dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We are particularly grateful to  Steve Devonish , Director of  Natural Heritage ,  Kim Downes Agard ,  Environmental Officer  (both at the  Ministry of Environment and Drainage of Barbados ) and  Lyndon John  ( Forestry Department, Ministry of Agriculture of St Lucia ) for granting us the permission to capture and ring  Zenaida Doves ,  Alison Mayers ,  Wayne Worrell  and  Cyril Bhola  for hospitality. We thank  Nicole Atherley ,  Laurent Brucy ,  Marc Lavoie ,  George Prato ,  Amelie Slaski ,  Franciane Le Quellec  ( Reserve Naturelle de Saint Barthelemy ),  Anthony Levesque  ( Office National de la Chasse et de la Faune Sauvage/AMAZONA association ) and  David Laffitte  ( Office National de la Chasse et de la Faune Sauvage ) for their help in catching and banding birds, and  Stephane De Palmas ,  Christine Dubreuil  and  Estelle Harrang  for molecular lab work.
KM was supported by a doctoral grant from the  Ministere de la Recherche et de l9Enseignement Superieur. Financial support was provided by the  Agence Nationale pour la Recherche  (programme blanc Monogamix), and the  Conseil regional de Bourgogne. Fieldwork in the  British Virgin Islands  was supported by  National Science Foundation  grant  DEB-0542390. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
High-throughput SNP genotyping was performed at the Vesalius Research Center in Leuven, Belgium, using the Sequenom MassArray platform (Sequenom, San Diego, CA, USA)  (Reumers et al, 2011). Genotyping analysis was performed by investigators blinded for the clinical data. Overall, 16 SNPs were successfully genotyped, with success rates X85% for each SNP and an overall average success rate of 96%. We failed to genotype SNP rs1126647 in IL-8 because of technical reasons. For most of the SNPs, genotypes were analysed in the same way as they were communicated in the original reports (i. e. , according to dominant, recessive or co-dominant genetic models or in the context of a specific haplotype). Clinical data were collected at 15 different sites in France and Belgium. The primary objective was PFS and OS, and the secondary objective was RR.
We defined PFS as the time between the first day on sunitinib and the date of radiological PD or death. Patients who had not progressed at database closure were censored at last follow-up. Overall survival was defined as the time between the first day on sunitinib and the date of death or last date of follow-up. Objective response was assessed by the treating doctors and classified as complete response (CR), partial response (PR), stable disease (SD), or PD. Timing for assessments was dictated by individual institution policy. All patient characteristics were tested in an univariate analysis for association with PFS and OS using Kaplan-Meier statistics and in a multivariate model using Cox proportional hazards. Fisher's exact tests and logistic regression were used to compare the incidence of poor-prognostic variants in patients with PD vs a group with SD, PR or CR as best response.
The MSKCC score was used as a covariate in the multivariate analysis, as well as all other variables with a Pp0. 2 on univariate analysis that are not part of the MSKCC score. Results with a P-value of o0. 05 were considered as significant in the multivariate analysis. Because this is a confirmatory rather than an exploratory study, SNPs were selected based on literature evidence and, hence, no correction for multiple testing was made. Of the 11 clinical parameters assessed in the univariate analysis (for 88 patients), there were 13 missing values (1. 3%). For the multivariate analysis, 82 patients with complete data could be included. Statistical analyses were conducted using GraphPad Prism 5 (GraphPad Software, La Jolla, CA, USA) and XLSTAT software (Addinsoft, Paris, France).
