dataesr/scientific-paragraphs-categorization huggingface dataset:
For each strain the highest tested concentration was based on toxicity in the first experiment and narrowed concentration ranges were employed. In addition, all treatments in the presence of S9-mix were further modified by the inclusion of a 1-hour pre-incubation step. Clear evidence of toxicity was observed in strains TA98 and TA102 following treatment at the maximum test concentration in both the absence and presence of S9-mix, and in the strain TA1537 following treatment at the maximum concentration in the presence of S9-mix. However, toxicity was not seen at the concentrations tested in TA100 and TA1535 in the presence and absence of S9-mix or in TA1537 in the absence of S9-mix, and therefore it was considered that higher concentrations should be evaluated. For the other strains data from a sufficient number of concentrations were obtained.
Treatments were performed both in the absence and presence of Aroclor 1254 induced rat liver S9-mix  (Lloyd, 2011). Experiment 1 was conducted using blood from female donors and Experiment 2 was conducted using blood from male donors. Treatment with 5-methyl-2-thiophenecarbaldehyde was conducted 48 hours following culture initiation (stimulation by phytohaemagglutinin). A preliminary toxicity range-finding experiment was conducted with S9-mix and 3 hours treatment and without S9-mix with 3 and 24 hours treatment. Toxicity was evaluated as the effect of treatment on the Replication Index (RI). Twelve concentrations from 4. 6 to 1262 μg/mL were tested. The concentrations selected for the main experiments were based on toxicity data from this preliminary test. In experiment 1 (female donors), cells were exposed to 5-methyl-2-thiophenecarbaldehyde for 3 hours and 21 hours recovery (21 + 3) both with and without S9-mix.
Levels of aspartate aminotransferase were increased following dosing at 700 mg/kg bw/day compared to control values. Additionally, a histological observation of glycogen deposits in the liver of animals dosed at 350 and 700 mg/kg bw/day, along with changes in liver enzymes, indicate that the liver was exposed to the test article, 5methyl-2-thiophenecarbaldehyde. These observations indicated exposure to the target organ (the liver) of the Comet assay (see below). In the micronucleus assay femoral bone marrow was filtered through cellulose columns to remove the majority of nucleated cells, smears were made, fixed and stained with acridine orange. Two thousand polychromatic erythrocytes (PCE) per animal were scored for micronuclei under fluorescence microscopy. The data revealed that rats treated with 5-methyl-2-thiophenecarbaldehyde at all doses exhibited group mean % PCE (out of total erythrocytes) that were similar to the vehicle control group confirming there was no evidence of test article-related bone marrow toxicity.
The number of 'clouds' out of 100 cells was scored for each slide. 'Clouds' were not used for comet analysis. Vehicle control animals exhibited quite low comet scores, but significant DNA damage was induced by the positive control. The Comet analysis revealed that animals treated with 5-methyl-2-thiophenecarbaldehyde exhibited elevated mean tail intensities and tail moments compared to concurrent vehicle control animals. However, the majority of animals, including the vehicle controls, had tail intensity values below the laboratory's historical control range and the elevated mean level was due to only one animal in each group. Thus, the data generated for this assay is considered to fall within the normal level of variation for the assay. In addition, there was no indication of dose response relationship.
Application of the For seven substances the Procedure could not be applied due to indication of genotoxic potential in vitro  15. 086, 15. 090, 15. 099, 15. 114, 15. 119 and 15. 133]. The substances were allocated into structural subgroups (for description and explanation, see FGE. 21Rev3) and were evaluated at step B4 in the Procedure, i. e. the substances are not expected to be metabolised to innocuous products and the estimated intakes are below the thresholds for their structural classes II and III. In summary, the Panel concluded that 26 of the candidate substances evaluated through the Procedure, from the structural subgroups A-Ic (thiophenes with thiol-containing ring substituents) and A-II (thiazoles) are not of safety concern at their estimated levels of intake based on the MSDI approach, whereas for 26 candidate substances from the structural subgroups A-Ia (thiophene), A-Ib (thiophenes with non-thiol-containing ring substituents), A-III (benzothiazoles), B-I (dihydrothiophenes), B-IV (dithiazines) and B-V (dihydrothiazines) additional data are required.
