dataesr/scientific-paragraphs-categorization huggingface dataset:
New finite-element approximations for tensor dynamics on surfaces may however be required from a more numerical perspective  [96, 97]. Our theory may also be readily extended to account for transverse gradients in myosin or turnover activity that may generate additional active torques, for variations in actomyosin gel density as a result permeation  [98] , or for possible two-dimensional chiral effects at the cell level  [99, 100]. From a numerical perspective, we provided an easily modifiable Python implementation of the model within the general-purpose finite-element library FEniCS. We proposed a numerical scheme based on a penalization method that circumvents the need for 1 elements to use more simple 0 elements. In the cortex, gradients in contractile stress can lead to strong tangential motions, and convergent flows, which create excessive distortions of the computational mesh linked to the material  [7]  (see Fig.
Preparation of Bacteria The strains used in this study were selected from each group based on our previous results  [9]. The two main selection criteria are the capacity of the strain to induce platelet activation and the profile toward the platelet inhibitory effect (Table  1 ). The strains represent the following profiles: E. coli J53, platelet sensitive strain which induces platelet activation; E. coli K12, platelet resistant strain which induces platelet activation; and E. coli LH30, platelet resistant strain which does not induce platelet activation (Table  1 ). Identification was confirmed using matrix-assisted laser desorption/ionization timeof-flight (MALDI-TOF) mass spectrometry and the Biotyper database (Bruker, Dresden, Germany). Strains were grown at 37 • C in an overnight culture of Columbia agar +5% sheep blood (bioMérieux, Marcy l'Etoile, France).
Grids were attached with double-side tape to a glass slide and platinum-coated at 10 mA for 20 s with a MC1000 sputter coater (Hitachi High-Technologies, Japan). Electron micrographs were obtained on a SU5000 scanning electron microscope (Hitachi High-Technologies, Japan) operated in high-vacuum at 7 kV accelerating voltage and observation mode (spot size 30) with BSE detector. The abundance of bacteria in each mixture was determined by measuring the surface occupied by the bacteria using Fiji software with 10 images for each mixture. The criteria used to indicate that the platelets are hyper-activated are: the presence of pseudopodia and the presence of platelet aggregates; moderately activated: the presence of pseudopodia and the absence of platelet aggregates; not activated: presence of intact platelets in lenticular shape, absence of pseudopodia and platelet aggregates.
Using SE-SEM, we observed that K12 and J53 E. coli bacteria possessed a 'rough' surface, composed of a complex network of many thin surface reliefs (Figure  5A2 ,C2; 14 cells analysed). Measurement of membrane thickening was performed using Fiji software with X bacteria analysed for each strain. In contrast, the surface of LH30 E coli bacteria was 'smooth', with a simpler network of larger surface reliefs (Figure  4B2 ; 14 cells analysed). The thickness of these bacterial reliefs surface was measured, and the results were analysed statistically. The analysis showed that indeed the J53 strain has reliefs that are less thick (47. 34 µm ± 18. 23) compared to the two other strains (107. 8 µm ± 26. 81 and 115. 2 µm ± 43. 04 for K12 and LH30 respectively. p = 0. 001 and p = 0. 0008 for K12 and LH30 respectively.
No significant difference was observed between K12 and LH30 strains). These SEM images also confirmed the presence of flagella on the J53 strain E. coli bacteria (not shown) and were used for measuring bacteria dimensions. The average dimensions of the bacteria were 2854 ± 961 nm length and 826 ± 71 nm width for K12 (n = 14), 2570 ± 731 nm length and 1073 ± 121 nm width for LH30 (n = 14) and 2931 ± 483 nm length and 917 ± 329 nm width for J53 (n = 14). No significant differences were observed between strains regarding length and width. The results of this part have been summarized in Table  3. Using SE-SEM, we observed that K12 and J53 E. coli bacteria possessed a 'rough' surface, composed of a complex network of many thin surface reliefs (Figure  5 (A2,C2); 14 cells analysed). Measurement of membrane thickening was performed using Fiji software with X bacteria analysed for each strain.
Acknowledgments: This work was supported by the  Institut Hospitalo-Universitaire (IHU) Méditerranée-Infection, Marseille, France. We sincerely thank  Takashi Irie ,  Kyoko Imai ,  Shigeki Matsubara ,  Yusuke Ominami ,  Akiko Hisada , and the entire  Hitachi Team in Japan  for the installation of the TM4000 and SU5000 microscopes in our facility. The authors would like to thank the  Algerian Ministry of Higher Education and Scientific Research  for supporting AE during his thesis in the  IHU Méditerranée Infection.
