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1. Molecular Characterization of Monocyte Subsets Reveals Specific and Distinctive Molecular Signatures Associated With Cardiovascular Disease in Rheumatoid Arthritis

Author

Patricia Ruiz-Limon, Rafaela Ortega-Castro, Nuria Barbarroja, Carlos Perez-Sanchez, Christophe Jamin, Alejandra Maria Patiño-Trives, Maria Luque-Tevar, Alejandro Ibáñez-Costa, Laura Perez-Sanchez, Iván Arias de la Rosa, MaCarmen Abalos-Aguilera, Yolanda Jimenez-Gomez, Jerusalem Calvo-Gutierrez, Pilar Font, Alejandro Escudero-Contreras, Marta E. Alarcon-Riquelme, Eduardo Collantes-Estevez, Chary López-Pedrera, the PRECISESADS Clinical Consortium and Flow Cytometry Study Group, C Marañón, L Le Lann, N Varela, B Muchmore, A Dufour, Alvarez, C Carlo Montserrat Chizzolini, E, NB De Langhe, CL-P, V Gerl, A De Groof, J Ducreux, E Trombetta, T Li, D Alvarez-Errico, S Rao, JO Pers, L Beretta, R AguilarQuesada, MA Aguirre-Zamorano, JL Callejas Rubio, MC Castro-Villegas, R Cervera, C Chizzolini, E Collantes, D Cornec, E De Langhe, V Devauchelle-Pensec, AE-C, G Espinosa, MC Fernández Roldán, T Gomes Anjos, F Hiepe, I Jiménez Moleón, S Jousse-Joulin, B Lauwerys, A López-Berrio, R Lories, J Marovac, PL Meroni, B Miranda, H Navarro-Linares, R Ortega-Castro, N Ortego, E Ramón Garrido, E Raya, R Ríos Fernández, I Rodríguez-Pintó, and A Saraux

Subjects
rheumatoid arthritis, cardiovascular disease, monocyte subsets, microRNAs, gene profile, Immunologic diseases. Allergy, RC581-607
Abstract

Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA.Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed.Results: CD14++CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro, RA serum promoted differentiation of CD14+CD16− to CD14++CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells.Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.

Published
2019
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2. Cohort Enrichment Strategies for Progressive Interstitial Lung Disease in Systemic Sclerosis From European Scleroderma Trials and Research

Author

Hoffmann-Vold, A.-M. Brunborg, C. Airò, P. Ananyeva, L.P. Czirják, L. Guiducci, S. Hachulla, E. Li, M. Mihai, C. Riemekasten, G. Sfikakis, P.P. Valentini, G. Kowal-Bielecka, O. Allanore, Y. Distler, O. Vacca, A. Giollo, A. Balbir-Gurman, A. Gheorghiu, A.M. Marcoccia, A. Herrick, A. Radic, M. Stamenkovic, B. Anic, B. Granel, B. Ribi, C. Selmi, C.F. Carlos de la Puente, M. de Souza Müller, C. Denton, C. Kayser, C. Tanaseanu, C.-M. Majewski, D. Rimar, D. Krasowska, D. Veale, D. Walker, U. Kerzberg, E. Rezus, E. Zanatta, E. Siegert, E. De Langhe, E. Oksel, F. Ingegnoli, F. Cantatore, F.P. Szücs, G. Cuomo, G. Seskute, G. Litinsky, V. Castellví, I. Morovic-Vergles, J. Sibilia, J. Henes, J. Solanki, K. Perdan-Pirkmajer, K. Herrmann, K. Saketkoo, L.A. Stamp, L. Mouthon, L. Salvador, M.J. Pozzi, M.R. Üprus, M. Vanthuyne, M. Engelhart, M. Köhm, M. Iudici, M. Inanc, M. Fathi, N. Pamuk, N. García de la Peña Lefebv, P. Carreira, P.E. Bancel, D.F. Moroncini, L. Montecucco, C. Ancuta, C. Sunderkötter, C. Müller-Ladner, U. Rosato, E. Kucharz, E.J. Iannone, F. Del Galdo, F. Poormoghim, H. Kötter, I. Distler, J. Cutolo, M. Tikly, M. Damjanov, N. Hunzelmann, N. Vlachoyiannopoulos, P. Hasler, P. Sarzi Puttini, P. Wiland, P. Becvar, R. Yavuz, S. Zdrojewski, Z. Pellerito, R. Foti, R. Ionescu, R.M. Adler, S. Kahl, S. Moiseev, S. Stebbings, S. Rednic, S. Negrini, S. Heitmann, S. Ullman, S. Agachi, S. Martin, T. Schmeiser, T. Riccieri, V. Smith, V. Bernardino, V. Ortiz-Santamaria, V. Hsu, V.M. Abdel Atty Mohamed, W.A. EUSTAR collaborators and Hoffmann-Vold, A.-M. Brunborg, C. Airò, P. Ananyeva, L.P. Czirják, L. Guiducci, S. Hachulla, E. Li, M. Mihai, C. Riemekasten, G. Sfikakis, P.P. Valentini, G. Kowal-Bielecka, O. Allanore, Y. Distler, O. Vacca, A. Giollo, A. Balbir-Gurman, A. Gheorghiu, A.M. Marcoccia, A. Herrick, A. Radic, M. Stamenkovic, B. Anic, B. Granel, B. Ribi, C. Selmi, C.F. Carlos de la Puente, M. de Souza Müller, C. Denton, C. Kayser, C. Tanaseanu, C.-M. Majewski, D. Rimar, D. Krasowska, D. Veale, D. Walker, U. Kerzberg, E. Rezus, E. Zanatta, E. Siegert, E. De Langhe, E. Oksel, F. Ingegnoli, F. Cantatore, F.P. Szücs, G. Cuomo, G. Seskute, G. Litinsky, V. Castellví, I. Morovic-Vergles, J. Sibilia, J. Henes, J. Solanki, K. Perdan-Pirkmajer, K. Herrmann, K. Saketkoo, L.A. Stamp, L. Mouthon, L. Salvador, M.J. Pozzi, M.R. Üprus, M. Vanthuyne, M. Engelhart, M. Köhm, M. Iudici, M. Inanc, M. Fathi, N. Pamuk, N. García de la Peña Lefebv, P. Carreira, P.E. Bancel, D.F. Moroncini, L. Montecucco, C. Ancuta, C. Sunderkötter, C. Müller-Ladner, U. Rosato, E. Kucharz, E.J. Iannone, F. Del Galdo, F. Poormoghim, H. Kötter, I. Distler, J. Cutolo, M. Tikly, M. Damjanov, N. Hunzelmann, N. Vlachoyiannopoulos, P. Hasler, P. Sarzi Puttini, P. Wiland, P. Becvar, R. Yavuz, S. Zdrojewski, Z. Pellerito, R. Foti, R. Ionescu, R.M. Adler, S. Kahl, S. Moiseev, S. Stebbings, S. Rednic, S. Negrini, S. Heitmann, S. Ullman, S. Agachi, S. Martin, T. Schmeiser, T. Riccieri, V. Smith, V. Bernardino, V. Ortiz-Santamaria, V. Hsu, V.M. Abdel Atty Mohamed, W.A. EUSTAR collaborators

Abstract

Background: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort. Research Question: Do enrichment strategies for progressive ILD impact efficacy, representativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database? Study Design and Methods: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline ≥10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. Results: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 ± 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was –0.1%, in patients who fulfilled criteria from focuSSced was –3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression. Interpretation: The application of enrichment criteria from previous

Published
2023

5. E-book: Reumatologie – Uitgave 2023

Author

P. Carron, A.-S. De Craemer, F. Van den Bosch, J.-B. Vulsteke, X. Bossuyt, E. De Langhe, N. Willers, P. Berteloot, I. Wittevronghel, G. Jacomen, V. Schelfhout, K. Vanwambeke, S. Desmedt, V. Desmedt, T. Billiet, C. George, W. Meersseman, F. D'Heygere, E. De Bondt, A. Betrains, S. Vanderschueren, J. Hanssens, B. Werbrouck, W. Terryn, B. Deconinck, A. Nollet, K. Cokelaere, K. Timmermans, M. Nachtergaele, C. Vanfraechem, A.-M. Bogaert, W. Hublou, M. Gijsen, P. Declercq, I. Spriet, L. Van der Linden, and C. Quintens

Subjects
General Medicine
Published
2023
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6. EJ-antisynthetase syndrome presenting as severe acute respiratory distress syndrome

Author

Arne Neyrinck, Alexander Wilmer, D. Van Raemdonck, Rita Vos, Laurens J. Ceulemans, Marijke Peetermans, Greet Hermans, Philippe Meersseman, Joost Wauters, E. De Langhe, and M Ralki

Subjects
Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, 2019-20 coronavirus outbreak, medicine.medical_specialty, Myositis, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Antisynthetase syndrome, Acute respiratory distress, medicine.disease, Infectious Diseases, Internal medicine, medicine, Humans, business
Published
2021
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9. Pneumocystis jirovecii pneumonia in patients treated for systemic autoimmune disorders: a retrospective analysis of patient characteristics and outcome

Author

Liesbet Henckaerts, M Verhaert, Daniel Engelbert Blockmans, E. De Langhe, Faculty of Medicine and Pharmacy, Clinical sciences, and Medical Oncology

Subjects
Adult, Glucocorticoids/therapeutic use, Male, medicine.medical_specialty, Immunology, Population, Human immunodeficiency virus (HIV), Patient characteristics, medicine.disease_cause, 03 medical and health sciences, Autoimmune Diseases/complications, 0302 clinical medicine, Rheumatology, Internal medicine, parasitic diseases, Retrospective analysis, Humans, Immunology and Allergy, Pneumocystis jirovecii, Medicine, In patient, 030212 general & internal medicine, education, Aged, Retrospective Studies, Immunocompromised host, 030203 arthritis & rheumatology, education.field_of_study, biology, business.industry, Pneumocystis jirovecii Pneumonia, virus diseases, General Medicine, Middle Aged, biology.organism_classification, Pneumonia, Pneumocystis/complications, Pneumocystis carinii/isolation & purification, Immunosuppressive Agents/therapeutic use, Female, aged, 80 and over, business
Abstract

Objectives: Pneumocystis jirovecii is an opportunistic fungus. Pneumocystis jirovecii pneumonia (PJP) is well known in the human immunodeficiency virus (HIV)-infected population, but in non-HIV-related immunosuppressed patients, risk factors are largely unknown. We studied the characteristics and outcome of patients treated for systemic autoimmune disorders infected with P. jirovecii, aiming to clarify risk stratification to guide prophylaxis. Method: Clinical charts collected between 2010 and 2016 at the University Hospital of Leuven (Belgium) were reviewed. Information on type of systemic disorder, organ involvement, immunosuppressant use, and comorbidity was collected, and laboratory results were consulted. Results: In total, 39 cases of non-HIV PJP were retrieved, 24 of whom had pre-existing pulmonary disease. All were on immunosuppressant medication at the time of infection, the majority (36/39) taking glucocorticoids, with a median dose of 16 mg methylprednisolone over the past 3 months. Of the 39 cases, 21 were admitted to the intensive care unit and mortality reached 35%. Age and pulmonary disease correlated positively and methotrexate use negatively with mortality. When applying current prophylactic strategies to our cohort, 50% of infections could theoretically have been prevented. Conclusion: PJP is a rare but relevant clinical problem when caring for immunosuppressed patients with autoimmune systemic disorders. Pulmonary disease and age are risk factors for acquiring the infection and carry a worse prognosis. More studies are needed to further define prophylactic criteria.

Published
2020
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10. OP0094 IDENTIFICATION OF NEW AUTOANTIGENS IN PATIENTS WITH SYSTEMIC SCLEROSIS THROUGH IMMUNOPRECIPITATION COMBINED WITH LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

Author

J. B. Vulsteke, D. Blockmans, P. De Haes, S. Vanderschueren, P. Verschueren, K. G. Claeys, W. Wuyts, J. L. Lenaerts, E. De Langhe, and X. Bossuyt

Subjects
Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract

BackgroundIn up to 20% of patients with systemic sclerosis (SSc) none of the established SSc-specific autoantibodies are present [1]. Notwithstanding, in many of these patients high-titer autoantibodies can be detected on the HEp-2 indirect immunofluorescence assay (HEp-2 IIFA) which suggests the presence of an autoantibody to an intracellular protein expressed by the HEp-2 cell line. Immunoprecipitation of unlabeled cell extract followed by gel-free liquid chromatography tandem mass-spectrometry analysis has the potential to identify new autoantigens in an unbiased manner.ObjectivesTo identify new autoantigens through immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP + LC-MS/MS) in HEp-2 IIFA-positive patients with SSc in whom none of the established SSc-specific autoantibody specificities are present.MethodsForty-nine patients from the University Hospitals Leuven that fulfilled the EULAR-ACR 2013 classification criteria for systemic sclerosis or LeRoy and Medsger’s criteria for early systemic sclerosis and who were negative on the EliA CTD Screen (Thermo Fisher Scientific, United States), which includes centromere protein B, topoisomerase I, RNA polymerase III, fibrillarin, PM-Scl and U1 ribonucleoprotein, were identified. Immunoprecipitation was performed by incubation of sera of these patients (1/30 in 300 µl Tris-buffered saline) with Pierce A/G magnetic beads, subsequent cross-linking with bissulfosuccinimidyl suberate (BS3) followed by incubation with nuclear extract of HeLa cells (100-150 µg) overnight at 4°C. The eluted protein was analyzed through liquid chromatography with tandem mass spectrometry. Mass spectrometry data were matched against the Uniprot Homo Sapiens database with the Mascot search engine. Candidate autoantigens were confirmed through immunoprecipitation followed by western blot of the eluate with target-specific polyclonal rabbit antibodies or western blot of recombinant protein incubated with sera of the index patients.ResultsWe identified multiple new autoantigens, including the THO complex subunit 1 (THOC1) and other subunits of the THO complex in 3 patients, nuclear valosin-containing protein like-2 (NVL) in 2 patients, nucleolar and coiled-body phosphoprotein 1 (NOLC1) and multiple interacting proteins in 1 patient, probable 28S rRNA (cytosine(4447)-C(5))-methyltransferase (NOP2) in 1 patient, telomeric repeat-binding factor 2 (TERF2) and TERF2-interacting protein (TERF2IP) in 1 patient and regulator of chromosome condensation 1 (RCC1) in 1 patient. The new targets were confirmed through immunoprecipitation-western blot or western blot of recombinant protein incubated with sera (Figure 1). Furthermore, in 10 patients known SSc-associated autoantigens were strongly immunoprecipitated including multiple Th/To subunits in 5 patients, RuvBL1/2 in 2 patients, multiple PM-Scl subunits in 2 patients (who both were negative on the EliA CTD Screen), and fibrillarin in 1 patient (who was also negative on the EliA CTD .).Figure 1.Immunoprecipitation-western blot with target-specific rabbit polyclonal antibody (1/500-2000 dilution), numbers corresponding to order of description of patients, HC healthy control. NE nuclear extract. RP recombinant protein WB-RP western blot of recombinant protein incubated with patient’s sera.ConclusionMultiple new autoantigens were identified and confirmed in patients with SSc without previously identified autoantibody specificity. Further evaluation of reactivity against the newly identified autoantigens in patients with SSc with known autoantibody specificities and other cohorts is required. IP + LC-MS/MS can identify new and established autoantigens in patients with SSc.References[1]Meier FMP, Frommer KW, Dinser R, et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 2012;71:1355–60. doi:10.1136/annrheumdis-2011-200742Disclosure of InterestsJean-Baptiste Vulsteke: None declared, Daniel Blockmans: None declared, Petra De Haes: None declared, Steven Vanderschueren: None declared, Patrick Verschueren: None declared, Kristl G Claeys: None declared, Wim Wuyts Grant/research support from: Boehringer-Ingelheim, Galapagos, Roche, Jan Leo Lenaerts: None declared, Ellen De Langhe: None declared, Xavier Bossuyt Consultant of: Inova Diagnostics, Thermo Fisher Scientific.

Published
2022
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11. Evolutie van detectiemethodes voor autoantilichamen bij systemische auto-immune reumatische aandoeningen

Author

E. De Langhe, Xavier Bossuyt, and Jean-Baptiste Vulsteke

Subjects
General Medicine
Abstract

Detectie van autoantilichamen is relevant voor de diagnose, prognose, classificatie en stratificatie van systemische auto-immune reumatische aandoeningen (SARD). De belangrijke detectiemethodes zijn indirecte immunofluorescentie bij HEp-2-cellen (HEp-2-IIF) en solid-phase assays (SPA). Bij HEp-2-IIF kunnen een fluorescentie-intensiteit en een patroon gerapporteerd worden. De laatste jaren wordt volop ingezet op automatisatie en standaardisatie van HEp-2-IIF. Meer en meer worden ook solid-phase assays gebruikt, waarbij recombinante, synthetische of opgezuiverde antigenen op een vast substraat worden geplaatst. Daarbij is er een evolutie naar het gebruiken van multiplextesten, waarbij meerdere autoantilichamen in één test opgespoord kunnen worden. In dit artikel worden de eigenschappen van die detectiemethodes en de implicaties voor de klinische praktijk besproken.

Published
2021
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12. Myocardial T1 mapping and extracellular volume quantification as novel biomarkers in risk stratification of patients with systemic sclerosis

Author

Rolf Symons, V. Bordonaro, Jan Bogaert, Tom Dresselaers, D. Bivort, and E. De Langhe

Subjects
Male, medicine.medical_specialty, Heart Diseases, Risk Assessment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Extracellular fluid, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Multiparametric Magnetic Resonance Imaging, skin and connective tissue diseases, Scleroderma, Systemic, integumentary system, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Heart, General Medicine, Disease monitoring, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, Heart failure, Risk stratification, Cardiology, Biomarker (medicine), Myocardial fibrosis, Female, business, Biomarkers
Abstract

To study the prognostic value of myocardial native T1 and extracellular volume (ECV), measured by cardiovascular magnetic resonance (CMR), in patients with systemic sclerosis (SSc).Thirty-three SSc patients (16/33 male, 48.5%) were studied using multiparametric CMR including native T1 mapping with ECV calculation, T2 mapping, and late gadolinium enhancement (LGE). Patients were followed-up for cardiac death, haemodynamically significant arrhythmia, or heart failure. Results were compared with 33 age- and gender-matched healthy controls.When compared with controls, SSc patients had higher myocardial native T1 (1,058.9±71 versus 989.4±21.4 ms, p0.001), higher T2 (54.9±5.7 versus 50±2.5 ms, p0.001), and ECV values (27.9±5.4% versus 24.8±2%, p0.004). LGE was present in eight patients (24%), two subendocardial, five midwall, and four subepicardial. LGE, native T1, and ECV were significantly associated with adverse events during follow-up in multivariate Cox regression analysis. Kaplan-Meier analysis demonstrated significant divergence of the survival curves based on the presence of elevated native T1 (≥1,069 ms) or ECV (≥31.4%) values.Cardiac involvement is frequent in SSc. Both native T1 mapping and ECV represent novel non-invasive markers of myocardial fibrosis and could be used in the risk stratification of patients with SSc. CMR mapping may provide a novel biomarker for disease monitoring and study of therapies aiming to reduce myocardial fibrosis in SSc.

