dataesr/scientific-paragraphs-categorization huggingface dataset:
The unfavourable results are associated with large treatment volumes. Large inter-observer variability in defining the tumor bed for postoperative irradiation has been shown in many studies, resulting in larger irradiated volumes  [12] [13] [14]. In a previous study we showed less inter-observer variation in tumor delineation preoperatively compared to postoperatively  [15]. When RT is given preoperatively more accurate tumor delineation can be performed. After RT surgery is performed, thereby removing the area of the breast that received the highest RT dose. As a result, limited fibrosis and a good cosmetic result are expected. In the multi-center phase II preoperative accelerated partial breast irradiation (PAPBI) trial (registered with ClinicalTrials. gov, Number NCT01024582) low risk patients of 60 years and older are irradiated preoperatively instead of postoperatively with external beam APBI.
Also breast pain, rib pain and the presence of rib fracture(s) were evaluated according to the EORTC/RTOG/late radiation morbidity scoring. Cosmesis was evaluated by the physician before start of RT, 6 months after completion of treatment and thereafter every year. The treated breast was compared to the contralateral breast for visible sequelae, telangiectasia and global cosmetic result scored as (0) excellent, (1) good, (2) fair, (3) poor or (4) not evaluable. Dutch patients received a questionnaire concerning cosmetic outcome yearly. Digital photos of both breasts were taken before the start of RT, 6 months after completion of treatment and thereafter every year. The photos will be used in the future for objective assessment of cosmetic outcome by the BCCT. core project software program.
Study Design The PEARL-I study (ClinicalTrials. gov identifier: NCT01685203) is an ongoing phase 2b, open-label, combination treatment study being conducted at 47 sites in France, Hungary, Italy, Poland, Puerto Rico, Romania, Spain, Turkey, and the United States. Screening for the trial began in August 2012; the last patient completed treatment in March 2014. The study was designed as an open-label study to maximize the probability of all patients in the study achieving SVR. Additionally, an active comparator group that contained pegylated interferon was not included because it could not be effectively blinded. All GT1b-infected patients without cirrhosis were enrolled and completed treatment before enrollment of the patients with cirrhosis to allow for a sequential evaluation of the 2-DAA regimen in these 2 patient populations.
Statistical Analyses A sample size of 40 patients per group was estimated to provide approximately 80% power using a Fisher exact test with a 2-sided significance level of 0. 05 to detect a 25% difference between HCV GT1b-infected treatment-naive and prior null responder patients without cirrhosis, assuming that 70% of prior null responders and 95% of treatment-naive patients would achieve SVR 12. Efficacy and safety analyses were performed using data from the intent-to-treat population, defined as all patients who received 1 dose of study drug. Missing HCV RNA values were imputed using flanking imputation. The number and percentage of patients achieving efficacy endpoints were summarized, and corresponding exact 95% confidence intervals (CIs) were calculated. SVR rates in patient groups without cirrhosis were compared using a logistic regression model with treatment group, baseline log 10 HCV RNA level, and interleukin 28B (IL28B) genotype as predictors; the difference in SVR 12 response was assessed using the stratum-adjusted Mantel-Haenszel method adjusted for IL28B genotype.
Virologic Response All but 3 patients achieved RVR at week 4, and SVR 12 rates were similarly high in patients with and without cirrhosis (Figure  1 ). SVR 12 was achieved in 95. 2% (n ¼ 40/42; 95% CI, 83. 8%-99. 4%) of treatment-naive and 90. 0% (n ¼ 36/40; 95% CI, 76. 3%-97. 2%) of prior null responder patients without cirrhosis. Among patients with cirrhosis, SVR 12 was achieved in 97. 9% (n ¼ 46/47; 95% CI, 88. 7%-99. 9%) of treatment-naive and 96. 2% (n ¼ 50/52; 95% CI, 86. 8%-99. 5%) of treatment-experienced patients. After the primary database lock, 1 treatment-naive patient who was thought to be lost to follow-up returned for a visit and had undetectable HCV RNA levels, making the SVR 12 rate following the database lock 100% (n ¼ 47/47) in treatment-naive patients with cirrhosis. No clinically meaningful differences in SVR 12 rates were observed between any of these groups.
