dataesr/scientific-paragraphs-categorization huggingface dataset:
The expression patterns of the three MtDELLA genes, based on the M. truncatula Gene Expression Atlas (MtGEA database, http://mtgea. noble. org/v3/; ref. 39), revealed that MtDELLA1 and MtDELLA2 have similar transcript levels in roots and nodules, and that MtDELLA3 has an overall weaker expression level. In addition, the three MtDELLA genes do not show any strong transcriptional regulation in response to bacterial NFs 32 (Supplementary Fig. 3a, b   2 ). The spatial expression pattern of the three MtDELLA genes was investigated using MtDELLA promoter:GUS (b-glucuronidase) transcriptional fusions. Under non-symbiotic and symbiotic conditions (1 day after inoculation with Sinorhizobium meliloti), the expression of the three MtDELLA genes was detected in the rhizobial infection zone (located above the root apical meristem, in the region where root hairs differentiate), in the root stele and cortex, and additionally in the epidermis for MtDELLA1 and MtDELLA2 (Fig.
MtDELLA1 symbiotic nuclear localization in the root epidermis. To determine the subcellular localization of the three MtDELLA proteins, a transient expression assay in Nicotiana benthamiana was first used to ectopically express MtDELLA-GFP (green fluorescent protein) translational fusions from the 35S-CaMV promoter. The three MtDELLA-GFP fusions were detected in the nucleus, as expected from data gained in Arabidopsis (Supplementary Fig. 3f ; ref. 42). To monitor DELLA subcellular localization in M. truncatula roots, we used the same translational fusions, but no GFP signal could be detected, either using the strong constitutive 35S-CaMV promoter or the endogenous MtDELLA1 promoter, in agreement with data obtained by Floss et al. 32  To overcome the fast DELLA protein turn over due to their continuous degradation by the proteasome pathway  43  , we used an N-terminal GFP translational fusion with the GA-insensitive della1-D18 variant expressed from the MtDELLA1 promoter, previously used and functionally validated in M.
Methods Materials and treatments. Seeds of the M. truncatula genotypes Jemalong A17 or R108 were used in this study. The della1 (NF12399), della2 (NF4302) and della3 (NF10539) mutant lines were identified by a PCR-based reverse screening  60  of M. truncatula Tnt1 insertion population  61  , generated in the R108 genotype, at the Noble Foundation (http://bioinfo4. noble. org/mutant/database. php). Mutant plants were genotyped by PCR using specific primers to amplify the endogenous loci, which were also combined with the transposon-specific primer LTR4 or LTR6 (Supplementary Table  5  for primer combinations and sequences) and backcrossed twice. The pENOD11:GUS line was initially identified in Journet et al. 8. Seeds were scarified and sterilized as described in Gonzalez-Rizzo et al. 18. For in vitro nodulation experiments, germinated seeds were grown vertically on a Fahraeus medium without nitrogen 62 with 1.
Gene expression analysis. Transcriptomic data were retrieved from the M. truncatula Gene Expression Atlas (MtGEA database, http://mtgea. noble. org/v3/; ref. 39), or from the SYMBIMICS website (https://iant. toulouse. inra. fr/symbimics/; ref. 41). For RT-qPCR experiments, total RNA was extracted from frozen roots using the RNeasy plant mini kit (Qiagen). First-strand complementary DNA (cDNA) was synthesized from 1 mg of total RNA using the Superscript II First-Strand Synthesis System (Invitrogen). Primer design was performed using Primer3 software (http://frodo. wi. mit. edu/cgi-bin/primer3/). Primer combinations, showing a minimum amplification efficiency of 80%, were used in RT-qPCR experiments (Supplementary Table  5 ). Specificity was checked both using a melting curve and by sequencing the PCR amplicons.
RT-qPCR reactions were performed using the LightCycler480 SYBR Green I Master Kit on a LightCycler480 apparatus according to manufacturer's instructions (Roche). Reference genes (RBP1 and ACTIN11) were selected using the geNorm software  64. For in situ hybridizations, the protocol described in Bustos-Sanmamed et al. 65  was used on an Intavis InsituPro automat (http://www. intavis. com/en/), on nodules 21 days after S. meliloti (strain 1021) inoculation. Antisense RNA probes corresponding to MtDELLA1, MtDELLA2 and MtDELLA3 were generated. Sense and antisense RNA probes corresponding to a carbonic anhydrase (MtCA1) gene were included as negative and positive controls, respectively  21. All primers used are shown in Supplementary Table  5. Cloning procedures. For transcriptional GUS fusions, available sequences upstream of MtDELLA1, MtDELLA2 or MtDELLA3 start codon (1,987, 1,121 or 2,431 bp, respectively) were amplified by PCR with a Pfx polymerase (Invitrogen) using primers listed in Supplementary Table  5.