Published
2020

13. AB0723 Anti-TIF1-beta autoantibodies in a patient with cancer-associated dermatomyositis

Author

J. B. Vulsteke, P. De Haes, M. Satoh, E. De Langhe, and X. Bossuyt

Subjects
Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract

BackgroundAnti-transcriptional intermediary factor 1-gamma (TIF1-gamma) autoantibodies are strongly linked to cancer-associated dermatomyositis (DM). In addition to anti-TIF1-gamma autoantibodies, autoantibodies to TIF1-alpha and TIF1-beta have been described, often coexisting with TIF1-gamma or other known autoantibodies [1,2]. Thus far, anti-TIF1-beta autoantibodies without other known autoantibodies have been identified in only 3 patients with dermatomyositis, of which none had cancer [1,2].ObjectivesTo report on a patient with cancer-associated dermatomyositis and isolated anti-TIF1-beta autoantibodies.MethodsSerum of a patient with cancer-associated dermatomyositis without known autoantibody specificity was evaluated by immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP + LC-MS/MS). Mass spectrometry data were matched against the Uniprot Homo Sapiens database with the Mascot search engine using Proteome Discoverer. Additional immunoprecipitation of radiolabeled cell extract followed by autoradiography were performed. Clinical and laboratory data were retrieved from the electronic health record.ResultsTIF1-beta was identified in the immunoprecipitate of the serum of the patient by IP + LC-MS/MS, but not TIF1-gamma or TIF1-alpha. These results were confirmed by immunoprecipitation of radiolabeled cell extract (Figure 1A). The HEp-2 indirect immunofluorescence assay showed a nuclear fine speckled pattern (AC-4, maximum titre > 1/1280, Figure 1B), which corresponds to the subcellular localization of TIF1-beta [3]. The patient, a 64-year old male, presented with dermatomyositis with classical cutaneous and muscular involvement (max. serum creatine kinase level 370 U/l). A renal cell carcinoma was found during the diagnostic work-up for which a partial nephrectomy was performed. There was a good response of both cutaneous and muscular disease activity to treatment with hydroxychloroquine and methylprednisolone.Figure 1.A Immunoprecipitation with 35S-methionine labeled K562 cells with subsequent radiography. C Positive control with anti-TIF1-beta and anti-U1-RNP autoantibodies, 1 anti-TIF1-beta-positive patient (patient here described), 2 negative patient, 3 anti-TIF1-gamma/alpha-positive patient B Nuclear fine speckled pattern on HEp-2 indirect immunofluorescence assay, 40X magnificationConclusionIsolated anti-TIF1-beta autoantibodies should be considered in patients with dermatomyositis without known myositis-specific autoantibodies and can be associated with cancer.References[1]Fujimoto M, Hamaguchi Y, Kaji K, et al. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 2012;64:513–22. doi:10.1002/art.33403[2]Satoh M, Chan JYF, Ross SJ, et al. Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis. Arthritis Res Ther 2012;14:1–8. doi:10.1186/AR3802/FIGURES/2[3]Thul PJ, Åkesson L, Wiking M, et al. A subcellular map of the human proteome. Science 2017;356. doi:10.1126/science.aal3321Disclosure of InterestsJean-Baptiste Vulsteke: None declared, Petra De Haes: None declared, Minoru Satoh: None declared, Ellen De Langhe: None declared, Xavier Bossuyt Consultant of: Inova Diagnostics, Thermo Fisher Scientific

Published
2022
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14. The morphological diversity of plantain in the Democratic Republic of Congo

Author

D. B. Dhed'a, Guy Blomme, D. Karamura, J.G. Adheka, E. De Langhe, and Rony Swennen

Subjects
0106 biological sciences, 010404 medicinal & biomolecular chemistry, Horticulture, Plant morphology, Cultivar, Biology, 01 natural sciences, 010606 plant biology & botany, 0104 chemical sciences
Abstract

This work focused on the morphological characterization of plantain cultivars collected in the period 2005-2014 in 280 villages across 9 provinces of the Democratic Republic of Congo. These cultivars were established in two field collections at the University of Kisangani.Existing descriptors were adapted to better differentiate their variation to address better the taxonomic handicap and the synonymy handicap to improve future research on plantains.Most of the collected cultivars were French plantains (64 out of 98), followed by False Horn (23) and Horn (10) plantains. The bunch type was the main striking difference which allows the quick separation of plantain cultivars into three main types. Other striking differences within plantain were the size of the pseudostem (giant, medium-sized and small-sized) and the bunch orientation (which was generally pendulous or sub-horizontal, and rarely horizontal and erect). These three descriptors were considered as main descriptors. Other descriptors (pseudostem colour, immature fruit peel colour, fruit shape, fruit apex, fruit position, number of hands, fruit size, number of fingers per hand and flower relicts at the fruit apex) allowed the differentiation of one cultivar from another within the same main group of bunch type, pseudostem size or bunch orientation. These descriptors are considered as secondary descriptors. Rare descriptors allowed to differentiate one cultivar from all the others in the subgroup. This approach makes the cultivar description logical and faster because it moves from general to particular characteristics, and it offers a platform for reflections on the Pan-African scale of plantain diversity. Highlights • Adapted descriptors according to the degree of their differentiating performance is feasible in plantain characterization. • The bunch type, the plant size and the bunch orientation allow a quick separation between plantain cultivars. • French plantains are the most numerous in the DR Congo. • The most recorded colour (of the pseudostem of fruit immature peel) is the green.

Published
2018
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15. Banana diversity in the Oriental provinces, north-eastern Democratic Republic of Congo

Author

D. Karamura, R. Swennen, D. B. Dhed'a, C Tamaru, E. de Langhe, C Sivirahauma, J Adheka, J Komoy, and Guy Blomme

Subjects
0106 biological sciences, Germplasm, Agroforestry, business.industry, media_common.quotation_subject, 04 agricultural and veterinary sciences, Horticulture, 01 natural sciences, Democracy, Geography, Agriculture, Plant morphology, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Crop quality, Cultivar, business, 010606 plant biology & botany, Diversity (politics), media_common
Published
2018
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16. FRI0575 BIOMARKER ANALYSIS FROM THE RISE-SSC STUDY OF RIOCIGUAT IN EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (DCSSC)

Author

T. Ishii, Peter Sandner, E. De Langhe, Gabriella Szücs, Valeria Riccieri, Masataka Kuwana, Osamu Ishikawa, Marie-Elise Truchetet, M. Matucci-Cerinic, Sindhu R. Johnson, E. Hachlla, Dinesh Khanna, R. Bečvář, Kaisa Laapas, O. Distler, Frank Kramer, Christopher P. Denton, Melanie Wosnitza, Toshiya Atsumi, Wendy Stevens, Elena Schiopu, Vanessa Smith, Virginia D. Steen, Yannick Allanore, M. Ghadessi, Richard M. Silver, L. Czirják, J. Höfler, Janet E. Pope, and Chiara Stagnaro

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, Skin score, medicine.medical_specialty, business.industry, Steering committee, Mrna expression, Immunology, Target engagement, Riociguat, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Chemokine Ligand 4, Rheumatology, Family medicine, Immunology and Allergy, Medicine, Disease biomarker, Platelet endothelial cell adhesion molecule-1, business, medicine.drug
Abstract

Background:RISE-SSc (NCT02283762) was a multicenter, double-blind, Phase IIb study of riociguat in early dcSSc. Primary endpoint was change in mRSS from baseline to Wk 52.Objectives:Exploratory, descriptive analyses of riociguat target engagement and effects on disease biomarkers in RISE-SSc and their relationship with effects on the primary endpoint. All biomarker p-values are for information only.Methods:Pts with dcSSc (duration ≤18 mo; modified Rodnan skin score [mRSS] 10–22 units) were randomized to riociguat 0.5−2.5 mg tid (n=60) or placebo (n=61). Biomarkers of target engagement (cGMP), inflammation and/or vascular/endothelial function (e.g. high-sensitivity C-reactive protein [hsCRP], soluble platelet endothelial cell adhesion molecule 1 [sPECAM-1], soluble E-selectin, chemokine ligand 4 [CXCL-4]), and fibrosis (e.g. alpha-smooth muscle cell actin [alphaSMA], pro-collagen mRNA expression) were measured in plasma, serum, and skin biopsies at baseline and Wk 14.Results:Mean±SD change from baseline in mRSS was –2.09±5.66 (n=57) with riociguat and –0.77±8.24 (n=52) with placebo (p=0.08). From baseline to Wk 14, plasma cGMP rose by mean (SD) 94% (78%) (n=52) with riociguat and 10% (39%) (n=52) with placebo (nominal pConclusion:Primary study endpoint (change in mRSS) was not met. Plasma cGMP rose with riociguat, confirming engagement with the NO-sGC-cGMP pathway. Serum sPECAM-1 (marker of endothelial activation) and CXCL-4 (marker of progressive SSc) fell with riociguat; hsCRP and E-selectin did not. Some serum and skin biomarkers of higher disease activity at baseline were associated with a greater effect of riociguat on skin fibrosis.Acknowledgments:RISE-SSc was jointly funded by Bayer AG and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Disclosure of Interests:Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Frank Kramer Employee of: Bayer AG, Josef Höfler Employee of: Josef Höfler is an employee of Staburo GmbH, Munich, Germany, contracted by Bayer AG to perform the biomarker analyses, Mercedeh Ghadessi Employee of: Bayer AG, Peter Sandner Employee of: Bayer AG, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Radim Bečvář Consultant of: Actelion, Roche, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Ellen De Langhe Consultant of: member of advisory board for Boehringer, Eric Hachlla: None declared, Tomonori Ishii: None declared, Osamu Ishikawa: None declared, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Kaisa Laapas Employee of: Partly in-sourced to Bayer, Valeria Riccieri: None declared, Elena Schiopu: None declared, Richard Silver: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Chiara Stagnaro: None declared, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Wendy Stevens: None declared, Gabriella Szücs: None declared, Marie-Elise Truchetet: None declared, Melanie Wosnitza Employee of: Bayer AG, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB

Published
2020
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18. OP0321 DELINEATING THE IMMUNOGENIC DOMAINS OF MDA5 USING PATIENT DERIVED AUTOANTIBODIES

Author

Olivier Benveniste, E. Wigren, E. Van Gompel, C. Cerqueira, Susanne Gräslund, I.E. Lundberg, E. De Langhe, Karine Chemin, and B. Horuluoglu

Subjects
Rheumatology, business.industry, Immunology, Autoantibody, Immunology and Allergy, Medicine, MDA5, business, General Biochemistry, Genetics and Molecular Biology
Abstract

Background:The presence of myositis specific anti-melanoma differentiation associated protein 5 (MDA5) autoantibodies is associated with mucocutaneous ulcerations, rapidly progressing interstitial lung disease (RPILD), arthritis and mild muscle involvement in patients. RPILD is the major cause of mortality. At present it is unknown which domain of the MDA5 protein is the main elicitor of an immunogenic response.Objectives:The aim of this study is to delineate the domains in the MDA5 protein that are the target of autoantibodies.Methods:Anti-MDA5 IgG were isolated from MDA5(+) patient plasma (7 UPMC, 1 KI and 1 KULeuven) by affinity chromatography using an in-house affinity column as described earlier in Ossipova et al, 2014(1). 8 constructs covering different regions of the MDA5 protein were recombinantly produced in E.coli (Uniprot ID Q9BYX4, Figure 1). An in-house ELISA was developed to identify the domains with the main epitope(s) by measuring the reactivity of the plasma samples and purified autoantibodies against these MDA5 protein constructs, similar to what was reported by Fernandes-Cerqueira et al, 2018(2). The biotinylated MDA5 proteins were immobilized on streptavidin coated plates and subsequently incubated with primary antibodies (purified autoantibodies(2) or original plasma) and a HRP-conjugated secondary antibody. The ELISA was developed by the addition of TMB substrate and the optical density (OD) was measured at 450 nm.Figure 1.Graphical presentation of the constructs representing different (combinations of) domains of the MDA5 protein.Results:The preliminary data suggest the main reactivity of the plasma samples and the corresponding purified autoantibodies is directed towards the helicase domains and that there is variability between the patients in the reactivity towards domains located at the end of the protein.Conclusion:The study aims to resolve the main immunogenic domain of the MDA5 protein, which will lead to more insight in the disease mechanisms. The preliminary results suggest this domain is in the center of the MDA5 protein, but further experiments are necessary. We will use this set up to study differences in reactivity between patients (from different cohorts) and assess if differences in antibody reactivity could be linked to clinical features such as RPILD. Such correlations might be beneficial to predict the disease progression and to apply personal treatment approaches.References:[1]Ossipova E, Cerqueira CF, Reed E, Kharlamova N, Israelsson L, et al. Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint. Arthritis Res Ther. 2014;16(4):R167.[2]Fernandes-Cerqueira C, Renard N, Notarnicola A, Wigren E, Gräslund S, et al. Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies. Scientific reports. 2018;8(1):17958.Disclosure of Interests:Eveline Van Gompel: None declared, Catia Cerqueira: None declared, Edvard Wigren: None declared, Susanne Gräslund: None declared, Karine Chemin: None declared, Begum Horuluoglu: None declared, Ellen De Langhe: None declared, Olivier Benveniste: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and AstraZeneca.

Published
2021
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19. P110/O18 Epigenetic changes by inhibition of DOT1L affect wnt signaling, proliferation and cell cycle in dermal fibroblasts, with no overall effect on collagen deposition in models of fibrosis

Author

J Cremer, E. De Langhe, Rik Lories, and Nathalie Berghen

Subjects
biology, business.industry, Wnt signaling pathway, Cell cycle, medicine.disease, Cell biology, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Fibrosis, In vivo, medicine, biology.protein, Propidium iodide, ACTA2, business, Fibroblast, Transforming growth factor
Abstract

Career situation of first and presenting author Student for a master or a PhD. Introduction The role of epigenetic factors in the pathophysiology of fibrosis, a hallmark of Systemic Sclerosis, is increasingly explored. DOT1L, the unique H3K79-methyltransferase, methylates histone 3 at the Lysine residue at position 79, thereby regulating gene expression programs. In cartilage and bone, DOT1L has cell-type specific effects on Wnt signaling, a pathway suggested to play an important role in fibrosis. Objectives To study the role of DOT1L in fibrosis. Methods Primary human dermal fibroblasts were treated with DOT1L-inhibitor EPZ-5676 or vehicle and stimulated with TGF-β. Expression of smooth muscle alpha 2 actin (ACTA2) and Wnt target genes was measured by RT-qPCR. Western Blot was done for dimethylated H3K79 and β-catenin. Picrosirius Red staining measured collagen deposition. 5-Bromo-2’-deoxy-uridine (BrdU) labeling for proliferation and flow cytometry with Propidium Iodide for cell cycle analysis was done. Col1a2;Cre-ERT2;DOT1lfl/flmice, injected with tamoxifen to induce a fibroblast-specific DOT1L knockout, were injected subcutaneously with bleomycin or vehicle. Injected skin was analyzed by OH-prolin assay and by histology. Results The DOT1L-inhibitor EPZ-5676 reduced H3K79 dimethylation in all samples. In breast dermal fibroblasts, the induction of ACTA2 with TGF-β was reduced with DOT1L inhibition, while in abdominal dermal fibroblasts this induction was more pronounced. After 48 hours of TGF-β, collagen deposition was higher in DOT1L-inhibited fibroblasts. After 72 hours of TGF-β however, this deposition was comparable with controls. DOT1L inhibition induced canonical Wnt signaling in fibroblasts, with a small increase in active β-catenin and expression of Lymphoid enhancer-binding factor 1 (LEF1). With DOT1L inhibition, more proliferation of fibroblasts, but also proportionally more cells in the G1/G0 phase and less cells in S and M/G2 phase were seen. In vivo, subcutaneous bleomycin increased murine dermal thickness and skin collagen content. No difference was observed between wild type and mice with a fibroblast-specific deletion of DOT1L. Conclusions In an in vitro model of fibrosis, ACTA2 induction in DOT1L-inhibited human dermal fibroblasts was dependent on the fibroblast origin. DOT1L inhibition resulted in an earlier deposition of collagen, without differences in deposition at the end points. Inhibition of DOT1L induced canonical Wnt signaling and proliferation but also led to a higher proportion of cells in the G0/G1 phase. In an in vivo murine model of skin fibrosis, no difference in bleomycin-induced skin thickness and collagen content was found when the DOT1L gene was deleted in fibroblasts. Disclosure of Interest None declared.

