dataesr/scientific-paragraphs-categorization huggingface dataset:
SUMMARY We present the first analysis of a solar occultation by Titan's atmosphere observed with Cassini/UVIS. The densities shown are comparable to most of those presented in previous work, within factors 1 -3. The derived temperature is comparable with that obtained from INMS and UVS measurements. The data presented here correspond to a location/period combination that was unexplored before, complementing the measurements of the upper atmosphere made 28 years ago by Voyager 1/UVS and recently by Cassini/INMS and UVIS. Based on the dates and locations of the observations, the differences observed could be attributed to horizontal and temporal variations. However, the restricted sampling of the available data does not allow a firm conclusion on horizontal/seasonal variations. Future analysis of other solar and stellar occultations might fill in the spatial and temporal gaps among the data, and help to clarify if the differences observed are due to temporal or horizontal variations, or uncertainties in the measurements.
Methods/design RESILIENCE is a multinational, randomized, doubleblind, placebo-controlled, phase 3 trial designed to assess the efficacy and safety of sorafenib in combination with capecitabine in patients with locally advanced or metastatic HER2-negative breast cancer who received previous treatment with a taxane and anthracycline. The study is being conducted in accordance with Good Clinical Practice guidelines, the guiding principles of the Declaration of Helsinki, and applicable local laws and regulations. The study protocol has been approved by both Regulatory Authorities and internal review boards of the participating centers. All patients will provide written informed consent. The trial is registered at ClinicalTrials. gov (NCT01234337). (For a complete listing of study centers see Additional file 1).
Discussion Data from the SOLTI-0701 showed a statistically significant improvement in PFS when sorafenib was added to capecitabine as a first-or second-line treatment and supported and informed the development of the phase 3 RESILIENCE study  [26]. The RESILIENCE study is similar in design to SOLTI-0701 but with some differences in total daily dose of sorafenib. RESILIENCE will provide definitive PFS data for the addition of sorafenib to capecitabine in patients with advanced breast cancer. It will better characterize the benefit-to-risk profile for these doses of sorafenib and capecitabine and provide information on the benefits of prophylactic management and treatment of HFSR/HFS. Because of the high incidence of HFSR/HFS during SOLTI-0701 as well as the sorafenib mean dose of 584 mg, the RESILIENCE study will start sorafenib at a 600 mg/day (200 mg in the morning and 400 mg in the evening) dose with ability to titrate the dose up to 400 mg BID as tolerated or down to manage toxicity.
67; 95% CI = 0. 40 to 1. 11) but not in the second-line treatment subgroup (HR = 1. 08; 95% CI = 0. 65 to 1. 78). The PROs of RESILIENCE will help to better define the benefit-to-risk profile of the sorafenib-capecitabine combination. Maintaining patient QoL has become an important clinical goal of MBC treatment. Although toxicities associated with sorafenib, like HFSR/HFS, are reversible and non-life threatening in most cases, they can have a significant impact on QoL  [41]. In addition, the exploratory analysis of biomarkers may help to better characterize the effect of disease biology on treatment response that may be useful in the design of future studies, particularly those that investigate the impact of patient selection on clinical outcomes. The RESILIENCE study is an essential step for the development of sorafenib in MBC, as it will provide definitive PFS data and more definitive OS data and inform on the management of HFSR/HFS.
myosuroides ACCase (Genbank/EMBL accession AJ310767). This amplicon thus encompasses codons 1753 to 1794. Primer ACVII27 was fully homologous to the ACCase sequence of A. myosuroides. dCAPS primer ACVII-NspIR contained one mismatched nucleotide at its penultimate position to create a NspI recognition site specifically in amplicons carrying a wild-type sequence at ACCase codon 1781 (ATA). Design was performed following previously described rules allowing to avoid false positive detection of mutant, Leu1781 alleles (TTA or CTA)  [20]. We used the Fast Cycling® PCR kit including the Q-solution (Qiagen) for PCR. DNA was added to the reaction mixes as 2 µL of the 50µL DNA solutions. Amplification was carried out as recommended in a total volume of 20µL in 0. 2 mL microtubes, with primers ACVII27 and ACVII-NspIR used at a final concentration of 0.
Acknowledgements The authors are grateful to the curators of the herbaria of Dijon (France),  Geneva (Switzerland)  and  Montpellier (France)  for allowing access to plant material, to the  Service de Séquençage et de Génotypage of the SERCOBIO (INRA -Université de Bourgogne, Dijon, France)  for allowing access to their plant-DNA-free facilities, to  Dr Valérie Le Corre  ( INRA Dijon, France ) for talented assistance in statistics, and to  Karelle Boucansaud ,  Fanny Pernin  and  Séverine Michel  ( INRA Dijon, France ) for skilful assistance in contributing to set up the analysis procedures.
