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223 result(s) for "Kramer, Philipp"
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Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells
It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered and developmentally differentiated NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers. After sorting to purity, these primordial lung progenitors exhibited lung epithelial maturation. In the absence of mesenchymal coculture support, this NKX2-1+ population was able to generate epithelial-only spheroids in defined 3D cultures. Alternatively, when recombined with fetal mouse lung mesenchyme, the cells recapitulated epithelial-mesenchymal developing lung interactions. We imaged these progenitors in real time and performed time-series global transcriptomic profiling and single-cell RNA sequencing as they moved through the earliest moments of lung lineage specification. The profiles indicated that evolutionarily conserved, stage-dependent gene signatures of early lung development are expressed in primordial human lung progenitors and revealed a CD47hiCD26lo cell surface phenotype that allows their prospective isolation from untargeted, patient-specific PSCs for further in vitro differentiation and future applications in regenerative medicine.
M1-like, but not M0- or M2-like, macrophages, reduce RSV infection of primary bronchial epithelial cells in a media-dependent fashion
Respiratory syncytial virus (RSV) is a common childhood infection that in young infants can progress into severe bronchiolitis and pneumonia. Disease pathogenesis results from both viral mediated and host immune processes of which alveolar macrophages play an important part. Here, we investigated the role of different types of alveolar macrophages on RSV infection using an in vitro co-culture model involving primary tissue-derived human bronchial epithelial cells (HBECs) and human blood monocyte-derived M0-like, M1-like, or M2-like macrophages. It was hypothesized that the in vitro model would recapitulate previous in vivo findings of a protective effect of macrophages against RSV infection. It was found that macrophages maintained their phenotype for the 72-hour co-culture time period and the bronchial epithelial cells were unaffected by the macrophage media. HBEC infection with RSV was decreased by M1-like macrophages but enhanced by M0- or M2-like macrophages. The medium used during the co-culture also impacted the outcome of the infection. This work demonstrates that alveolar macrophage phenotypes may have differential roles during epithelial RSV infection, and demonstrates that an in vitro co-culture model could be used to further investigate the roles of macrophages during bronchial viral infection.
M1-like, but not M0- or M2-like, macrophages, reduce RSV infection of primary bronchial epithelial cells in a media-dependent fashion
Respiratory syncytial virus (RSV) is a common childhood infection that in young infants can progress into severe bronchiolitis and pneumonia. Disease pathogenesis results from both viral mediated and host immune processes of which alveolar macrophages play an important part. Here, we investigated the role of different types of alveolar macrophages on RSV infection using an in vitro co-culture model involving primary tissue-derived human bronchial epithelial cells (HBECs) and human blood monocyte-derived M0-like, M1-like, or M2-like macrophages. It was hypothesized that the in vitro model would recapitulate previous in vivo findings of a protective effect of macrophages against RSV infection. It was found that macrophages maintained their phenotype for the 72-hour co-culture time period and the bronchial epithelial cells were unaffected by the macrophage media. HBEC infection with RSV was decreased by M1-like macrophages but enhanced by M0- or M2-like macrophages. The medium used during the co-culture also impacted the outcome of the infection. This work demonstrates that alveolar macrophage phenotypes may have differential roles during epithelial RSV infection, and demonstrates that an in vitro co-culture model could be used to further investigate the roles of macrophages during bronchial viral infection.
Friction Measurement under Consideration of Contact Conditions and Type of Lubricant in Bulk Metal Forming
The tribological system plays a critical part in designing robust and efficient cold forging operations. The appropriate selection of lubrication allows to forge defect-free workpieces with high dimensional precision and desired surface finish while ensuring that no defects, such as cracks or seams, occur. Additionally, friction and wear are highly affected by the choice of tribological system, which in turn influence the cost-effectiveness of the forging operation by preventing premature tool failure. Next to the employed tool coating and work piece material, the lubrication system and work piece surface topography are the main factors influencing the aforementioned constraints when designing efficient forging operations. In order to choose the appropriate tribological system before implementing it within an industrial forging operation, tribometers are used to characterize the performance of the tribological system. In this paper, the necessity to account for not only the tribological loads when designing these tribometer tests as is typical for existing methodologies, but also for process and lubricant specific properties will be highlighted. With the help of the tribometer sliding compression test, it will be shown that using liquid lubricants necessitates the need to account for the escape of lubricant, while this is not true for solid lubricants. The escape of lubricant from the contact zone is governed by lubricant properties as well as the contact kinematics and may lead to significantly different results regarding friction and wear. In order to account for this escape, the tribometer test must be specifically designed to reproduce the contact kinematics of the investigated industrial forging operation.