Published
2019
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20. THU0367 INCIDENCE AND PREVALENCE OF SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE IN FLANDERS: A 12-YEARS COLLABORATIVE MULTICENTER PROSPECTIVE COHORT STUDY

Author

Els Vandecasteele, Wim A. Wuyts, Amber Vanhaecke, C. Carton, Bernard Lauwerys, Yves Piette, Guy Brusselle, F De Keyser, Vanessa Smith, E. De Langhe, Daniel Engelbert Blockmans, K. Verbeke, and Karin Melsens

Subjects
medicine.medical_specialty, business.industry, Incidence (epidemiology), Immunology, Interstitial lung disease, medicine.disease, University hospital, General Biochemistry, Genetics and Molecular Biology, Pulmonary function testing, Rheumatology, Internal medicine, Cohort, Epidemiology, medicine, Immunology and Allergy, Prospective cohort study, business, Cause of death
Abstract

Background:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the main cause of death in SSc and accounts for up to 30-35% of SSc-mortality (1-2). All SSc cases, irrespective of the extent of the skin disease, should be evaluated for ILD (3). The epidemiology of SSc-ILD in Belgium is unknown. In literature, the prevalence of ILD in SSc varies between 19% and 52%. However, different criteria were used to diagnose ILD (4). In 2008, Goh et al. proposed a flow diagram to diagnose SSc-ILD based on chest high-resolution CT-scan (HRCT) and pulmonary function tests (PFTs). Their categorization into limited or extensive ILD has prognostic value (5).Objectives:To determine the prevalence and incidence rate of SSc-ILD in Flanders.Methods:Up to 12-year follow-up data of consecutive SSc patients were obtained by 2 Flemish expert centres (University Hospitals Ghent and Leuven). Patients fulfilling the LeRoy and/or ACR-EULAR classification criteria were included consecutively in the prospective cohort (6). Patients received HRCT at baseline and on indication thereafter, as well as yearly PFT. All HRCTs were centrally analyzed (Ghent) and patients were categorized according to the Goh criteria as without ILD, with limited ILD (limILD) or with extensive ILD (extILD) (5).Results:Between 2006 and 2018, 797 SSc patients (557 Ghent/240 Leuven; 22% limited SSc (LSSc)/59% limited cutaneous SSc (LcSSc)/19% diffuse cutaneous SSc (DcSSc)) had baseline HRCT and PFT. The baseline characteristics are depicted in the table. The mean age (SD) was 53 +/-15 years and the majority of patients was female (76%).272 SSc patients had ILD at baseline, implicating a baseline prevalence of 34% (272/797). The baseline prevalences were 35% and 55% for the LcSSc and DcSSc subgroups respectively. During a median follow-up of 39 months (IQR: 11-79 months), 44 patients were diagnosed with incidental SSc-ILD, resulting in an incidence rate of 21,0/1000 person-years (PY), 95% CI:15,2-28,1. The incidence rates were 21,7/1000 PY, 95%CI: 14,3-31,6 and 43.9/1000PY, 95%CI: 22.7-76.8 for the LcSSc and DcSSc subgroups respectively.Table.Baseline characteristicsSSc (n=797)LcSSc (n=470)DcSSc (n=149)age (years) °53+/-1554+/-1554+/-14♂/♀ *193(24%)/604(76%)109(23%)/361(77%)58(39%)/91(61%)Disease Duration (months) #for 718: 22 (5-72)for 443: 25 (5-80)for 145: 16 (7-52)LSSc/LcSSc/DcSSc *178(22%)/470(59%)/149(19%)follow-up (months) #39 (11-79)38.5 (9.75-81)44 (17.5-78)Anti-centromere antibodies§252/538 (47%)163/317 (51%)19/108 (18%)Anti-topoisomeraseI antibodies§119/519 (23%)66/297 (22%)45/112 (40%)ILD at baseline, *272 (34%)163 (35%)82 (55%)LimILD, *230 (29%)139 (30%)67 (45%)ExtILD, *42 (5%)24 (5%)15 (10%)New ILD during follow-up, §44/52527/30712/67°: mean +/- standard deviation, *: number of patients (percent), #: median (interquartile range), §= number of patients/total number of patients with available data (%)Conclusion:In an unselected cohort of SSc patients, a third of the patients has ILD at baseline which is in line with previous prevalence reports. Importantly, this is the first study reporting incidence rates of SSc-ILD.References:[1]Steen VD and Medsger TA, Ann Rheum Dis 2007;66:940-4[2]Elhai M et al. Ann Rheum Dis 2017;76:1897-1905[3]Smith V et al. RMD Open 2019;4:e000782. doi:10.1136/rmdopen-2018-000782[4]Bergamasco A et al. Clinical Epidemiology 2019;11:257-73[5]Goh N et al. Am J Respir Crit Care Med 2008;177:1248-54[6]van den Hoogen et al. Arthritis Rheumatol 2013;65:2737-47Disclosure of Interests:Els Vandecasteele Grant/research support from: my institution has received a research grant from the Research Foundation Flanders FWO), Speakers bureau: my institution has received speaker fees from Actelion, Karin Melsens: None declared, Daniel Blockmans Consultant of: yes, Speakers bureau: yes, Charlotte Carton: None declared, Filip De Keyser: None declared, Ellen De Langhe Consultant of: member of advisory board for Boehringer, Bernard Lauwerys: None declared, Yves Piette: None declared, Amber Vanhaecke: None declared, Koen Verbeke: None declared, Wim Wuyts Grant/research support from: my institution has received a grant from Boehringer Ingelheim and Roche, Consultant of: my institution has received payments for consultancy from Boehringer Ingelheim and Roche, Speakers bureau: my institution has received speaker fees from Boehringer Ingelheim and Roche, Guy Brusselle: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Published
2020
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21. OP0249 LONG-TERM EXTENSION RESULTS OF RISE-SSC, A RANDOMIZED TRIAL OF RIOCIGUAT IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (DCSSC)

Author

Yannick Allanore, M. Matucci-Cerinic, E. De Langhe, Masataka Kuwana, Toshiya Atsumi, O. Distler, Wendy Stevens, T. Ishii, Marie-Elise Truchetet, Janet E. Pope, Dinesh Khanna, Virginia D. Steen, Sindhu R. Johnson, L. Czirják, Valeria Riccieri, Vanessa Smith, Chiara Stagnaro, R. Bečvář, Christopher P. Denton, Melanie Wosnitza, Frank Kramer, Gabriella Szücs, Elena Schiopu, Richard M. Silver, E. Hachlla, and Osamu Ishikawa

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, Skin score, medicine.medical_specialty, business.industry, Immunology, Riociguat, Placebo group, General Biochemistry, Genetics and Molecular Biology, PHASE IIB TRIAL, law.invention, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Rheumatology, Randomized controlled trial, Rescue therapy, law, Internal medicine, medicine, Immunology and Allergy, Disease characteristics, In patient, business, medicine.drug
Abstract

Background:RISE-SSc (NCT02283762) was a multicenter Phase IIb trial of riociguat in pts with early (duration ≤18 months) dcSSc and modified Rodnan skin score (mRSS) 10−22 units. Pts were randomized double-blind to placebo or riociguat 0.5–2.5 mg t.i.d. for 52 weeks. The primary endpoint, mRSS change from baseline to Week (Wk) 52, did not reach statistical significance (p=0.08, riociguat vs placebo), but there were favorable trends in some other outcomes.Objectives:To present open-label long-term extension (LTE) results of RISE-SSc.Methods:Pts who completed Wk 52 of double-blind therapy could enter LTE on riociguat. Endpoints included mRSS, adverse events (AEs), and serious AEs (SAEs).Results:Of 60 pts randomized to riociguat and 61 to placebo, 42 (riociguat−riociguat group) and 45 (former placebo group), respectively, entered LTE. At LTE start, mean±SD mRSS was 16.4±3.2 and 16.3±4.2 units, and mean disease duration was 8.9±7.8 and 8.9±5.8 months, in the riociguat−riociguat and former placebo groups, respectively. Other demographics/disease characteristics were also comparable. Median duration of riociguat treatment was 1092 d in riociguat−riociguat pts and 649 d in former placebo pts. Throughout the study, mRSS decreased in both groups (Figure 1). From Wk 52 to last visit, mRSS fell by −3.02±5.51 in riociguat−riociguat patients and −3.96±5.43 in former placebo pts. Rates of mRSS regression (decrease by >5 units and ≥25% from Wk 52 to last visit) and of % declines in mRSS were similar in the two groups (Figure 2). mRSS progression (increase by >5 units and ≥25% from Wk 52 to last visit) occurred in 1 pt (2%) in each group. During the entire study, rescue therapy agents were used in 15 (36%) riociguat−riociguat pts and 17 (38%) former placebo pts. AEs were reported from Wk 52 to last visit in 82 pts (94%): 40 (95%) riociguat−riociguat and 42 (93%) former placebo. Most common AEs overall: nasopharyngitis (24%), gastroesophageal reflux disease (17%), diarrhea (15%), and hypotension (14%). AEs of special interest (dizziness, postural dizziness, or hypotension) occurred in 5 riociguat−riociguat pts (12%) and 4 former placebo pts (9%). SAEs were reported in 21 (24%) pts: 10 (24%) riociguat−riociguat pts and 11 (24%) former placebo pts, with no SAE reported in >1 patient, no SAEs of special interest, and no deaths.Conclusion:During LTE riociguat treatment, mRSS decreased in both groups from Wk 52 onwards and mRSS progression was uncommon. Riociguat had acceptable safety, similar to the main study, with no new safety signal.Acknowledgments:RISE-SSc was jointly funded by Bayer AG and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Disclosure of Interests:Dinesh Khanna Shareholder of: Eicos, Grant/research support from: NIH NIAID, NIH NIAMS, Consultant of: Acceleron, Actelion, Bayer, BMS, Boehringer-Ingelheim, Corbus, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-Aventis/Genzyme, UCB Pharma, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Melanie Wosnitza Employee of: Bayer AG, Marie-Elise Truchetet: None declared, Gabriella Szücs: None declared, Wendy Stevens: None declared, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Chiara Stagnaro: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Richard Silver: None declared, Elena Schiopu: None declared, Valeria Riccieri: None declared, Frank Kramer Employee of: Bayer AG, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Osamu Ishikawa: None declared, Tomonori Ishii: None declared, Eric Hachlla: None declared, Ellen De Langhe Consultant of: member of advisory board for Boehringer, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Radim Bečvář Consultant of: Actelion, Roche, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

Published
2020
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22. AB1401-HPR An exploratory study evaluating feasibility and effectiveness of two different exercise programs in systemic sclerosis associated microstomia

Author

Seher Arat, J. Lenaerts, E. De Langhe, S. Severi, Rene Westhovens, and Ellinor Sydow

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Rehabilitation, business.industry, Microstomia, medicine.medical_treatment, Arthritis, medicine.disease, Connective tissue disease, Oral hygiene, Group B, Scleroderma, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Physical therapy, business
Abstract

Background Systemic sclerosis (SSc) is a severe chronic connective tissue disease with a high disease burden. Oral involvement with impaired oral aperture (microstomia) is frequent and associated with impaired food intake, oral hygiene and secondary dental problems. Preventive measures through mouth-stretching and oral augmentation exercises have been shown to reverse the progression of microstomia. Objectives This exploratory study assesses the effectiveness and feasibility of two different exercise approaches designed to increase oral aperture. Methods Two groups had to exercise for 10 min, 3 times/day for 3 months. Group A exercised with a passive jaw motion device (Therabite), and Group B did mouth-stretching exercises. Patients were contacted 4 times by telephone to address encountered problems. The subjects used an exercise diary to document compliance. Patients were evaluated at baseline, 3 months (period without intervention), 6 months (at the end of the treatment after 3 months of intervention) and 9 months (follow-up). Results At present, 9 patients (Therabite n=4, mouth-stretching exercises n=5) were included and recruitment is ongoing. Seven patients completed the study and increase of oral aperture was observed in all patients in both groups. In the Therabite group, after 3 months of exercise, increase of oral aperture was 9, 2, 9 and 10 mm. In the mouth-stretching exercise group the increase of oral aperture was 11, 10 and 4 mm after 3 months. The compliance, measured as the ratio of executed exercises relative to the planned number of exercises was 95,2%, 85,7%, 98,9% and 63,7% in the Therabite group and 97,4%, 48,6% and 68,3% in the mouth-stretching exercise group. Conclusions An increase of oral aperture is observed in all patients after 3 months of exercising with the Therabite device as well as after mouth-stretching exercises. No clear differences are observed between both groups, but the study was not designed nor powered for this. Remarkably, a high compliance for the treatment regime was observed in most patients. References [1] Agarwal SK. The genetics of systemic sclerosis. Discov Med. 2010Aug;10(51):134–43. [2] Alantar A, Cabane J, Hachulla E, Princ G, Glinist D, Hassin M, Sorel M, Maman L, Pilat A, Mouthon L. Recommendations for the Care of Oral Involvement in Patients With Systemic Sclerosis. Arthritis Care and Research. VOL. 63. No8, august 2011, pp 1126–1133. [3] Albilia JB, Lam DK, Blanas N, Clokie CML, Sandor GKB. Small Mouths…Big Problems? A review of Scleroderma and its Oral Health Implications. www.cda-adc.ca/jcda. November 2007, vol 73,no 9. [4] Maddali-Bongi S, Landi G, Galluccio F, Del Rosso A, Miniati I, Conforti M.L, Casale R, Matucci-Cerinic M. The rehabilitation of facial involvement in systemic sclerosis: efficacy of the combination of connective tissue massage, Kabat’s technique and kinesitherapy: a randomized controlled trial. Rheumatol Int (201131:895–901. [5] Pizzo G, Scardina GA, Mesina P. Effects of nonsurgical exercise program on the decreased mouth opening in patient with systemic sclerosis. Clin Oral Invest2003; 7:175–178. Disclosure of Interest None declared

Published
2018
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23. THU0392 Systemic sclerosis and primary biliary cholangitis: an overlap syndrome? preliminary data from a multicentre eustar study

Author

Yannick Allanore, Oliver Distler, Gemma Lepri, Y. Braun-Moscovici, Cosimo Bruni, Marco Matucci-Cerinic, E. De-Langhe, Paolo Airò, and Kristofer Andréasson

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Population, Liver transplantation, Gastroenterology, Pulmonary function testing, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Internal medicine, Statistical significance, medicine, skin and connective tissue diseases, education, 030203 arthritis & rheumatology, education.field_of_study, Creatinine, integumentary system, business.industry, Overlap syndrome, medicine.disease, digestive system diseases, 030104 developmental biology, chemistry, Portal hypertension, business
Abstract

Background The association between systemic sclerosis (SSc) and primary biliary cholangitis (PBC) is well known. However, classifications criteria of the 2 diseases have been recently revised and may change the relationships. Furthermore, the specific outcomes with regards to organ involvement and also of liver aspects have been only scarcely investigated. Objectives To describe clinical characteristics of SSc-PBC patients compared to SSc using a large series Methods A multicentre EUSTAR study collection data of SSc patients with known PBC or with PBC-specific antibodies (abs) and of SSc controls matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results 229 patients were enrolled (85 SSc-PBC and 144 SSc). The mean age of the population at the SSc diagnosis was of 53±12.8. Baseline characteristics. The limited cutaneous subset was the most common. Anticentromere abs (ACA) were present in 82.9% of SSc-PBC patients (vs 68.5% in SSc, p-value=0.01) while anti-topoisomerase I abs were less frequently (1.2% vs 9.7%), p-value=0.02. Out of 85 SSc-PBC patients, antimitochondrial abs (AMA) were present in 80%, only 9.4% presented anti-gp210 abs and 7.1% anti-sp100 abs. The two populations did not differ for fibrosis at HRCT, lung function tests, the value of creatinine and for pulmonary arterial hypertension. A trend towards statistical significance was found in the prevalence of digital ulcers (DUs) as patients that have never suffered from past or current DUs were greater in the SSc-PBC group (78.6% vs 66%, p-value=0.051). Regarding other autoimmune associated diseases, a greater prevalence of Hashimoto thyroiditis was found in SSc-PBC (p-value=0.03). At baseline, transaminase, alkaline phosphatase and γGT levels were all higher in PBC-SSc (p-value Conclusions PBC is more present in ACA positive lcSSc; SSc-PBC patients have a higher risk of polyautoimmunity. Of the most interest, SSc-PBC patients seem to have a milder SSc phenotype with less severe organ involvement and progression. Regarding PBC phenotype, only 4 patients presented portal hypertension and nobody was subjected to liver transplantation. At baseline, the SSc-PBC group had higher cholestatic liver enzymes and more than 60% were treated with deoxycholic acid. In the future, it will be useful to evaluate the PBC phenotype during the follow-up enrolling a greater number of patients. Disclosure of Interest None declared

Published
2018
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24. Altitude effect on plantain growth and yield during four production cycles in North Kivu, eastern Democratic Republic of Congo

Author

K. Valimuzigha, Walter Ocimati, I. Sikyolo, L. Vutseme, Charles Sivirihauma, David Turner, Guy Blomme, and E. de Langhe

Subjects
0106 biological sciences, Abiotic stress, Yield (finance), Forestry, 04 agricultural and veterinary sciences, Horticulture, 01 natural sciences, Geography, Altitude, Agronomy, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Production (economics), 010606 plant biology & botany
Published
2016
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25. On-farm banana (Musa) cultivar diversity status across different altitudes in North and South Kivu provinces of eastern Democratic Republic of Congo

Author

Guy Blomme, Charles Sivirihauma, H. Muhindo, Walter Ocimati, D. Karamura, B. Dhed'a Djailo, J.G. Adheka, Jules Ntamwira, P.E. Ragama, V. Ndungo, and E. De Langhe

Subjects
0106 biological sciences, Agroforestry, media_common.quotation_subject, Forestry, 04 agricultural and veterinary sciences, Horticulture, 01 natural sciences, Democracy, Geography, South kivu, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Cultivar, Genetic erosion, 010606 plant biology & botany, media_common, Diversity (politics)
Published
2016
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26. P101 DOT1L inhibition increases dermal fibroblast proliferation but has no effects on in vitro or in vivo collagen deposition in models of fibrosis

Author

Nathalie Berghen, E. De Langhe, and Rik Lories

Subjects
medicine.diagnostic_test, business.industry, Human skin, Bleomycin, medicine.disease, Molecular biology, Extracellular matrix, Dermal fibroblast, chemistry.chemical_compound, chemistry, Western blot, In vivo, Fibrosis, Gene expression, medicine, business
Abstract

Introduction Fibrosis is a key process in Systemic Sclerosis, a devastating disease that is not well understood. The role of epigenetic disease mechanisms is increasingly explored. DOT1L, the unique H3K79-methyltransferase, methylates histone 3 at the Lysine residue at position 79, and regulates gene expression. Inhibition of DOT1L has cell-type specific effects on Wnt-signalling, a pathway suggested to play an important role in fibrosis. Objectives To study the role of DOT1L in fibrosis. Methods Primary cell cultures of fibroblasts, isolated from healthy human skin and treated with DOT1L-inhibitor EPZ-5676 or vehicle for 14 days, were stimulated with TGFβ 5 ng/ml after starvation. Smooth muscle alpha 2 actin (ACTA2) gene expression was measured by RT-qPCR. Efficiency of DOT1L-inhibition was analysed with Western Blot for dimethylated H3K79. Picrosirius Red staining measured collagen I and III deposition. Proliferation was analysed with 5-Bromo-2’-deoxy-uridine (BrdU) labelling. 7–9 week old Col1a2; Cre-ERT2; DOT1lfl/fl mice were injected intraperitoneally with tamoxifen (1 mg/day,5 days) to induce a fibroblast-specific DOT1L knockout. Bleomycin (0.1 mg) or vehicle was injected subcutaneously (5 days/week, 4 weeks). Injected skin was analysed by OH-prolin assay for collagen content, and by histology for dermal thickness measurement. Results The DOT1L-inhibitor EPZ-5676 reduced H3K79 dimethylation in all samples. TGFβ increased expression of ACTA2 but 3 out of 4 DOT1L inhibited samples showed a significantly reduced effect of TGFβ on ACTA2 expression. The amount of collagen I and III in the extracellular matrix after 72 hours of TGFβ, was comparable between control and EPZ treated fibroblasts. BrdU labelling assay showed increased proliferation with DOT1L inhibition. In vivo, subcutaneous bleomycin induced an increased dermal thickness and skin collagen content in mice. No difference in the effect of bleomycin was found between mice with a conditional fibroblast-specific DOT1L knockout or wild type mice. Conclusions In an in vitro model of fibrosis, primary human dermal fibroblasts treated with a DOT1L-inhibitor showed increased proliferation and reduced upregulation of ACTA2 but did not result in detectable differences in collagen deposition. In an in vivo murine model of skin fibrosis, no difference in bleomycin-induced skin thickness and collagen content was found when DOT1L was knocked out in fibroblasts. Disclosure of interest None declared

Published
2018
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27. The 2016 Global Strategy for the conservation and use of Musa genetic resources - key strategic elements

Author

Robert Domaingue, John E. Thomas, Jean-Pierre Horry, I. van den Houwe, Max Ruas, I. van den Bergh, B. Laliberte, D. Karamura, Rachel P. Chase, J. Sardos, Nicolas Roux, Mathieu Rouard, and E. de Langhe

Subjects
0106 biological sciences, 0301 basic medicine, media_common.quotation_subject, Horticulture, 010603 evolutionary biology, 01 natural sciences, Conservation des ressources génétiques, Ecosystem services, F30 - Génétique et amélioration des plantes, 03 medical and health sciences, Ressource génétique végétale, Effects of global warming, F01 - Culture des plantes, Global network, Variété, Resilience (network), Environmental planning, media_common, End user, Global strategy, Musa, 030104 developmental biology, Mandate, Business, Biodiversité, Diversity (politics)
Abstract

The Global Strategy for the Conservation and Use of Musa Genetic Resources (hereafter referred to as the ‘Global Strategy’) has been expanded in 2016 by Musa genetic resources and breeding experts within the framework of the Global Musa Genetic Resources Network, MusaNet. MusaNet’s mandate is to oversee the further development and monitoring of the implementation of the Global Strategy. The updated Global Strategy aims to provide a clear framework and roadmap to be used by the Musa community for the efficient and effective conservation of the globally important collections of Musa and to strengthen the utilization of the genetic resources toward an increased use of available diversity. It includes recommendations and priorities indicated in several consultation processes following the 2006 Global Musa Strategy and particularly the expertise and key groups represented, including the Regional Research Networks (BAPNET, BARNESA, Innovate Plantain and MusaLAC) and global networks such as ProMusa. The Global Strategy covers numerous topics dealing with Musa genetic resources, with the 12 chapters divided into four main parts: Diversity, Identity, Management and Use. Each chapter contains the sections titled Where we are now, Where do we want to go and How will we get there. For Musa researchers, including taxonomists and breeders, but also end users such as farmers, decisions on the management of banana diversity are often made with limited information. With this in mind, the Global Strategy is a core reference on the taxonomy, characterization, evaluation and genetic improvement of cultivars, leading to actions such as the selection of new and improved cultivars. The use of a more diverse genepool can lead to higher production while at the same time promote ecosystem services such as resilience to pest and disease and the effects of climate change.

