dataesr/scientific-paragraphs-categorization huggingface dataset:
Post-equinox, Titan's south pole began to enter winter, which provides an opportunity to observe vortex formation in the south. This complements previous observations of the well established mid-winter vortex in the north. Following equinox, the vertical circulation at the south pole reversed almost immediately  21, 22. The resulting south polar subsidence created a mesospheric hotspot (~180 K at 300-400 km altitude) and high-altitude enrichment of trace gases. The reversal was accompanied by a two-cell transitional global circulation, with upwelling around the equator and subsidence at both poles, which persisted for two years before a fully reversed single circulation cell was established  22. The   1  Cassini orbital information and CIRS data coverage. a Grey line shows the latitude of Cassini's sub-spacecraft point on Saturn as a function of calendar year and solar longitude (L s ).
Trace gas a-priori profiles were assumed to be uniform above the condensation level and relative abundances were based on Huygens GCMS measurements  52, 53  or previous CIRS results  1, 5, 54, 55. The main photochemical aerosol was assumed to have the spectral properties defined in  56  and a 65 km scale height  57. Spectroscopic parameters of the atmospheric gases were primarily based on the HITRAN  58  and GEISA  59  databases. CIA absorption coefficients were taken from the standard tabulations in  [60] [61] [62] [63] [64] [65]. For both nadir and limb observations we used a two-stage retrieval process following our previous studies  3, 8, 21, 50. In the first stage, a continuous atmospheric temperature profile was retrieved using the FP4 ν 4 CH 4 emission band. The abundance of CH 4 is known from the Huygens GCMS measurements to be 1.
Case definition Most study centers considered all individuals with histologically confirmed incident primary diagnoses of multiple myeloma that occurred during the respective enrollment periods (ICD-O-3 diagnostic codes of 9731. 3, 9732. 3, 9734. 3, ICD-9 of 203, and the equivalent) as eligible for enrollment. The Utah study included both prevalent and incident cases. Sensitivity analyses conducted without the Utah study sample yielded similar findings to those with all eight studies, and thus we focus on the analyses that include the Utah data in this report.
Data collection Study data were obtained in person by trained interviewers or by self-administered questionnaire. The vast majority of questionnaires or interviews were completed directly by the enrolled cases or controls; three studies obtained data from a proxy respondent when the enrolled case was too ill or deceased. The interviews/questionnaires included items on the participants' date of birth, sex, education level, race/ethnicity, height, weight during a reference period (typically one year) before interview and/or "usual" adult weight, and habits pertaining to use of tobacco or alcohol. Two population-based studies (NCI Black-White, FHCRC) also collected information on weight in younger adulthood, specifically at age 25 or 30, respectively. Participants in the Utah study reported weight at age 40 as a usual adult weight, and therefore cases (n ¼ 6) and controls (n ¼ 1) from Utah who were younger than 40 years at interview were removed from the analysis.
Classification of anthropometric variables We determined sex-specific cutoff points for quartiles of height (m), usual adult weight [kg, referring to the year pre-interview or (for Utah) at age 40], and younger adult weight (kg, referring to weight at age 25 or 30) among the pooled control subjects with non-missing data on those variables. We also computed the usual adult and younger adult BMI (kg/m 2 ) from the height and usual or younger adult weight. We categorized the BMI variables into the World Health Organization (WHO)-defined categories of "underweight" (<18. 5 kg/m 2 ), "normal" (18. 5 to <25 kg/m 2 ), "overweight" (25 to <30 kg/m 2 ), "obese" (30 to <35 kg/m 2 ), and "severely obese" ( 35 kg/m 2 ; refs. 36, 37).
Statistical analysis To evaluate the association of usual or younger adult BMI, height and usual or younger adult weight with risk of multiple myeloma, we computed ORs and 95% confidence intervals (CI) using unconditional logistic regression models. We first computed study-specific and study center-specific ORs to evaluate heterogeneity in the associations across the participating studies and study centers. To assess the heterogeneity of the usual adult BMI-multiple myeloma associations across study populations, we performed a meta-analysis of study center-specific ORs and variances from covariable-adjusted models (see below) using both fixed and random effects models. We also directly pooled the data across all participating study centers and computed ORs and 95% CIs in the combined population using logistic regression.
We examined the joint classification of usual (<25, 25 to <30, 30 kg/m 2 ) and younger adult BMI (<25, 25 to <30, 30 kg/ m 2 ) in pooled data from the NCI Black-White and FHRC studies. To evaluate linear trend across the categories of a given anthropometric variable we assigned exposure category medians to ordinal variables that we modeled as continuous variables in additional multivariable logistic regression models. For comparison, we also assessed the increase in multiple myeloma risk per 5-kg/m 2 increase in usual or younger adult BMI. We used SAS version 9. 2 for all statistical analyses except for the meta-analyses, which we performed using the MiMa package  (39)  in R. All tests of statistical significance assumed a two-tailed alpha error level of 0. 05.