Prediction of the Evolution of the Surface Roughness in Dependence of the Lubrication System for Cold Forming Processes
Lubricants for cold forging operations do not only enable a reliable forging process, but also affect the results of forging processes. A sound lubrication decreases the occurring forces and may result in a smooth specimen surface. However, some lubricants are known to increase the initial surface roughness of the specimen as a consequence of the forming. Therefore, the decision which lubricant should be used is of special interest for near-net shape operations. The paper at hand presents the results of a finite element investigation of the first stage of an industrial rod extrusion process which was investigated with two different lubrication systems. The numerical investigations focus on a reliable prediction of the development of the surface roughness in due consideration of the lubricant.
PolyQ Length of the Clock Gene Is Correlated With Pelagic Larval Duration in the Damselfishes (Pomacentridae), but Within a Species Habitat Availability Counts
ABSTRACT Immediately after hatching, larvae of coral reef fish leave their natal reef environment and begin their pelagic larval phase probably to avoid high predation on the reef. The time they spend in the open ocean (pelagic larval duration, PLD), before settlement varies from species to species and depends partly on developmental processes that eventually require re‐settlement to a reef. The polyglutamine region (PolyQ) as part of the clock gene has been suggested as a possible candidate that could control developmental processes and potentially the time until settlement, which can be determined by counting the rings of the otoliths. We studied the potential relationship between the number of glutamine repeats in 20 species of pomacentrids and their PLDs. Most pomacentrids came from similar locations, so we avoided the impact of latitudinal clines on PLD. Within the clock gene, we found two main distinguishable, variable glutamine‐rich regions (PolyQ and Qrich). Considering phylogenetic relationships, PolyQ/Qrich repeat length and pelagic larval duration were significantly positively correlated. However, when analyzing this relationship in a single species, the neon damselfish (Pomacentrus coelestis), we did not find a significant correlation between PolyQ length variation and PLD. Instead, we found a significant reduction of PLD in years with increased habitat availability. Our results show that glutamine‐rich regions can influence the timing of settlement on a broader scale, but that ecological factors—such as habitat availability—can also have a significant impact. The length of a part of the ‘clock’ gene explains the duration of dispersal in coral reef fishes. However, ecological factors such as the availability of habitats can override this effect.
Linguistique coloniale au XIXesiècle: Le discours racialiste dans la recherche française sur les langues créoles
Toward the end of the nineteenth century, a strong racist discourse was displayed in texts about Creole languages. Authors such as Mauritius-born Charles Baissac established explanations about the emergence of Creole languages and their specific structure, arguing that these particularities can only be seen as a result of contact between two races of different physical, mental, and social predispositions. As shown in Edward Said's “Orientalism,” scientific work in philology (and other disciplines) cannot be separated from structures of power and domination. Creole languages formed an urgent problem for colonial France as they initially emerged from the prestigious French language and yet had to be integrated into the paradigm of inferiority of colonized peoples and cultures. Linguistic descriptions of Creoles are therefore marked with a strong effort to reconcile the French heritage of these languages with the claim of domination over the community of Creole speakers. Still, contradictions and nuances in the texts of late-nineteenth-century research on Creole languages, carried out often by native speakers who had grown up in the colonies, may help to identify statements that transport an individual view of the triangular relation between language, race, and mind. Even in its not quite institutionalized state as a discipline, early creolistics displays a remarkable degree of cross-national connections that demonstrate how difficult it is to classify philological branches along national affiliation.