Published
2018

28. FRI0393 Prevalence of myositis-specific antibodies in idiopathic inflammatory myopathy compared to disease and healthy controls

Author

P. De Haes, J. Lenaerts, Kristl G. Claeys, Daniel Engelbert Blockmans, E. De Langhe, Rene Westhovens, Doreen Dillaerts, J-B Vulsteke, Xavier Bossuyt, and Koen Poesen

Subjects
medicine.medical_specialty, business.industry, Autoantibody, Chronic inflammatory demyelinating polyneuropathy, Disease, Dermatomyositis, medicine.disease, Polymyositis, Gastroenterology, Rheumatoid arthritis, Internal medicine, mental disorders, Cohort, Immunology, Medicine, business, Myositis
Abstract

Background Myositis-specific autoantibodies (MSA) are increasingly recognized as important diagnostic and prognostic markers in idiopathic inflammatory myopathies (IIM) (polymyositis, dermatomyositis, sporadic inclusion body myositis and necrotizing autoimmune myositis). The prevalence of these MSAs in other systemic autoimmune rheumatic diseases and neuromuscular diseases is unclear. Objectives To compare positivity of MSA in a cohort of IIM patients to positivity in healthy controls and different systemic autoimmune rheumatic diseases (SARD) or chronic inflammatory demyelinating polyneuropathy (CIDP). Methods A line immunoassay (Myositis 12 IgG DOT for BlueDiver) for IgG autoantibodies against Jo-1, PL-7, PL-12, EJ, SRP, Mi-2, MDA-5, TIF1-γ, HMGCR, SSA/Ro52kD, SAE1/2 and NXP-2 antigens was performed in patients with IIM (n=146), healthy controls (blood donors, n=40) and disease controls (n=200). The disease control group consisted of patients with other SARD (rheumatoid arthritis, RA; systemic sclerosis, Ssc; Sjogren9s syndrome, SjS; and systemic lupus erythematosus, SLE) (n=40 for each disease group) and CIDP (n=40). A result >10 arbitrary units was considered significantly positive. Results 50% of 146 patients with IIM tested positive for an MSA (table 1), compared to 3,5% of 200 disease controls (table 1). 1 SSc patient was positive for Jo-1, 1 CIDP patient was positive for PL12, 2 SSc patients were positive for TIF1-gamma, 2 patients (1 SSc and 1 SjS patient) were positive for SAE1/2, and 1 SjS patient was positive for NXP2. The prevalence of SAE1/2 and TIF1-gamma positivity was similar in the IIM and disease control group. No healthy control had a significantly positive MSA. Conclusions MSA positivity in patients with a clinical non-IIM diagnosis (other SARD or CIDP) is infrequent compared to positivity in the IIM group. For TIF1-gamma and SAE1/2 assay performance may need to be optimized. The distribution of subtypes of MSA in this IIM cohort is consistent with data of previous studies.1 References Allenbach Y, Benveniste O. Diagnostic Utility of Autoantibodies in Inflammatory Muscle Diseases. J Neuromuscul Dis. 2015; 2:13–25. Disclosure of Interest None declared

Published
2017
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29. AB0638 Cardiac transplant in systemic sclerosis-associated cardiomyopathy: monocentric experience of 3 cases

Author

J Lenaerts, R Westhovens, W Droogne, A Ciarka, J Van Cleemput, and E De Langhe

Subjects
medicine.medical_specialty, Ejection fraction, Heart disease, business.industry, medicine.medical_treatment, Interstitial lung disease, Cardiomyopathy, Immunosuppression, medicine.disease, Tacrolimus, Internal medicine, Heart failure, cardiovascular system, Cardiology, Medicine, skin and connective tissue diseases, business, Complication
Abstract

Background Cardiac involvement in systemic sclerosis (SSc) is a frequent complication, but end-stage cardiac failure remains uncommon and represents a poor prognosis. Heart-lung and lung transplant is an established treatment option for SSc-related pulmonary disease. Due to the limited published data, no recommendations exist for cardiac transplant in the context of SSc. Objectives We present our monocentric experience of 3 patients with SSc who underwent cardiac transplant for SSc-related end-stage heart disease (multiple hospitalisations due to failure of medical therapy and life-threatening complications). Results Case 1 is a 59-year-old male with limited cutaneous SSc. Antinuclear antibody (ANA) was negative. He had vascular (digital ulcers) and cardiac (heart failure (left ventricular ejection fraction (LVEF) 20%, NYHA class IV)) involvement, without major gastrointestinal or pulmonary involvement (no interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH: assessed by right heart catheterization (RHC))). He underwent a cardiac transplant at the age of 51, after a disease duration of 6 years. Post-transplantation immunosuppressant therapy consists of tacrolimus and mycophenolic acid, initially associated with methylprednisolon, which is the standard immunosuppression protocol at our institution. Case 2 is a 55-year-old male with limited cutaneous SSc. ANA was positive, 1/320, speckled pattern, but no SSc-related autoantibody has been identified. He had gastrointestinal (upper gastrointestinal tract dysmotility), muscular (myositis) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 54, after a disease duration of 7 years. Standard immunosuppressants were initiated. Case 3 is a 50-year-old male with diffuse cutaneous SSc. ANA was negative. He had vascular (digital ulcers), gastrointestinal (upper gastrointestinal tract dysmotility) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 49, after a disease duration of 4 years. Standard immunosuppressants were initiated. At present, 1,5 years (case 2 and 3) and 8 years (case 1) after transplant, the donor hearts are still functioning well. No other SSc-related organ manifestations have occurred. Conclusions We present 3 patients with SSc who successfully underwent cardiac transplant for SSc-related end-stage heart disease. None had other major SSc-related organ involvement. This supports the limited published data that cardiac transplant is feasible and can be considered in end-stage SSc-related cardiomyopathy. Disclosure of Interest None declared

Published
2017
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30. A historical overview of the appearance and spread ofMusapests and pathogens on the African continent: highlighting the importance of cleanMusaplanting materials and quarantine measures

Author

E. De Langhe, D. Karamura, P. Lepoint, Michael Pillay, Clifford S. Gold, Altus Viljoen, W. Tinzaara, N. Price, Pierre-Yves Teycheney, D. Jones, Guy Blomme, Andrew D. W. Geering, Eldad Karamura, Randy C. Ploetz, and I.W. Buddenhagen

Subjects
biology, business.industry, Weevil, Distribution (economics), biology.organism_classification, Fusarium wilt, Banana bunchy top virus, law.invention, Crop, Tanzania, Agronomy, law, Quarantine, business, Agronomy and Crop Science, Tropical Asia
Abstract

The genus Musa is not native to Africa. It evolved in tropical Asia, from southwest India eastward to the island of New Guinea. There is a growing circumstantial evidence which suggests that the East African Highland banana and the tropical lowland plantain were cultivated on the African continent since before 1 AD. It is also probable that ABB cooking and AB and AAB dessert cultivars were brought to the continent from India by Arabian traders from 600 AD, and that these were disseminated throughout East Africa. During the colonial era, the main centres of distribution for banana cultivars were botanical gardens, such as Zomba in Malawi, Entebbe in Uganda and Amani in Tanzania. It appears that the very early introductions of Highland banana and plantain arrived in Africa as a relatively clean material without the conspicuous pests and diseases that affect them in Asia. In contrast, several devastating problems now impact the crop in Africa, including nematodes, the borer weevil and diseases, most notably banana bunchy top, banana streak, Sigatoka leaf spots, Xanthomonas wilt and Fusarium wilt. We (a) provide chronological overviews of the first reports/observations of different Musa pests and pathogens/diseases in Africa, (b) highlight specific examples of when a pest or pathogen/disease was introduced via planting materials and (c) give recent examples of how the pests and pathogens spread to new regions via planting materials. In total, these production constraints threaten banana and plantain production throughout the continent and impact those who can ill afford lost production, the small-holder producer. Our intent in this review is to highlight the significance of these problems and the great importance that infested planting materials have played in their development.

Published
2012
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31. La phyllotaxie du bananier et ses conséquences pour la compréhension du système rejetonnant

Author

E. De Langhe

Subjects
Horticulture, Agronomy and Crop Science, Food Science
Abstract

1) A la suite de plusieurs observations, l'auteur s'est limite a decrire l'allure generale des angles de divergence des noeuds de la spirale. 2) Apres avoir etudie l'hypothese de SKUTCH, selon laquelle le bananier avait une structure sympodiale, le nombre de points ne concordant pas avec cette idee, fait plutot croire a une structure monopodiale. 3) Le bananier emet un certain nombre de rejets dont chacun correspond a une feuille. Le plan de rejetonnage suit donc celui de la phyllotaxie. Au moment du rejetonnage, c'est le stade ou les feuilles se succedent avec un angle de divergence inferieur a 140¼, et les groupes de 5 rejets successifs formeront donc en theorie des pentagones irreguliers qui se superposent en tournant legerement vers la droite (20¼ environ). En pratique, les rejets ne se developpent pas tous et selon leur emission, le systeme rejetonnant presentera une grande variation, dont chaque cas peut caracteriser une variete. Enfin l'emploi du "systeme pentagonal" est tres utile dans les recherches sur le rejetonnage et la conduite d'un bananier

Published
2011
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33. Collecting banana diversity in eastern Indonesia

Author

A. Sutanto, H.S. Edison, null Riska, F. Nasution, C. Hermanto, J. Cizkova, E. Hribova, J. Dolezel, N. Roux, J.-P. Horry, J.W. Daniells, and E. De Langhe

Subjects
0106 biological sciences, Flora, biology, Agroforestry, International community, Forestry, 04 agricultural and veterinary sciences, Horticulture, Wallace Line, biology.organism_classification, Phytogeography, 01 natural sciences, F30 - Génétique et amélioration des plantes, Race (biology), Geography, Musa acuminata, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Cultivar, 010606 plant biology & botany, Hybrid, H20 - Maladies des plantes
Abstract

Major diseases, including Fusarium wilt tropical race 4, threaten banana production systems worldwide. New sources of genetic resistance are considered necessary in the fight against such diseases. The triangular region of Indonesia taking in Sulawesi, the Maluku Islands and Lesser Sunda Islands was prioritized by the Global Musa Genetic Resources Network, MusaNet for exploration and collecting. It is just east of the 'Wallace Line', which is recognized as a transition zone for flora in southeast Asia, and had been little explored. Bioversity International funded a team of scientists from Indonesia and Australia to make collecting missions in the triangle in October 2012 and February 2013. Suckers and seeds of 35 promising new accessions were collected. About 90% of these are either wild species or diploid cultivars of more direct use to breeding programs. These were morphologically characterized during the collecting missions and included a set of photographs recommended by Bioversity's Taxonomic Advisory Group. Cigar leaf samples were also collected and sent as fresh samples to the International Banana Genotyping Centre in the Czech Republic. Ploidy and DNA (SSR) genotyping determinations from these samples have been invaluable in quickly interpreting and better appreciating what has been discovered. The new accessions have been grown on at Solok field collection, West Sumatra and will be made available by Indonesia to the international community, including breeding programs, for evaluation and utilization. Information on wild Eumusa prompts a rethinking of the phytogeography of Musa acuminata. The variation within the Australimusa species M. lolodensis highlights the need for broader study of this Musa section. French Plantain-like edible AAs and prospects for the generation of African plantains in the region were identified. The mission indicated existence of local edible ABs in eastern Indonesia in association with balbisiana hybrids origins in the region. Further explorations in the region should add to Musa diversity knowledge.

Published
2016

34. Differentiating banana phytoliths: wild and edible Musa acuminata and Musa balbisiana

Author

Jason Manwaring, E. De Langhe, Luc Vrydaghs, Terry Ball, and I. Van Den Hauwe

Subjects
Archeology, biology, Phytolith, Musa acuminata, Musa balbisiana, Botany, biology.organism_classification, Domestication, Archaeological evidence
Abstract

Recent reports indicate that phytoliths may provide direct archaeological evidence of banana cultivation. However, archaeologists may, in many places, recover phytoliths generated by banana plants with quite different historical backgrounds. Hence the need for a differentiation among phytoliths produced by specific banana groups. The present paper discusses the morphometric distinction between phytoliths produced by the constitutive diploid species Musa acuminata and Musa balbisiana. Our study suggests that domestication of the banana, which was initiated at the diploid M. acuminata level, does not appear to have influenced phytolith morphometry.

Published
2006
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35. Integrating morphological and molecular taxonomy in Musa: the African plantains (Musa spp. AAB group)

Author

Michael Pillay, Rony Swennen, E. De Langhe, and Abdou Tenkouano

Subjects
Numerical taxonomy, Genetic diversity, Critical regions, Evolutionary biology, Botany, Taxonomy (biology), Amplified fragment length polymorphism, Plant Science, Morphological descriptors, Biology, Merge (version control), Ecology, Evolution, Behavior and Systematics, Molecular taxonomy
Abstract

Plantains (Musa spp. AAB) are regarded as the most diverse subgroup of the triploid bananas. Initially they were classified on the basis of morphological characters. New molecular techniques are now being used to explain plantain diversity. Prior to this study no attempt has been made to merge morphological and molecular data in classifying plantains. The objectives of this study were (i) to review the different efforts in plantain taxonomy, (ii) to apply numerical taxonomy to morphological descriptors, and (iii) to evaluate the integration of morphological and molecular data with a common numerical taxonomy method. The results indicate that numerical taxonomy can be an appropriate instrument to compare morphological and molecular data under certain conditions. In the case of plantains, the data sets obtained from morphological and molecular characteristics needs to be quite large. An incomplete match of morphological and molecular data sets could imply that some morphological characters are being influenced by the environment or that the molecular markers have not sampled critical regions of the genome.

Published
2005
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37. Nuclear genome size and genomic distribution of ribosomal DNA in Musa and Ensete (Musaceae): taxonomic implications

Author

Jaroslav Doležel, E. De Langhe, O. Alkhimova, Jan Bartoš, and M. Doleželová

Subjects
Genetics, Nuclear gene, biology, biology.organism_classification, Nuclear DNA, Musaceae, Musa schizocarpa, Musa balbisiana, Musa acuminata, Musa textilis, Molecular Biology, Ribosomal DNA, Genetics (clinical)
Abstract

Nuclear DNA content and genomic distributions of 5S and 45S rDNA were examined in nineteen diploid accessions of the genus Musa representing its four sections Eumusa, Rhodochlamys, Callimusa and Australimusa, and in Ensete gilletii, which was the outgroup in this study. In the Eumusa (x = 11), 2C DNA content ranged from 1.130 to 1.377 pg, M. balbisiana having the lowest DNA content of all sections. M. beccarii (x = 9), a representative of Callimusa, had the highest 2C nuclear DNA content (1.561 pg). Species belonging to Rhodochlamys (x = 11) and Australimusa (x = 10) had 2C DNA contents ranging from 1.191 to 1.299 pg and from 1.435 to 1.547 pg, respectively. E. gilletii (x = 9) had 2C DNA content of 1.210 pg. The number of 5S rDNA loci in Musa varied from 4 to 8 per diploid cell. While different numbers of 5S rDNA loci were observed within Eumusa and Rhodochlamys, four 5S rDNA loci were observed in all accessions of Australimusa. M. beccarii (Callimusa) and E. gilletii contained 5S rRNA gene clusters on five and six chromosomes, respectively. The number of 45S rDNA loci was conserved within individual sections. Hierarchical cluster analysis of genome size, number of chromosomes and 45S rDNA sites suggested a close relationship between Rhodochlamys and Eumusa; Australimusa was clearly separated as were M. beccarii and E. gilletii. Within the Eumusa-Rhodochlamys group, M. balbisiana, M. schizocarpa and M. ornata formed distinct subgroups, clearly separated from the accessions of M. acuminata, M. mannii, M. laterita and M. velutina, which formed a tight subgroup. The results expand the knowledge of genome size and genomic distribution of ribosomal DNA in Musa and Ensete. They aid in clarification of the taxonomical classification of Musa and show a need to supplement the analyses on the DNA sequence level with cytogenetic studies.