Acknowledgments The authors would like to acknowledge  Mudra Kapoor ,  Carolyn Setze ,  Rajeev M. Menon ,  Barbara McGovern ,  Kerstin Krauss ,  Charles Meyer ,  Ingrid Facey ,  Cordula Ubrig ,  Christina Giannoulis ,  Christine Collins ,  Preethi Krishnan ,  Gretja Schnell ,  Rakesh Tripathi ,  Tom Reisch , and  Jill Beyer  of  AbbVie  for assistance in the preparation and operation of the study. This study was funded by  AbbVie Inc. Editorial and medical writing support was provided by  Katherine Groschwitz, PhD , at Complete Publication Solutions, LLC; this support was funded by  AbbVie Inc. The authors disclose the following: E. L. has received research grants from  AbbVie ,  Achillion Pharmaceuticals ,  Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline ,  Idenix Pharmaceuticals ,  Janssen ,  Merck & Co.
Instrumentation 2. 1. 1 Light source and light delivery-An optical parametric oscillator (OPO) system (VersaScan L-532, VersaScan L-532, GWU-Lasertechnik, Erftstadt, Germany) pumped by an Nd:YAG laser (repetition rate: 10 Hz; Quanta-Ray, INDI-40-10, Spectra-Physics, Santa Clara, California) was used as the PA excitation light source (Fig. 1 ). The OPO has two outputs: the signal (700 to 900 nm) and the idler (1100 to 2200 nm). Wavelength tuning was performed with a motorized crystal controlled by a custom Labview program (National Instruments, Berkshire, United Kingdom). The OPO outputs were focused onto separate silica-silica optical fibers with 910 μm cores (Thorlabs, Newton, New Jersey) with achromatic doublet lenses (focal length: 50 mm; AC254-050-B, and AC254-050-C, Thorlabs). One of these two optical fibers directed light at an optical fiber of the same type, with its distal section positioned in the cannula of a 14 gauge needle (Fig.
2. 1. 2 Ultrasound detection-Ultrasound detection [Fig. 1(a) ] was performed with a commercial US imaging system (SonixMDP, Analogic Ultrasound, Richmond, British Columbia, Canada) that was operated in its research mode. The system used a linear array imaging probe (L14-5/38, 128-element, 300 μm pitch, Analogic Ultrasound). Prebeamformed channel data from the transducer element were sampled at 40 MHz with a 12bit analog-to-digital converter by a 128-channel data acquisition system (SonixDAQ, Analogic Ultrasound)21 and were sent to a personal computer for postprocessing. Two amplification stages were performed with built-in amplifiers. A first amplification stage boosted the incoming signals from each channel using a set of low noise amplifiers (LNA). The amplification at the first stage could be set using parameter values of 0, 1, and 2, which corresponded to amplifications of 16, 18, and 21 dB, respectively.
System synchronization- The acquisitions of the US and PA images were triggered by light pulses. With the OPO operating continuously at 10 Hz, acquisitions were controlled by the Labview program via a digital I/O card (NI-USB-6501, National Instruments). As illustrated in Fig. 1 (b), this scheme was realized using a logic AND gate (CD74HCT08E, Texas Instruments, Dallas, Texas) with two input signals: the optical trigger and the digital control window signal. The optical trigger was derived from an oscilloscope (DPO3000, Tektronix, Oregon) with a photodiode signal as its input. The control window signal was 100 ms in duration; the oscilloscope trigger hold-off ensured that only one pulse occurred within the window. When the SonixDAQ was triggered, 128 channels of radio frequency (RF) data from the transducer elements of the US imaging probe were acquired.
