Flüssigkeit und Korrektheit – Flüssigkeit oder Korrektheit?: Ergebnisse einer Interventionsstudie in niederschwelligen Intensivkursen für erwachsene DaZ-Anfängerinnen und -Anfänger

Cette étude examine l’efficacité d’un enseignement basé principalement sur l’approche lexicale (lexical approach) (Lewis, 1993 ; Lewis, 1997), soit sur l’apprentissage de séquences de mots avec des parties variables (chunks) et sur un entraînement régulier àla fluidité (Nation & Meara, 2002), dans le cadre de cours d’allemand langue seconde, destinés à des adultes débutants en partie peu scolarisés. L’étude, conçue de manière quasi-expérimentale, a comporté un groupe expérimental (GE) et un groupe témoin (GT). Elle a porté sur douze classes, réparties en six paires de deux classes, qui ont étudié un manuel de cours complet. Pour chaque paire, une classe a suivi un enseignement basé sur le concept expérimental et utilisé les ressources didactiques adaptées, tandis quel’autre classe a travaillé selon le concept et avec les ressources didactiques témoin qui, pour l’essentiel, correspondaient au matériel didactique original. Le concept témoin repose principalement sur un enseignement explicite de la grammaire et sur une étude du vocabulaire par mots isolés. Lors d’un test initial puis d’un test final, diverses compétences orales et écrites des participants ont été évaluées. En outre, des entretiens menés avec les enseignants ont permis de récolter des informations quant à l’adéquation des concepts didactiques aux besoins du groupe cible ainsi qu’aux particularités des processus d’enseignement et d’apprentissage propres aux deux groupes. Les entretiens donnent à penser que, dans l’ensemble, les deux concepts permettent un enseignement de bonne qualité. Les participants du groupe expérimental qui ont del’expérience dans l’apprentissage des langues étrangères et ceux qui mettent la priorité sur la correction de leur expression déplorent parfois que les ressources et l’enseignement ne soient pas plus axés sur la grammaire. Ils voient généralement dans l’entraînement à la fluidité une bonne occasion d’apprendre. Les observations des enseignants confirment que le concept expérimental correspond mieux à des apprenants peu scolarisés, alors que le concept témoin est plus adapté à des apprenants disposant d’un bon bagage scolaire. Les enseignants du groupe expérimental regrettent parfois l’absence de la métalangue grammaticale pour corriger les erreurs. De plus, ils déplorent que des erreurs de langue soient souvent répétées et assimilées lors de l’entraînementà la fluidité, et qu’ils n’aient pas suffisamment d’occasions de les corriger.The present study explores the potential value of implementing the Lexical Approach (Lewis, 1993; 1997) and regular fluency trainings (Nation & Meara, 2002) in courses teaching German as a second language to adult beginners who, to varying degrees, have not had much previous schooling. When implementing the Lexical Approach, learning chunks (multiple-word items, partially with open slots) is crucial. Based on a quasi-experimental design with an intervention group (IG) and a control group (CG), twelve classes divided into six pairs worked their way through an entire textbook. The teaching concept and the materials used in one class of each pair implemented the intervention concept, while the concept and the materials used in the other class were mainly in line with the course design foreseen by the original materials, and thus served as a control. Major features of the CG concept include explicit grammar instruction and vocabulary work with single words. Various written and oral language skills were measured in an initial and a final test. Interviews with teachers were held to shed light on the suitability of the teaching concepts for the target group and to better understand the specific features of the teaching and learning processes in both groups. The interviews lead to the conclusion that, in general, both concepts can be applied to good effect. In part, IG learners with experience in learning foreign languages as well as students interested in improving accuracy missed grammar instruction and exercises. Overall they viewed fluency training as a good opportunity to learn. According to the teachers, the IG concept is better suited for students who have had less formal schooling, while the CG approach meets the needs of students with a stronger educational background. Teachers in the IG sometimes missed having a grammatical metalanguageto correct errors; they furthermore found it problematic that they had few opportunities to intervene during fluency training, in which learners frequently repeated, and thus reinforced, incorrect language.Die vorliegende Studie geht der Frage nach, mit welchem Erfolg in Deutsch-als- Zweitsprache-Kursen für teilweise schulungewohnte erwachsene Deutsch- Anfänger/innen mi teinem Unterrichtskonzept gelernt wird, das weitgehend auf dem Lexikalischen Ansatz (Lexical Approach) (Lewis, 1993; 1997), und damit dem Lernen von Chunks (Mehrworteinheitenmit teilweise variablen Stellen), sowie auf regelmässigem Flüssigkeitstraining(Nation & Meara, 2002) beruht. In einem quasi- experimentellen Design mit Interventions- und Kontrollgruppe (IG und KG) arbeiteten zwölf Klassen in sechs Klassenpaaren jeweils einen ganzen Lehrwerkband durch. Unterricht und Materialien der einen Klasse jedes Paares setzten dabei das skizzierte Interventionskonzept um, Unterricht und Materialien der anderen Klasse das Kontrollkonzept, das im Wesentlichen mit dem Konzept derOriginalmaterialien übereinstimmt. Wichtige Elemente des Konzepts der KG sind expliziter Grammatikunterricht und Wortschatzarbeit mit Einzelwörtern. Bei einem Eingangstest und einem Abschlusstest wurden verschiedene schriftliche und mündliche Sprachkompetenzen gemessen. Interviews mit den Kursleitenden sollten zudem u. a. Aufschluss geben über die Eignung der Unterrichtskonzepte für die Zielgruppe sowie über Besonderheiten der Unterrichts- und Lernprozesse in den beiden Gruppen. Aus den Interviews geht hervor, dass nach beiden Konzepten insgesamt gut unterrichtet werden konnte. Kursteilnehmerinnen und -teilnehmer der IG mit Erfahrung im Fremdsprachenlernen sowie solche mit einem Fokus auf Korrektheit vermissten teilweise Grammatikunterricht und -materialien. Das Flüssigkeitstraining anerkannten sie insgesamt als gute Lerngelegenheit. Die Erfahrungen der Kursleitenden bestätigen, dass sich das Konzept der IG eher für Schulungewohnte und das Konzept der KG eher für Schulgewohnte eignet. Den Kursleitenden der IG fehlte gelegentlich bei der Fehlerkorrektur die grammatische Metasprache. Weiter hatten sie Mühe damit, dass beim Flüssigkeitstraining oft fehlerhafte Sprache wiederholt und somit eingeübt wurde, ohne dass sie genügend Gelegenheit für Korrekturen hatten.Il presente studio si interroga sull’efficacia di un insegnamento basato principalmente sull’approccio lessicale (lexical approach) (Lewis, 1993; 1997), focalizzato sull’apprendimento di chunk (sequenze di parole con parti variabili) e sulle esercitazioni di fluenza (Nation & Meara, 2002) in classi di tedesco L2 con apprendenti principianti adulti inparte poco abituati all’apprendimento formale. All’interno di un setting simil-sperimentale, costituito da un gruppo d’intervento eun gruppo di controllo (GI e GC), dodici classi suddivise in sei coppie hanno appreso il tedesco L2 seguendo un manuale. Nelle sei classi composte dal GI, la struttura e i materiali didattici delle lezioni seguono un paradigma didattico orientato allo studio d’intervento appena citato, mentre nelle sei classi composte dal GC, l’insegnamento siattiene principalmente alla traccia prevista da un manuale, le cui caratteristiche principalisono un insegnamento esplicito della grammatica e un apprendimento del lessico con singole parole. Grazie a un test di entrata e un test finale, è stato possibile valutare differenti competenze orali e scritte. Alcune interviste con i docenti hanno in oltre permesso di chiarire questioni legate all’idoneità dei due piani di studio per i gruppi target ma anche di tematizzare particolarità nel processo d’insegnamento e apprendimentodi entrambi i gruppi. Dalle interviste emerge che, seguendo entrambi i piani di studio, è stato possibile insegnare con profitto. Gli apprendenti del GI con esperienze pregresse nell’apprendimentodi LS e tendenti a volersi esprimere correttamente hanno tuttavia lamentato inparte la mancanza dell’insegnamento della grammatica e di materiali didattici su temi grammaticali. Essi hanno tuttavia riconosciuto nelle esercitazioni di fluenza delle buone occasioni d’apprendimento. Le esperienze dei docenti confermano che il piano di studi del GI è più adatto a apprendenti non abituati a studiare una lingua, mentre quello del GC si presta piuttosto a chi è abituato all’apprendimento formale. I docenti del GI hanno sentito la mancanza della metalingua grammaticale in occasione della correzione di errori;inoltre, hanno avuto poche occasioni per correggere errori durante le esercitazioni di fluenza: gli errori erano così ripetuti e parzialmente interiorizzati. I risultati dei due test che valutano lo sviluppo delle diverse competenz