Published
2005
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39. CMS technical design report, volume II: Physics performance

Author

G. L. BAYATIAN, S. CHATRCHYAN, G. HMAYAKYAN, A. M. SIRUNYAN, W. ADAM, T. BERGAUER, M. DRAGICEVIC, J. ERO, M. FRIEDL, R. FRUEHWIRTH, V. GHETE, P. GLASER, J. HRUBEC, M. JEITLER, M. KRAMMER, I. MAGRANS, I. MIKULEC, W. MITAROFF, T. NOEBAUER, M. PERNICKA, P. PORTH, H. ROHRINGER, J. STRAUSS, A. TAUROK, W. WALTENBERGER, G. WALZEL, E. WIDL, C. E. WULZ, A. FEDOROV, M. KORZHIK, O. MISSEVITCH, R. ZUYEUSKI, V. CHEKHOVSKY, O. DVORNIKOV, I. EMELIANTCHIK, A. LITOMIN, V. MOSSOLOV, N. SHUMEIKO, A. SOLIN, R. STEFANOVITCH, J. SUAREZ GONZALEZ, A. TIKHONOV, V. PETROV, J. D'HONDT, S. DE WEIRDT, R. GOORENS, J. HEYNINCK, S. LOWETTE, S. TAVERNIER, W. VAN DONINCK, L. VAN LANCKER, O. BOUHALI, B. CLERBAUX, G. DE LENTDECKER, J. P. DEWULF, T. MAHMOUD, P. E. MARAGE, L. NEUKERMANS, V. SUNDARARAJAN, C. VANDER VELDE, P. VANLAER, J. WICKENS, S. ASSOUAK, J. L. BONNET, G. BRUNO, J. CAUDRON, B. DE CALLATAY, J. DE FAVEREAU DE JENERET, S. DE VISSCHER, C. DELAERE, P. DEMIN, D. FAVART, E. FELTRIN, E. FORTON, G. GREGOIRE, S. KALININ, D. KCIRA, T. KEUTGEN, G. LEIBENGUTH, V. LEMAITRE, Y. LIU, D. MICHOTTE, O. MILITARU, A. NINANE, S. OVYN, T. PIERZCHALA, K. PIOTRZKOWSKI, V. ROBERFROID, X. ROUBY, D. TEYSSIER, O. VAN DER AA, M. VANDER DONCKT, E. DAUBIE, P. HERQUET, A. MOLLET, A. ROMEYER, W. BEAUMONT, M. CARDACI, E. DE LANGHE, E. A. DE WOLF, L. RURUA, M. H. G. SOUZA, V. OGURI, A. SANTORO, A. SZNAJDER, M. VAZ, E. M. GREGORES, S. F. NOVAES, T. ANGUELOV, G. ANTCHEV, I. ATANASOV, J. DAMGOV, N. DARMENOV, L. DIMITROV, V. GENCHEV, P. IAYDJIEV, B. PANEV, S. PIPEROV, S. STOYKOVA, G. SULTANOV, I. VANKOV, A. DIMITROV, V. KOZHUHAROV, L. LITOV, M. MAKARIEV, A. MARINOV, E. MARINOVA, S. MARKOV, M. MATEEV, B. PAVLOV, P. PETKOV, C. SABEV, S. STOYNEV, Z. TOTEVA, V. VERGUILOV, G. M. CHEN, H. S. CHEN, K. L. HE, C. H. JIANG, W. G. LI, H. M. LIU, X. MENG, X. Y. SHEN, H. S. SUN, M. YANG, W. R. ZHAO, H. L. ZHUANG, Y. BAN, J. CAI, S. LIU, S. J. QIAN, Z. C. YANG, Y. L. YE, J. YING, J. WU, Z. P. ZHANG, N. GODINOVIC, I. PULJAK, I. SORIC, Z. ANTUNOVIC, M. DZELALIJA, K. MARASOVIC, V. BRIGLJEVIC, D. FERENCEK, K. KADIJA, S. MOROVIC, M. PLANINIC, C. NICOLAOU, A. PAPADAKIS, P. A. RAZIS, D. TSIAKKOURI, A. HEKTOR, M. KADASTIK, K. KANNIKE, E. LIPPMAA, M. MUNTEL, M. RAIDAL, P. A. AARNIO, S. CZELLAR, E. HAEGGSTROEM, A. HEIKKINEN, J. HARKONEN, V. KARIMAKI, R. KINNUNEN, T. LAMPEN, K. LASSILA PERINI, S. LEHTI, T. LINDEN, P. R. LUUKKA, S. MICHAL, T. MAENPAA, J. NYSTEN, M. STETTLER, E. TUOMINEN, J. TUOMINIEMI, L. WENDLAND, T. TUUVA, J. P. GUILLAUD, P. NEDELEC, D. SILLOU, M. ANFREVILLE, S. BEAUCERON, E. BOUGAMONT, P. BREDY, R. CHIPAUX, M. DEJARDIN, D. DENEGRI, J. DESCAMPS, B. FABBRO, J. L. FAURE, S. GANJOUR, F. X. GENTIT, A. GIVERNAUD, P. GRAS, G. HAMEL DE MONCHENAULT, P. JARRY, F. KIRCHER, M. C. LEMAIRE, B. LEVESY, E. LOCCI, J. P. LOTTIN, I. MANDJAVIDZE, M. MUR, E. PASQUETTO, A. PAYN, J. RANDER, J. M. REYMOND, F. RONDEAUX, A. ROSOWSKY, Z. H. SUN, P. VERRECCHIA, S. BAFFIONI, F. BEAUDETTE, M. BERCHER, U. BERTHON, S. BIMBOT, J. BOUROTTE, P. BUSSON, M. CERUTTI, D. CHAMONT, C. CHARLOT, C. COLLARD, D. DECOTIGNY, E. DELMEIRE, L. DOBRZYNSKI, A. M. GAILLAC, Y. GEEREBAERT, J. GILLY, M. HAGUENAUER, A. KARAR, A. MATHIEU, G. MILLERET, P. MINE, P. PAGANINI, T. ROMANTEAU, I. SEMENIOUK, Y. SIROIS, J. D. BERST, J. M. BROM, F. DIDIERJEAN, F. DROUHIN, J. C. FONTAINE, U. GOERLACH, P. GRAEHLING, L. GROSS, L. HOUCHU, P. JUILLOT, A. LOUNIS, C. MAAZOUZI, D. MANGEOL, C. OLIVETTO, T. TODOROV, P. VAN HOVE, D. VINTACHE, M. AGERON, J. L. AGRAM, G. BAULIEU, M. BEDJIDIAN, J. BLAHA, A. BONNEVAUX, G. BOUDOUL, E. CHABANAT, C. COMBARET, D. CONTARDO, R. DELLA NEGRA, P. DEPASSE, T. DUPASQUIER, H. EL MAMOUNI, N. ESTRE, J. FAY, S. GASCON, N. GIRAUD, C. GIRERD, R. HAROUTUNIAN, J. C. IANIGRO, B. ILLE, M. LETHUILLIER, N. LUMB, H. MATHEZ, G. MAURELLI, L. MIRABITO, S. PERRIES, O. RAVAT, R. KVATADZE, V. ROINISHVILI, R. ADOLPHI, R. BRAUER, W. BRAUNSCHWEIG, H. ESSER, L. FELD, A. HEISTER, W. KARPINSKI, K. KLEIN, C. KUKULIES, J. OLZEM, A. OSTAPCHUK, D. PANDOULAS, G. PIERSCHEL, F. RAUPACH, S. SCHAEL, G. SCHWERING, M. THOMAS, M. WEBER, B. WITTMER, M. WLOCHAL, A. ADOLF, P. BIALLASS, M. BONTENACKELS, M. ERDMANN, H. FESEFELDT, T. HEBBEKER, S. HERMANN, G. HILGERS, K. HOEPFNER, C. HOF, S. KAPPLER, M. KIRSCH, D. LANSKE, B. PHILIPPS, H. REITHLER, T. ROMMERSKIRCHEN, M. SOWA, H. SZCZESNY, M. TONUTTI, O. TSIGENOV, F. BEISSEL, M. DAVIDS, M. DUDA, G. FLUGGE, T. FRANKE, M. GIFFELS, T. HERMANNS, D. HEYDHAUSEN, S. KASSELMANN, G. KAUSSEN, T. KRESS, A. LINN, A. NOWACK, M. POETTGENS, O. POOTH, A. STAHL, D. TORNIER, A. FLOSSDORF, B. HEGNER, J. MNICH, C. ROSEMANN, G. FLUCKE, U. HOLM, R. KLANNER, U. PEIN, N. SCHIRM, P. SCHLEPER, G. STEINBRUCK, M. STOYE, R. VAN STAA, K. WICK, P. BLUM, V. BUEGE, W. DE BOER, G. DIRKES, M. FAHRER, M. FEINDT, U. FELZMANN, J. FERNANDEZ MENENDEZ, M. FREY, A. FURGERI, F. HARTMANN, S. HEIER, C. JUNG, B. LEDERMANN, T.H. MULLER, M. NIEGEL, A. OEHLER, T. ORTEGA GOMEZ, C. PIASECKI, G. QUAST, K. RABBERTZ, C. SAOUT, A. SCHEURER, D. SCHIEFERDECKER, A. SCHMIDT, H. J. SIMONIS, A. THEEL, A. VEST, T. WEILER, C. WEISER, J. WENG, V. ZHUKOV, G. KARAPOSTOLI, P. KATSAS, P. KREUZER, A. PANAGIOTOU, C. PAPADIMITROPOULOS, G. ANAGNOSTOU, M. BARONE, T. GERALIS, C. KALFAS, A. KOIMAS, A. KYRIAKIS, S. KYRIAZOPOULOU, D. LOUKAS, A. MARKOU, C. MARKOU, C. MAVROMMATIS, K. THEOFILATOS, G. VERMISOGLOU, A. ZACHARIADOU, X. ASLANOGLOU, I. EVANGELOU, P. KOKKAS, N. MANTHOS, I. PAPADOPOULOS, G. SIDIROPOULOS, F. A. TRIANTIS, G. BENCZE, L. BOLDIZSAR, C. HAJDU, D. HORVATH, A. LASZLO, G. ODOR, F. SIKLER, N. TOTH, G. VESZTERGOMBI, P. ZALAN, J. MOLNAR, N. BENI, A. KAPUSI, G. MARIAN, P. RAICS, Z. SZABO, Z. SZILLASI, G. ZILIZ, H. S. BAWA, S. B. BERI, V. BHANDARI, V. BHATNAGAR, M. KAUR, R. KAUR, J. M. KOHLI, A. KUMAR, J. B. SINGH, A. BHARDWAJ, S. BHATTACHARYA, S. CHATTERJI, S. CHAUHAN, B. C. CHOUDHARY, P. GUPTA, M. JHA, K. RANJAN, R. K. SHIVPURI, A. K. SRIVASTAVA, S. BORKAR, M. DIXIT, M. GHODGAONKAR, S. K. KATARIA, S. K. LALWANI, V. MISHRA, A. K. MOHANTY, A. TOPKAR, T. AZIZ, S. BANERJEE, S. BOSE, N. CHEERE, S. CHENDVANKAR, P. V. DESHPANDE, M. GUCHAIT, A. GURTU, M. MAITY, G. MAJUMDER, K. MAZUMDAR, A. NAYAK, M. R. PATIL, S. SHARMA, K. SUDHAKAR, S. C. TONWAR, B. S. ACHARYA, S. BHEESETTE, S. DUGAD, S. D. KALMANI, V. R. LAKKIREDDI, N. K. MONDAL, N. PANYAM, P. VERMA, M. ARABGOL, H. ARFAEI, M. HASHEMI, M. MOHAMMADI, M. MOHAMMADI NAJAFABADI, A. MOSHAII, S. PAKTINAT MEHDIABADI, M. GRUNEWALD, M. ABBRESCIA, L. BARBONE, A. COLALEO, D. CREANZA, N. DE FILIPPIS, M. DE PALMA, G. DONVITO, L. FIORE, D. GIORDANO, G. IASELLI, F. LODDO, G. MAGGI, M. MAGGI, N. MANNA, B. MARANGELLI, M. S. MENNEA, S. MY, S. NATALI, S. NUZZO, G. PUGLIESE, V. RADICCI, A. RANIERI, F. ROMANO, G. SELVAGGI, L. SILVESTRIS, P. TEMPESTA, R. TRENTADUE, G. ZITO, G. ABBIENDI, W. BACCHI, A. BENVENUTI, S. BRAIBANT GIACOMELLI, F. R. CAVALLO, C. CIOCCA, G. CODISPOTI, I. D'ANTONE, G. M. DALLAVALLE, P. GIACOMELLI, C. GRANDI, M. GUERZONI, S. MARCELLINI, F. ODORICI, S. ALBERGO, M. CHIORBOLI, S. COSTA, M. GALANTI, G. GATTO ROTONDO, F. NOTO, R. POTENZA, G. RUSSO, A. TRICOMI, C. TUVE, A. BOCCI, G. CIRAOLO, V. CIULLI, C. CIVININI, R. D'ALESSANDRO, E. FOCARDI, C. GENTA, P. LENZI, A. MACCHIOLO, N. MAGINI, F. MANOLESCU, C. MARCHETTINI, L. MASETTI, S. MERSI, M. MESCHINI, S. PAOLETTI, G. PARRINI, R. RANIERI, M. SANI, P. FABBRICATORE, S. FARINON, M. GRECO, G. CATTANEO, A. DE MIN, M. DOMINONI, F. M. FARINA, F. FERRI, A. GHEZZI, P. GOVONI, R. LEPORINI, S. MAGNI, M. MALBERTI, S. MALVEZZI, S. MARELLI, D. MENASCE, L. MORONI, P. NEGRI, M. PAGANONI, D. PEDRINI, A. PULLIA, S. RAGAZZI, N. REDAELLI, C. ROVELLI, M. ROVERE, L. SALA, S. SALA, R. SALERNO, T. TABARELLI DE FATIS, S. VIGANO, G. COMUNALE, F. FABOZZI, D. LOMIDZE, S. MELE, P. PAOLUCCI, D. PICCOLO, G. POLESE, C. SCIACCA, P. AZZI, N. BACCHETTA, M. BELLATO, M. BENETTONI, D. BISELLO, E. BORSATO, A. CANDELORI, P. CHECCHIA, E. CONTI, M. DE MATTIA, T. DORIGO, V. DROLLINGER, F. FANZAGO, F. GASPARINI, U. GASPARINI, M. GIARIN, P. GIUBILATO, F. GONELLA, A. KAMINSKIY, S. KARAEVSKII, V. KHOMENKOV, S. LACAPRARA, I. LIPPI, M. LORETI, O. LYTOVCHENKO, M. MAZZUCATO, A. T. MENEGUZZO, M. MICHELOTTO, F. MONTECASSIANO, M. NIGRO, M. PASSASEO, M. PEGORARO, G. RAMPAZZO, P. RONCHESE, E. TORASSA, S. VENTURA, M. ZANETTI, P. ZOTTO, G. ZUMERLE, G. BELLI, U. BERZANO, C. DE VECCHI, R. GUIDA, M. M. NECCHI, S. P. RATTI, C. RICCARDI, G. SANI, P. TORRE, P. VITULO, F. AMBROGLINI, E. BABUCCI, D. BENEDETTI, M. BIASINI, G. M. BILEI, B. CAPONERI, B. CHECCUCCI, L. FANO, P. LARICCIA, G. MANTOVANI, D. PASSERI, M. PIOPPI, P. PLACIDI, V. POSTOLACHE, D. RICCI, A. SANTOCCHIA, L. SERVOLI, D. SPIGA, P. AZZURRI, GIUSEPPE BAGLIESI, A. BASTI, L. BENUCCI, J. BERNARDINI, T. BOCCALI, L. BORRELLO, F. BOSI, F. CALZOLARI, R. CASTALDI, C. CERRI, A. S. CUCOANES, M. D'ALFONSO, R. DELL'ORSO, S. DUTTA, L. FOA, S. GENNAI, A. GIAMMANCO, A. GIASSI, D. KARTASHOV, F. LIGABUE, S. LINARI, T. LOMTADZE, G. A. LUNGU, B. MANGANO, G. MARTINELLI, M. MASSA, A. MESSINEO, A. MOGGI, F. PALLA, F. PALMONARI, G. PETRUCCIANI, F. RAFFAELLI, A. RIZZI, G. SANGUINETTI, G. SEGNERI, D. SENTENAC, A. T. SERBAN, G. SGUAZZONI, A. SLAV, P. SPAGNOLO, R. TENCHINI, G. TONELLI, A. VENTURI, P. G. VERDINI, M. VOS, S. BACCARO, L. BARONE, A. BARTOLONI, F. CAVALLARI, S. COSTANTINI, I. DAFINEI, D. DEL RE, M. DIEMOZ, C. GARGIULO, E. LONGO, P. MERIDIANI, G. ORGANTINI, S. RAHATLOU, E. ACCOMANDO, M. ARNEODO, A. BALLESTRERO, R. BELLAN, C. BIINO, S. BOLOGNESI, N. CARTIGLIA, G. CERMINARA, M. CORDERO, M. COSTA, G. DELLACASA, N. DEMARIA, E. MAINA, C. MARIOTTI, S. MASELLI, P. MEREU, E. MIGLIORE, V. MONACO, M. NERVO, M. M. OBERTINO, N. PASTRONE, G. PETRILLO, A. ROMERO, M. RUSPA, R. SACCHI, A. STAIANO, P. P. TRAPANI, S. BELFORTE, F. COSSUTTI, G. DELLA RICCA, A. PENZO, K. CHO, S. W. HAM, D. HAN, D. H. KIM, G. N. KIM, J. C. KIM, W. Y. KIM, M. W. LEE, S. K. OH, W. H. PARK, S. R. RO, D. C. SON, J. S. SUH, J. Y. KIM, S. Y. JUNG, J. T. RHEE, B. S. HONG, S. J. HONG, K. S. LEE, I. PARK, S. K. PARK, K. S. SIM, E. WON, S. B. KIM, S. CARRILLO MORENO, H. CASTILLA VALDEZ, A. SANCHEZ HERNANDEZ, H. A. SALAZAR IBARGUEN, A. MORELOS PINEDA, R. N. C. GRAY, D. KROFCHECK, N. BERNARDINO RODRIGUES, P. H. BUTLER, J. C. WILLIAMS, Z. AFTAB, M. AHMAD, U. AHMAD, I. AHMED, J. ALAM JAN, M. I. ASGHAR, S. ASGHAR, M. HAFEEZ, H. R. HOORANI, M. IBRAHIM, M. IFTIKHAR, M. S. KHAN, N. QAISER, I. REHMAN, T. SOLAIJA, S. TOOR, J. BLOCKI, A. CYZ, E. GLADYSZ DZIADUS, S. MIKOCKI, J. TURNAU, Z. WLODARCZYK, P. ZYCHOWSKI, K. BUNKOWSKI, H. CZYRKOWSKI, R. DABROWSKI, W. DOMINIK, K. DOROBA, A. KALINOWSKI, M. KONECKI, J. KROLIKOWSKI, I. M. KUDLA, M. PIETRUSINSKI, K. POZNIAK, W. ZABOLOTNY, P. ZYCH, M. BLUJ, R. GOKIELI, L. GOSCILO, M. GORSKI, K. NAWROCKI, P. TRACZYK, G. WROCHNA, P. ZALEWSKI, R. ALEMANY FERNANDEZ, C. ALMEIDA, N. ALMEIDA, A. ARAUJO TRINDADE, P. BORDALO, P. DA SILVA RODRIGUES, M. HUSEJKO, A. JAIN, M. KAZANA, P. MUSELLA, S. RAMOS, J. RASTEIRO DA SILVA, P. Q. RIBEIRO, M. SANTOS, J. SEMIAO, P. SILVA, I. TEIXEIRA, J. P. TEIXEIRA, J. VARELA, S. AFANASIEV, K. BABICH, I. BELOTELOV, V. ELSHA, Y. ERSHOV, I. FILOZOVA, A. GOLUNOV, I. GOLUTVIN, N. GORBOUNOV, I. GRAMENITSKI, V. KALAGIN, A. KAMENEV, V. KARJAVIN, S. KHABAROV, V. KHABAROV, Y. KIRYUSHIN, V. KONOPLYANIKOV, V. KORENKOV, G. KOZLOV, A. KURENKOV, A. LANEV, V. LYSIAKOV, A. MALAKHOV, I. MELNITCHENKO, V. V. MITSYN, K. MOISENZ, P. MOISENZ, S. MOVCHAN, E. NIKONOV, D. OLEYNIK, V. PALICHIK, V. PERELYGIN, A. PETROSYAN, E. ROGALEV, V. SAMSONOV, M. SAVINA, R. SEMENOV, S. SHMATOV, S. SHULHA, V. SMIRNOV, D. SMOLIN, A. TCHEREMOUKHINE, O. TERYAEV, E. TIKHONENKO, S. VASSILIEV, A. VISHNEVSKIY, A. VOLODKO, N. ZAMIATIN, A. ZARUBIN, P. ZARUBIN, E. ZUBAREV, N. BONDAR, V. GOLOVTSOV, A. GOLYASH, Y. IVANOV, V. KIM, V. KOZLOV, V. LEBEDEV, G. MAKARENKOV, E. ORISHCHIN, A. SHEVEL, V. SKNAR, I. SMIRNOV, V. SULIMOV, V. TARAKANOV, L. UVAROV, G. VELICHKO, S. VOLKOV, A. VOROBYEV, Y.U. ANDREEV, A. ANISIMOV, S. GNINENKO, N. GOLUBEV, D. GORBUNOV, M. KIRSANOV, A. 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NUSSBAUM, B.P. PADLEY, J. ROBERTS, A. TUMANOV, P. YEPES, A. BODEK, H. BUDD, Y.S. CHUNG, P. DE BARBARO, R. DEMINA, R. EUSEBI, G. GINTHER, Y. GOTRA, A. HOCKER, U. HUSEMANN, S. KORJENEVSKI, W. SAKUMOTO, P. SLATTERY, P. TIPTON, M. ZIELINSKI, E. BARTZ, J. DOROSHENKO, E. HALKIADAKIS, P.F. JACQUES, M.S. KALELKAR, D. KHITS, A. LATH, A. MACPHERSON, L. PERERA, R. PLANO, K. ROSE, S. SCHNETZER, S. SOMALWAR, R. STONE, G. THOMSON, T.L. WATTS, N. AKCHURIN, K.W. CARRELL, K. GUMUS, C. JEONG, H. KIM, V. PAPADIMITRIOU, A. SILL, M. SPEZZIGA, E. WASHINGTON, R. WIGMANS, L. ZHANG, T. BAPTY, D. ENGH, W. JOHNS, T. KESKINPALA, E. LUIGGI LOPEZ, S. NEEMA, S. NORDSTROM, S. PATHAK, P. SHELDON, E.W. VAANDERING, M. WEBSTER, M.W. ARENTON, S. CONETTI, B. COX, R. HIROSKY, R. IMLAY, A. LEDOVSKOY, D. PHILLIPS, H. POWELL, M. RONQUEST, D. SMITH, Y.W. BAEK, J.N. BELLINGER, D. BRADLEY, D. CARLSMITH, I. CROTTY, S. DASU, F. FEYZI, T. GORSKI, M. GROTHE, W. HOGG, M. JAWORSKI, P. KLABBERS, A. LANARO, R. LOVELESS, M. MAGRANS DE ABRIL, D. REEDER, W.H. SMITH, D. WENMAN, G.S. ATOYAN, S. DHAWAN, V. ISSAKOV, H. NEAL, A. POBLAGUEV, M.E. ZELLER, and B.S. YULDASHEV