A della1-D18 PCR fragment amplified from the pMtDELLA1:della1-D18 plasmid with Asc1-and Stu1-containing primers (Supplementary 5) was produced and inserted into the pFRN-pSlEXT vector to generate the pSlEXT: della1-D18 construct. For transactivation assay, the ARR6 promoter was removed from the pARR6-luciferase plasmid (NCBI accession number EF090414) using BamHI and NcoI restriction enzymes, and replaced by the ERN1 promoter region defined in Cerri et al. 14  , amplified from genomic DNA using BamHI-and NcoI-containing primers (Supplementary Table  5 ). NSP1, NSP2, NF-YA1 and MtDELLA1 cDNAs were PCR-amplified and cloned in BamHI and StuI restriction sites downstream of a 35S-CaMV promoter in the pHBT plasmid (ref. 67; NCBI accession number EF090408). Agrobacterium rhizogenes root transformation.
; ref. 40). Laser dissection of different nodule zones associated with RNAseq revealed a preferential expression of the three DELLA genes in the meristematic zone (I), and a lower expression of MtDELLA1 and MtDELLA2 in the differentiation/infection zone (II; SYMBIMICS database, https://iant. toulouse. inra. fr/symbimics/; ref. 41; Supplementary Table.
Site False detection discrimination. In any acoustic database, interferences of various types can occur (e. g. airguns, other baleen whale calls, seismic events, etc). Yet, the number of false detections generated by such interferences are limited due to the Z-detector characteristics  [28]. Nevertheless we develop a method for removing potential false detections. For each detection, the Z-detector output the frequency of the signal at its maximum amplitude. If this frequency departs from the frequency of unit A of the Z-call, which is the most energetic part of the call, it is likely that the detection is not a Z-call, but rather a false detection. Thus, we exclude all the detections with a frequency above and below the selected frequency for unit A for the processed year. Ambient noise measurement.
This chorus could indicate that whales are in the area, but not close enough to the hydrophone to be detected. The power of this chorus and more precisely, the Chorus to Noise-without-chorus Ratio (CNR) may thus usefully complement the detection results, since a lack of detection does not necessarily mean an absence of calling whales. To estimate this CNR, the chorus level is calculated in a frequency band set to 25. 5-26. 8 Hz for 2010 and 2011 datasets; 25. 5-26. 7 Hz for 2012 data; 25. 5-26. 5 Hz for 2013 and 2014; and 25. 5-26. 1 Hz for 2015. These bands are chosen to take only into account the Unit A of Z-calls and to avoid the 20-Hz fin whale pulses very abundant in our recordings. The 20-Hz fin whale pulses are centered around 20 Hz, but begin at around 15 Hz and end at around 30 Hz, with a maximum amplitude at about 18 Hz.
Seasons are defined by the dates of the solstices and equinoxes for each year. Distribution of Z-calls per site, per year or month or light regime are not normally distributed. So to compare distributions between sites of a triad, or between years or light regimes at a same site, we use Friedman or Kruskal-Wallis tests  [33]. In cases of significant differences between distributions, additional Wilcoxon pairwise comparison tests with Bonferroni correction are used  [34, 35]. Statistical analyses were performed using R  [36] , and GLMM was run using STAN called from R with the package RStanArm (http://mc-stan. org/) [37].
Seasonal patterns For MAD, NEAMS, NCRO, WKER and SWAMS sites, statistical comparisons show no significant difference among the normalized monthly distributions of Z-calls between years (Friedman tests, respectively for MAD, NEAMS, NCRO, WKER and SWAMS, Friedman chi -squared = 0. 8; 1. 13; 1. 84; 3. 1; 0. 26; all with a probability p in favor of the null hypothesis > 0. 05). For SSEIR site, a Wilcoxon test for paired data (V) shows no significant difference between the two years of data (Wilcoxon paired test, V = 34, p = 0. 96). This allows averaging the normalized monthly distributions over the available years for these sites and to compare them with the corresponding averaged Chorus to Noise-without-chorus Ratio (CNR) levels (Fig  6). At these six sites, Z-calls are recorded throughout the year, but with strong seasonal patterns that differ between locations.