Magnetic Protostars and Planets (MaPP) is a project aiming at measuring the large-scale topologies in a small sample of about 15 prototypical cTTSs of various masses and ages, and at assessing, on the basis of theoretical modelling, whether and how these fields are able to control/contribute to the observed dissipation of angular momentum of cTTSs. A total of 640 h of telescope time was allocated to MaPP on the 3. 6 m Canada-France-Hawaii Telescope (CFHT) with the ESPaDOnS high-resolution spectropolarimeter, over a time-scale of nine semesters (2008b-2012b) -the collected data set being now complete. Regarding low-and intermediatemass cTTSs (with masses ranging from 0. 35 to 1. 35 M ), eight stars have been studied in detail so far (and in some cases at various epochs) using an upgraded version of the imaging code  (Donati et al.
Ca II IRT emission Narrow emission in the core of Ca II IRT lines is a very convenient proxy of accretion at the surface of low-mass cTTSs, despite tracing simultaneously their non-accreting chromospheres. Being formed closer to the stellar surface and in a more static atmosphere than the He I D 3 emission line (the usual accretion proxy for cTTSs), the narrow emission cores of the Ca II IRT lines feature Zeeman signatures that are simple in shape (almost antisymmetric with respect to the line centre) and thus quite easy to model (with no need to account for velocity gradients in the line formation region); moreover, the triplet nature and the IR location of these lines both ensure highdata quality, usually overcompensating the signal dilution from the non-accreting chromospheres. The accretion proxy we consider here (as in the previous papers of the series) is an LSD-like weighted average of the three IRT lines, whose unpolarized profile is corrected by subtracting the underlying (much wider) Lorentzian absorption profile (with a single Lorentzian fit to the far line wings, see, e.
We carry out several tests to determine if kinematic inversion models of limited resolution may still carry useful information on the scaling of dynamic source properties. We take advantage of a large earthquake rupture model database (now at http://equake-rc. info/srcmod/), and analyse a suite of 31 rupture models from 21 crustal events with various styles of faulting, and with M w ranging from 5. 7 to 7. 7. We propose empirical models defining the distribution of fracture energy, static and dynamic stress drops that may be useful in advanced source modelling for ground-motion simulation (such as 'pseudo-dynamic' models or spontaneous rupture simulations). Finally, we investigate if the inferred dynamic properties exhibit any relation with respect to geologically observable quantities, like cumulative slip on fault.
Data and data preparation To analyse the distribution and scaling of the average dynamic parameters, we use a dataset of 31 finite-source rupture models obtained by kinematic inversion, from 21 crustal events with various styles of faulting (Table  1 ). Rupture models have been selected based on the availability of a complete rupture history in space and time. Source models derived from inversion of teleseismic data, whose spatio-temporal resolution is in general limited, have been dismissed (except the model of  Dreger (1994)  for the 1994 Northridge earthquake, which is included to complete the analysis of the epistemic uncertainty due to variations in the input kinematic models). Also, rupture models obtained on segmented/curved faults have been 'flattened' and mapped onto a single planar fault surface.
DY N A M I C PA R A M E T E R S V E R S U S C U M U L AT I V E S L I P Some recent studies adress the link between long-term properties of faults, like the degree of 'maturity', and earthquakes dynamics or ground-motion (e. g. Manighetti et al. 2007; Choy & Boatwright 2009; Radiguet et al. 2009). The fault maturity depends on the fault geometry and long-term fault history, that is age, maximum slip rate and cumulative displacement. In this section, we show how static stress drop, fracture energy and apparent stress drop evolve with cumulative displacement for six of the 22 analysed earthquakes (Table  7 ). Estimates of cumulative displacement are from  Radiguet et al. (2009) , from the Fault Morphology Database (http://isterre. fr/recherche/equipes/mecanique-desfailles/observatoires-et-plateforme-de/article/fault-morphologydatabase) and from  Yue et al.