EFSA Considerations The Panel agrees with the application of the Procedure, as performed by the JECFA, for 21 of the 26 substances in the group of sulphur-containing heterocyclic compounds. Three of the 26 substances evaluated by the JECFA, 2-(sec-butyl). 029], 4,. 030] and  4,. 032] were considered by the Panel to have genotoxic potential in vitro, and therefore the Panel concluded that the Procedure should not be applied to these three flavouring substances until adequate in vivo genotoxicity data become available. Additionally, the Panel noted the presence of a terminal conjugated double bond in the substances  2,. 005] and. 018] which raised concern for genotoxicity. The Panel concluded, contrary to the JECFA, that the Procedure should not be applied to these two substances either until genotoxicity data become available.
,. 004], cleared for genotoxicity concern in FGE. 224. Additionally, new toxicity data have become availablefor 5,4,3,. Therefore, the present revision of FGE. 76, FGE. 76Rev1, considers 26 flavouring substances evaluated by the JECFA. In Flavouring Group Evaluation 76 (FGE. 76), the EFSA considered 26 sulphur-containing heterocyclic compounds evaluated by the JECFA at its 59 th meeting. Since publication of FGE. 76, one substance, thiazole [FL-no: 15. 028], is no longer supported by Industry for use as a flavouring substance in Europe and will therefore not be considered any further. The present revision is made due to inclusion of one additional substance, 5-methyl-2-thiophenecarbaldehyde [FL-no: 15. 004], cleared for genotoxicity concern in FGE. 224. Additionally, new toxicity data have become available for 5,6dihydro-2,4,6-tris(2-methylpropyl)-4H-1,3,5-dithiazine [FL-no: 15.
capita/day) Class 2) Evaluation procedure path 3) Outcome on the named compound [ 4) or 5] Outcome on the material of commerce [6), 7), or 8)] Amount added to food as flavour in (kg / year) x 10E9 / (0. 1 x population in Europe (= 375 x 10E6) x 0. 6 x 365) = µg/capita/day. 2) Thresholds of concern: Class I = 1800, Class II = 540, Class III = 90 µg/person/day. 15. 087 15. 088 15. 106 15. 108 15. 135 15. 114 15. 133 BW CAS CEF CoE DNA EFFA EFSA EU FAO FEMA FGE FLAVIS (FL) Flavour Information System (database) 2-Methyl-3-mercaptothiophene S SH 2-Methyl-4,5-benzothiazole N S Thiophene S 2-Thiophenemethanethiol S SH Ethyl thialdine S N H S 5-Acetyl-2,3-dihydro-1,4-thiazine N H S O 5-Acetyl-2,3-dihydro-1,4-thiazine S N H O body weight Chemical Abstract Service Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids 0.
CTC number changes during treatment were not correlated with the outcome (data not shown), but no definite conclusion can be drawn, as these statistical analyses were clearly underpowered. We believe that a longer follow-up of the REMAGUS02 CTC study will not make any significant impact on our original findings previously published, as survival data have now reached maturity. However, these data will be included in a planned metaanalysis of the studies that use the CellSearch technique in non-metastatic breast cancer setting. This would allow a more accurate comparison of prognostic significance of CTC detection before and after treatment.
Funding F. -C. Bidard  received a fellowship from the  Nuovo-Soldati Research Foundation. The  REMAGUS02  was funded by the  French Ministry of Health  ( French Programme Hospitalier de Recherche Clinique ISRCTN10059974 ,  PHRC: AOM 0211 ). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the paper.
Acknowledgements This work was supported by grants from the  7th Framework Program  of the  European Commission :  CASCADE  ( FP7-HEALTH-233236 ) and  REBORNE  ( FP7-HEALTH-241879 ), award of the  European Regional Development Fund (ERDF)  allocated by the  European Union  and by grants from the  European Center for Transplantation Sciences and Immunotherapy (IHU CESTI ,  ANR-10-IBHU-0005 ) and the  Infrastructure Program ECELLFRANCE  ( ANR-11-INSB-005 ).
Materials and methods This is a retrospective review of children with diplegic pattern CP who: had an initial gait analysis between 1993 and 1999, had an element of flexed-knee gait, and had a follow-up gait analysis at least 8 years later. All evaluations included a kinematic assessment performed with a motion analysis system (Motion Analysis, Santa Rosa, CA), data reduction using OrthoTrak (Motion Analysis), and a complete physical examination including measures of passive range of motion. Gait interpretation was performed by a team of orthopedists and physical therapists. Flexed-knee gait  [7]  was defined as [15°of knee flexion at initial contact, which corresponds to one standard deviation (SD) above the mean knee flexion at initial contact of a typically developing 6-year-old child. Children with a wide range of maximal knee extension during stance were included to examine differences in outcome in children with crouch (excessive knee flexion through the gait cycle) and children with mid-stance extension.
