experimental group were monitored with NIRS, and continuous cerebral tissue oxygenation levels were available for the clinician together with a dedicated treatment guideline (4), listing possible interventions if the cerebral oxygenation level was out of range (55-85%). The infants in the control group were also monitored with cerebral NIRS, and the data were recorded but blinded to the clinicians. They were given standard care. In both groups, the cerebral NIRS monitoring was started within 3 h after birth and continued until 72 h of life  (5).
Initial cUS images from two times 20 random infants were scored by the central readers to ensure common use of the scoring system. Then, the central readers scored all cUS series individually according to the predefined diagnoses (Table  4 ). Disagreements were resolved by consensus meetings. Each cUS was categorized on a three-level scale as no brain injury, mild/moderate brain injury, or severe brain injury  (18, 20, 26, 27). DICOM images were analyzed using the software program OsiriX version 6. 0. (Pixmeo, Geneva, Switzerland). Images uploaded in other formats were viewed in Preview. The scores of all cUS images for each infant were combined into an overall cUS score reflecting the worst scan in any of the serial cUSs. In case of death, the overall cUS score would reflect the worst scan in.
The Atmospheric Drag, Occultation 'N' Ionospheric Scintillation mission (ADONIS) studies the dynamics of the terrestrial thermosphere and ionosphere in dependency of solar events over a full solar cycle in Low Earth Orbit (LEO). The objectives are to investigate satellite drag with in-situ measurements and the ionospheric electron density profiles with radio occultation and scintillation measurements. A constellation of two satellites provides the possibility to gain near real-time data (NRT) about ionospheric conditions over the Arctic region where current coverage is insufficient. The mission shall also provide global highresolution data to improve assimilative ionospheric models. The low-cost constellation can be launched using a single Vega rocket and most of the instruments are already space-proven allowing for rapid development and good reliability.
ADONIS is a low-cost and efficient method for monitoring the ionosphere globally and providing a valuable new source of data for assimilative models. It will be able to run continuously, improving on and complementing current efforts based on ground-and space-based GNSS TEC measurements as well as ground-based ionosonde networks. This paper is organised as follows: In Section 2 a mission overview is given, Sections 3 and 4 describe the mission and the spacecraft designs. The development and costs are presented in Section 5, and finally the conclusions are presented in Section 6.
Global coverage is currently achieved using both ground-based and space-based GNSS TEC measurements used in products such as SWACI (http://swaciweb. dlr. de), which is part of ESA's Space Situational Awareness (SSA) programme. Additionally, ionosondes measure vertical density profiles of the lower ionosphere, providing valuable constraints to assimilative models, but their coverage is less global. The ADONIS mission shall improve the global coverage and the provision of TEC NRT data for the Arctic region. Objective 3: Provide measurements relevant to satellite drag and to the ionospheric response to space weather events over a full solar cycle. A long mission lifetime allows the observation of a large number of similar solar events and the ionospheric and thermospheric response to the electromagnetic flux and particle precipitation.
This yields a comprehensive dataset for statistical studies and improved modelling of drag as well as the ionospheric and thermospheric response to space weather events. The ADONIS mission will not measure parameters such as the solar wind parameters or the X-ray flux, which directly affect the ionisation in the ionosphere. The interpretation of the ADONIS measurements in terms of correlations to space weather will rely on the network of existing and planned missions. For example, the Active Composition Explorer (ACE), the SOlar and Heliospheric Observatory (SOHO) and the Wind spacecraft are currently providing solar wind parameters from orbits around the Lagrangian point L1, the Solar TErrestrial RElations Observatory (STEREO) and the Solar Dynamics Observatory (SDO) monitor solar activity while the constellation of GOES spacecraft monitors radiation and particle fluxes.
The Deep Space Climate Observatory (DSCOVR) is scheduled to be launched soon and to be placed near L1. Due to its use of a solar sail, the planned Sunjammer mission is even designed to monitor from a location upstream of L1. The Chinese KL5 mission is now in preparation with ample provision of international instruments. KL5 considers space weather monitoring at both L1 and L5 Lagrangian points. In the highly complex atmosphere-ionosphere system it will be a challenge to integrate in-situ measurements of the thermosphere and spatially non-collocated ionospheric measurements. The mission nevertheless aims at investigating the reaction of the two regions to space weather events, and to contribute to better modelling with high-resolution data in both cases. The strength of ADONIS is that measurements of thermospheric and ionospheric parameters are carried out at the same time with high cadence, so as to identify and follow changes caused by space weather.