Discussion In 2007, Branch et al. [5]  reviewed existing datasets of catches, sightings and acoustic records, and concluded that, despite records in the northern Indian Ocean, along the Australian coast, and south of 35°S, blue whales were absent in the south-central Indian Ocean. In 2010 and 2013, Samaran et al. [11, 12]  showed, however, that Antarctic blue whales are in fact present in this area, especially during winter months. Furthermore, these authors found that the central and southern Indian Ocean could be a year-round habitat for at least four populations of blue whales, including the Antarctic subspecies. Although this evidence changed our view of the Antarctic blue whale seasonal distribution in the Southern and Indian oceans, they are based on limited sites and years of observation.
In this latter study, the monthly number reached a maximum of about 20,000 Z-calls and was usually comprised between 5,000 and 10,000 calls for most of the other months, whereas over all our years of data, this number reaches a maximum of about 10,000 Z-calls and is below 5,000 for most of the other months. The location near Crozet Islands of the hydrophones used in  [22]  may explain these differences, since the shallow environmental conditions off Crozet Islands  [11]  would make the habitat more favorable than in the open ocean. But it is also possible that changes in these conditions and/or in the attendance of the area occurred since 2005. SSEIR station is also globally less attended than the other sites, meaning that its location is less favorable in terms of environmental conditions, but two years of data are insufficient to draw any definitive conclusion.
Wintering at such northern latitudes would explain the passage of whales and hence the important number of Z-calls until late spring near MAD and NEAMS on their way to the Antarctic feeding grounds. Nonetheless, this observation near Diego Garcia being from 2002-2003  [6] , it may also be possible that Antarctic blue whale seasonal presence has changed since then. The exact location of the Antarctic blue whale breeding areas is still not precisely known  [44]. It appears therefore that, contrary to other baleen whale species such as humpback, gray or right whales, blue whales seem to spread out very widely across the oceans for breeding. Complementing earlier observations  [6, 12] , our data suggest that wintering, possibly breeding, grounds encompass all latitudes between 26°S (MAD) or 31°S (NEAMS) and up to a northern limit at 7°S (Diego Garcia), since no Z-calls are recorded at RAMA (4°S).
The limited dataset (2 years) at the SSEIR station suggests that this site is located on a migration path from/to wintering areas north of MAD and NEAMS latitudes and Antarctica. It would explain the larger occurrence of Z-calls in autumn, late winter and spring than in summer. For the three subantarctic stations, the CNR patterns, which increase in autumn, decrease during winter and increase again in spring indicate that in this areas, whales are mainly present during autumn and spring, matching respectively with their northward and southward migrations, and are less present in winter, when they are at northern latitudes, in the wintering area. At SWAMS, Z-calls are mainly detected in autumn, then in early spring, suggesting the passage of blue whales near the site in autumn to wintering areas, and in spring to feeding areas.
Even if not fully understood, CNR provides a useful metric for interpreting Z-call numbers and tempering any conclusion on the absence or presence of Antarctic whales from Z-call detections only (SSEIR and WKER are good examples). Finally, the NCRO station is the most peculiar. Antarctic blue whales are present almost throughout the year, with no obvious pattern in the detection number. Our results are consistent with those of Samaran et al. [49] , who suspected a mid-latitude Antarctic blue whale wintering area, or a time-lagged migration. According to the migration paradigm described earlier  [3] , Antarctic blue whales winter in subtropical to subantarctic latitudes and feed in the summer in the high latitudes near Antarctica. Our data confirm this general picture, however Z-calls are also recorded in the summer at all sites.
Conclusion This study, based on an analysis of Antarctic blue whale Z-calls, provides a more comprehensive picture about this whale species distribution in the Southern Indian Ocean, than in previous studies  [11, 12]. Our extended acoustic dataset spanning up to 6 years, 42 degrees in latitude and 28 degrees in longitude shows 1) that Antarctic blue whales are present yearround in subantarctic and subtropical latitudes of the Indian Ocean, with a lesser presence in the austral summer, 2) that the distribution of Antarctic blue whales is highly seasonal, 3) that the seasonal patterns differ between sites but remain stable over the years, 4) that their wintering area may expand from 26°S and 7°S, and 5) the existence of a diel pattern in the emission of Z-calls, more frequent in daytime than in nighttime.