Subjects
High Energy Physics::Phenomenology, STANDARD MODEL, High Energy Physics::Experiment, EXTRA DIMENSIONS, LHC, SUPERSYMMETRY, HIGGS
Abstract

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking—through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb-1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb-1 to 30 fb-1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2–6 describe examples of full analyses, with photons, electrons, muons, jets, missing ET, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7–15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model.

Published
2007

42. Musa germplasm diversity status across a wide range of agro-ecological zones in Rwanda, Burundi and Eastern Democratic republic of Congo

Author

A. Rutikanga, H. Muhindo, V. Ndungo, D. Karamura, J.G. Adheka, E. de Langhe, S. Hakizimana, S.V. Gaidashova, P. Lepoint, A. Nsabimana, Charles Sivirihauma, C. Murekezi, G. Blomme, J. P. Kanyaruguru, F. Ngezahayo, D. B. Dhed'a, J. Ntamwira, P.E. Ragama, and Walter Ocimati

Subjects
Germplasm, Genetic diversity, Geography, Range (biology), Agroforestry, media_common.quotation_subject, Forestry, Democracy, Diversity (politics), media_common
Published
2013
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43. Plantain in the Early Bantu World

Author

E. De Langhe, Dirk Vuylsteke, and Rony Swennen

Subjects
Archeology, Political science, Ethnology, Bantu languages, Humanities
Abstract

Une recente etude comaparative exhaustive des langues bantoues et malgaches suggere que les Malgaches ne sont pas les premiers a avoir introduit la banane en Afrique et que les Bantous devaient connaitre cette plante avant d'entrer en contact avec les Malgaches. Les auteurs de cette contribution adoptent cette these, mais considerent egalement la probabilite d'une entree sur le continent africain, par vagues successives, de groupes distincts de bananes et de l'arrivee des plaintains en premier. Apres un rappel des categories de bananes presentes sur le continent, ils developpent plus particulierement l'histoire de l'introduction et de la diffusion des plantains dans le monde bantou ancien

Published
1994
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44. Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group

Author

Chris T. Derk, Wanda Maglione, Ileana Nicoara, Ulrich A. Walker, Alexandra Balbir-Gurman, Evelien Ton, R. E. de Souza, Branimir Anić, Roberto Caporali, L. Lonzetti, Jiri Stork, Daniela Opris, Ina Kötter, Stefan Heitmann, Stefano Bombardieri, J.M. van Laar, Evgeny Nasonov, Paul Hasler, Srdan Novak, S. Alhasani, Yannick Allanore, James R. Seibold, Murat Inanc, C. A. Von Mühlen, Raffaella Scorza, P. Eilbacher, G. Udrea, Oliver Distler, Brigitte Krummel-Lorenz, Britta Maurer, Otylia Kowal-Bielecka, Valeria Riccieri, Gianluca Moroncini, Alberto Sulli, Daniel E. Furst, Susanne Ullman, Y. Braun, Alessandro Mathieu, F. Stoeckl, I. Miniati, Percival D. Sampaio-Barros, Nemanja Damjanov, Henrik Nielsen, Patricia Carreira, Raffaele Pellerito, M. Buslau, Marco Matucci-Cerinic, E. De Langhe, Thierry Zenone, Peter Nash, D. Comina, Armando Gabrielli, Luc Mouthon, Jae Bum Jun, G. Riemekasten, Blaž Rozman, N. Del Papa, L. Alhajjar, Jutta G Richter, Jaap Fransen, Eric Hachulla, Stanislaw Sierakowsky, Miroslav Mayer, Małgorzata Widuchowska, Nicolas Hunzelmann, Ingo H. Tarner, M. Saracco, Coziana Ciurtin, Carlo Chizzolini, Maurizio Cutolo, P. Rehberger, Matthias Seidel, R. Ionitescu, Simona Rednic, Ulf Müller-Ladner, Paola Caramaschi, F.H.J. van den Hoogen, J.A. Pereira da Silva, Camillo Ribi, Christopher P. Denton, S. Bellando Randone, Magdalena Szmyrka-Kaczmarek, A Tyndall, Carmen Pizzorni, D. Launay, Jérôme Avouac, Rene Westhovens, Margitta Worm, Frank A. Wollheim, M. Lemos Lopes, C. Mihai, A. Sipek-Dolnicar, Alessandra Vacca, M. Meurer, Laura Bazzichi, Cord Sunderkötter, Cecília Varjú, Eugeniusz J. Kucharz, Søren Jacobsen, Vanessa Smith, Richard M. Silver, Gabriele Valentini, AT Kotulska, F De Keyser, M. Baresic, E. Rath, Marie Vanthuyne, Carolina de Souza Müller, S. Popa, Guido Valesini, Madelon C. Vonk, Dominique Farge, Ruxandra Ionescu, P. Coelho, B. Granel, A. Della Rossa, Maria João Salvador, T. Tourinho, Annegret Kuhn, Ewa Morgiel, C. Durant, L. Czirják, Maria Uprus, Tatiana Nevskaya, Paolo Amerio, Paolo Airò, Hans P. Kiener, D. Vealex, Avouac, J, Fransen, J, Walker, Ua, Riccieri, V, Smith, V, Muller, C, Miniati, I, Tarner, Ih, Randone, Sb, Cutolo, M, Allanore, Y, Distler, O, Valentini, Gabriele, Czirjak, L, MÜLLER LADNER, U, Furst, De, Tyndall, A, MATUCCI CERINIC, M, Eustar, Group, and University of Zurich

Subjects
medicine.medical_specialty, Delphi Technique, 2745 Rheumatology, Immunology, MEDLINE, Delphi method, 610 Medicine & health, Skin Diseases, General Biochemistry, Genetics and Molecular Biology, Scleroderma, Microscopic Angioscopy, Diagnosis, Differential, Fingers, Rheumatology, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Immunology and Allergy, Edema, Humans, skin and connective tissue diseases, computer.programming_language, Core set, 2403 Immunology, Scleroderma, Systemic, business.industry, 10051 Rheumatology Clinic and Institute of Physical Medicine, Raynaud Disease, medicine.disease, Surgery, Early Diagnosis, Family medicine, Antibodies, Antinuclear, Cohort, 2723 Immunology and Allergy, diagnostic criteria, early diagnosis, systemic sclerosis, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Observational study, business, computer, Delphi, Rheumatism
Abstract

ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting.ConclusionThe three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Published
2010