Discussion The etiology of flexed-knee gait in CP has many contributory factors and requires a treatment algorithm customized to the individual child. The standard method for diagnosis includes a combination of (1) serial history and physical examinations to define the progression of the deformity and (2) three-dimensional gait analysis for quantitative measurement and definition of the biomechanics of the pathologic gait pattern. The GDI and GMFM provide quantitative measurements of overall gait severity and motor function. Specific kinematic and kinetic measures, such as KFFC and ankle moments, help to assess the pathomechanical etiologies of flexed-knee gait. This study aimed to describe gait outcome over a 10-year period in a diverse group of children with flexed-knee gait. Most experts agree that the natural history of flexed-knee gait is one of gradual decline and loss of walking function  [13, 32] , although objective data defining the untreated natural history is lacking in the literature.
Instituting the use of clinical gait analysis in this population allowed for a decrease in recurrent minor birthday syndrome surgery procedures. There are, however, no published data on the frequency or total number of surgical procedures for children receiving orthopedic care guided by gait analysis over this length of time. Our sample of 97 children underwent 158 surgical events, with 815 total procedures, in a 10-year period. The concept of SEMLS does not imply that the child has surgery once in their lifetime, but conveys a philosophy intended to reduce surgical events as much as possible. The goal at our institution is to limit a child to two surgical events through growth to skeletal maturity in order to decrease the impact and cost on the child and their family. Looking at the total number of surgical procedures up until the time of the final gait analysis, 69 % of children in the study had two or fewer surgical events, while 31 % had three or more.
All primary antibodies used have been shown to cross-react successfully with rainbow trout proteins of interest  [25, 27, [29] [30] [31]. After washing, membranes were incubated with an IRDye infrared secondary antibody (LI-COR Inc. Biotechnology, Lincoln, NE, USA). Bands were visualized by Infrared Fluorescence using the OdysseyH Imaging System (LI-COR Inc. ) and quantified by Odyssey infrared imaging system software (Application software, version 1. 2).
The methods This is a retrospective monocentric study concerning an observational cohort of patients. Our hospital institutional review board (Comite de Protection des Personnes-Sud-Est 1) gave specific approval for this study. Each patient chart was thoroughly reviewed with collection of clinical, biological, and pathological data at onset, at diagnosis and at last follow-up. The risk factors studied were:-hypertension defined as blood pressure over 140/90 mmHg at different occasions or already treated with antihypertensive agents including diuretics;-daily proteinuria with a cut-off value of ≥1 g/day; and-global optical score, GOS, integrating all elementary lesions (glomerular index: 0 to 6, vascular index: 0 to 5, tubular index: 0 to 4 and interstitial index: 0 to 5); the cut-off value of ≥8 was previously extracted from ROC curve with dialysis as the final event.
The statistics We have used basic statistics with number and % for qualitative variables and mean (+/-SD) for continuous variables. Comparisons were done accordingly with contingency tables or unpaired T or U tests. We used Cox regression models for survival without the event (dialysis/death) with both univariate or multivariate analyses (with different covariates: categorical or dichotomous or continuous). The survival curves were built according to the Kaplan-Meier method which accepts only categorical variables, and the curves were compared by the Logrank test. We have also done these statistics with dialysis alone as end-point. All tests were done with Statview 5 or SPSS 19 softwares.
Baseline data at diagnosis All 74 patients presented with cutaneous purpura at least on one occasion with the classical characteristics; the initial presentation was associated with arthralgia in 57 (77. 0%) together with abdominal pain in 33 (44. 6%) leading to the diagnosis of Henoch-Schönlein purpura. Renal involvement occurred at the same time of purpura or within few weeks: microscopic haematuria was detected at time of biopsy in all patients but one, and gross haematuria was symptomatic in 29 (39. 2%); significant proteinuria ≥0. 30 g/d was detected in 54 patients (73. 0%). The The % of patients with HT according to ARR 0, 1, 2, or 3, was at diagnosis 0, 37, 58 and 100 contrasting at last follow-up with 30, 63, 92, and 100 respectively The % of patients with proteinuria ≥1 g/d was at diagnosis 0, 37, 71, and 100 and at any time 4, 47, 75, and 100 respectively for ARR 0, 1, 2, and 3.