Acknowledgments The authors wish to thank the Captains and crews of RV  Marion Dufresne  for the successful deployments and recoveries of the hydrophones of the OHASISBIO experiment and of  ORV Sagar Kanya  for the recovery of the RAMA hydrophone. French cruises were funded by the  French Polar Institute  (IPEV; cruises  VT109/112-MD174/175 ,  VT115-MD185 ,  VT119-MD189 ,  VT128-MD193 ,  VT135-MD197 ,  VT141-MD200  and  VT146-MD201 ), with additional support from  INSU-CNRS. We thank  NOAA/PMEL  and  INCOIS  for the opportunity to recover the RAMA hydrophone. E. C. L. was supported by a Ph. D. fellowship from the  University of Brest  and from the  Regional Council of Brittany  ( Conseil Régional de Bretagne ). The contribution of  Mickael Beauverger  at LGO in the preparation and realization of the cruises is greatly appreciated.
Deployment and recovery cruises were funded by the  French Polar Institute  (IPEV;  MD174/ 175 ,  MD185 ,  MD189 ,  MD193 ,  MD197 ,  MD200 ,  MD201  cruises) and by  NOAA/PMEL  and  INCOIS  ( SK 307 ). Additional support for the acoustic experiments was provided by the  Institut National des Sciences de l'Univers of CNRS. E. C. L. was supported by a Ph. D. fellowship from the  University of Brest  and from the  Regional Council of Brittany (Conseil Regional de Bretagne). Moorings and hydrophones were funded by the  Regional Council of Brittany (CPER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Study selection and data extraction Randomised controlled trials comparing either standard of care versus standard of care plus docetaxel or standard of care versus standard of care plus bisphosphonate (at a therapeutic dose) were eligible if they aimed to include men with high-risk localised or metastatic, hormonesensitive (ie, not castrate-resistant) prostate cancer. We had no formal exclusion criteria. We sought to identify all trials, irrespective of whether a trial was ongoing or completed, published or unpublished, with no language restrictions. We searched MEDLINE,  14  Embase,  15  LILACS,  16  and the Cochrane Central Register of Controlled Trials from inception to Sept 30, 2015, using fi lters to include only randomised controlled trials. These searches were supplemented by searching trial registers, conference proceedings, review articles, and reference lists of trial publications (appendix pp 1-5).
Collaborators were asked throughout the project if they knew of any additional trials. CLV, LHMR, and SB assessed all relevant trial reports or protocols. Search terms used are listed in the appendix. For all eligible trials, we extracted data on: the accrual period, actual or (if ongoing) planned number of participants; whether previous androgen deprivation therapy was allowed; control group treatments (eg, type of androgen deprivation therapy used); docetaxel dose and scheduling; bisphosphonate type; dose and duration of bisphosphonate treatment; median patient age; metastatic status; performance status; TNM status; Gleason score; and median PSA concentration at the start of androgen deprivation therapy. We also extracted reported survival and failure-free survival results by trial and by participant subgroup (if available) from published reports and presentations.
Results Our searches of bibliographic databases, trial registers, and conference proceedings identifi ed 5141 articles and records (fi gure 1). After removing obvious duplicates and records that were clearly irrelevant, 83 records of potentially eligible trials were thoroughly scrutinised. 24 of these records were duplicates, and a further 24 records were ineligible. In total, 35 trials were eligible; 14 trials were eligible for inclusion in the docetaxel comparison, and 22 trials were eligible for the bisphosphonate comparison (table 1, table  2 ). One  rge multiarm trial (STAMPEDE),  8  which incorporates multiple treatment comparisons in men with both M0 and M1 disease, contributes to both the docetaxel and bisphosphonates meta-analyses. Five trials compared standard of care with or without docetaxel in men with M1 disease.
One trial (GOUP 01/04 [NCT00796458]), including 200 men, is still recruiting, and another trial, 32 including 14 men, has yet to report suitable outcome data (table  2 ). In the three remaining trials,  7, 8, 10   given at a standard dose of 75 mg/m² per cycle every 3 weeks for six to nine cycles, and median follow-up ranged from 29 months to 82•9 months (table  1 ). All trials were assessed as being at low risk of bias (table  3 ). Survival data from these three trials  7, 8, 10  were available for 2992 (93%) of 3206 men with M1 disease (table 1), and 1271 deaths had been recorded. Assuming a typical 4-year survival with standard of care of 40%, the meta-analysis HR of 0•77 (95% CI 0•68-0•87; p<0•0001),  translates to a 9% (95% CI 5-14) absolute improvement with standard of care plus docetaxel relative to standard of care alone (fi gure 2).