The first step of the screening approach consists in sorting the data and keep only emission contributions that are relevant enough. In a second step, the method identifies, among those significant differences, the most important ones that are evidence of methodological divergence and/or errors that can be found and resolved in at least one of the inventories. The approach has been used to compare two versions of the CAMS-REG European 25 scale inventory over 150 cities in Europe for selected activity sectors. Among the 4500 screened pollutant-sectors, about 450 were kept as relevant among which 46 showed inconsistencies. The analysis indicated that these inconsistencies were almost equally arising from large scale reporting and spatial distribution differences. They mostly affect SO2 and PM coarse emissions from the industrial and residential sectors.
260 The method starts from the reported emissions by European countries to UNFCCC (for greenhouse gases) and to EMEP/CEIP (for air pollutants) and have been aggregated into 246 different combinations of sectors and fuels. Reported data are analysed by sector and completed with alternative emission estimates where the completeness, consistency and/or quality of the reported data was not sufficiently accurate. In practice, reported data were found fit for purpose for EU Member States and the UK, Norway, Iceland and Switzerland, while for other countries 265 alternative emission estimates were used. In addition, some further modifications were made to the dataset for which we refer to  Kuenen et al. (2021). This results in a complete emission inventory for all countries, which is then spatially distributed at high resolution using a consistent methodology over the whole domain.
2 contains among others an improved split in road transport emissions between urban, rural and highway shares, agriculture (new proxies for manure spreading, fertilizer application based on JRC CAPRI model 285  (Britz et al. 2015) ). It also uses a new approach for Agricultural Waste Burning, improves the point source database, and uses updated harmonized inland and sea shipping based on the FMI STEAM model  (Jalkanen et al. , 2009). Further details on these changes are provided in  Kuenen et al. (2021). It is important to stress that the proposed screening methodology assesses the overall consistency of the two 290 inventory versions, i. e. it covers the consistency of the inventory compilation itself but also the consistency of its input data (in this case: country reported emissions). In terms of pollutants,  , and  , include the following: NOx, NMVOC, PM2.
HDACi have previously been studied in the context of DMD models but not for their effect on dystrophin transcript synthesis. 7] [18]  These studies have led to the clinical evaluation of the HDACi givinostat, which is currently in a phase III clinical trial for DMD treatment (www. clinicaltrials. gov, clinical trial identifier NCT02851797). Positive topline data from this phase III trial were announced at the Annual PPMD Conference on June 25 th , 2022, showing the beneficial effect of givinostat in DMD patients (https://www. businesswire. com/ news/home/20220625005001/en/Italfarmaco-Group-Announces-Positive-Topline-Data-from-Phase-3-Trial-Showing-Beneficial-Effectof-Givinostat-in-Patients-with-Duchenne-Muscular-Dystrophy). We hypothesize that on top of these beneficial effects, HDACi could significantly improve the effect of exon-skipping strategies by increasing the level of Dmd transcript.
PCR products were analyzed on 1. 5% agarose gels with ethidium bromide. Exon 23 skipping levels were quantified using real-time qPCR using TaqMan assays designed against the exon 23-24 junction and exon 22-24 junction as previously described. 9 Seventy nanograms of cDNA was used as input per reaction, and all assays were carried out in triplicate. Assays were performed under fast cycling conditions on a Bio-Rad CFX384 Touch Real-Time PCR Detection System, and all data were analyzed using the absolute copy number method. For a given sample the copy number of skipped product (exon 22-24 assay) and unskipped product (exon 23-24 assay) were determined using the standards Ex20-26 and Ex20-26Delta23 respectively (gBlocks gene fragments from Integrated DNA Technologies). Exon 23 skipping was then expressed as a percentage of total dystrophin (calculated by the addition of exon Exon-skipping levels of samples derived from in vitro cultures were determined using RT-PCR with exon-specific primers (Table  S1 ) followed by analysis of skipping ratios using an Agilent Femto Pulse.
Peaks were called, and molarity of each PCR product was determined using the corresponding ProSize data analysis software (Agilent). Further data analysis and visualization was performed using GraphPad Prism version 9. Follistatin quantification was performed using real-time qPCR using TaqMan assays (Mm. PT. 58. 11399784 from IDT). DDCt analysis was performed with GAPDH as normalization.