Image reconstruction- Immediately after an acquisition of RF data for PA imaging, image reconstruction was performed using a custom delay-and-sum beam-forming algorithm. The B-mode US images were reconstructed using electronic beamforming, and the post-beamformed data were displayed alongside the PA images. As such, reconstructed PA and US images were displayed in real time. Offline image reconstruction of PA images was performed using a Fourier-domain reconstruction algorithm,23 which was implemented with the k-Wave MATLAB® toolbox. 24.
Acknowledgments This work was supported by an  Innovative Engineering for Health  award by the  Wellcome Trust  ( WT101957 ) and the  Engineering and Physical Sciences Research Council (EPSRC)  ( NS/A000027/1 ), by a Starting Grant from the  European Research Council  (ERC-2012-StG, Proposal 310970 MOPHIM), and by an  EPSRC   First Grant  ( EP/ J010952/1 ). ALD is supported by the  UCL/UCLH NIHR Comprehensive Biomedical Research Centre. The authors are grateful for the support for obtaining the human placenta provided by  Efthymios Maneas  of the  University College London.
Data collection X-ray powder diffraction (XRPD) measurements were performed on all samples, as well as on CeO 2 (Aldrich, !99. 0%) and Gd 2 O 3 (Aldrich, 99. 9%), using the high-resolution diffractometer on the ID31 beamline of the ESRF (the European Synchrotron, Grenoble, France;  Fitch, 2004). The samples were loaded into glass capillaries (1. 0 mm diameter), mounted on the diffractometer axis and spun during measurements in order to promote powder randomization. The samples were cooled to T = 90 K using a liquid nitrogen gas blower (Oxford Cryosystems) mounted coaxially; the set point of T = 90 K was selected in order to minimize the atomic thermal vibrations, which cause broadening of the PDF peaks in real space. Data were collected during two different experiments. For x Gd = 0. 313, 0.
344, 0. 375 and 0. 438, an X-ray wavelength = 0. 35412 (1) A ˚was used in the angular range 0 < 2 < 120 , covering a range of the wavevector Q (= 4 sin/) up to Q max ' 29. 4 A ˚À1 , while for the compositions x Gd = 0, 0. 125, 0. 25, 0. 50, 0. 75, 0. 875 and 1, data were collected at = 0. 30975 (1) A in the range 0 < 2 < 100 with Q max ' 31 A ˚À1 (see  Scavini et al. , 2012). In all cases, the counting time at higher angles was much longer, in order to increase the statistical significance of the data. ESR measurements were carried out on the same samples and, in addition, on samples with x Gd = 0. 05 and 0. 20, using a Bruker ELEXSYS spectrometer equipped with an ER4102ST standard rectangular cavity at X band (9. 4 GHz) frequency and at room temperature. The powdered samples were placed in a quartz tube and the derivative dP/dH of the absorbed power P was recorded as a function of the static magnetic field H.
XRPD data analysis The XRPD patterns were analysed via the Rietveld method as implemented in the GSAS software suite of programs  (Larson & Dreele, 2004) , which feature the graphical user interface EXPGUI  (Toby, 2001). Deviations from the longrange structure were investigated by means of the PDF method. For this purpose, we used the so-called reduced PDF, G(r), which can be obtained via the Fourier sine transform of the experimental total scattering function S(Q) GðrÞ ¼ 4r ðrÞ À 0 Â Ã ¼ 2 Z 1 0 Q½SðQÞ À 1 sinðQrÞ dQ; ð1Þ where (r) is the atomic number density function and indicates the probability of finding an atom at a distance r from another atom, while 0 is the average number density. The G(r) curves corresponding to the experimental data were computed using the program PDFGetX2  (Qiu et al.