BRAF inhibitor treatment of classical hairy cell leukemia allows successful vaccination against SARS-CoV-2

In classical hairy cell leukemia (HCL), standard treatments including purine analogs achieve a durable response (up to 90%), but lead to severe immunosuppression and long-lasting depletion of CD4 + T lymphocytes. The BRAF inhibitor vemurafenib is effective in HCL, but its use in first-line treatment is restricted to select clinical situations (e.g. active infection). Its impact on immune function or response to vaccines in HCL is unclear. We treated four HCL patients with vemurafenib during the COVID-19 pandemic and monitored immune reconstitution and response to SARS-CoV-2 immunization. All patients responded to HCL treatment with normalization of peripheral blood counts. No severe infections occurred. As an indication of limited immunosuppression by vemurafenib, stable CD4 + and CD8 + T lymphocyte counts and immunoglobulin levels were observed. Three out of four patients received SARS-CoV-2 vaccination (Pfizer-BioNTech) during treatment with vemurafenib. IgG antibody levels against the spike-protein of SARS-CoV-2 were detected (40-818 AE/ml). Our data suggest that vemurafenib has limited effects on cellular and humoral immune function in HCL, which allows for successful SARS-CoV-2 vaccination. These data support the use of BRAF inhibitors during the current pandemic where continued immune response is necessary for minimizing the COVID-19-related risk of non-vaccinated patients