DELEGITIMISING CREOLES AND MULTIETHNOLECTS: STEREOTYPES AND (MIS-)CONCEPTIONS OF LANGUAGE IN ONLINE DEBATES
Youth languages in urban multicultural settings that are often labelled \"multiethnolects\" have received growing attention in the last two decades. In public debate, they are sometimes described as a step towards imminent \"creolisation.\" Judgements about Creoles and multiethnolects that form part of public debates show considerable similarities on many levels: Laypersons' metalinguistic commentary reveals that these two types of languages are held in low esteem in public opinion. They are sometimes seen as the results of linguistic decay with \"impoverished\" grammars that are allegedly a hindrance for mental and moral development of the speakers and also a sign for the lack thereof. In addition, research on these languages has been dismissed as a \"waste of resources\" given that it does not contribute to a desired refinement of language. An analysis of 1,240 comments about multiethnolects and Creoles in online discussions shows that contact phenomena trigger demands for purity and conservation that reproduce commonplace arguments from standard language ideology. The aim of this paper is to shed light on shared discourse patterns in Creole societies (Jamaica, Trinidad, Réunion, Mauritius) on the one hand, and European societies (Germany, Norway, the Netherlands) on the other. Such a comparative perspective reveals how standard language ideologies can be adapted in different contexts as means of delegitimising entire speech communities. Las variedades juveniles de contextos urbanos multiculturales, corrientemente llamadas “variedades polilectales” han capturado el interés de varios estudios en la últimas décadas. En el foro público, se describen como variantes próximas a la criollización. Por cierto, existen similitudes en valorización de las lenguas criollas y las variedades multilectales en el foro público. Para los que no son especialistas sobre estos temas, ambas variantes gozan de poco prestigio en comentarios metalingüísticos. En ocasiones, éstas se describen como el resultado del decaimiento y empo-brecimiento de las gramáticas de otras lenguas, lo cual, según estas creencias, repercute en el poco desarrollo moral y mental de sus hablantes, o la falta completa de éste. Por otra parte, el estudio de estas variantes se describe como un “gasto innecesario de recursos económicos”, ya que, según éstos, no aportan al desarrollo de la excelencia en el lenguaje. Este trabajo analiza 1,240 comentarios sobre variedades multilectales publicados en la red cibernética. Éstos muestran que fenómenos de contacto lingüístico suscitan reclamos de conservación y pureza lingüística sustentados por creencias comunes típicas de la ideología de la lengua estándar. El propósito de este trabajo es ilustrar los patrones comunes a los discursos en sociedades criollas (Jamaica, Trinidad, Reunión y Mauricio) y en sociedades europeas (Alemania, Noruega y Países Bajos). Este punto de vista comparativo demuestra que las mismas ideologías sobre el lenguaje pueden adaptarse a contextos lingüísticos distintos para deslegitimar comunidades lingüísticas enteras. Depuis deux décennies environ, on s'intéresse de plus en plus à des phénomènes de langage d'adolescents qu'on désigne désormais comme « multiethnolectes » et qui ont émergé dans un contexte de contacts culturels et linguistiques urbains. Dans la sphère publique, on les décrit parfois comme un pas vers la « créolisation » des langues européennes. Les débats sur les multiethnolectes et celles sur les langues créoles sont similaires à bien des égards : Ces langues souffrent d'une dépréciation énorme dans l'opinion publique, elles sont vues comme les résultats d'un déclin linguistique, elles auraient des grammaires appauvries, et elles seraient non seulement un obstacle au développement mental et moral de leurs locuteurs mais aussi un signe du manque de ceci. Souvent, la recherche sur ces langues est critiquée comme un gaspillage de ressources car elle n'aurait pas le résultat souhaité, notamment une protection et un raffinement des langues. A l'aide d'une analyse de 1.240 commentaires sur des multiethnolectes et des langues créoles dans des discussions en ligne, cet article montre que des phénomènes de contact linguistique provoquent des demandes de pureté et de conservation qui reproduisent des arguments usuels de l'idéologie des langues standardisées. Cet article offre une analyse des mécanismes discursifs partagés dans des sociétés créoles (Jamaïque, Trinité, La Réunion, île Maurice) et dans des sociétés européennes (Allemagne, Norvège, Pays-Bas). Une telle perspective comparative démontre comment les arguments idéologiques sont utilisés, dans des contextes différents, comme moyens de délégitimation d'une communauté entière de locuteurs.