RESULTS We enroled 88 patients who started sunitinib between November 2005 and July 2011 and closed the follow-up database in April 2012. Table  2  shows the clinical characteristics of enroled patients. Mean age at diagnosis was 59 years (range 38-84). The majority of patients (494%) were of Caucasian origin. According to the MSKCC prognostic criteria, 15% of patients were categorised into the favourable risk group, and 56% had intermediate and 28% poor risk. At the time of analysis, 57 (64. 8%) patients had reached progression and 48 (54. 5%) had died. The median follow-up was 46. 0 months (range 1. 0-73. 0 months; 95% confidence interval (CI) 42. 0-51. 0 months) after the start of sunitinib. The median PFS was 15. 0 months (95% CI 11. 0-23. 0 months) and the median OS was 29. 0 months (95% CI 23.
0-42. 0 months). Best response assessment was available in 82 patients (in the 6 remaining patients, there was a clinical benefit, but response assessment was poorly defined in the medical records, and as a consequence, it was unclear whether the best response was either PR or SD in these 6 patients). In all, 6 out of 82 (7. 3%) patients had a CR, 30 out of 82 (36. 6%) patients a PR, 36 out of 82 (43. 9%) SD and 10 out of 88 (11. 4%) PD as best response. For each of these 16 polymorphisms, the respective genotypes, allele frequencies and changes at the amino acid level are given in Table  3. The allele frequencies of the genotyped polymorphisms were similar as previously reported in the dbSNP database (dbSNP build 136) or 1000 Genomes Project, except for SNPs rs2276707 and rs307821. Their observed minor allele frequencies were slightly higher compared with their frequency reported in dbSNP.
ACKNOWLEDGEMENTS This project is a common project of two kidney tumour banks: the  CIT-rein tumour bank (Paris, France)  and the  University Hospitals Leuven kidney tumour bank (Leuven, Belgium). The CIT-rein project is headed by  Professor Stephane Oudard  and  Professor Jean-Jacques Patard  and was part of the PNES 2007 ( Programme National d'Excellence Specialisee ) from the  INCa (Institut du Cancer). We sincerely thank the urologists, medical oncologists and pathologists of the next centers, whose biological material was used in the analysis, for their collaboration: Angers:  Centre oncologique Paul Papin: Abdel Azzouzi, Remy Delva, Stephane Triau, Pierre Bigot; Caen: Centre Franc¸ois Baclesse :  Henri Bensadoun ,  Emmanuel Sevin ,  Franc¸ois Comoz ; Creteil: Hopital  Henri Mondor: Alexandre de la Taille ,  Bernard Paule , Yves Allory; Suresnes: Hopital Foch:  Thierry Lebret , Christine Theodore,  Yves Denoux ; Leuven:  University Hospitals Leuven :  Hendrik Van Poppel ,  Evelyne Lerut ,  Joost Berkers ,  Pascal Wolter ,  Patrick Scho ¨ffski ,  Robert Paridaens ;  Limoges: Hopital Dupuytren: Aurelien Descazeaud ,  Julien Berger ; Lyon:  Centre Leon Be  ´rard:  Marc Colombel ,  Sylvie Negrier ,  Florence Mege-Lechevallier ; Marseille:  Institut Paoli-Calmettes :  Franck Bladou ,  Gwenaelle Gravis ,  Myriam Marcy ; Nantes: ICO Gauducheau:  Olivier Bouchot ,  Frederic Rolland ,  Karine Reanudin ;  Paris: Hopital Necker and Saint Joseph: Arnaud Mejean ,  Virginie Verkarre , Vincent Molinie; Poitiers:  Jacques Irani ,  Jean Marc Tourani ,  Pierre Marie Le Villain ; Rennes:  Brigitte Laguerre ,  Jean-Jacques Patard ,  Nathalie Rioux-Leclercq ; Paris:  Clinique St-Joseph : HerveBaumert,  Gael Deplanque ,  Vincent Molinie; Strasbourg: CHRU Strasbourg :  Didier Jacqmin ,  Brigitte Duclos , Veronique Lindler; Tours: CHU Tours:  Olivier Haillot ,  Claude Linassier ,  Franck Fetissof.