(1996) ,  Dreger (1994)  and  Hartzell et al. (1996) , respectively. at King Abdullah University of Science and Technology on May 20, 2015 http://gji. oxfordjournals. org/ Downloaded from Table  5. Inversion parameters used by different authors for the 1994 M 6. 7 Northridge earthquake, and inferred values of averaged dynamic source quantities. Note that magnitudes are slightly different. Since G is expected to be magnitude-dependent (see next sections), we generated 'scaled' versions of the models of  Hartzell et al. (1996)  and  Dreger (1994)  to set all M w to 6. 80 (by simply scaling static slip). though supported by only a sparse dataset (six source models), may simply be explained by fault-plane surfaces tending to become smoother with increasing cumulative displacement (e. g. Brodsky et al.
This was the case for the 1999 Izmit earthquake, associated with high σ A and large cumulative slip. However, given the limited number of reported super-shear ruptures, there is no statistical meaningful database at present to further examine this scaling aspect in detail. Note that the rupture of the 1979 Imperial Valley was also reported to be locally super-shear, but the average rupture velocity was less than the shear wave velocity  (Archuleta 1984). As mentioned by  Ben-Zion & Sammis (2003) , the increasing amount of slip on faults may progressively destroy small-scale structures, and thereby produce more linear fault structures. However,  Ben-Zion & Sammis (2003)  claim that faults with large cumulative displacement are also associated with wider zones of damaged rock with a high crack density.
A C K N O W L E D G E M E N T S We thank  Michel Bouchon ,  Fabrice Cotton ,  Francois Renard  and  Jean Virieux  for discussions. This work as been supported by the  NERA  project ( Network of European Research Infrastructures for Earthquake Risk Assessment and Mitigation ) from the 7th Framework Programme by the  European Commission. Partial support has been provided through grant  ANR-2001-BS56-017  of the  French 'Agence Nationale de la Recherche '. All the numerical computation have been performed on the  IBM BlueGene/P Shaheen  at the  KAUST Supercomputing Laboratory.
for supporting next-gen sequencing among the  Berkeley Natural History Museums ; and  T. Gregory  for providing cycad tissue and fi nancial support. Additional funding was provided by the  National Science Foundation  ( IOS 0845641 ,  DEB 1110461 ), the  University of California Institute for Mexico (UC MEXUS)-Consejo Nacional de Ciencia y Tecnología (CONACYT) , the  Hellman Family Fund , and a  Prytanean Junior Faculty Award.
0; Lynnon BioSoft, Quebec, Canada). Sequences generated from representatives of MEAM1 and Med previously collected in Morocco  (Tahiri et al. 2006)  were included in the comparison. A phylogenetic tree was set up with a Jukes and Cantor distance matrix using the neighbor-joining method of DNA-MAN  (Saitou and Nei 1987). One thousand bootstrap iterations were performed. Sequences that were divergent from sequences of MEAM1 and Med representatives were compared to the 24 consensus sequences reported to be representative of 24 species at a 3. 5% sequence divergence limit  (Dinsdale et al. 2010). The percentage of nt divergence was calculated with the BIOEDIT software  (Hall 1999).
The resulting adjusted P-values are called Q-values. This procedure is implemented in the R package QVALUE  (Storey and Tibshirani 2003). Mean number of alleles per locus ( A), observed heterozygosities (H O ), and unbiased expected heterozygosities (H E , calculated following  Nei [1973] ) were calculated using GENETIX 4. 05. 2  (Belkhir et al. 2004 ). To test for HW equilibrium within populations, Weir and Cockerham estimators of F IS  (Weir and Cockerham 1984)  were calculated using FSTAT 2. 9. 3. 2  (Goudet et al. 1996)  for each locus and overall loci. The estimation of exact P-values of the difference of F IS from 0 (departure from HW equilibrium) was tested with the Markov chain method of GENEPOP using the default settings.
Population differentiation tests Pairwise F ST estimates were obtained using GENEPOP. A hierarchical analysis of molecular variance (AMOVA) was performed, using HIERFSTAT  (Goudet 2005) , to test for geographical structure. This test was performed on eight Med populations using four hierarchical levels: individuals within populations, among populations within regions, among regions within years, and among years. Associated P-values were calculated with 10,000 permutations of the appropriate unit as advised in  (Goudet 2005). A correspondence analysis (COA) was performed using GENETIX 4. 05. 2  (Belkhir et al. 2004 ) to visualize the major axes of genetic variation within the sample, and the position of the groups and the potential hybrid individuals detected by the STRUCTURE software along these axes.