In the two population-based study populations with data on younger adult weight, younger adult BMI was calculated from height at study enrollment and weight reported for younger adulthood. c P values for heterogeneity were obtained from likelihood ratio tests that compared logistic regression models with only main effects variables to models that also included a term for the interaction of BMI with the specified stratifying variable. d From logistic regression models controlling for age (<50, 50-59, 60-69, >70), sex, race (White, Black, Other/unknown), and study center. e P values for trend were obtained by modeling category of BMI as an ordinal variable in logistic regression models with the same covariables as in the models that generated the corresponding ORs. could not evaluate anthropometric measure associations with multiple myeloma separately for Asian and Hispanic participants for whom multiple myeloma risk factor data are generally more limited.
Grant Support Financial support for this study was provided by the  NCI Intramural Program Division of Cancer Epidemiology and Genetics , and by  NCI  grants  K07 CA115687  (to B. M. Birmann),  R01 CA149445 ,  R01 CA127435 ,  P30 CA014089 ,  R21CA198239  , and  R13 CA159842. B. M. Birmann  was also supported in part by the  American Cancer Society  ( RSG-11-020-01-CNE ), and  W. Cozen  was supported in part by Federal funds from the  National Cancer Institute (SEER) :  N01-CP-67010 SOW 16. Additional support was provided by  Rio Hortega  ( CM13/00232 ),  MV15/00025  and public grants from  Health Ministry of Spain  ( PI11/01810  and  PI14/01219 ) and the  Catalan Government  ( 2014SGR756 ). The Utah studies were supported by the  Research Informatics Shared Resource , which in part is funded by  NCI   P30CA042014  and  Leukemia and Lymphoma Society  award  6067-09  (to N.
Time-lapse sequences were recorded every 5 or 10 min for 24 or 72 h using a Nikon Eclipse Ti (more details in section Immunofluorescence) inverted microscope with a Â 20 0. 45NAPlan FluorELWD or Â 60 1. 4 NA PL-APO VC objective controlled by Metamorph software (Universal Imaging). Correlative light and SEM. HeLa cells that express GFP-Actin were used to select intercellular bridges of appropriate stage using fluorescent light microscope, and subsequently to re-localize the same cells in SEM Method for SEM preparation is described in details in ref. 42. Briefly, cells were successively fixed with 2. 5% glutaraldehyde (Sigma-Aldrich), postfix with 2% osmium tetroxide (Electron Microscopy Science), dehydrated into baths of ethanol and dried into the critical point dryer's chamber (Leica EM CPD300).
12 mM actin to become fully ADP-actin, prior to depolymerization  50. In surface-anchored experiments, steady-state filaments were anchored and exposed to depolymerization conditions B120 s before observation  23. Images were acquired in epifluorescence or TIRF microscopy, and were analysed using Image J and homemade Python software. Proteins and buffers. Actin was purified from rabbit muscle acetone powder (Pel-freez) using the following protocol 61 : the powder was resuspended in G-buffer (5 mM TRIS pH 7. 8, 0. 2 mM ATP, 0. 1 mM CaCl 2 , 1 mM DTT and 0. 01% NaN 3 ) and centrifuged at 18,000 r. p. m. , keeping the supernatant which was then filtered through cheese cloth. To remove contaminants, 3. 3 M KCl was added and the solution was centrifuged at 18,000 r. p. m. , keeping the supernatant, which was again filtered through cheese cloth.
Images were analysed with image J or using homemade software written in Python. In Image J, the Multiplekymograph plugin was used to generate the kymographs shown in Fig. 6  and Supplementary Fig. 7. The depolymerization rates shown in Fig. 6f  and Supplementary Fig. 7a  were determined by measuring the slope of regular portions of these kymographs, excluding pausing events, be they photoinduced or caused by multiple surface anchors. The depolymerization rates of Fig. 6b  and Supplementary Fig. 7d, e  were determined with the Python software: filament lengths were determined from intensity linescans of their contour, and tracked over time. Depolymerization rates were determined by a linear fit of the length over 3 consecutive time points (that is, a total interval of 20 s). Photoinduced pauses were excluded from the analysis.