The tissue collection was coordinated by the  Plateforme de Ressources Biologiques de l'Hopital Europeen Georges Pompidou in Paris. We are grateful to  Corine Takouchop Teghom ,  Claudia De Toma  and  Reza Elaidi  for the coordination of the tissue and clinical data collection. Benoit Beuselinck  received a grant from the  Fondation Martine Midy (Paris, France)  ( 2009-2010 ). His work is also funded by the  Fonds voor Wetenschappelijk Onderzoek Vlaanderen (Belgium)  ( 2011-2013 ). Alexandra Karadimou  received a grant from the  Hellenic Society of Medical Oncology (Athens, Greece)  ( 2010-2011 ). Bart Claes is supported by the  Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT)  and by the  Emmanuel van der Schueren  grant of the Vlaamse Liga tegen Kanker.
3 15. 9 rs4073054 7837T4G Intron 87 40 (46) 35 (40) 12 (14) 33. 9 40. 7 Sunitinib pharmacodynamics HIF1A rs11549467 1790G4A A588T 84 83 (99) 1 (1) 0 (0) 0. 6 1. 7 PDGFRA rs35597368 1580T4C S478P 88 69 (78) 18 (20) 1 (1) 11. 3 13. 3 VEGFR2 rs1870377 1718T4A Q472H 81 46 (57) 28 (35) 7 (9) 25. 9 27. 5 VEGFR3 rs307821 3971G4T R1324L 88 64 (73) 23 (26) 1 (1) 14. 2 5. 8 rs307826 1480A4G T494A 88 65 (74) 22 (25) 1 (1) 13. 6 10. 2 Alternative VEGF-independent proangiogenic pathways FGFR2 rs2981582 906C4T Intron 87 23 (26) 52 (60) 12 (14%) 43. 6 45. 6 IL8 rs4073 251T4A 5 0 near gene 79 25 (31) 42 (53) 12 (15%) 41. 8 42. 5 Abbreviations: SNP ¼ single-nucleotide polymorphism; VEGF ¼ vascular endothelial growth factor; UTR ¼ untranslated region; dbSNP ¼ SNP database.
Age mean at the beginning of the study differed between these five villages: Agniam (mean±SD): 4. 40 ± 2. 48, Niandane: 5. 17 ± 2. 42, Pendao: 4. 49 ± 2. 61, Guede: 5. 84 ± 3. 06 and Fanaye: 5. 32 ± 2. 46) (p=0. 008). Thick blood smears were stained with Giemsa to identify Plasmodium species and the number of malaria parasites was counted. Parasite density was defined as the number of Plasmodium parasites/μl of blood. In parallel, sera collected by finger prick were used for immunological tests. In June 2009, a large scale distribution of Long-Lasting Insecticidal Nets (LLINs) was performed around the endemic regions, and particularly in the studied region by the National Malaria Control Program (NMCP) of Senegal  [36]. The present study was approved by the National Ethics Committee of the Ministry of Health of Senegal, (October 2008; 0084/MSP/DS/CNRS, ClinicalTrials.
Statistical analysis of data Data were analysed with Graph Pad Prism W (Graph Pad Software, San Diego, USA). After checking that values in each group did not fit a Gaussian distribution, one-way analysis of variance (ANOVA) was used to compare age differences between children of all villages. The nonparametric Mann-Whitney U test was used to compare Ab response levels between two villages while the Kruskal-Wallis test was used for the comparison of Ab response levels between more than two villages. The Wilcoxon matcher-paired test was used for the comparison of Ab response levels between two visits in each village. All differences were considered as significant at p<0. 05.
The use of vector control tools (spray, ITNs or LLINs, personal protection. ) as well as household characteristics (traditional, modern. ) could significantly reduce the human-vector contact. Moreover, individual exposure to Anopheles was evaluated by HLC (using adult volunteers) and therefore, could present considerable limitations for evaluation of entomological exposure in children  [44, 45]. Entomological data was also collected in limited number of areas (five randomised houses/village) and cannot represent the individual exposure to Anopheles bites and its micro-geographical variations. The use of the gSG6P1 biomarker could therefore be relevant and useful for assessing human exposure to Anopheles bites at the population and individual level. We also reported that both IgG Ab levels and the percentage of immune responders to the salivary biomarker varied according to the season and remained high in October corresponding to the peak of exposure to Anopheles bites.