Acknowledgements We thank  A. S. S. E. T. A. R. ( Association Scientifique Stephanoise pour l'Etude et le Traitement des Affections Renales) , a non-profit organization, for its full financial support in conducting this study at all different stages. Received: 11 January 2013 Accepted: 30 July 2013 Published: 1 August 2013.
18 F-FDG-PET/CT imaging. Patients fasted for 6 h. Blood glucose level had to be o7 mmol l À 1. 18 F-fluorodeoxyglucose (5 MBq kg À 1 ; not exceeding 500 MBq) was administered 60 min before data were acquired on a Gemini XL PET/CT scanner (Philips Healthcare, Eindhoven, The Netherlands). Computed tomography was acquired first (120 kV; 100mAs; no contrast enhancement). Positron emission tomography three-dimensional (3D) data were acquired in a listmode format with 2 min per bed position, and images were reconstructed using a 3D row-action maximum-likelihood algorithm. Positron emission tomography/CT images were interpreted by two nuclear medicine specialists blinded to the patient's record. 18 F-fluorodeoxyglucose uptake was expressed as SUV (standardised uptake value). A 3D region of interest (3D-ROI) was drawn around the primary tumour and around axillary lymph nodes when present.
Absence of in situ carcinoma was not required to define pCR. Statistical analysis. Statistical analyses were performed using Medcalc (MedCalc Software, Ostend, Belgium). Po0. 05 was considered statistically significant. Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUV max at baseline, at two cycles and DSUV max ) was examined with the t-test and log-transformed data because of non-normality of the distributions. The predictive performance regarding the identification of non-responders was evaluated using ROC analysis. Correlations between clinical or biological parameters (axillary status, tumour grade, ER expression) and pathologic response were assessed with the t-test.
Background: The family Mimiviridae belongs to the large monophyletic group of Nucleo-Cytoplasmic Large DNA Viruses (NCLDV; proposed order Megavirales) and encompasses giant viruses infecting amoeba and probably other unicellular eukaryotes. The recent discovery of the Cafeteria roenbergensis virus (CroV), a distant relative of the prototype mimiviruses, led to a substantial expansion of the genetic variance within the family Mimiviridae. In the light of these findings, a reassessment of the relationships between the mimiviruses and other NCLDV and reconstruction of the evolution of giant virus genomes emerge as interesting and timely goals. Results: Database searches for the protein sequences encoded in the genomes of several viruses originally classified as members of the family Phycodnaviridae, in particular Organic Lake phycodnaviruses and Phaeocystis globosa viruses (OLPG), revealed a greater number of highly similar homologs in members of the Mimiviridae than in phycodnaviruses.
Comparative genomics of the putative expanded family Mimiviridae In the course of phylogenomic study of the NCLDV, we noticed that in sequence database searches the proteins from some large DNA viruses assigned to the family Phycodnaviridae, namely Organic Lake phycodnaviruses  [33]  and Phaeocystis globosa viruses 12 T and 14 T  [34, 35]  produce a substantially greater number of best hits into mimiviruses than into phycodnaviruses (Figure  1 , Additional file 1). To further investigate the evolutionary provenance of these poorly characterized giant viruses (hereinafter OLPG, after Organic Lake and Phaeocystis globosa viruses), we conducted an in depth phylogenomic analysis of the previously identified and putative new members of the family Mimiviridae. To this end, we constructed clusters of orthologous genes (COGs  [36, 37] ) from the genomes of 4 mimiviruses (Acanthamoeba castellanii mamavirus, Acanthamoeba polyphaga mimivirus, Megavirus chiliensis, and Moumouvirus), CroV, and 3 OLPG [Organic Lake phycodnavirus 1, Organic Lake phycodnavirus 2 (these two genomes are still incomplete) and Phaeocystis globosa virus 12 T)].
The gene products encoded in these 8 genomes were retrieved from GenBank yielding a total of 5,677 protein sequences. These viral proteins were grouped into clusters of likely orthologs using a modified COG procedure  [38]  (see Methods for details). Clusters were manually edited and annotated using the results of RPS-BLAST and PSI-BLAST searches for the constituent proteins (Additional file 2 and see Methods). This procedure yielded 898 clusters of candidate orthologous genes from the putative expanded family Mimiviridae (hereinafter mimiCOGs). The mimiCOGs then were merged into the previously constructed clusters of orthologous genes for all NCLDV (NCVOGs  [8] ) (see Methods for details). Fifty-two genes are present in all 8 genomes of the members of the putative expanded family Mimiviridae (Table  1 ).