Hybrid detection We used the NEWHYBRIDS (1. 1) software that implements a Bayesian assignment approach dedicated to the quantification of hybridization events from individual multilocus genotypes  (Anderson and Thompson 2002). The strength of this method is that no pedigree information is required, allowing application to natural populations  (Manel et al. 2005). Assignments were performed considering two hybridization schemes. First, we focused on the first generation of hybridization between the parental species (MEAM1 and Med), hence assuming only three classes (the two parental classes and the F1 hybrid). Second, we considered a more complex scheme including the second generation of hybridization, even if the detection of backcrosses may require many more loci (almost 50) that we actually amplified  (V€ ah€ a and Primmer 2006).
tabaci was above the 3. 5% divergence threshold characteristic of a new putative species  (Dinsdale et al. 2010). It was also above the 3. 5% divergence threshold with the putative species "Ru" recently detected in Italy  (Parrella et al. 2012). The smallest divergence was obtained with the consensus of the Italy group, with 5. 5-6. 4% divergence. One individual of this new putative species was collected in 2003 in the region of Oujda and the other in 2005 in the region of Nador. If individuals of Med and MEAM1 are sufficiently isolated regarding reproduction, mitochondrial-based differentiation should be supported by markers targeted to the nuclear genome. Of the 344 individuals of B. tabaci belonging to Med and MEAM1 groups according to mtCOI data (see above), 340 amplified for all seven microsatellite loci and four amplified for only six loci.
Spatial distribution and evolution over time of individuals of MEAM1 and Med species The abundance of individuals belonging to MEAM1 species compared to those belonging to Med species (assessed from the distribution of the 341 unambiguously   Table 1 ). The GenBank sequences are identified by their accession number and the country where the corresponding whitefly was collected. The Western Mediterranean Q1 group and the Eastern Mediterranean Q2 group are indicated according to previous reports  (Chu et al. 2008). The scale measures the Jukes and Cantor distance between sequences. Numbers associated with nodes represent the percentage of 1,000 bootstrap iterations supporting the nodes; only percentages ≥95% are indicated. assigned individuals) was found to differ significantly across sampled fields and years of collection (Fisher's exact test P < 0.
The two Med hybrids were detected in the only field where no MEAM1 representatives were found, which is apparently surprising but not unexpected because the hybrids were not from an F1 generation. Consistently, MEAM1 individuals were detected in the same field or at least in a neighboring field 2 years before. The detection of fertile hybrids between MEAM1 and Med needs to be confirmed because it can presently not be excluded that alleles thought to be private to one species, and which reveal putative hybrids, may be detectable in other species but at an extremely low frequency. The available data suggest, however, that a limited gene flow between MEAM1 and Med still exists and that it may contribute to the evolution of the nascent Med and MEAM1 species by hybridization. Crossing experiments between Israeli representatives of MEAM1 and Med did not produce any hybrids  (Elbaz et al.
Figure2. Rooted neighbor-joining tree based on a 587-nucleotide fragment of the mtCOI gene of Bemisia tabaci. The sequences generated in this study are identified by their accession number and the code number of the corresponding whitefly (see Table1). The GenBank sequences are identified by their accession number and the country where the corresponding whitefly was collected. The Western Mediterranean Q1 group and the Eastern Mediterranean Q2 group are indicated according to previous reports (Chu et al. 2008). The scale measures the Jukes and Cantor distance between sequences. Numbers associated with nodes represent the percentage of 1,000 bootstrap iterations supporting the nodes; only percentages ≥95% are indicated.
Acknowledgments This study was funded by two projects within the program " Projet de Recherche Agronomique pour le D eveloppement " ( PRAD 01/14  and  PRAD 04/04 ) and the project " BemisiaRisk " within the program " Agriculture et D eveloppement Durable " of the  Agence Nationale de la Recherche  (http://www. agence-nationale-recherche. fr/). It was also supported by  CIRAD  (http://www. cirad. fr/)and  ENA Mekn es (Morocco).
Funding Information This study was funded by two projects within the program " Projet de Recherche Agronomique pour le D eveloppement " ( PRAD 01/14  and  PRAD 04/04 ) and the project " BemisiaRisk " within the program " Agriculture et D eveloppement Durable " of the  Agence Nationale de la Recherche  (http:// www. agence-nationale-recherche. fr/). It was also supported by  CIRAD  (http://www. cirad. fr/) and  ENA Mekn es (Morocco).