Bands were visualized using the Odyssey CLx system (Li-Cor), and quantification was carried out using the Empiria Studio software (Li-Cor) based on a standard curve made from pooled lysates from C57BL10 (WT) and mdx control for each tissue. For myomesin-3 detection, mouse sera were diluted at 1:20 before loading onto 3%-8% Criterion XT Tris-Acetate Protein Gel, following the manufacturer's instructions (Bio-Rad). Myomesin-3 protein was detected by probing the nitrocellulose membrane with MYOM3 primary rabbit polyclonal antibody (MYOM3; Proteintech, Manchester, UK), followed by incubation with a goat anti-rabbit secondary antibody (IRDye 800CW Goat anti-rabbit IgG; Li-Cor). Bands were visualized using the Odyssey Imaging System (Biosciences, Lincoln, NE, USA). Signal intensities in treated samples were quantified and normalized to PBS control mouse signals using Image Studio software (Li-Cor).
Immunohistochemistry analysis Sections of 10 mm were cut from triceps and heart and examined for dystrophin expression using the rabbit polyclonal antibody dystrophin (dilution 1:500; Thermo Fisher Scientific, cat. no. RB-9024-P), which was then detected by donkey anti-rabbit IgG Alexa 594 (dilution 1:400; Jackson ImmunoResearch). Controls prepared by omitting primary antibody showed no specific staining. Images were taken at equivalent locations and exposure times using a Zeiss Axio Imager with an Orkan camera (Hamamatsu) and AxioVision software, and analyzed with ImageJ software. To visualize ASO in kidney, 5-mm sections were cut from paraffin blocks, dewaxed (3Â 5 min in xylene and 3Â 3 min in ethanol 100) and stained with a complementary DNA probe fluorescently labeled with Alexa 594. Controls prepared by omitting the probe showed no specific staining.
Scans were taken at equivalent exposure times using an IX83 inverted microscope (Olympus) with an Orca-R2 camera (Hamamatsu) and cellSens Dimension software. For measurement of muscle fiber size, sections of 10 mm were cut from triceps and stained with the rabbit polyclonal antibody laminin (dilution 1:200; Sigma, ref. L9393-2ML), which was then detected by donkey anti-rabbit IgG Alexa 488 (dilution 1:400; Thermo Fisher Scientific, ref. A11008). Images were taken using a Zeiss Axio Imager with an Orkan camera (Hamamatsu) and AxioVision software, and analyzed with ImageJ software.
Statistical analysis All in vivo data were analyzed with GraphPad Prism8 software (GraphPad, San Diego, CA, USA) and expressed as means ± SEM. "n" refers to the number of mice per group. Group comparisons were performed using one-and two-way ANOVA with repeated-measures comparisons when needed (e. g. , effects at different exon junctions or in different muscle tissues), followed by post hoc Dunnett's or Sidak's multiple comparisons when appropriate. To compare the overall effect of two treatments across the different tissues or different exon junctions, the two groups were directly compared using a two-way ANOVA, and the p value of the treatment effect is indicated in the figure legends. The Kruskal-Wallis test was used to compare groups that did not follow a normal distribution (assessed with the Shapiro-Wilk test).
The statistical analysis of gene expression and transcript imbalance assessed by qPCR at various exon-exon junctions was also performed using a linear model, in which exons were included as a covariate (continuous) and group was included as a factor. Pairwise contrasts were assessed using the emmeans R package, and multiple testing correction was performed with the Tukey method. Statistical analysis of all in vitro data was performed using GraphPad Prism version 9. Kruskal-Wallis test followed by Dunn's multiple correction was performed as indicated. Repeated-measures (RM)-A-NOVA was used as indicated. Data are plotted as means ± SEM. "n" refers to independently acquired and processed samples (biological replicates) as indicated. Biological replicates consist of technical triplicates in the case of qRT-PCR and ChIP-qPCR measurements.