45. Performance studies of the CMS Strip Tracker before installation

Author

Roberto Castello, P. Siegrist, Sukanta Dutta, A. Syed, J. Rochet, Pierre Marage, C. Mc Guinness, L. Quertermont, A. Bonnevaux, M. Galanti, S. Butt, Renato Potenza, M. Nigro, R. Brauer, A. Zatserklyaniy, Boris Mangano, Fabrizio Palla, C. Maazouzi, A. C. Kraan, A. Profeti, Kevin Burkett, M. Costa, Dario Bisello, Ariella Cattai, Frank Hartmann, Alin Titus Serban, Laura Borrello, V. Roberfroid, S. Steiner, P. Van Mechelen, Frederic Jean Ronga, Filippo Bosi, Jean-Laurent Agram, P. Sharp, Michael Wlochal, M. Cardaci, A. Linn, F. Maletta, Otilia Militaru, P. Cariola, M. Ceccanti, Donato Creanza, E. Skup, A. Satpathy, S. Schmid, Corrinne Mills, R. Stark, T. Affolder, J. Heyninck, Duong Nguyen, J. Lamb, Volker Adler, N. Luzhetskiy, E. Anttila, G. Martinelli, G. Guillot, G. De Robertis, D. Uhl, Nuno Leonardo, N. Estre, L. Simms, C. Avanzini, M. Wingham, R. Hamdorf, V. Radicci, T. Boccali, Christopher Martin, Josef Hrubec, E. A. De Wolf, J. L. Bonnet, C. Regenfus, Stephen Robert Wagner, A. Basti, S. Schael, Jorgen D'Hondt, Krzysztof Piotrzkowski, Geoffrey Hall, Finn Rebassoo, Guido Tonelli, Sebastiano Albergo, C. Cerri, D. Pandoulas, S. Hänsel, Pascal Vanlaer, Frank Raupach, Salvatore My, S. Reznikov, S. Linari, Othmane Bouhali, David Mason, F. Calzolari, Joe Incandela, W. Beaumont, Wolfgang Waltenberger, Ghislain Grégoire, Piergiulio Lenzi, Th. Hermanns, G. Maggi, Maurizio Biasini, C. Genta, Henrik Jeldtoft Jensen, R. Hooper, K. V. Tsang, B. Checcucci, Simone Gennai, Burton Betchart, A. Kuronen, N. De Filippis, L. Perchalla, T. Rommerskirchen, L. Zaccarelli, S. Kreyer, M. Pernicka, J. Chen, A. Furgeri, G. Magazzu, F. Manolescu, H. Postema, Devis Pantano, Teimuraz Lomtadze, M. Eppard, G. Gelin, S. Korjenevski, Nicola Pozzobon, I. Pal, R. Frühwirth, Max Weber, Alessandro Paccagnella, A. Onnela, N. Lumb, Matthew Scott Rudolph, P. Blüm, Mia Tosi, M. De Mattia, Y. Gotra, E. Delmeire, G. Segneri, Giuseppe Zito, Y. Shah, F. Didierjean, D. Benedetti, Olivier Devroede, Giovanni Petrucciani, Achim Stahl, F. Ambroglini, I. M. Anghel, Ettore Focardi, Gordon H. Hanson, Leonard Spiegel, Nicola Bacchetta, F. Dumitrache, S. Elgammal, M. Preda, Jonathan Fulcher, Tapio Lampén, L. Berretta, Dieter Jahn, C. Hinchey, Tommaso Dorigo, Markus Friedl, C. Ljuslin, Oliver Gutsche, T. Moulik, Horst Breuker, Lutz Feld, G. Baulieu, C. Sigaud, N. Rubinstein, T. Dupasquier, M. Fahrer, G. A. Lungu, Panja-Riina Luukka, M. Loreti, Robert Klanner, G. Dirkes, D. Heydhausen, Kristian Allan Hahn, I. Villella, Andrey Ostapchuk, Livio Fanò, D. Rizzi, P. Steck, L. Masetti, Ivan Reid, Ijaz Ahmed, A. S. Giolo-Nicollerat, S. Burke, K. Affolder, S. Moccia, Stefano Mersi, S. Tkaczyk, David Stuart, A. Moggi, Peter Schleper, S. Michal, Keith Ulmer, Philip Baringer, Jorma Tuominiemi, Piero Giorgio Verdini, Nicholas Cripps, Pierre Juillot, S. Cihangir, N. Giudice, Alexander Schmidt, Th. Müller, T. Speer, Gabriele Balestri, Gero Flucke, E. Bock, V. E. Bazterra, J. D. Richman, John A Coughlan, R. Stringer, C. Noeding, L. Benucci, M. De Palma, Daniel E. Hale, D. Ricci, F. Mariani, Veikko Karimäki, Oliver Pooth, M. Giorgi, C. Kukulies, Gaelle Boudoul, Gian Mario Bilei, G. De Lentdecker, Alexander Dierlamm, Lorenzo Foà, Otman Charaf, Roberto Dell'Orso, L. Kottelat, Roberto Chierici, Giancarlo Mantovani, Oliver Buchmuller, N. Magini, G. Bagliesi, J. Olzem, Vincent Lemaitre, A. Kaminsky, D. Michotte, G. Sala, M. Marcantonini, Piero Giubilato, J. Kostesmaa, T. Lindén, Jochen Kaminski, E. Butz, Georg Steinbrück, F. Raffaelli, M. A. Saizu, R. Ranieri, G. Kaussen, Barbara Clerbaux, M. Brianzi, Georgios Anagnostou, S. Giusti, Nhan Viet Tran, Jan Troska, Robert Bainbridge, Claude Amsler, Peter R Hobson, Domenico Giordano, M. Massa, Cristina Tuve, E. Zerev, Alberto Messineo, B. Trocme, John H. Wickens, Jean-Marie Brom, Meenakshi Narain, C. Vander Velde, M. Noy, J. Ribnik, Mark Pesaresi, H. Incandela, Alessia Tricomi, R. Robinson, S. Heier, I. Goitom, O. Zorba, A. Macchiolo, A. S. Cucoanes, D. Callahan, F. Drouhin, A. Crook, Philip Harris, U. Pein, Jaakko Härkönen, M. A. Borgia, Vitaliano Ciulli, Paolo Azzurri, U. Cazzola, P. Buhmann, Ulrich Goerlach, N. Guardone, L. Teodorescu, Elizaveta Shabalina, D. Kartashov, S. Taghavi, P. Van Hove, S. Vanzetto, Duccio Abbaneo, Andrea Rizzi, M. Oberegger, A. K. Honma, S. Frosali, C. Wastiels, I. Church, R. Strub, Eric Christian Chabert, C. Olivetto, A. Bocci, A. Candelori, Andrea Venturi, Rino Castaldi, Th. Keutgen, Valery Zhukov, Steve Nahn, Marco Meschini, R. Grabit, M. Gateau, Mariarosaria D'Alfonso, S. De Weirdt, S. Müller, D. Kcira, C. Bloch, X. Rouby, Alice Bean, Katja Klein, D. Sentenac, Derek Barge, E. Widl, B. Broccolo, Laurent Mirabito, J. Dietch, Steven Lowette, J. Hosselet, Regina Demina, Sandor Czellar, D. White, Johannes Hauk, Paolo Petagna, Serena Mattiazzo, G. Pierschel, Z. C. Yang, Peter Robmann, Paolo Spagnolo, B. Florins, Daniel Teyssier, Jean-Charles Fontaine, Andromachi Tsirou, A. Marchioro, Francisco Yumiceva, Karl Heinz Hoffmann, M. Thomas, A. Ronzhin, Attilio Santocchia, M. Frey, I. Akhtar, Francois Vasey, Karl Gill, M. Delattre, Marko Dragicevic, J. Stoner, C. K. Lae, V. Postolache, Geng-Yuan Jeng, H. Esser, F. Noto, D. Sprenger, Natale Demaria, J.D. Berst, Marvin Johnson, P. Van Mulders, M. Pioppi, Ernesto Migliore, Hans-Jürgen Simonis, G. Petragnani, Andrea Giammanco, S. Sanhueza, Gregory Habib Hammad, J. F. Pernot, H. Liu, Jean-Roch Vlimant, J. Muffat-Joly, G. Schwering, P. Tropea, Stefaan Tavernier, W. De Boer, Luigi Fiore, Cecilia Elena Gerber, M. H. Zoeller, Roberto Covarelli, Ian R Tomalin, P. Tempesta, J. P. Ernenwein, D. Orbaker, B. Ledermann, R. Farano, A. Soldani, R. Goorens, J. P Dewulf, G. Sanguinetti, E. Scarlini, S. Swain, Didier Contardo, S. Kyre, William J Spalding, Salvatore Costa, D. C. Miner, G. Parrini, E. De Langhe, L. Van Lancker, B. Caponeri, J. Kortesmaa, E. Babucci, Didar Dobur, F. Schirra, Paolo Lariccia, M. Ageron, N. Manna, S. Bianucci, Manfred Krammer, T. Miao, Kevin Sung, Thomas Bergauer, Roberto Cecchi, P Petit, Vincenzo Chiochia, Claudio Campagnari, Teppo Mäenpää, Mika Huhtinen, F. Benotto, C. Piccut, C. Paillard, R. Della Negra, Abdenour Lounis, M. Poettgens, A. Slav, L. Christofek, L. M. Edera, Bruno Wittmer, Joris Maes, Lucia Silvestris, Franco Ligabue, M. Vander Donckt, M. Tessaro, Joanne Cole, F. Bracci, Hien Nguyen, Eija Tuominen, L. Wilke, Roberto Tenchini, Pieter Everaerts, P. Graehling, T. Liamsuwan, Marcel Vos, S. Jaditz, R. Haroutunian, G. Landi, Simone Paoletti, Greg Landsberg, E. Daubie, D. Staszak, M. Nikolic, P. Mammini, H. Steininger, Francesco Fiori, F. P. Schilling, R. Ferorelli, Eric Chabanat, L. Gross, Stephane Perries, Raffaello D'Alessandro, F. Beissel, Gabriella Pasztor, S. Karaevski, Matthias Ulrich Mozer, Massimiliano Chiorboli, Giovanna Selvaggi, Günter Flügge, Wolfgang Adam, Patrizia Azzi, N. Giraud, P. Kalavase, Andrei Gritsan, S. Khalatian, Markus Stoye, E. Alagoz, V. Sparti, L. Servoli, Carlo Civinini, J. Garberson, Shreya Sarkar, E. Albert, Giacomo Sguazzoni, P. Engström, S. Tolaini, Alessandra Romero, Waclaw Karpinski, Alessandro Giassi, M. Abbas, Pushpalatha C Bhat, Gigi Rolandi, C. Gillissen, V. Khomenkov, Marcello Mannelli, C. M. Sutera, F. Palmonari, David Mark Raymond, Christophe Delaere, Giuseppe Benedetto Cerati, Kostas Kloukinas, A. Allen, Daniele Spiga, M. Hashemi, Giacomo Bruno, L. Bagby, R. Blaes, B. De Callatay, Jacopo Bernardini, Institut de Physique Nucléaire de Lyon (IPNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), informatique, Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Groupe de Recherche en Physique des Hautes Energies (GRPHE), Institut Universitaire de Technologie de Colmar-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Département Recherches Subatomiques (DRS-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), European Organization for Nuclear Research (CERN), CMS, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut Universitaire de Technologie de Colmar, Adam, W., Bergauer, T., Dragicevic, M., Friedl, M., Fruehwirth, R., Haensel, S., Hrubec, J., Krammer, M., Oberegger, M., Pernicka, M., Schmid, S., Stark, R., Steininger, H., Uhl, D., Waltenberger, W., Widl, E., Van Mechelen, P., Cardaci, M., Beaumont, W., de Langhe, E., de Wolf, E. A., Delmeire, E., Hashemi, M., Bouhali, O., Charaf, O., Clerbaux, B., Dewulf, J. P., Elgammal, S., Hammad, G., de Lentdecker, G., Marage, P., Velde C., Vander, Vanlaer, P., Wickens, J., Adler, V., Devroede, O., De Weirdt, S., D'Hondt, J., Goorens, R., Heyninck, J., Maes, J., Mozer, M., Tavernier, S., Van Lancker, L., Van Mulders, P., Villella, I., Wastiels, C., Bonnet, J. L., Bruno, G., De Callatay, B., Florins, B., Giammanco, A., Gregoire, G., Keutgen, T. h., Kcira, D., Lemaitre, V., Michotte, D., Militaru, O., Piotrzkowski, K., Quertermont, L., Roberfroid, V., Rouby, X., Teyssier, D., Daubie, E., Anttila, E., Czellar, S., Engstrom, P., Harkonen, J., Karimaki, V., Kostesmaa, J., Kuronen, A., Lampen, T., Linden, T., Luukka, P. R., Maenpaa, T., Michal, S., Tuominen, E., Tuominiemi, J., Ageron, M., Baulieu, G., Bonnevaux, A., Boudoul, G., Chabanat, E., Chabert, E., Chierici, R., Contardo, D., Della Negra, R., Dupasquier, T., Gelin, G., Giraud, N., Guillot, G., Estre, N., Haroutunian, R., Lumb, N., Perries, S., Schirra, F., Trocme, B., Vanzetto, S., Agram, J. L., Blaes, R., Drouhin, F., Ernenwein, J. P., Fontaine, J. C., Berst, J. D., Brom, J. M., Didierjean, F., Goerlach, U., Graehling, P., Gross, L., Hosselet, J., Juillot, P., Lounis, A., Maazouzi, C., Olivetto, C., Strub, R., Van Hove, P., Anagnostou, G., Brauer, R., Esser, H., Feld, L., Karpinski, W., Klein, K., Kukulies, C., Olzem, J., Ostapchuk, A., Pandoulas, D., Pierschel, G., Raupach, F., Schael, S., Schwering, G., Sprenger, D., Thomas, M., Weber, M., Wittmer, B., Wlochal, M., Beissel, F., Bock, E., Flugge, G., Gillissen, C., Hermanns, T., Heydhausen, D., Jahn, D., Kaussen, G., Linn, A., Perchalla, L., Poettgens, M., Pooth, O., Stahl, A., Zoeller, M. H., Buhmann, P., Butz, E., Flucke, G., Hamdorf, R., Hauk, J., Klanner, R., Pein, U., Schleper, P., Steinbrueck, G., Bluem, P., De Boer, W., Dierlamm, A., Dirkes, G., Fahrer, M., Frey, M., Furgeri, A., Hartmann, F., Heier, S., Hoffmann, K. H., Kaminski, J., Ledermann, B., Liamsuwan, T., Mueller, S., Mueller, T. h., Schilling, F. P., Simonis, H. J., Steck, P., Zhukov, V., Cariola, P., De Robertis, G., Ferorelli, R., Fiore, L., Preda, M., Sala, G., Silvestris, L., Tempesta, P., Zito, G., Creanza, D., De Filippis, N., De Palma, M., Giordano, D., Maggi, G., Manna, N., My, S., Selvaggi, G., Albergo, S., Chiorboli, M., Costa, S., Galanti, M., Giudice, N., Guardone, N., Noto, F., Potenza, R., Saizu, M. A., Sparti, V., Sutera, C., Tricomi, A., Tuve, C., Brianzi, M., Civinini, C., Maletta, F., Manolescu, F., Meschini, M., Paoletti, S., Sguazzoni, G., Broccolo, B., Ciulli, V., D'Alessandro, R., Focardi, E., Frosali, S., Genta, C., Landi, G., Lenzi, P., Macchiolo, A., Magini, N., Parrini, G., Scarlini, E., Cerati, G., Azzi, P., Bacchetta, N., Candelori, A., Dorigo, T., Kaminsky, A., Karaevski, S., Khomenkov, V., Reznikov, S., Tessaro, M., Bisello, D., De Mattia, M., Giubilato, P., Loreti, M., Mattiazzo, S., Nigro, M., Paccagnella, A., Pantano, D., Pozzobon, N., Tosi, M., Bilei, G. M., Checcucci, B., Fano, L., Servoli, L., Ambroglini, F., Babucci, E., Benedetti, D., Biasini, M., Caponeri, B., Covarelli, R., Giorgi, M., Lariccia, P., Mantovani, G., Marcantonini, M., Postolache, V., Santocchia, A., Spiga, D., Bagliesi, G., Balestri, G., Berretta, L., Bianucci, S., Boccali, T., Bosi, F., Bracci, F., Castaldi, R., Ceccanti, M., Cecchi, R., Cerri, C., Cucoanes, A. S., Dell'Orso, R., Dobur, D., Dutta, S., Giassi, A., Giusti, S., Kartashov, D., Kraan, A., Lomtadze, T., Lungu, G. A., Magazzu, G., Mammini, P., Mariani, F., Martinelli, G., Moggi, A., Palla, F., Palmonari, F., Petragnani, G., Profeti, A., Raffaelli, F., Rizzi, D., Sanguinetti, G., Sarkar, S., Sentenac, D., Serban, A. T., Slav, A., Soldani, A., Spagnolo, P., Tenchini, R., Tolaini, S., Venturi, A., Verdini, P. G., Vos, M., Zaccarelli, L., Avanzini, C., Basti, A., Benucci, L., Bocci, A., Cazzola, U., Fiori, F., Linari, S., Massa, M., Messineo, A., Segneri, G., Tonelli, G., Azzurri, P., Bernardini, J., Borrello, L., Calzolari, Federico, Foa, L., Gennai, S., Ligabue, Franco, Petrucciani, G., Rizzi, A., Yang, Z., Benotto, F., Demaria, N., Dumitrache, F., Farano, R., Borgia, M. A., Castello, R., Costa, M., Migliore, E., Romero, A., Abbaneo, D., Abbas, M., Ahmed, I., Akhtar, I., Albert, E., Bloch, C., Breuker, H., Butt, S., Buchmuller, O., Cattai, A., Delaere, C., Delattre, M., Edera, L. 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Subjects
Chiller, Physics - Instrumentation and Detectors, Physics::Instrumentation and Detectors, Silicon Detectors, CMS, education, Monte Carlo method, FOS: Physical sciences, 114 Physical sciences, 01 natural sciences, Large detector systems for particle and astroparticle physics ARXIV EPRINT, High Energy Physics - Experiment, High Energy Physics - Experiment (hep-ex), Data acquisition, Particle tracking detectors, 0103 physical sciences, Electronics, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Detectors and Experimental Techniques, 010306 general physics, Instrumentation, Mathematical Physics, Physics, Large Hadron Collider, 010308 nuclear & particles physics, business.industry, Large detector systems for particle and astroparticle physics, Emphasis (telecommunications), Detector, Electrical engineering, Instrumentation and Detectors (physics.ins-det), Coolant, CMS strip tracker, business, performance
Abstract

In March 2007 the assembly of the Silicon Strip Tracker was completed at the Tracker Integration Facility at CERN. Nearly 15% of the detector was instrumented using cables, fiber optics, power supplies, and electronics intended for the operation at the LHC. A local chiller was used to circulate the coolant for low temperature operation. In order to understand the efficiency and alignment of the strip tracker modules, a cosmic ray trigger was implemented. From March through July 4.5 million triggers were recorded. This period, referred to as the Sector Test, provided practical experience with the operation of the Tracker, especially safety, data acquisition, power, and cooling systems. This paper describes the performance of the strip system during the Sector Test, which consisted of five distinct periods defined by the coolant temperature. Significant emphasis is placed on comparisons between the data and results from Monte Carlo studies., Comment: 40 pages, 39 figures

Published
2009
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46. Increasing in vitro germination of Musa balbisiana seed

Author

J. C. Afele and E. De Langhe

Subjects
biology, food and beverages, Plant physiology, Embryo, Horticulture, biology.organism_classification, In vitro, Musaceae, Plantlet, Germination, Musa balbisiana, embryonic structures, Botany, Longitudinal axis
Abstract

Seeds of Musa balbisiana were soaked in water for five days prior to excision of embryos. Embryos with their longitudinal axis laid flat and half-way embedded on agar-solidified medium produced the highest germination and the most desirable plantlet characteristics. Germination in vitro was 94% within 7 days compared to 50% after 54 days for greenhouse-sown seeds.

Published
1991
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47. Influence of explant source on in vitro axillary shoot formation in oak seedlings

Author

E. De Langhe, A. Pieters, H. Volkaert, and J. Schoofs

Subjects
Axillary shoot formation, integumentary system, Physiology, fungi, food and beverages, Plant Science, Biology, In vitro, Quercus robur L, Tissue culture, Activated charcoal, Shoot, Botany, Woody plant, Explant culture
Abstract

In vitro shoot development was slower for apical shoot explants of young oak (Quercus robur L.) seedlings growing on Woody Plant Medium containing activated charcoal than for nodal shoot explants. The rate of in vitro shoot development was slowest in explants taken from seedlings that were undergoing rapid shoot elongation and most rapid in explants taken from seedlings that had stopped elongating and had fully expanded leaves. Maximum rooting was achieved on half-strength Woody Plant Medium containing activated charcoal. Rooting ability was not influenced by explant source.

Published
1990
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48. Inspiratory flow rates at different levels of resistance in elderly COPD patients

Author

E Hardeman, Marc Decramer, P VandenBrande, T Philps, Wim Janssens, Thierry Troosters, and E De Langhe

Subjects
Pulmonary and Respiratory Medicine, Spirometry, Male, medicine.medical_specialty, Vital capacity, Aging, Inspiratory Capacity, Pulmonary Disease, Chronic Obstructive, Internal medicine, Forced Expiratory Volume, Administration, Inhalation, Medicine, Humans, Metered Dose Inhalers, Peak flow meter, Lung, measurement_unit, Aged, Aged, 80 and over, COPD, medicine.diagnostic_test, business.industry, Inhaler, Nebulizers and Vaporizers, Peak Inspiratory Flow Rate, medicine.disease, Dry-powder inhaler, Inhalation, Case-Control Studies, measurement_unit.measuring_instrument, Cardiology, Physical therapy, Powders, business
Abstract

Dry powder inhalers (DPIs) are increasingly replacing metered dose inhalers in elderly chronic obstructive pulmonary disease (COPD) patients. However, most DPIs are dependent on inspiratory flow, which is compromised by the ageing process itself. Using the in-check dial method, the present study compared peak inspiratory flow (PIF) rates in 26 elderly COPD patients and 14 matched control subjects, at a pre-set resistance level of the Aeroliser, Diskus and Turbuhaler inhalers. It was found that the PIF measured by the in-check method positively correlated with the PIF derived from spirometry, forced vital capacity and maximal inspiratory pressure, while a negative, but significant, correlation was observed with age. PIF derived from spirometry and age were independent variables which determined PIF across the device, whereas the presence or absence of COPD was not related. When comparing elderly COPD patients with matched elderly controls no difference could be found in PIF at the different resistances. However, an important number of patients did not reach the recommended flow rate, especially when using the Turbuhaler (30%). In conclusion, the present study demonstrates that, in elderly patients, the ability to generate sufficient inspiratory flow across a dry powder inhaler is compromised, irrespective of the presence of chronic obstructive pulmonary disease.