The exchange reaction was quenched by addition of 10 mM MgCl 2 , and excess nucleotide was removed by gel filtration chromatography. Crystallization and structure determination. The crystallization experiments were performed at 17 °C by vapour diffusion in hanging drops. Crystals of the Se-Met MICAL1  were grown in 35% ethylene glycol and 4% 1,6-hexanediol. The crys als were flash-frozen in liquid nitrogen. An anomalous X-ray diffraction data set was collected to 3. 3 Å resolution at Soleil synchrotron PX1 beamline. The X-ray diffraction data were indexed, integrated and scaled with the XDS program suite  64  The structure was determined by single-wavelength anomalous diffraction method with the Phenix (Autosol)  65. The program determined positions of two selenium atoms (see the anomalous difference map in Supplementary Fig.
3a ), subsequent phasing and density modification resulted in an interpretable electron density map allowing to build an initial model with Phenix (Autobuild)  65. The model was refined using the Phenix (Refine) programs  65  and manual rebuilding using COOT  66. The data collection and refinement statistics are summarized in Supplementary Table  2. Isothermal titration calorimetry. Isothermal titration calorimetry was performed using a MicroCal ITC-200 titration microcalorimeter (Malvern) at 10 °C. The C-terminal MICAL1 domain at a concentration of 60 mM in the interaction buffer (50 mM Tris buffer, pH 8, 150 mM NaCl, 2 mM MgCl 2 , 2 mM TCEP and 5% Glycerol), was placed in the calorimeter cell, and GppNHp-Rab35 (480 mM in the interaction buffer) was added sequentially in 2 ml aliquots. The heat of reaction per injection (microcalories per second) was determined by integration of the peak areas using the Origin software and provided the heat of binding, the binding stoichiometry, and the interaction association constant using a one-site model.
The heats of dilution were determined in parallel control experiments by injecting GppNHp-Rab35 (480 mM in the interaction buffer) into the interaction buffer. The heat of dilution was subtracted from the interaction heat before fitting the curve. SEC-MALS. Absolute molar masses of proteins were determined using size-exclusion chromatography combined with multi-angle light scattering (SEC-MALS). Protein samples (50 ml; 10 mg ml À 1 ) were loaded onto a Superdex-75 column (GE Healthcare) or XBridge BEH SEC 200 Å in 50 mM Tris pH 8. 0, 150 mM NaCl, 2 mM MgCl 2 , 2 mM TCEP, 5% glycerol, at 0. 5 ml min À 1 using a Dionex UltiMate 3000 HPLC system. The column output was fed into a DAWN HELEOS II MALS detector (Wyatt Technology). Data were collected and analysed using Astra X software (Wyatt Technology).
Molecular masses were calculated across eluted protein peaks. SAXS measurements and data analysis. Small angle X-ray scattering (SAXS) data were collected on the SWING beamline (synchrotron SOLEIL, France). MICAL1 918-1067 WT, S1, S2 and S3 constructs 50 ml at 10 mg ml À 1 were injected on the online HPLC system (Agilent SEC-5 500 Å) in 50 mM Tris pH 8, 150 mM NaCl, 2 mM TCEP, 2 mM MgCl 2 , 5% glycerol. Twenty to 29 frames of 1. 5 s exposure (and 45 for the buffer) were averaged and buffer scattering was subtracted from the sample data. The radius of gyration and the intensity at the origin were determined using the Guinier law  67. Side chains and loops missing in the X-ray structure were modelled using COOT 66. FoXS web-server  68  was used to fit the theoretical scattering intensity from the X-ray structure into the experimental SAXS data.
Acknowledgements We thank  R. Basto ,  A. Gautreau  and  G. Langsley  for critical reading of the manuscript; the Echard Lab members for helpful discussions; the  Romet/Jegou Lab  members for help with in vitro experiments;  G. Hickson , the  Plateforme Anticorps Recombinants  ( Institut Curie, Paris ) and the  DHSB (University of Iowa ) for reagents and plasmids. We thank the imaging facilities Imagopole and  Ultrapole Institut Pasteur. We thank  P. H. Commere  from the  Cytometry platform Institut Pasteur  for FACS sorting. We thank beamline scientists of PX1 (SOLEIL synchrotron) for excellent support during data collection. This work has been supported by  Institut Pasteur ,  CNRS ,  FRM  (Equipe FRM  DEQ20120323707 ),  INCa  ( 2014-1-PL BIO-04-IP1 ),  ANR (AbCyStem)  and IXCORE foundation to A.