Sensitive Quantitative Proteomics of Human Hematopoietic Stem and Progenitor Cells by Data-independent Acquisition Mass Spectrometry

Physiological processes in multicellular organisms depend on the function and interactions of specialized cell types operating in context. Some of these cell types are rare and thus obtainable only in minute quantities. For example, tissue-specific stem and progenitor cells are numerically scarce, but functionally highly relevant, and fulfill critical roles in development, tissue maintenance, and disease. Whereas low numbers of cells are routinely analyzed by genomics and transcriptomics, corresponding proteomic analyses have so far not been possible due to methodological limitations. Here we describe a sensitive and robust quantitative technique based on data-independent acquisition mass spectrometry. We quantified the proteome of sets of 25,000 human hematopoietic stem/multipotent progenitor cells (HSC/MPP) and three committed progenitor cell subpopulations of the myeloid differentiation pathway (common myeloid progenitors, megakaryocyte-erythrocyte progenitors, and granulocyte-macrophage progenitors), isolated by fluorescence-activated cell sorting from five healthy donors. On average, 5,851 protein groups were identified per sample. A subset of 4,131 stringently filtered protein groups was quantitatively compared across the 20 samples, defining unique signatures for each subpopulation. A comparison of proteomic and transcriptomic profiles indicated HSC/MPP-specific divergent regulation of biochemical functions such as telomerase maintenance and quiescence-inducing enzymes, including isocitrate dehydrogenases. These are essential for maintaining stemness and were detected at proteome, but not transcriptome, level. The method is equally applicable to almost any rare cell type, including healthy and cancer stem cells or physiologically and pathologically infiltrating cell populations. It thus provides essential new information toward the detailed biochemical understanding of cell development and functionality in health and disease

Proteomic identification of proliferation and progression markers in human polycythemia vera stem and progenitor cells

Polycythemia vera (PV) is a stem cell disorder characterized by hyperproliferation of the myeloid lineages and the presence of an activating JAK2 mutation. To elucidate mechanisms controlling PV stem and progenitor cell biology, we applied a recently developed highly sensitive data-independent acquisition mass spectrometry workflow to purified hematopoietic stem and progenitor cell (HSPC) subpopulations of patients with chronic and progressed PV. We integrated proteomic data with genomic, transcriptomic, flow cytometry, and in vitro colony formation data. Comparative analyses revealed added information gained by proteomic compared with transcriptomic data in 30% of proteins with changed expression in PV patients. Upregulated biological pathways in hematopoietic stem and multipotent progenitor cells (HSC/MPPs) of PV included mammalian target of rapamycin (MTOR), STAT, and interferon signaling. We further identified a prominent reduction of clusterin (CLU) protein expression and a corresponding activation of nuclear factor-kB (NF-kB) signaling in HSC/MPPs of untreated PV patients compared with controls. Reversing the reduction of CLU and inhibiting NF-kB signaling decreased proliferation and differentiation of PV HSC/MPPs in vitro. Upon progression of PV, we identified upregulation of LGALS9 and SOCS2 protein expression in HSC/MPPs. Treatment of patients with hydroxyurea normalized the expression of CLU and NF-kB2 but not of LGALS9 and SOCS2. These findings expand the current understanding of the molecular pathophysiology underlying PV and provide new potential targets (CLU and NF-kB) for antiproliferative therapy in patients with PV

Reduced CXCL4/PF4 expression as a driver of increased human hematopoietic stem and progenitor cell proliferation in polycythemia vera

ISSN:2044-538

Proteomic identification of proliferation and progression markers in human polycythemia vera stem and progenitor cells

Polycythemia vera (PV) is a stem cell disorder characterized by hyperproliferation of the myeloid lineages and the presence of an activating JAK2 mutation. To elucidate mechanisms controlling PV stem and progenitor cell biology, we applied a recently developed highly sensitive data-independent acquisition mass spectrometry workflow to purified hematopoietic stem and progenitor cell (HSPC) subpopulations of patients with chronic and progressed PV. We integrated proteomic data with genomic, transcriptomic, flow cytometry and in vitro colony formation data. Comparative analyses revealed added information gained by proteomic compared with transcriptomic data in 30% of proteins with changed expression in PV patients. Upregulated biological pathways in hematopoietic stem and multipotent progenitor cells (HSC/MPPs) of PV included MTOR, STAT and interferon signalling. We further identified a prominent reduction of clusterin (CLU) protein expression and a corresponding activation of NFĸB signalling in HSC/MPPs of untreated PV patients compared with controls. Reversing the reduction of CLU and inhibiting NFĸB signalling decreased proliferation and differentiation of PV HSC/MPPs in vitro. Upon progression of PV, we identified upregulation of LGALS9 and SOCS2 protein expression in HSC/MPPs. Treatment of patients with hydroxyurea normalized the expression of CLU and NFĸB2, but not of LGALS9 and SOCS2. These findings expand the current understanding of the molecular pathophysiology underlying PV and provide new potential targets (CLU and NFĸB) for antiproliferative therapy in PV patients