5 for the fluorescein-labeled ZF and of 17,940, 1,370, and 2,740 M Ϫ1 ⅐cm Ϫ1 at 280 nm for F-ZF, mono-Ub, and di-Ub, respectively. Sedimentation Velocity (SV) Analytical Ultracentrifugation (AUC)-Sedimentation velocity experiments were carried out at 20 °C in a Beckman Coulter XL-I analytical ultracentrifuge equipped with double UV and Rayleigh interference detection. After refolding the ZF peptide with a molar excess of zinc, all protein samples were extensively dialyzed overnight against buffer A without ZnCl 2. Data were collected at 42,000 rpm for 6 h using an AN50 Ti rotor containing 12-mm path-length epoxy double-sector cell filled with 400 l of sample and 410 l of reference buffer. Sedimentation profiles were recorded from absorbance measurements at 280 nm for individual proteins, whereas those of samples containing a mixture of ZF and different forms of ubiquitin (mono-ubiquitin, Lys-63-, Lys-48-, or linear di-ubiquitin) were recorded from the specific absorbance of the fluorescein-labeled ZF at 440 nm in combination with interferometric measurements obtained from the on-board Rayleigh interferometer.
The partial specific volume (v bar ) as well as the extinction coefficient (⑀) at 280 nm of ZF and different di-ubiquitins were calculated at 20 °C from their amino acid composition using Sednterp software Version 1. 09. Similarly, the density and the viscosity of the buffer were calculated with the same software. Differential sedimentation coefficient distributions c(s) were determined using the software SEDFIT 13. 0b  (31). The stoichiometry of different ubiquitin⅐ZF complexes were determined using both interferometric and absorbance data as previously described  (32). The ⑀ value for the fluorescein-labeled ZF at 440 nm and at pH 7. 5, calculated from its absorbance spectra, was 4,700 M Ϫ1 ⅐cm Ϫ1 and 0 for all ubiquitins, whereas the refractive increment for all proteins was 0. 185 ml⅐g Ϫ1.
6 mM ZnCl 2. The emission spectra and the fluorescence quantum yields were obtained using an N-acetyl tryptophanamide (Sigma) standard as described previously  (15). Structural Modeling-The ZF⅐Lys-63 di-Ub complex shown in Fig. 7 , A and B, was generated using the standard protocols implemented in HADDOCK 2. 0 (34) with initial atom coordinates of NEMO ZF and Lys-63 di-Ub (Protein Data Bank (PDB) entries 2JVX and 2WWZ, respectively). The ambiguous restraints were defined on the basis of the mutagenesis data on NEMO ZF shown in this study and of the NMR data on ubiquitin described previously  (15). NEMO residues were considered as "active residues" in the HADDOCK procedure when mutations induce a difference of binding free energy Ͼ1 kJ⅐mol Ϫ1. During docking calculations, side chains and back-  NOVEMBER 22, 2013  • VOLUME 288 • NUMBER 47 bone flexibility (semi-flexible segments) were included both in the proximal and distal ubiquitins  (6 -12, 32-39, 42-48, 66 -72).
However, a detailed analysis showed that the linear chain bound corresponded to a linear Ub3, likely due to an uncontrolled deubiquitinase activity in our assay. It is worth pointing out that no deubiquitinase inhibitor based on a thiol-specific reagent such as NEM or iodoacetamide could be added in the buffer, as these compounds may alter the ubiquitin binding activity of NEMO ZF by modifying the free cysteine residue at position 396. Thus, these data indicate that the defective D406V mutation in NF-B activation impairs ZF-dependent polyubiquitin binding activity toward Lys-63 and linear chains without any contribution of the NOA UBD. The D406V Mutation Does Not Interfere with Either Zincinduced Folding of NEMO ZF or with Mono-ubiquitin-NEMO ZF Binding-Because alteration of ubiquitin binding activity may result from impairment of the ZF structure, we next investigated whether the D406V mutation affects NEMO ZF folding.
This indicates that the FP signal change of F-ZF upon ubiquitin titration is not due to any ubiquitin-dependent ZF:ZF interaction or nonspecific interaction between fluorescein and mono-ubiquitin. A dissociation constant (K D ) of 750 Ϯ 30 M was obtained for WT F-ZF at 25 °C and pH 7. 0, which is close to the value observed for D406V F-ZF at the same pH and temperature. Moreover, competition experiments of WT F-ZF with unlabeled ZF for the mono-ubiquitin binding gave an IC 50 value of 750 Ϯ 80 M similar to the K D of WT F-ZF (Fig. 2C ), again ruling out the possibility that the N-terminal fluorescein probe interferes with mono-ubiquitin binding. Hence, these data indicate that D406V mutation has no detrimental effect on monoubiquitin binding to NEMO ZF. This is consistent with the structural model of the ZF complex with mono-ubiquitin  (15).