MimiCOG construction For the construction of mimiCOGs, the following genomes were downloaded from GenBank (http://www. ncbi. nlm. nih. gov/): Acanthamoeba polyphaga mimivirus (GI:311977355), Acanthamoeba castellanii mamavirus (GI:351737110), Megavirus chiliensis (GI:350610932), Cafeteria roenbergensis virus BV-PW1 (GI:310830989), Phaeocystis globosa virus 12 T (GI: 357289534), Organic Lake phycodnavirus 1 (GI:322510471),Organic Lake phycodnavirus 2 (GI:322510873), Marseillevirus (GI:284504040), and Lausannevirus (GI:327409548). The complete dataset consisted of 6,548 protein sequences. The mimiCOGs were constructed as previously described  [38]. Briefly, the procedure included the following steps: 1) Initial clusters based on triangles of symmetrical best hits were constructed using a modified COG algorithm using as the input the results of all-against-all BLASTP [48] comparison; 2) Multiple alignments of the initial cluster members were constructed using the MUSCLE program  [49].
The alignments were used to generate position-specific scoring matrices (PSSM) for a PSI-BLAST search  [48]  against the original protein dataset. Significantly similar proteins were added to the corresponding clusters; 3) Clusters with nearly complementary phyletic patterns and high inter-cluster sequence similarity were manually examined and merged whenever appropriate; 4) The mimiCOGs were manually edited and annotated using annotations of Moumouvirus and Mamavirus proteins present and RPS-BLAST  [50]  and PSI-BLAST of other cluster members; 5) MimiCOG-NCVOG correspondence was established by PSI-BLAST search initiated with PSSMs constructed from NCVOG alignments  [8]  against proteins included in the mimiCOGs. The mimiCOGs are available at ftp://ftp. ncbi. nih. gov/pub/ koonin/mimivirus/mimiCOGs.
Multiple alignment and phylogenetic tree construction The sequences for phylogenetic analysis were collected using (i) BLAST searches against nr and environmental (env_nr) databases initiated by distant mimiCOG members; (ii) the corresponding NCVOG sequences  [8] ; and (iii) reference sequences used for the core NCVOG study  [41]. Nearly identical sequences were eliminated using BLASTCLUST (http://www. ncbi. nlm. nih. gov/IEB/ ToolBox/C_DOC/lxr/source/doc/blast/blastclust. html). The sequences were aligned using MUSCLE  [49]. All alignments were manually checked for the conservation of domain architecture and presence of diagnostic motifs. Positions including gaps in more than one-third of the sequences and positions with low information content were removed prior to tree computation  [52].
A preliminary maximum-likelihood tree was constructed using the FastTree program with default parameters (JTT evolutionary model, discrete gamma model with 20 rate categories;  [53] ). The preliminary tree and the alignment were then used to determine the best substitution matrix using Prottest  [54]. Final maximum-likelihood trees were constructed using TreeFinder (1,000 replicates, Search Depth 2  [55] ), with the substitution matrix found to be the best for a given alignment. The Expected-Likelihood Weights (ELW) of 1,000 local rearrangements were used as confidence values of TreeFinder tree branches. For topology testing, whenever applicable, alternative (constrained) topologies were constructed and compared to the initial trees using TreeFinder. Approximately unbiased (AU) test P value cutoff 0.
The rotation axes allow fine adjustment of the plate tilt in order to ensure perfect single mode and linearly polarized oscillation. The translation axis allows the Si plate to be translated along the optical axis of the resonator in order to change the photon density within the Si plate. Indeed, according to the plano-convex architecture of the optical resonator, and to the fact that its length is adjusted close to the limit of stability, the beam diameter on the Si plate increases when the plate is translated towards the output mirror. The active medium is pumped by a cw multimode fiber-coupled laser diode (from Jenoptik) operating at 975 nm. The pump power is fixed at 275 mW during data acquisition. The optical spectrum is continuously analyzed with a Fabry-Perot interferometer to check that the laser remains monomode without any mode hop during data acquisition.
Acknowledgements This work has been supported by Projects  P08-FQM-3993 ,  P09-FQM-4787  ( Junta de Andalucía, Spain ) and  FIS2009-07321  ( MICINN, Spain ). In addition,  L. Rodríguez-Arco  and  M. T. López-López  acknowledge financial support by  Secretaría de Estado de Educación, Formación Profesional y Universidades (MECD, Spain)  through its  FPU program  and  University of Granada (Spain)  respectively.