E. , J. B. and K. K. have been awarded a doctoral fellowship from the  Pasteur Paris Universites International PhD program  and  Carnot-Pasteur MI , and a fellowship from  FRM  ( FDT20150532389 ). A. H. was supported by grants from the  CNRS  and  INCa  ( 2014-1-PL BIO-04-ICR-1 ). H. H. has been awarded a doctoral fellowship from the  PSL Universite. The A. H. team is part of  Labex CelTisPhyBio   11-LBX-0038 , which is part of the  Initiative d'Excellence at PSL Research University  ( ANR-10-IDEX-0001-02 PSL ). H. W. has been supported by a postdoctoral grant from the  Fondation ARC  pour la recherche sur le cancer.
2) samples, as indicated by the presence of the peaks around 58 and 18 ppm, associated with the resonance of ethoxyl carbon atoms. The existence of a resonance at 10 ppm confirms that only a small percentage of the Si-CH 2 bonds were cleaved during the reaction (Figure  S2  of Supplementary Information and Table  1 ). It is noteworthy that the chemical shift of the triazole quaternary carbon moved from ca. 145 ppm for the Cn/siloxane-AC (600:w) materials with w = 0 and 0. 2, the typical resonance for neutral triazole rings, to 137 ppm in the case of w = 1. 2 (Table  1 ). A simple calculation of  13  C NMR chemical shifts using ChemDraw software suggests that the triazole rings were either protonated on the N(2) nitrogen atom, or were at least strongly hydrogen-bonded between the amine group and the triazole ring.
Acknowledgements This work was supported by  FEDER  ( POCI-01-0145-FEDER-016884 ,  POCI-01-0145-FEDER-007491  and  POCI-01-0145-FEDER-007679 ) and Fundaca ˜o para a Ciencia e a  Tecnologia (FCT)  (contracts  PTDC/CTM-NAN/0956/2014 ,  UID/QUI/00616/2013 ,  UID/Multi /00709/2013  and  UID/CTM/50011/2013   CICECO-Aveiro Institute of Materials). S. C. Nunes and P. Ferreira acknowledge FCT  for the grants ( SFRH/BPD/63152/2009  and  IF/ 00327/2013 , respectively). The authors thank  Dr. Sonia Sousa  and  Prof. Ana Ramos  ( University of Beira Interior ) for the contact angle measurements.
In a similar way,  Thomas (2009)  developed design rules for SLM. Using basic geometric entities found in lightweight structures and a set of manufacturing experiment,  Kranz, Herzog, and Emmelmann (2015)  produced a structured database of basic design guidelines focused on Laser Additive Manufacturing of TiAl6V4; the influence of part position and direction on dimension accuracy and surface quality were studied. A list of recommendations or principles was also proposed by  Becker, Grzesiak, and Henning (2005)  to free designers' minds, so that they can take full advantage of the freedom enabled by AM techniques. The main point made is to save as much as possible material (and therefore energy and time) by putting material only where it is needed regardless of tooling.
Surveying the existing DFAM contribution  (Rias, Bouchard, Segonds, & Abed, 2016)  came up with the conclusion that concept generated for AM were only partially original with ''a maximum of 75% newness". They have then proposed a 5 stages ''creative DFAM" methods fostering the generation of creative concepts exploiting the unique capabilities of AM; the proposed method is somewhat based on the AM design features database presented in Bin  Maidin, Campbell, and Pei (2012). The method is mostly intended to early design stages. The 5 stages include: features discovery, exploration, ideas evolution, concept generation and concept evaluation. This contribution is mainly related to part design. A similar contribution related to assembly design was made in  Yang and Zhao (2016) , where it was established that AM has no influence on functional analysis and the recognition of desired behaviors.
Control experiments (compound injected into buffer) were performed under the same experimental conditions. The association constant (K a ) and the enthalpy change (Δ H) of the binding reaction were obtained through non-linear regression of experimental data to a model for a protein with a single ligand binding site. Experiments were performed in replicates and data were analyzed using in-house developed software implemented in Origin 7 (OriginLab, Northampton, MA). Fluorescence measurements. Fluorescence spectra were collected in a Cary Eclipse spectrofluorometer (Varian-Agilent Technologies, Santa Clara, CA) interfaced with a Peltier-thermostated multicell holder. The slit widths were 5 nm for both excitation and emission wavelengths. Excitation wavelength was 280 nm. Emission spectra from 300 to 400 nm were acquired at 25 °C, in a 1-cm-pathlength quartz cell (Hellma Analytics, Müllheim, Germany).