Published
2007

49. CMS physics technical design report, volume II: Physics performance

Author

G. Russo, R. Halsall, H. L. Zhuang, Stephan Linn, Stefanos Dris, J.F. Gunion, D. Delikaris, David Mark Raymond, Christophe Delaere, J. Caballero Bejar, Alex Kamenev, Victor Kim, Armando Lanaro, Sajjad Asghar, Vivek Sharma, P. Mereu, S. B. Kim, M. G. Albrow, Kostas Kloukinas, R. A. Kvatadze, Y. Velikzhanin, C. Mavrommatis, J. T. Rhee, M. Guerzoni, Robert M Harris, F. Romano, Daniele Spiga, Flera Rizatdinova, Dmitry Gorbunov, Giacomo Bruno, Laszlo Boldizsar, W. E. Johns, B. De Callatay, Pushpalatha C Bhat, M. Pioppi, Lawrence Sulak, L. J. Gutay, M. Hashemi, W. Badgett, A. Bartoloni, C. Y. Chien, E. Marinova, Daniel Robert Marlow, J. M. Barcala, C. Sabev, Roberto Sacchi, P. Bartalini, B. Panev, J. Reinhold, Yves Sirois, J. Ying, M. Demarteau, Alicia Calderon, Arno Heister, Lothar At Bauerdick, Marco Meschini, R. Wilkinson, Tejinder Virdee, Mirko Planinic, G. Martinelli, Y. Ershov, Piotr Traczyk, M. Ageron, Kirill Prokofiev, S. De Visscher, W. Bertl, Julia Thom, D. S. Bailey, N. Manna, Francesco Navarria, A. Karar, Pierre Ramond, Lucia Silvestris, R. Eichler, Neeti Parashar, S. Cucciarelli, R. Gokieli, Christopher George Tully, L. Masetti, I. Gonzalez Cabellero, Klaus Rabbertz, S. Zelepoukine, Sebastiano Albergo, A. Bonnevaux, P. Fabbricatore, Claudio Campagnari, V. Timciuc, O. Zorba, Igor Lokhtin, Ezio Maina, Colin Bernet, Nadia Pastrone, M. Galanti, K. Marasovic, Jim Kowalkowski, M. Zielinski, P. Aspell, Teppo Mäenpää, Pamela Klabbers, V. B. Francis, I. Diaz Merino, H. A. Sanchez Hernandez, Valery Zhukov, Christos Leonidopoulos, Gyorgy Bencze, Dimitri Bourilkov, Vassili Kachanov, Marina Passaseo, Patrick Slattery, J. Schümann, K. Cho, Hans-Christian Kaestli, Filip Moortgat, Francesca Nessi-Tedaldi, S. K. Lalwani, P. Trüb, D. Wenman, Aliaksandr Litomin, P. Siegrist, S. K. Oh, M. Kossov, A. Slav, Nicanor Colino, Z. Wlodarczyk, J. Amundson, H. Mathez, A. Papageorgiou, Pete Markowitz, J. Blocki, I. Soric, L. Stepanova, Pierluigi Paolucci, Amitabh Lath, Jianhong Wu, N. Sinanis, R. Imlay, Dario Menasce, T. Grassi, S. Lusin, H. von Gunten, T. Weiler, Gyorgy Vesztergombi, J. P. Dewulf, G. Marian, B. A. Barnett, N. Iyurin, Frank Jm Geurts, T. Hesselroth, Nikolaos Manthos, Martin Grunewald, Oleg Prokofyev, Wolfram Erdmann, V. Elsha, A. Krokhotin, Livio Fanò, David Barney, Stephanie Beauceron, Mark Raymond Adams, Nicolo Cartiglia, Alexander Oh, Safdar Abbas, Giorgio Apollinari, M. Jenkins, G. Belli, E. E. Boos, Elena Accomando, M. Afaq, Yan-Lin Ye, M. Serin-Zeyrek, Karl Gill, H. S. Chen, Roland Horisberger, S. Mersi, Serguei Ganjour, P. Tempesta, Sergio Cittolin, Julien Caudron, I. Schmidt, Stefan Schael, R. Dabrowski, Sudhir Malik, M. Cardenas Montes, P. S. Flower, K. Gabathuler, T. L. Watts, D. A. Sanders, V. Bhandari, G. Lukhanin, Y. Fu, S. Vassiliev, I. Legrand, Srecko Morovic, Francois Vasey, Yuan Chao, Y. Geerebaert, Michele Arneodo, Steve Reucroft, Boaz Klima, Richard G Kellogg, Pavel Demin, G. Schwering, V. Papadimitriou, Daijin Kim, Paolo Vitulo, William J Spalding, Jay Roberts, I. Pal, N. Estre, L. Tauscher, Andras Laszlo, S. Spangler, Darien Wood, H. Suter, Ia Iashvili, W. Tanenbaum, Yury Ivanov, Andre Sznajder, F. Rondeaux, S. Y. Jung, Yuri Gershtein, Monoranjan Guchait, Brajesh C Choudhary, Paul David Luckey, M. Sani, D. Lanske, N. Ilina, Ian Shipsey, J. G. Shiu, Artur Kalinowski, Igor Emeliantchik, B. Heltsley, Robin Erbacher, Henryk Czyrkowski, L. Rurua, R. Beuselinck, Umesh Joshi, Irina Vardanyan, David B. Cline, M. Hansen, P. Bordalo, Ariella Cattai, G. Gomezo, J. A. Bakken, Jordan Nash, Sung Keun Park, E. Luiggi Lopez, M. Wensveen, R. Folch, E. Carrone, Cristina Riccardi, D. Krpic, S. Magni, Nicholas John Hadley, Karl Matthew Ecklund, M. Stettler, S. Vanini, Andrey Vorobyev, Matteo Risoldi, J. Bourotte, Kati Lassila-Perini, A. De Benedetti, M. Aldaya Martin, M. Duda, A. Sadovski, K. Freudenreich, Javier Cuevas, Georgios Anagnostou, Melody A. Swartz, Maxwell Chertok, Danek Kotlinski, N. M. Cason, Carmen Albajar, Erhan Gülmez, S. C. Tonwar, Kaori Maeshima, Martin Erdmann, A. Oehler, G. Eulisse, V. Kozlov, Frank Hartmann, Luciano Orsini, Vasile Mihai Ghete, Giuseppe Bagliesi, A. Cyz, Harvey B Newman, Christof Roland, Y. S. Chung, V. V. Mitsyn, Roman Ryutin, E. Isiksal, L. Lueking, Petra Merkel, Pelin Kurt, S. Erhan, F. M. Farina, M. Cerutti, O.V. Dvornikov, V. Lysiakov, L. Barbone, V. Drollinger, Robert Stone, J. N. Butler, A. Kayis Topaksu, H. A. Salazar Ibarguen, Marcello Abbrescia, K. Datsko, J. Grahl, David Colling, M. Michelotto, Sergey Petrushanko, Patricia McBride, Krzysztof Doroba, Jorge Luis Rodriguez, Claire Shepherd-Themistocleous, Alan Sill, Z. Gao, Mikhail Korzhik, Paolo Lariccia, M. Letheren, Daniel Denegri, M. H.G. Souza, Vyacheslav Valuev, Thomas Ferguson, Alain Ninane, D. Phillips, Ren-Yuan Zhu, Pascal Vanlaer, Luciano Barone, C. 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Foeth, Belforte, S., Cossutti, F., DELLA RICCA, Giuseppe, Gobbo, B., Penzo, A., Laboratoire d'Annecy de Physique des Particules (LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Département Recherches Subatomiques (DRS-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), informatique, Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), CMS, Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire d'Annecy de Physique des Particules (LAPP), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Bayatian, G, Chatrchyan, S, Hmayakyan, G, Sirunyan, A, Adam, W, Bergauer, T, Dragicevic, M, Ero, J, Friedl, M, Fruehwirth, R, Ghete, V, Glaser, P, Hrubec, J, Jeitler, M, Krammer, M, Magrans, I, Mikulec, I, Mitaroff, W, Noebauer, T, Pernicka, M, Porth, P, Rohringer, H, Strauss, J, Taurok, A, Waltenberger, W, Walzel, G, Widl, E, Wulz, C, Fedorov, A, Korzhik, M, Missevitch, O, Zuyeuski, R, Chekhovsky, V, Dvornikov, O, Emeliantchik, I, Litomin, A, Mossolov, V, Shumeiko, N, Solin, A, Stefanovitch, R, Gonzalez, J, Tikhonov, A, Petrov, V, D'Hondt, J, De Weirdt, S, Goorens, R, Heyninck, J, Lowette, S, Tavernier, S, Van Doninck, W, Van Lancker, L, Bouhali, O, Clerbaux, B, De Lentdecker, G, Dewulf, J, Mahmoud, T, Marage, P, Neukermans, L, Sundararajan, V, Vander Velde, C, Vanlaer, P, Wickens, J, Assouak, S, Bonnet, J, Bruno, G, Caudron, J, De Callatay, B, De Jeneret, J, De Visscher, S, Delaere, C, Demin, P, Favart, D, Feltrin, E, Forton, E, Gregoire, G, Kalinin, S, Kcira, D, Keutgen, T, Leibenguth, G, Lemaitre, V, Liu, Y, Michotte, D, Militaru, O, Ninane, A, Ovyn, S, Pierzchala, T, Piotrzkowski, K, Roberfroid, V, Rouby, X, Teyssier, D, Van Der Aa, O, Vander Donckt, M, Daubie, E, Herquet, P, Mollet, A, Romeyer, A, Beaumont, W, Cardaci, M, De Langhe, E, De Wolf, E, Rurua, L, Souza, M, Oguri, V, Santoro, A, Sznajder, A, Vaz, M, Gregores, E, Novaes, S, Anguelov, T, Antchev, G, Atanasov, I, Damgov, J, Darmenov, N, Dimitrov, L, Genchev, V, Iaydjiev, P, Panev, B, Piperov, S, Stoykova, S, Sultanov, G, Vankov, I, Dimitrov, A, Kozhuharov, V, Litov, L, Makariev, M, Marinov, A, Marinova, E, Markov, S, Mateev, M, Pavlov, B, Petkov, P, Sabev, C, Stoynev, S, Toteva, Z, Verguilov, V, Chen, G, Chen, H, He, K, Jiang, C, Li, W, Liu, H, Meng, X, Shen, X, Sun, H, Yang, M, Zhao, W, Zhuang, H, Ban, Y, Cai, J, Liu, S, Qian, S, Yang, Z, Ye, Y, Ying, J, Wu, J, Zhang, Z, Godinovic, N, Puljak, I, Soric, I, Antunovic, Z, Dzelalija, M, Marasovic, K, Brigljevic, V, Ferencek, D, Kadija, K, Morovic, S, Planinic, M, Nicolaou, C, Papadakis, A, Razis, P, Tsiakkouri, D, Hektor, A, Kadastik, M, Kannike, K, Lippmaa, E, Muntel, M, Raidal, M, Aarnio, P, Czellar, S, Haeggstroem, E, Heikkinen, A, Harkonen, J, Karimaki, V, Kinnunen, R, Lampen, T, Lassila Perini, K, Lehti, S, Linden, T, Luukka, P, Michal, S, Maenpaa, T, Nysten, J, Stettler, M, Tuominen, E, Tuominiemi, J, Wendland, L, Tuuva, T, Guillaud, J, Nedelec, P, Sillou, D, Anfreville, M, Beauceron, S, Bougamont, E, Bredy, P, Chipaux, R, Dejardin, M, Denegri, D, Descamps, J, Fabbro, B, Faure, J, Ganjour, S, Gentit, F, Givernaud, A, Gras, P, De Monchenault, G, Jarry, P, Kircher, F, Lemaire, M, Levesy, B, Locci, E, Lottin, J, Mandjavidze, I, Mur, M, Pasquetto, E, Payn, A, Rander, J, Reymond, J, Rondeaux, F, Rosowsky, A, Sun, Z, Verrecchia, P, Baffioni, S, Beaudette, F, Bercher, M, Berthon, U, Bimbot, S, Bourotte, J, Busson, P, Cerutti, M, Chamont, D, Charlot, C, Collard, C, Decotigny, D, Delmeire, E, Dobrzynski, L, Gaillac, A, Geerebaert, Y, Gilly, J, Haguenauer, M, Karar, A, Mathieu, A, Milleret, G, Mine, P, Paganini, P, Romanteau, T, Semeniouk, I, Sirois, Y, Berst, J, Brom, J, Didierjean, F, Drouhin, F, Fontaine, J, Goerlach, U, Graehling, P, Gross, L, Houchu, L, Juillot, P, Lounis, A, Maazouzi, C, Mangeol, D, Olivetto, C, Todorov, T, Van Hove, P, Vintache, D, Ageron, M, Agram, J, Baulieu, G, Bedjidian, M, Blaha, J, Bonnevaux, A, Boudoul, G, Chabanat, E, Combaret, C, Contardo, D, Della Negra, R, Depasse, P, Dupasquier, T, El Mamouni, H, Estre, N, Fay, J, Gascon, S, Giraud, N, Girerd, C, 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Feyzi, F, Gorski, T, Grothe, M, Hogg, W, Jaworski, M, Klabbers, P, Lanaro, A, Loveless, R, De Abril, M, Reeder, D, Smith, W, Wenman, D, Atoyan, G, Dhawan, S, Issakov, V, Neal, H, Poblaguev, A, Zeller, M, Yuldashev, B, TR1918, Demir, Durmuş Ali, Izmir Institute of Technology. Physics, Çukurova Üniversitesi, Fen-Edebiyat Fakültesi, Fizik Bölümü, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics beyond the Standard Model, Large Hadron Collider (LHC), 01 natural sciences, 7. Clean energy, HIGGS-BOSON PRODUCTION, TO-LEADING-ORDER, PRODUCTION CROSS-SECTION, LARGE HADRON COLLIDER, SUPERSYMMETRIC STANDARD MODEL, ELECTROWEAK SYMMETRY-BREAKING, LARGE TRANSVERSE-MOMENTUM, B-C MESON, SUPERCONDUCTING SUPER COLLIDER, SOFTLY BROKEN SUPERSYMMETRY, Vector boson, Settore FIS/04 - Fisica Nucleare e Subnucleare, PARTICLE PHYSICS, CMS, Energy density, technical design report, CERN, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Physics, Large Hadron Collider, Settore FIS/01 - Fisica Sperimentale, Supersymmetry, Physics and Astronomy (all), Nuclear and High Energy Physics, FIS/01 - FISICA SPERIMENTALE, High-density QCD matter, Higgs boson, CMS, LHC, Physics, particles, Higgs, particle physics, detector, accelerator, Particle physics, Standard Model, Settore FIS/03 - Fisica della Materia, Nuclear physics, 0103 physical sciences, 010306 general physics, Settore MAT/07 - Fisica Matematica, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, Little Higgs, pp, LHC, Higgs, supersymmetry, heavy ion, High Energy Physics::Experiment, CERN Large Hadron Collider (LHC), Parton momentum fraction, Minimal Supersymmetric Standard Model
Abstract

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking - through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb-1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z′ and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb-1 to 30 fb-1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing E T, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model. © 2007 IOP Publishing Ltd.

Published
2007
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50. The effect of highly ionising particles on the CMS silicon strip tracker

Author

R. van Staa, L. Perera, Pierre Juillot, A. Linn, V. Bellini, D. Coppage, Simon Kwan, Frank Raupach, Ch. Hörmann, D. Pandoulas, Roberto Dell'Orso, Salvatore My, D. Benedetti, J. P Dewulf, Andrea Candelori, B. De-Callatay, T. A. Bolton, P. Siegrist, Cecilia Elena Gerber, Mário Costa, T. Weiler, Marek Tasevsky, N. Lumb, Alessia Tricomi, K. Gabathuler, M. Nigro, Othmane Bouhali, R. Ranieri, Lutz Feld, C. Grab, Melody A. Swartz, Mika Huhtinen, Piero Giubilato, Tommaso Boccali, Jaakko Härkönen, Danek Kotlinski, Manfred Krammer, F. Defontaines, Salvatore Costa, M. Sani, A. Roy, Andrea Giammanco, Marc Weber, David Colling, Gordon H. Hanson, Benjamin Trocmé, Leonard Spiegel, Robert Klanner, R. Santinelli, M. Pernicka, A. Theel, B. Mangano, Laura Borrello, V. Roberfroid, B. Hegner, Thomas Bergauer, Stephane Perries, Costas Foudas, J. H. Wickens, S. Tkaczyk, Guido Tonelli, J.-M. Brom, Ghislain Grégoire, C. Vander-Velde, Giuseppe Zito, Ettore Focardi, D. Vintache, Raffaello D'Alessandro, B. Gobbi, G. Páztor, Daniel E. Hale, W. De Boer, W. Kahl, Timothy Koeth, Duccio Abbaneo, Karl Gill, A. Moggi, Donato Creanza, W. Braunschweig, Wolfram Erdmann, Wolfgang Waltenberger, J. Jones, J. Heyninck, M. Angarano, U. Holm, Giovanna Selvaggi, Wolfgang Adam, R. Goorens, Fabrizio Palla, T. Kress, F. Boegelspacher, B. A. Barnett, Alessandro Giassi, A. Marchioro, V. Radicci, M. Noy, Alessandra Romero, O. Zorba, Josef Hrubec, M. D’Alfonso, E. A. De Wolf, J. Lamb, Jean-Charles Fontaine, Denis Favart, D. Bisello, M. A. Kubantsev, T. Ten, S. Heier, R. Strub, Eva Halkiadakis, M.R. Pearson, Thomas Müller, G. Sguazzoni, Francois Vasey, A. Ostaptchouk, A. Schultz von Dratzig, N. De Filippis, E. Bartz, Michael Wlochal, A. Furgeri, Steve Schnetzer, Felicitas Pauss, Werner Lustermann, Andromachi Tsirou, Roland Horisberger, Waclaw Karpinski, Krzysztof Piotrzkowski, Paolo Azzurri, Bruno Wittmer, Lucia Silvestris, A. Onnela, S. Kyre, Matteo Risoldi, Alice Bean, Pascal Vanlaer, G. Schwering, Th. Hermanns, N. Dinu, L. Neuckermans, K. W. Bell, Frédéric Drouhin, Geoffrey Hall, L. Christofek, K. Hangarter, Didier Contardo, T. Ortega-Gomez, Umesh Joshi, Robert Stone, F. Charles, D. White, Paolo Petagna, A. Bocci, G. Pierschel, D. Kim, T. Franke, Marco Meschini, Gian Mario Bilei, G. Parrini, S. Kasselmann, C. M. Sutera, Oliver Pooth, N. Magini, N. W. Reay, M. Ageron, Kirill Prokofiev, Alain Ninane, W. Beaumont, U. Pein, A. Flossdorf, S. Korjenevski, M. Demarteau, Geng-Yuan Jeng, Eija Tuominen, Georg Steinbrück, R. N. Tilden, Arno Heister, N. Pukhaeva, S. Worm, Ulrich Goerlach, Claudio Campagnari, Teppo Mäenpää, B. Checcucci, Paolo Lariccia, Rudolf Fruehwirth, Barbara Clerbaux, Cristina Tuve, G. Maggi, R. Siedling, Cristina Biino, A. MacPherson, M. Duda, Gregory Iles, K. Freudenreich, H. Pruys, Gigi Rolandi, M. Bleyl, Andrea Rizzi, G. Segneri, Alan Garfinkel, P. Barrillon, Peter Schleper, A. Hocker, Vincent Lemaitre, Maiko Takahashi, G. Rogers, Marcello Mannelli, P. Blüm, F. Didierjean, J. Mnich, I. Troska, H.-Ch. Kästli, R. Halsall, M. Atac, S. König, A. K. Honma, Rino Castaldi, P. Gartung, R. Brauer, Paul Tipton, M. De Palma, Stefanos Dris, David Mark Raymond, Christophe Delaere, D. Michotte, J.D. Berst, Panja-Riina Luukka, R. L. Lander, Peter Robmann, Ph. Herquet, M. Loreti, B. Atz, Eric Chabanat, L. Gross, M. Frey, G. De Lentdecker, F. Ahmed, M. S. Mennea, F. Beissel, P. Steck, D. Ricci, Horst Breuker, D. A. Sanders, Tuure Tuuva, Cristiana Peroni, X. Rouby, G.W Liang, D. E. Pellett, Sandor Czellar, B. Perea-Solano, T. Speer, A. Basti, Flera Rizatdinova, Alexander Dierlamm, Tomas Lindén, Jacopo Bernardini, N. Bernardino-Rodriguez, Stefaan Tavernier, Paolo Spagnolo, Giacomo Bruno, Roberto Chierici, A. Kaminsky, Claude Amsler, R. Blaes, A. Macchiolo, M. Stoye, A. Dorokhov, Séverine Ovyn, Ricardo Eusebi, Ernesto Migliore, Hans-Jürgen Simonis, Carlo Civinini, S. De-Visscher, Livio Fanò, S. Mersi, P. Tempesta, R. Demina, C. Olivetto, N. Schirm, W. Bertl, J. 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Dirkes, Philip Baringer, John A Coughlan, Valery Zhukov, Sudhir Malik, Daniela Bortoletto, B. C. MacEvoy, F. Palmonari, Natale Demaria, Maria Teresa Brunetti, E. De Langhe, L. Van Lancker, E. Babucci, Vincenzo Chiochia, J. Leaver, S. Schael, G. Favro, Jorgen D'Hondt, J. P. Fernandez, Tilman Rohe, Lorenzo Foà, Joe Incandela, Veikko Karimäki, C. Kukulies, E. Grigoriev, J. Olzem, Domenico Giordano, Alberto Messineo, Laurent Mirabito, Steven Lowette, Robert Bainbridge, K. Wick, G. Magazzu, H. Postema, Markus Friedl, J. Doroshenko, R. Grabit, F. Raffaelli, Katja Klein, S. Assouak, H. Esser, F. Bosi, R. Adolphi, G. De Robertis, Alessandro Paccagnella, I. Boulogne, Nicola Bacchetta, Jonathan Fulcher, Tapio Lampén, A. Frey, M. Fahrer, Piero Giorgio Verdini, Abdenour Lounis, M. Giorgi, Giancarlo Mantovani, R. A. Sidwell, C. Maazouzi, C. Marchettini, S. Tesch, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut de Recherches Subatomiques (IReS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), CMS, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Nuclear and High Energy Physics, Silicon, Physics::Instrumentation and Detectors, Hadron, APV25, chemistry.chemical_element, 01 natural sciences, Nuclear physics, Highly ionising particles, 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], 07.50.-e, 07.89.+b, 29.40.Gx, 85.40.-e, Silicon strip tracker, Sensitivity (control systems), [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, Instrumentation, Compact Muon Solenoid, Physics, Large Hadron Collider, 010308 nuclear & particles physics, CMS, Detector, APV25, CMS, Highly ionising particles, Silicon strip tracker, Chip, Chemistry, chemistry, Engineering sciences. Technology, Beam (structure)
Abstract

Inelastic nuclear collisions of hadrons incident on silicon sensors can generate secondary highly ionising particles (HIPs) and deposit as much energy within the sensor bulk as several hundred minimum ionising particles. The large signals generated by these 'HIP events' can momentarily saturate the APV25 front-end readout chip for the silicon strip tracker (SST) sub-detector of the compact muon solenoid (CMS) experiment, resulting in deadtime in the detector readout system. This paper presents studies of this phenomenon through simulation, laboratory measurements and dedicated beam tests. A proposed change to a front-end component to reduce the APV25 sensitivity to HIP events is also examined. The results are used to infer the expected effect on the performance of the CMS SST at the future large hadron collider. The induced inefficiencies are at the percent level and will have a negligible effect on the physics performance of the SST. (c) 2005 Elsevier B.V. All rights reserved.

Published
2005
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