Acknowledgments The authors gratefully acknowledge the populations of  Agniam, Niandane, Guede ,  Ndiayene Pendao  and Fanaye villages, for their participation in this study. We also thank  Soihibou Guindo  and  Samy Boutouaba-Combe  ( CRB-EPLS ) for their technical assistance in the field and advice on statistical analysis, respectively. André Barembaye Sagna was supported by a fellowships provided by  CRB-EPLS and Jean Biram Sarr by a post-doctoral fellowship  provided by the  "Infectiopole Sud" Foundation (Marseille, France). Lobna Gaayeb  received support from the  Region Nord-Pas de Calais  and the  Pasteur Institute of Lille. This research was supported by the  Biomedical Research Center Espoir Pour La Santé (EPLS)  and the  Research Institute for Development (IRD-Direction de la Valorisation au Sud)  with a financial participation of the  FSD "Fond Social de Développement ", (BIOMARQPAL ref  2008-5901 )  Embassy of France in Senegal.
High level of antibiotic resistance is largely attributable to active efflux by the AcrAB-TolC system  [12]. The functions of MDR regulators are well documented. Data usually show the effect of inacti-vation of a repressor, inactivation or overexpression of an activator on the transcriptome of a susceptible reference strain. However, most of the studies dealing with clinical isolates only reports changes in acrAB expression using RT-PCR or immunoblotting techniques. Surprisingly, a recent study suggested no correlation between overproduction of acrAB and tolC  [165] , while these loci are both targets for MDR transcriptional activators such as MarA and RamA. 24 susceptible isolates and 36 resistant isolates with different MICs to fluoroquinolones were analyzed. Among the resistant isolates, 22 and 25 showed significant overexpression of acrA and acrB, respectively, though only 3 overexpressed tolC.
These data demonstrate that LV(a/miR-21) provides an effective means to target miR-21 in pancreatic tumors. We next monitored orthotopic pancreatic tumors progression using blood Lucia assay following LV(GFP) or LV(a/miR-21) intratumoral administration. Strikingly, the growth of this very aggressive tumor model was stopped by day 2 up to day 12 following in vivo depletion of miR-21, compared with green fluorescent protein (GFP)-expressing LVs (Figure  4a ). Animals were killed and tumor burden was assessed 2 weeks following intratumoral gene transfer. Animals treated with control vectors developed fulminant disease as tumor volume increased by more than eightfold during the course of the experiment (Figure  4a , insert). In contrast, LV(a/miR-21)-treated animals were dramatically protected, exhibiting only weak tumor progression (2.
Blood samples were collected every 2-3 days during the course of the experiment. We found that gemcitabine slightly inhibited PDA tumor progression, as compared with vehicle (-21%, P < 0. 05, Figure  5d ). On the other hand, miR-21 depletion strongly inhibited PDA tumor growth, as compared with LV(GFP)-transduced tumors (-75%, P < 0. 01, Figure  5d ). Because the data presented herein support that depletion of miR-21 stimulates angiogenesis in this experimental model of PDA, we hypothesized that targeting miR-21 may augment tumor drug delivery to enhance the efficacy of systemic therapies. The results presented Figure  5d  demonstrate that combining gemcitabine treatment and transduction with LV(a/miR-21) stopped tumor progression (Figure  5d ) and induced tumor shrinkage (-40 ± 5%, P < 0.