The NUPR1 concentration was 3 μ M in buffer in 20 mM sodium phosphate pH 7, and 100 μ M of Compound was added in each experiment. Difference spectra were obtained by subtracting the sum of the spectra for the individual components (NUPR1 and Compound) from that of the complex (NUPR1:Compound) at the same concentrations. NMR experiments. The NMR data were acquired at 25 °C, pH 4. 5 (acetate buffer), on a Bruker Avance DRX-500 spectrometer equipped with a triple-resonance probe and z-gradients. All spectra were referenced to external TSP. The 2D 1 H-  15  N heteronuclear single-quantum coherence (HSQC) spectra  42  were acquired in the phase sensitive mode for isolated  15  N-labelled NUPR1 (100 μ M) or  15  N-labelled NUPR1 (100 μ M) in the presence of the corresponding compound (400 μ M). Similar protein/drug ratios have been used in other studies aimed to test druggability of IDPs  21, 22, 34, 35.
Frequency discrimination in the indirect dimensions was achieved by using the echo/antiecho-TPPI method. The spectra were acquired with 1 K complex points in the 1 H dimension, 128 complex points in the  15  N dimension, and 200 scans. The carrier of the 1 H dimension was set at 8. 00 ppm, and that of  15  N at 120 ppm. The spectral widths used were 10 and 35 ppm in the 1 H and  15  N dimensions, respectively. Water signal was suppressed with the WATERGATE sequence  43. Data were zero-filled to double the number of original points in both dimensions, apodized with shifted squared sine-bell functions in the two dimensions and Fourier transformed with the program TopSpin 1. 2. Assignments were taken from those previously reported  19. The intensity of the signals from each row in the HSQC spectra was measured by using TopSpin 2.
12 Å 45. The value was 22 ± 3 Å, and it was used to compare with the gyration radii of the modeled molecules during the MD simulations. Computational methods. Protein and ligand structures were built by using VMD  46  and UCSF Chimera 47 , respectively. NUPR1 was initially modelled as an extended chain, then collapsed in very short (15-30 ps) MD simulations in vacuo, and equilibrated for 80-200 ns in the presence of water (TIP3P model  48  ) and five Cl -counterions. A rhombic dodecahedron box with minimum distance 10 Å from the solvent was employed and periodic boundary conditions were applied. A set of 16 simulations were performed by using the GROMACS 4. 5 package  49  with AMBER ff99SB-ILDN force field  50. Long-range electrostatic interactions were calculated through the particle-mesh Ewald method  51, 52.
Cell migration to the wounded region was observed using an automated fluorescence inverted microscope Leica DMI 6000B with MetaMorph MM AF analysis software (Leica Microsystems, Wetzlar, Germany). Images were captured at 0, 24 and 48 h to monitor the wound healing process. The wound areas were measured using ImageJ software (NIH, Bethesda, MD). Comparisons of treatment outcome were tested for statistical significance by using the t-test. Statistical significance was assumed at a p-value lower than 0. 05. Colony formation in soft agar assays. Colony formation assay was performed in order to measure the in vitro survival ability of a single cell to grow into a colony in an anchorage-independent growth environment. Briefly, after treating MiaPaCa-2 cells with either the compounds or DMSO (as control) for 24 and 48 h, they were seeded in DMEM complete media at a density of 7 × 10 3 cells in 6-well plates containing a top layer of 0.
7% agar and a bottom layer of 1% agar. Plates were incubated at 37 °C for 3 to 4 weeks and then stained with 0. 2% crystal violet. Colonies were observed with a Leica DMI 6000B microscope and counted (those with more than 20 cells) using the MetaMorph MM AF analysis software. Comparisons of treatment outcome were tested for statistical significance by using the t-test. Statistical significance was assumed at a p-value lower than 0. 05. Protein ligation (PLA) assays. MiaPaCa-2 cells were seeded on coverslips and transfected with 300 ng of DNA (NUPR1-Flag and MSL1-V5) using Fugene HDTM transfection reagent (Roche, Meylan, France). After one day, cells were treated simultaneously with Oxaliplatin (10 μ M) to induce DNA damage (thus promoting MSL1-NUPR1 interaction as a DNA-repair complex  19  ), and either DMSO or Compound.
Acknowledgements We thank two anonymous reviewers for their suggestions and advices. This work was supported by  La Ligue Contre le Cancer ,  INCa ,  Canceropole PACA ,  DGOS (labellisation SIRIC ) and INSERM to JLI;  Miguel Servet Program  from  Instituto de Salud Carlos III  ( CPII13/00017  to OA);  Fondo de Investigaciones Sanitarias  ( PI10/00186  and  PI15/00663  to OA,  PI11/02578  to AL);  Spanish Ministry of Economy and Competitiveness  ( BFU2013-47064-P  to AVC,  CTQ2015-64445-R  to JLN);  Diputación General de Aragón (Protein Targets Group   B89  to AVC, and Digestive Pathology Group  B01  to OA, MA and AL);  Generalitat Valenciana  ( Prometeo 018/2013  to JLN); and  Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.