ADONIS shall measure the acceleration of the spacecraft with a cadence of 1 Hz. Requirement 3: The mission shall provide a global daily coverage with a longitudinal separation lower than 15°, because Obj. 1 and 2 require a low longitudinal separation with a short repetition time. Measurements shall be made at altitudes covering a range from 300 to 800 km encompassing both the bottom-side and the top-side F-region of the ionosphere, because drag measurements require low passes whereas ionospheric measurements are more complete from higher altitudes. This allows to cover global changes affecting satellite drag and ionospheric conditions and to provide corresponding datasets. Requirement 4: The mission shall provide NRT coverage of the Arctic region (above 63°N latitude). The strongest and most recurrent ionospheric space weather effects occur at high latitudes, but ground-based measurements are sparse in these regions.
The instrument is also included on the planned ICON (Ionospheric Connection Explorer) mission. Since the instrument is proven at all altitudes where ADONIS will operate, it has a high TRL of 8-9. The multi-needle Langmuir probes (m-NLP) are used to measure the electron density and contribute to Req. 5. They also provide in-situ data complementary to the occultation and scintillation measurements. This instrument has been developed and tested on a sounding rocket as reported by  Bekkeng et al. (2010) , thus it has a TRL of 8-9. Radio occultation measurements shall satisfy Req. 4 and Req. 5. With the Integrated GPS Occultation Receiver (IGOR) instrument, A-DONIS and B-DONIS receive GNSS signals which get Doppler-shifted while gaining frequency-dependent (dispersive) ionospheric delay because of refraction.
Scintillation is not monitored by any operational spacecraft at the moment. At scales of metres to tens and hundreds of metres, the ionosphere changes in minutes, thus rapid sampling is important. TEC data in the Arctic region shall be directly downlinked to the Svalbard ground station, providing NRT ionospheric monitoring products valuable for assimilative modelling. Thermistors measure the surface temperature of the spacecraft, which is one of several parameters influencing the drag coefficient. Thus this measurement is needed to fulfil Req. 1. The solar panels are already equipped with thermistors. Additionally, there are thermistors on the front and back surfaces. Thermistors have a TRL of 9. The Fluxgate Magnetometer's (FGM) heritage from the Cluster and THEMIS missions  (Balogh et al.
Ground segment The ground segment of ADONIS consists of a ground station (GS), Mission Operations Centre (MOC), Science Operations Centre (SOC) and space weather services. An overview of the mission ground segment is shown in Figure  4. The ground station selected for the mission is the Svalbard SG-3 ground station (latitude 78°N), owned and operated by the Norwegian company Kongsberg Satellite Services AS (KSAT). It uses S-Band for downlinking housekeeping telemetry and uploading telecommands to the space segment. Science and operational telemetry data is received using X-band. The ground station location was picked due to its position close to the North Pole, mainly for good ground coverage of satellite passes and secondly to have short time delay for downlinking the NRT space weather data in the Arctic region.
The on-board scientific instruments generate up to 350 Mbit of data per orbit during nominal operations. In the worst-case scenario (four consecutive passes without coverage), 1750 Mbit of data is produced. The worst-case downlink capacity for a pass with ground station coverage is 4500 Mbit, giving a worst-case science data downlink margin of 2750 Mbit. This also means that in case bad ionospheric conditions prevent nominal telemetry, an additional seven orbits' worth of data can be stored on board and still downlinked in one pass afterwards. The total generated scientific data during the mission is roughly 20 Tbit.
Telecommunications The telecommunication system uses a combination of S-band and X-band links. S-band will be used for receiving telecommands and relaying housekeeping and control telemetry to the ground. X-band will be used for downlinking the science telemetry. Table  3  gives a summary of the typical telecommunication system of the SSTL-300 commercial platform. The data rate budget is given in Table  4. The on-board telecommunication system of the ADONIS spacecraft includes the following SSTL products: XTx400 X-Band Transmitter, S-Band Uplink Receiver and S-Band Downlink Transmitter. For the S-band systems, two oppositefacing SSTL S-Band Patch Antennas will be used (for a near spherical gain pattern), while for the X-band transmitter a SSTL Antenna-Pointing-Mechanism will be used. All antennas are redundant.
Applications also encompass the forecast of the re-entry of space debris or spacecraft to be disposed of. The interaction between the solar wind and radiation with the Earth is causing a variety of disturbances in the ionosphere influencing satellite radio signals at LEO as well as GNSS signals. Global monitoring of the ionosphere using radio occultation and scintillation measurements over a full solar cycle will lead to a more accurate determination of the signal refraction in real-time, to the valuable provision of a new source of data to assimilative models and will also contribute to the development of predictive models. ADONIS is a low-cost mission using a single Vega rocket as launch vehicle. The satellites carry an identical set of eight instruments in order to measure the drag and ionospheric properties.