The present study design involved the treatment of existing tumors with miR-21 inhibitors, a paradigm closely related to the clinical scenarios in which this approach may be employed. Indeed, we are currently conducting a first-in-man phase I gene therapy clinical trial in 24 patients diagnosed with advanced pancreatic cancer (Thergap clinical trial, ClinicalTrials. gov identifier NCT01274455). We demonstrated during this trial, the feasibility and the safety of transfecting PDA tumors with nonviral vectors using endoscopic ultrasound (data not shown). While groundbreaking, this unique clinical trial will strongly benefit from the characterization of new delivery vehicles and new molecular targets that may help alleviate the dismal prognosis of this disease. Because miR-21 is overexpressed in most human tumors,  7  therapeutic delivery of miR-21 antagonists may still be beneficial for a large number of cancers for which no cure is available.
Molecular modelling Swissmodel web service  (31)  was used to construct homology models for B. subtilis DnaG based on the crystal structure of the E. coli protein [(32); PDB code 3B29], and for DnaE Bs based on the crystal structure for Thermus aquaticus polIIa [(33), PDB code 3E0D]. Alignments and quality metrics are included in the supplementary information (Supplementary Table  S3 ). Using Chimera  (34) , the nucleic acid component of both models was elaborated to include a fuller length of the template strand both upstream and downstream of each catalytic site, while a 5-nt length of double-stranded (ds) nucleic acid was included to represent the situation where a short primer has been synthesized. For the DnaG model, this required extending the observed ssDNA in a 5 0 direction, while modelling the hybrid duplex into the basic groove, as described before  (32).
Characterization of the B. subtilis DnaG primase activity Bacillus subtilis DnaG initiation specificity was predicted to be similar to that of primases from other Firmicutes belonging to the Bacilli class  (28). To test this hypothesis, two oligonucleotides that comprised all 64 possible trinucleotide sequences were initially used to assess template specificity, followed by trinucleotide-specific ssDNA oligonucleotides to verify template specificity. These results confirmed that B. subtilis DnaG initiated primer synthesis preferentially on 5 0 -d(CTA) and, to a slightly lesser degree, on 5 0 -d(TTA; Figure  3A  and data not shown), similar to the primases from Bacillus anthracis, Geobacillus stearothermophilus and Staphylococcus aureus  (29, 38, 39). In addition, the trinucleotide 5 0 -d(TTT) was determined to support de novo primer synthesis.
Characterization of the B. subtilis DnaC helicase activity Helicase activity was assayed by monitoring the displacement of a 104-mer oligonucleotide annealed onto ssM13 and forming a double-fork substrate with poly(dT) tails. Purified monomeric or hexameric B. subtilis DnaC helicase did not exhibit detectable helicase activity in vitro under a variety of conditions tested (data not shown). The B. subtilis DnaG primase or the DnaE Bs polymerase did not activate the monomeric or hexameric DnaC helicase (Figure  5A  and data not shown). The helicase activity was only detectable when monomeric DnaC was mixed with the putative B. subtilis helicase loader protein DnaI, and increased with increasing concentrations of DnaI, reaching a maximum at 0. 5 mM DnaI (monomer), corresponding to 1:1 DnaI:DnaC molar ratio (Figure  5B ).
Another important point obtained from these data is that although in the reaction with ATP and dNTPs, DnaG was capable of forming only very small primers (2 or 3 nt) from the single 5 0 -d(TTTT) site, despite their small size, they were efficiently extended by DnaE Bs. Collectively, these data show that in this partially reconstituted lagging strand replication system, there is de novo RNA primer synthesis by DnaG and extension of RNA primers by DnaE Bs coupled to DnaC helicase translocation. More importantly, the DnaG-DnaE Bs hand-off is efficient even with the synthesis of very small RNA primers only 2-3 nt long, suggesting again that the RNA primer is handed off very early to DnaE Bs directly via a DnaG-DnaE Bs interaction. DnaE Bs native polymerase activity is not significantly affected by the DnaC helicase and/or the DnaG primase The DnaE Bs native polymerase activity was monitored by a primer extension assay using a synthetic oligonucleotide annealed onto ssM13 DNA.