, 2004). Only data up to Q max ' 28 A ˚À1 were used to obtain the experimental G(r) curves because of the insufficient signal-tonoise ratio at higher Q values. After background subtraction, the data were corrected for sample self-absorption and for multiple and Compton scattering. The G(r) analysis was carried out via the so called 'real-space Rietveld' method  (Egami & Billinge, 2003)  featured in the program PDFGui  (Farrow et al. , 2007). To avoid misunderstanding, we will use 'Rietveld' to denote the Rietveld data analysis in Q space and 'real-space Rietveld' to denote the Rietveld-like data analysis in real space. The extremely narrow instrumental resolution function of ID31  (Fitch, 2004)  leads to small Gaussian damping envelopes in real space  (Farrow et al. , 2007). This allows the calculation of G(r) functions over several hundreds of a ˚ngstro ¨ms, implying that an investigation of the local structure in real space is feasible over a large interatomic range.
In the fluorite zone, x(M2) is fixed to zero, whereas in the C* and C zones x(M2) decreases linearly versus increasing Gd concentration, but with two different slopes. In the inset, the difference between 'long' and 'short' M-M distances Ád(MM) [= d(MM) long À d(MM) short ] is shown as a function of composition (red circles). In the fluorite region, Ád(MM) 0 because there is only one NNN M-M distance. Ád(MM) increases monotonically with further increases in the Gd concentration and reaches a value as large as $0. 5 A ˚for Gd 2 O 3. In Fig. 3 (b), the average atomic mean-square displacement (msd) parameters are plotted as a function of composition. Since all data were collected at the same temperature, the msd parameters can be considered as fingerprints of disorder. Starting from CeO 2 , the msd values increase when varying x Gd , reaching a maximum for x Gd ' 0.
The amplification products were visualized on 1. 5% agarose gels. Multiplex genotyping was done using 1 μl of PCR-amplified DNA added to the Genescan 500LIZ internal size standard and 13. 5μl of formamide in an automated sequencer. Genotyping data were analyzed with the Genemapper software v. 4. 0 to determine the fragment sizes.
F is values range between -1 and 1. A negative value indicates an excess of heterozygotes, a positive value corresponds to heterozygote deficiency. Genotypes obtained from the concatenated sequences of the nine microsatellite loci were used to calculate the global genotypic diversity D g (D g = number of genotypes per population/total number of genotypes). The Neighbor-Joining (NJ) phenetic tree was constructed using the MEGA 5. 10 software  [35]  from a Cavalli-Sforza and Edwards  [36]  genetic distance matrix obtained using the POPU-LATIONS software (http://www. legs. cnrs-gif. fr/bioinfo/populations). strains: MON-109 (n = 3), MON-112 (n = 3), MON-264 (n = 1) and MON-311 (n = 2) (S1 Table ).
Microsatellite analysis of the Leishmania strains The 198 samples were amplified using primers for the nine investigated loci. Clear electropherograms and two alleles per locus and per sample were obtained (see supplementary data S3 Table ). Twenty nine alleles were obtained, ranging from two for the GA1, GM2 and LIST7027 loci to five for the GA11 and LIST7036 loci (mean: 3. 22 alleles per locus). The global genetic diversity was moderate (H s = 0. 261) and the global genotypic diversity was high (D g = 0. 53). The F is values were positive at all loci and ranged from 0. 120 for the LIST7040 locus to 0. 920 for the GA6 locus (mean value = 0. 664) (S2 Table ).
Discussion Despite a great knowledge on Leishmania parasites, many taxa, such as L. killicki (syn. L. tropica), are still not completely characterized. The main objective of this study was to understand the epidemiology and transmission dynamics of L. killicki (syn. L. tropica) by analyzing its population structure and by comparing the genetic patterns of L. killicki (syn. L. tropica) and L. tropica populations in Maghreb. The comparison of L. killicki (syn. L. tropica) and L. tropica revealed a strong genetic differentiation associated with a lower genetic polymorphism within L. killicki (syn. L. tropica). Furthermore, the NJ tree showed that L. killicki (syn. L. tropica) creates a homogeneous and monophyletic cluster within the L. tropica complex. These data support the recently obtained MultiLocus Sequence Typing (MLST) results  [22]  suggesting that L.