ACKNOWLEDGMENTS We thank the personnel of the platform 2CARE for taking care of the animals used in this work. We thank  Dr. Vincent Mouly  ( Institute of Myology, Paris, France ) for providing the myogenic cell lines used in the study. The authors are part of the  European BIND consortium  and the  COST Action DARTER. Several authors of this publication are members of the  Netherlands Neuromuscular Center , the  Duchenne Centrum Netherlands  (funded by  Spieren voor Spieren) , and the  European Reference Network for Rare Neuromuscular Diseases EURO-NMD. This work was supported by the  Institut National de la Santé et de la Recherche Médicale (INSERM) , the  Association Monegasque contre les Myopathies (AMM) , the  Paris Ile-de-France Region , and the  Fondation UVSQ. F. B. is the recipient of a MESRI thesis fellowship.
Study design and patients This analysis includes data from the ASAS-perSpA study, an observational, cross-sectional multicentre and international study, with 24 participating countries (23 actively involved) across four continents (Africa, America, Asia and Europe). Patients diagnosed with axSpA, PsA or pSpA by their rheumatologist were recruited consecutively between July 2018 and February 2020. 11 Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.
SR: study idea, design and set up, methodology, discussion and interpretation of the findings, manuscript revision. AM: study idea, design and set up, methodology, data collection, discussion and interpretation of the findings, manuscript revision. CL-M: study design and set up, data collection, manuscript revision. MD: methodology, manuscript revision. VN-C: study idea, design and set up, methodology, presentation of the data, discussion and interpretation of the findings, manuscript revision, supervision. Funding No funding was provided for the current analysis. The ASAS-perSpA study has been conducted under the umbrella of ASAS thanks to unrestricted grants from Pfizer, Lilly, AbbVie, Novartis, UCB, Janssen and Merck. Disclaimer The funders did not have any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.
Acknowledgements This study was conducted under the umbrella of the  International Society for Spondyloarthritis Assessment (ASAS). We would like to thank all the patients and investigators who participated in this research. We would like to thank all the collaborators who participated in the study:  José Maldonado-Cocco  ( Buenos Aires University School of Medicine, Buenos Aires, Argentina ),  Hernán Maldonado Ficco  ( Hospital San Antonio de Padua, Rio Cuarto, Argentina ),.
Study participants and blood collection HIV-negative subjects aged ⩾18 years with suspected TB infection or TB disease were recruited at the Dept of Infectious Diseases and Respiratory Medicine, Charité -Universitätsmedizin Berlin and the Dept of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring (Berlin, Germany). The study was approved by the local ethics committee (ethics approval number EA1/277/15) and informed written consent was obtained from all participants. Individual participant data were de-identified before analysis. Participant identities remain exclusively known to the study doctors and their staff. For this study, cohorts of subjects with TB infection and subjects with culture-confirmed TB disease were established. Study participants were prospectively recruited from 2017 to 2019 and followed-up for at least 12 months.
The lack of response to ESAT-6/CFP-10 stimulation in the TB-Flow Assay largely corresponded to the IGRA results for those subjects. Among nonresponders, 14 out of 15 subjects had negative (TB disease n=5) or borderline positive IGRA results close to the cut-off point of positivity of 0. 35 IU•mL -1 (TB disease n=2, TB infection n=7). Only one of the subjects had a strong positive IGRA result at study enrolment (TB infection n=1) (data not shown). A total of 47 patients with TB disease and 34 subjects with TB infection were included into cohorts for establishment and performance validation of the TB-Flow Assay (figure  1 , and supplementary tables E1 and E2). None of the subjects received systemic immunosuppressive or antineoplastic therapy. All subjects included in the TB disease cohort had started anti-TB treatment at the time of study enrolment or at latest 3 weeks after initial blood collection.
0 (7. 0-12. 0). In order to assess the influence of anti-TB therapy on our test system, we analysed 48 patients with culture-confirmed TB disease that had been under therapy for >5 days at the time of sample collection. The patients were stratified into the following groups according to days of completed therapy: 6-30 days (n=30), 31-90 days (n=8) and >90 days (n=10). The median (IQR) TB-Flow Score in these groups was 8. 5 (5. 8-11. 0) for 6-30 days, 6. 5 (2. 3-8. 8) for 31-91 days and 3. 0 (2. 0-5. 8) for >90 days (figure  5c ). The median TB-Flow Score clearly declined with progression of anti-TB therapy. This is in accordance with data from other groups who demonstrated a decline of TB antigen-specific T-cells expressing CD38, HLA-DR and Ki-67 under TB therapy  [8, 10]. One prerequisite for inclusion of subjects in the TB disease cohort was confirmation by TB culture.