Acknowledgements. Team Orange wants to thank our tutors  Jaan Praks  and  Martin Volwerk  for their support, dedication and contributions to our mission development. We also acknowledge in-depth discussions with and reviews from  A. Balogh ,  V. Bothmer , Caspar,  J. Eastwood ,  C. Erd ,  P. Falkner ,  A. de Groof ,  M. Hallmann ,  B. Lavraud ,  J-P. Luntama ,  D. Moura ,  M. Palmroth ,  A. Valavanoglou  and  A. Veronig  throughout the development process during and after the summer school. We are grateful to both Referees for their detailed reviews and suggestions which helped greatly improve this work. The editor thanks  Mike Hapgood  and  Rajagopal Sridharan  for their assistance in evaluating this paper.
roqueforti, P. camemberti, P. digitatum, P. italicum, P. aurantiogriseum, and P. expansum, with the latter two species being extremely closely related (Fig. 1A ). Indeed P. aurantiogriseum and P. expansum PEXP shared a 99. 76% average protein identity, which was very similar to the 99. 79% protein identity shared between the PEXP and PEX2 strains of P. expansum. This result is in sharp contrast to the existing taxonomic classification, which places these latter two Penicillium species in different sections and series within the subgenus Penicillium  (Frisvad and Samson 2004). Therefore, it was suspected that the current genome sequence purported to be P. aurantiogriseum  (Yang et al. 2014 ) may represent a case of misidentification. This premise was tested by comparing all strains with existing sequences from phylogenetic markers present in the database (e.
expansum interaction (GenBank accession number AJ518007) (Sánchez-Torres and González-Candelas 2003). PEX1_045470 is only expressed in spores. This latter gene seems to be specific to P. expansum, as no homologs could be identified in any of the current databases. Overall, the RNA-Seq results highlight the arsenal of putative pathogenicity factors deployed by P. expansum during infection of apple fruit and identify specific candidates that should be functionally analyzed in order to further understand their role in the pathogenicity of P. expansum.
1992). Penicillium italicum Wehmer PHI-1 (denoted as PITC) was isolated from a mandarin stored at 4°C in Valencia (Spain). Strains have been deposited in the Spanish Type Culture Collection (CECT) with accession codes CECT 20907 for P. expansum isolate d1, CECT 20906 for CMP-1, CECT 20908 for MD-8, and CECT 20909 for P. italicum PHI-1.
Libraries were quantified and loaded into Illumina flow cells at concentrations of 7 to 20 pM. Cluster generation was performed in an Illumina cluster station. Sequence runs of 2 × 100 (PEXP and PEX2 strains) or 2 × 55 (PEX1) cycles were performed on the sequencing instrument. Base calling was performed using Illumina pipeline software. In multiplexed libraries, we used 4-bp internal indices (5′ indexed sequences). Deconvolution was performed using the CASAVA software (Illumina).
Genome assembly and functional annotation. Reads were filtered using a quality threshold of 10 and a minimum read length of 31 when reads were trimmed. Genomes were then assembled using SOAP de novo  (Luo et al. 2012). GapCloser was used to fill in the gaps in the scaffolds. P. expansum genomes were annotated using Augustus  (Stanke et al. 2006) , making use of the RNA-Seq data. The basic annotation was complemented by a homology-based search in which proteins found in the UniProt database (The UniProt Consortium 2014) were compared with the genomes using GeneWise  (Birney et al. 2004 ). Those genes that did not overlap with the Augustus annotation were added to the annotation. Finally, a comparison was run among the three P. expansum strains in order to unify predictions when possible. The annotation of P.
italicum was done similarly, with the exception that RNA-Seq data was not available. For each predicted protein, GO, KEGG, InterPro, and Enzyme Code annotations were assigned by using Blast2GO  (Conesa et al. 2005). Functional annotation of the predicted proteins was performed by using the KOG database at the Web server for the MetaGenomic Analysis (WebMGA)  (Wu et al. 2011)  and by using the KEGG automatic annotation server  (Moriya et al. 2007 ). Carbohydrate-active enzymes (CAZymes) were identified by using the CAZymes analysis toolkit (CAT)  (Lombard et al. 2014; Park et al. 2010 ) and dbCAN, a web server and database for automated CAZyme Annotation  (Yin et al. 2012).