Flow cytometry analysis For cell death assay, cells were analyzed after immunostaining using the APO2. 7 antibody (Beckman Coulter, Villepinte, France), according to the manufacturer's instructions. For cell cycle analysis, cells were fixed and permeabilized with ethanol 70 % overnight, then stained with propidium iodide (PI). Flow-cytometry analysis was performed on a FACSCalibur using the CellQuestPro software (Becton-Dickinson, San Jose, CA, USA).
Recombination assay RG37 cell line that contains a single copy of a substrate that specifically monitors gene conversion induced by double-stranded cut targeted by the meganuclease I-SceI was a gift from Bernard Lopez (IGR, Paris, France)  [21]. RG37cells were first transfected with a I-Sce-I coding plasmid using jetPEI reagent, then 24 h later, with Survivin, BRCA1, or control siRNA for 48 h. Expression of a functional GFP gene reflecting powerful recombination was then measured by flow cytometry and % of GFP positive cells and data presented herein correspond to six independent experiments.
1  and data not shown). Importantly, ectopic Survivin reconstitution performed in rescue experiments using these latter siRNA sequences could prevent Survivin-depleted cells from DNA damage. These results clearly eliminated a potential off-target (Supplementary Fig. 1a ). To directly assess DNA breaks, Survivin-depleted cells were further analyzed in a single cell gel electrophoresis comet assay in comparison with siControl cells. As shown in Fig. 1c , Survivin depletion induced comet formation (in either alcali or neutral lysis buffer) and significant increase of the tail moment, in a range comparable to 2 Gray c-irradiation. Finally, a series of experiments indicate that, the early DNA repair marker 53BP1 localized on nuclear foci in Survivin-depleted cells, as we described above for cH2AX.
Prognostic informativity and correlative expression of BIRC5 and HR genes in primary breast tumors As our data on cell lines suggest that Survivin expression influences the expression of HR genes, we investigated whether the expression of these genes correlate in publically available data using the Breast Cancer Gene-Expression Miner v3. 1 microarray database and its correlation module analysis. A gene correlation targeted analysis between all genes identified above, pointed out significative linear dependences between BIRC5, EME1, EXO1, BLM as shown in the correlation map and table corresponding to analysis of all patients, in Fig. 3a  and Supplementary Fig. 2a. Altogether, these results from primary breast tumors corroborate those we revealed using breast cancer cell lines, and underscore a positive correlation between the level of expression of BIRC5 and EME1 or RAD51 or EXO1 mRNA.
By looking more precisely at the three major families of regulators of small GTPases expressed during HAECs differentiation or after miR-34/449 transfection, we detected 23 distinct ARHGAPs, including ARHGAP1; we also detected 22 distinct ARHGEF transcripts but none of them were predicted as direct miR-34/449 targets; regarding the three known mammalian ARHGDI transcripts  40  , only ARHGDIB was further analysed, as ARHGDIA expression levels did not change during HAECs differentiation or after miR-34/449 transfection and ARHGDIG was not detected (Supplementary Fig. 3b , see also GEO GSE22147). The transcripts ARHGAP1, ARHGDIB, DAAM1, NDRG1 and RRAS are all modulated during HAEC differentiation (Fig. 4a , see also GEO GSE22147). Figure  4a  shows that the transcript level of ARHGAP1, DAAM1 and NDRG1 decreased at late ciliogenesis (LC).
5a, b ). This is consistent with a recent gene expression profiling study performed in mouse trachea, which reported a higher level of expression of RRAS transcripts in non-ciliated cells than in ciliated cells  63  (GSE42500). We could not address this possibility for ARHGAP1 as none of the antibodies that we tested worked in immunofluorescence. In differentiating HAECs, both R-Ras and ARHGAP1 protein level strongly and continuously decreased from Po to LC, concomitantly with the increase in miR-449 expression (Fig. 5c, d ). Conversely, ARHGDIB protein level increased during human HAEC differentiation (Fig. 5d ). As ARHGDIB protein was mainly excluded from human MCCs (Fig. 5a, b ), the global protein increase observed during HAEC differentiation in western blotting is probably explained by its stronger expression in non-ciliated HAECs.