Again, we found no evidence of variation between the trial results. We identifi ed 11 trials that compared standard of care with or without docetaxel for men with non-metastatic disease (M0). Two trials (CAN-NCIC-PR12 [NCT00651326] and 05-043 [NCT00116142]), including 398 men, have fi nished accrual but have yet to report any results. Five trials,  [31] [32] [33] [34] [35]  including 1196 men, have yet to report any survival outcomes (table  2 ). The four remaining trials,  8, 25, 27, 28  all of which have reported survival or failure-free survival, or both, were included in the meta-analysis. Men of median age 62-66 years (ranges not reported for all trials) with non-metastatic disease and good performance status were randomly assigned to receive standard of care with or without docetaxel (table  1 ).
Failure-free survival was defi ned consistently in all four trials,  8, 25, 27, 28  but in the STAMPEDE trial,  8  only prostate cancer-specifi c deaths were included (rather than death by any cause), and the GETUG-12 trial 26 included time-to-salvage treatment. Results were available for 2348 (59%) of the 3798 men included in all four trials, and 851 events have been recorded. The meta-analysis HR of 0•70 (95% CI 0•61-0•81; p<0•0001) translates to an absolute improvement of 8% (95% CI 5-10), reducing 4-year failure rates from 30% to 22%, assuming a baseline 4-year failure-free survival of 70% (fi gure 2). Again, no evidence exists of variation between the trial results. We identifi ed seven trials that compared standard of care with or without bisphosphonates in men with M1 disease. The results of one trial (KYUH-TRIGU0705 [NCT00685646]), including 227 men, have yet to be reported, and in three other trials,  37, 42, 47  including 142 men, skeletal-related events, changes in bone mineral density, or both were the primary outcomes, and survival was not reported (table 2).
We identifi ed 17 trials that compared standard of care with or without bisphosphonates for men with M0 disease. The results of three trials (CECOG [NCT00181584], ZENITH [NCT00063609], and NU-02U1 [NCT00058188]), including 646 men, are unpublished, and ten other trials,  [36] [37] [38] [39] [40] [41] [43] [44] [45] [46]  including 1494 men, have reported results for outcomes other than survival (table  2 ). In th  four remaining trials  8, 12, 21, 29  included in the meta-analysis, men aged 40-87 years (median 66-70 years) with good performance status were randomly assigned to receive standard of care with or without either zoledronic acid  8, 21, 29  or sodium clodronate  12  (table  1 ). In two of the trials,  21, 29  zoledronic acid was given at a dose of 4 mg every 3 months for either 18 months or 4 years, whereas in the third trial, 8 zoledronic acid 4 mg was given every 3 weeks for 2 years.
men aged 36-91 years (median 63-66 years) with a good performance status received either androgen deprivation therapy-based treatments (standard of care) with or without docetaxel (table1). Most men had presented with metastatic disease and were starting long-term androgen deprivation therapy for the first time. Docetaxel was Accrual dates Number of Metastatic Primary outcome Secondary outcomes Reason not included patients status ADT vs ADT + docetaxel ARTIC AOM-03108 31 June, 2003- 254 M0 PSA progression-free PSA response; duration of PSA response; time to Reported results could not be used November, survival clinical progression; overall survival; tolerability; (safety 2010, progression-free 2009 quality of life survival* 2011, quality of life 2013) GENTAX 32 October, 2005- 30 M0 and M1 Progression-free survival Overall survival; toxicity; quality of life Reported results could not be used December, (progression-free survival*) 2009 SPCG-13 33 May, 2007- 378 M0 PSA progression PSA doubling time; quality of life; safety; metastasis- Reported results could not be used November, free survival; overall survival (safety) 2004 TAX 3503 34 July, 2007- 400 M0 Progression-free survival Overall survival; cancer-specifi c survival; adverse events Reported results could not be used September, (safety) 2012 CAN-NCIC-PR12 March, 2008- 48 M0 Disease-free survival Overall survival; time to biochemical disease No results reported yet (NCT00651326) January, 2011 progression; time to local or distant disease progression; time to next anti-cancer therapy; progression-free survival; degree of PSA suppression before radiotherapy; quality of life; adverse events QRT-SOGUG 35 December, 134 M0 PSA relapse Unclear Reported results could not be used 2008- (toxicity) September, 2012 05-043 June, 2005- 350 M0 Overall survival PSA doubling time; PSA failure; cancer-specifi c survival No results reported yet (NCT00116142) August, 2015 GOUP-01/04 April, 2005- 200 M1 2-year progression-free Overall survival; time to treatment failure; toxicity; PSA Ongoing (NCT00796458) ongoing survival response rate; disease response rate; PSA normalisation; quality of life; control of bone pain; change in chromogranin A concentration; cost analysis (Table 2 continues on next page).