Acknowledgements: The authors would like to thank  Nikolaj Menner  and the medical staff at the  Dept of Infectious Diseases and Pulmonary Medicine at Charité -Universitätsmedizin Berlin (Berlin, Germany)  and the study nurses  Yvonne Baltrusch  and  Patricia Pflugmacher  at the  Dept of Pneumology ,  Lungenklinik Heckeshorn , https://doi. org/10. 1183/13993003. 01780-202112 EUROPEAN RESPIRATORY JOURNAL ORIGINAL  RESEARCH ARTICLE | A. MANTEI ET AL. Helios Klinikum Emil von Behring (Berlin, Germany)  for sample collection as well as identification and retrieval of relevant patient information. The authors would also like to thank  Anna Brooks-Kasteel  ( Dept of Immunology, Labor Berlin -Charité Vivantes GmbH, Berlin, Germany ) for collecting and compiling patient data. Charlotte Banfield (Berlin, Germany)  provided editorial assistance during preparation of the manuscript.
Natural polymorphisms in the helicase and RNase III domain identified from Dcr2 haplotypes of Asian, African, and American Ae. aegypti were also assessed and had comparable silencing and antiviral activity. Importantly, functionally relevant amino acids were observed to be conserved throughout mosquito populations and mapped onto a Aaeg Dcr2 structure predicted by AlphaFold. Our data show a vital role for both the helicase and RNase III domains in Aaeg Dcr2 activity wherein: 1) loss of both domain activities strongly affected vsiRNA production and antiviral activity, and 2) loss of helicase function showed that RNase III activity and cleavage of viral dsRNA alone was insufficient to inhibit SFV replication. This demonstrates that the complete exo-siRNA pathway is necessary for antiviral activity against SFV.
Taking these conserved amino acids, mutations were introduced to Aaeg Dcr2 by mutagenesis cloning of a previously developed expression plasmid, pPUb-myc-Dcr2, encoding a myctagged wild-type (WT) Dcr2 (GenBank ID: AAW48725) under the control of a polyubiquitin (PUb) promoter  [46]  to assess loss of function  (Fig 1B, top panel). Mutations individually introduced into the helicase domain were K39N in Motif I, Y232G in Motif IV, and G488R in Motif VI. For the RNase III domains, an expression plasmid with mutations D1198A and E1341A in the RNase IIIA, and D1444A, E1548A in the RNase IIIB domain were collectively introduced and called mutant RNase III (mtR3), with mutations to alanine expected to inactivate RNase III activity. Sorting Intolerant From Tolerant (SIFT) algorithm  [49]  prediction scores suggested that the individual mutations would affect Dcr2 function (S1 Table ).
Naturally occurring Dcr2 polymorphisms in field-derived Ae. aegypti mosquitoes To determine the degree of conservation of the helicase and RNase III domains, Dcr2 cDNA from adult female Ae. aegypti originating from Cameroon (Ben), French Guiana (Cay), Guadeloupe (Guad), Cambodia (KC and Rat), and Gabon (Lope) were sequenced. Thirteen haplotype sequences were identified (S2 Table ) and examined further for single nucleotide polymorphisms (SNPs) by comparing them to our WT Dcr2 reference sequence (GenBank ID: AY713296) that was previously cloned to obtain pPUb-myc-Dcr2  [46]. SNP analysis showed that the majority of the polymorphisms were silent transition changes, but it was observed that all field-derived mosquito Dcr2 had a C variant nucleotide at position 1684 (S3 Table ). In addition, SNPs were identified spanning the entire length of Dcr2 with a number resulting in amino acid substitutions (Fig 2A ).
The putative structure of Ae. aegypti Dcr2 The structure of Aaeg Dcr2 was predicted, in order to locate the conserved amino acids important for Dcr2 activity ( This indicates a confident prediction, according to guidelines set out on EMBL's AlphaFold Protein Structure Database  [50] , available at https://alphafold. ebi. ac. uk. By examining the structure and assigning domain predictions (based on GenBank ID: AAW48725 annotations and InterProScan in Geneious Prime), it can be seen that the putative structure contains two main globular modules: a "foot" module comprising of the predicted helicase domain (yellow) and a "body" domain comprising of the two forecasted RNase IIIA (blue) and IIIB (purple) domains, and the PAZ (violet) domain protruding at the far end. The two domains are bridged by a predicted domain of unknown function (DUF; green).