We used target protection assays (cholesterol-conjugated modified oligonucleotides in HAECs or morpholino oligonucleotides in frog epidermis) to compete with the binding of miR-34/449 on sites identified within the human and Xenopus 3 0 -UTRs of RRAS mRNA. In human cells, the RRAS protector oligonucleotide (PO-RRAS) strategy effectively blocked the action of ectopic miR-449, as evidenced on RRAS 3 0 -UTR in luciferase assays (Supplementary Fig. 4b ). In addition, miR-34/449 knockdown or protection of RRAS mRNA from miR-34/449 in frog epidermis led to an increase in rras transcript levels (Supplementary Fig. 4c ). We checked that in both species the expression of RRAS2, an RRAS-related gene, did not interfere with R-Ras signalling. RRAS2 expression remained at a very low level during MCC and in response to miR-449 overexpression, and was not altered by miR-34/449 knockdown or PO-RRAS protection (HAECs, see GEO GSE22147; Xenopus, Supplementary Fig.
Complementary DNAs were synthesized using iScript Reverse Transcription Supermix (BioRad). Quantitative RT-PCR. Human. qRT-PCR was performed using TaqMan Gene Expression Assay and TaqMan MicroRNA Assay (Life Technologies) on a Lightcycler 480 (Roche) according to the manufacturer's instructions. Expression levels of mature miRNAs and mRNA were calculated using the 2-DCT method, using respectively RNU44 and UBC as endogenous controls. Xenopus. Primers were designed using Primer-BLAST Software. PCR reactions were carried out using SYBRGreen on a CFX Biorad qPCR cycler. All experiments were repeated at least twice on separate injections and the qRT-PCR was performed in triplicate. The relative expression of RRAS was normalized to the expression of the housekeeping gene ornithine decarboxylase.
Following double FISH analysis, immunostaining with anti-GFP antibody was performed and slides were processed for confocal imaging. Xenopus embryos at stage 34 were fixed in paraformaldehyde 4% overnight and frozen in 100% methanol at À 20 °C overnight before performing ISH with digoxigenin-labelled locked nucleic acid (Exiquon) probes against miR34b (5 0 -DIG-caatcagctaactacactgcctg-DIG-3 0 ) 9. Confocal microscopy. Human. Images were acquired using the Olympus Fv10i or the Leica SP5 confocal imaging systems. Xenopus. Flat-mounted epidermal explants were examined with a Zeiss LSM 780 confocal microscope. Three-colour confocal z-series images were acquired using sequential laser excitation, converted into single plane projection and analysed using ImageJ software. In Supplementary Table  1  is provided a list of the antibodies used in our study.
Acknowledgements This work was supported by  CNRS , the  French Government (National Research Agency, ANR)  through the ' Investments for the Future '  LABEX SIGNALIFE  ( ANR-11-LABX-0028-01 ) and  FRANCE GENOMIQUE  ( ANR-10-Infra-01 ),  Region PACA (Canceropole) ,  CG06  and by grants from  ANR  ( MERCi ,  ANR-09-GENO-039 ;  COMMIT ,  ANR-11-BSV2-021 ;  MITHRA ,  ANR-12-EMMA-0015-01 ),  Vaincre la Mucoviscidose ,  FRM  ( DEQ20130326464 ). We thank  V. Magnone ,  G. Rios ,  S. Fourre, M-J Arguel  and  K. LeBrigand  from the  IBISA Functional Genomics Platform, Sophia-Antipolis , for help with transcriptome analyses and bioinformatics,  F. Brau  and  J. Cazareth  for cellular imaging and  F. Aguila  for artwork. Authors in IBDM acknowledge  France-BioImaging infrastructure  ( ANR-10-INSB-04-01 , call ' Investissements d'Avenir' ) and thank the staff of the imaging platform and of the aquatic facility.