A structural model for the primase-polymerase hand-off Reasonable-quality homology models for both B. subtilis DnaG and DnaE Bs could be obtained from crystal  structure templates using the Swissmodel Web Service (see 'Materials and Methods' section). In preparation for the analysis of the possibility of direct hand-off from DnaG to DnaE Bs , the models of both proteins were elaborated to include a long length of template DNA strand both upstream and downstream of the two enzymes' catalytic sites (for details, see 'Materials and Methods' section). The resulting model for the DnaG complex is shown in Figure  11A. The short length of ssDNA present in the crystal structure of the template protein (PDB entry 3B29) was extended in a 5 0 direction, while a section of partially dsDNA/RNA was modelled into the basic groove, following the hypotheses discussed by Corn et al.
Aim: Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin. Methods: In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7. 3%) received subcutaneous lixisenatide QD (10 μg weeks 1-2, then 20 μg; n = 77) or liraglutide QD (0. 6 mg week 1, 1. 2 mg week 2, then 1. 8 mg; n = 71) 30 min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal. Results: Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC 0:30-4:30h : -12. 6 vs. -4. 0 h•mmol/L, respectively; p < 0. 0001 (0:30 h = start of meal)]. Change in maximum PPG excursion was -3. 9 mmol/l vs.
Acknowledgements Dr Christoph Kapitza  acts as guarantor and takes responsibility for the content of the article. We would like to thank all the investigators and their staff for the conduct of this study:  Dr Sybille Baumann  ( CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany );  Dr Halabi Atef  ( CRS Clinical Research Services Kiel GmbH, Kiel, Germany );  Dr Doris Neuenhofer  ( CRS Clinical Research Services Mönchengladbach GmbH, Mönchengladbach, Germany );  Dr Georg Golor  ( PAREXEL International GmbH, Berlin, Germany ) and  Dr Baerbel Huber  ( Harrison Clinical Research Deutschland GmbH, München, Germany ). We also thank all the patients who took part in the study. The authors thank  R&D Sanofi  colleagues ( Natacha Bosc  and  Jérôme Repincay ,  Chilly Mazarin, France ) for their contribution in data management and data analysis.
Conflict of Interest C. K. and H. -V. C. are employees and C. K. is a stockholder at the Profil Institut für Stoffwechselforschung GmbH, which received financial support for conducting this study from Sanofi. T. F. has received speaker fees from Sanofi. F. P. , P. R. and A. Hincelin-Méry are employees of Sanofi. The study was funded by Sanofi, the manufacturer of lixisenatide. The investigators and representatives from Sanofi were responsible for the study design, protocol, statistical analysis plans, analysis and reporting of the results. Final responsibility for the decision to submit the manuscript for publication was made jointly by all authors. C. K. was involved in the design and clinical performance of the study, discussion of results and the preparation of the manuscript. T. F. and H.
Despite the extremely large neutron absorption cross-section of 157 Gd (ca. 16% natural abundance), we managed to acquire INS spectra of 1 (Fig. 2  and Fig. S3 , ESI †). Although noisy, the energy loss peaks A, at 2. 2 cm À1 , and B, at 3. 0 cm À1 , are clearly discernible in the spectrum at l i = 6. 5 Å and assigned to magnetic excitations originating from the ground state, on the basis of their temperature dependence. Unfortunately, the poor quality of the observed Q-dependence, because of the presence of 157 Gd and large incoherent scattering from 1 H, does not allow affirming the magnetic nature of these excitations. The experimental spectra were interpreted by use of home-written software  11  invoking the anisotropic extension of spin-Hamiltonian (1) given in eqn (2): Ĥaniso ¼ Ĥiso þ D Cr Ŝz;Cr 2 À 1 3 S Cr S Cr þ 1 ð Þ (2) where D Gd is neglected.