3,420 research outputs found
Cartes del duc de Berwick als consellers de Sabadell (21 juliol 1714 - 7 octubre 1714)
A lâArxiu Històric de Sabadell (G82 23. Cartes del duc de Berwick) es guarden les cartes que el duc de Berwick va adreçar als consellers de la vila de Sabadell en el context del setge i la posterior presa de la ciutat de Barcelona.
SĂłn un total de 14 cartes que, cronològicament, van del 21 de juliol al 7 dâoctubre de 1714. A escala local, aquesta correspondència ens mostra com els consellers de Sabadell passaren dâun austriacisme militant durant tota la guerra (encara a la Junta de Braços de juliol de 1713 el representant de la vila de Sabadell votĂ a favor de la resistència a ultrança) a una actitud de col¡laboracionisme en els mesos finals de la contesa. Actitud que obeeix a la situaciĂł desesperada a tots nivells âeconòmic, polĂtic i militarâ en què es trobava immersa la vila de Sabadell els mesos finals de la guerra. Alhora, i a escala nacional, aquesta documentaciĂł ens mostra explĂcitament com el comandant en cap dels exèrcits borbònics amenaçà els pobles que no se sotmetessin a lâautoritat de Felip V de castigar-los amb lâĂşltim rigor, saquejant-los i cremant-los
Engineering in vitro models of the intestinal mucosa to study the role of the stroma on the epithelium
[eng] The standard in vitro model of the small intestine in the field of drug development still consists in a monolayer of cancer-derived cells seeded on a hard substrate. Despite the huge advances that this model has provided, it does not faithfully recapitulate the complexity of the native tissue. Recently, the long-term culture of primary intestinal epithelial cells has been achieved through intestinal organoids, self-organizing 3D structures retrieving many of the features of the native tissue. Yet, they still have some limitations: (i) they are closed structures whose apical side is difficult to access, (ii) to grow, they require to be embedded in a highly heterogeneous matrix where well-controlled gradients of biochemical factors cannot be established, (iii) despite recapitulating the native cell compartmentalization, they do not retrieve the dimensionality of the tissue and (iv) they do not include the stromal compartment (mainly fibroblasts), proven to be key to maintain the intestinal stem cell niche. Therefore, the general objective of this thesis is to contribute to the development of complex in vitro models of intestinal epithelium focusing on the incorporation of the input of the stroma. In the first section of this thesis, we successfully adapted an in-house developed photolithography-based technique to fabricate poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels with crypt-like cavities. Although the nature of the chemical reaction used yielded partially-crosslinked polymer trapped in the cavities, the fabricated hydrogels could be functionalized with collagen I and organoid-derived epithelial monolayers could be formed on top. In the second section of this thesis, we have developed an in vitro model that allows the culture of organoid-derived cells on hydrogels with villus-like architecture under gradients of the ISC niche. The fabricated hydrogels showed native tissue-like elasticity and microstructures resembling those of the native villi. The mesh size of the hydrogels allowed the diffusion of the factors of the ISC niche through the hydrogel, which formed stable gradients along the villus vertical axis. An in silico model of protein diffusion through the hydrogel was developed to predict the profiles of the gradients of the factors of the ISC niche. Organoid-derived single cells seeded on collagen I-functionalized hydrogels formed complete monolayers. Only under gradients of the ISC niche factors, as opposed to uniform concentrations, the monolayers displayed native-like cell compartmentalization. Finally, organoid-derived cells cultured under gradients that promote more the proliferation showed faster growth dynamics but also a depletion of the proliferative pool. Altogether, these findings demonstrate that our villus-like 3D intestinal epithelial model retrieves native-like cell compartmentalization under appropriate gradients of ISC niche factors. The in vitro model presented here could be used to systematically screen gradients of factors, of particular interest those secreted by fibroblasts, and study the cellular response. In the third section of this thesis, we aimed to study if intestinal fibroblasts have a physical role in epithelial cell migration under non-pathological conditions. Through the coculture of fibroblasts with intestinal organoids, we found that the paracrine signalling from the fibroblasts induced a cystic morphology in the organoids, whereas their physical presence triggered their expansion into 2D monolayers. This physical effect of fibroblasts leading the expansion of epithelial cells was also observed in a 2D engineered coculture in vitro model. Organoid-derived monolayers exposed to a cell-free space (gap) migrated directionally towards the gap and fully closed it. During this process, fibroblasts were found to also migrate but towards the monolayers, align perpendicularly to the migration front and produce equally oriented ECM proteins that might be used for epithelial cells to migrate directionally. Under only the paracrine signalling from fibroblasts, epithelial monolayers did not migrate that efficiently nor fully closed the gaps. Under no fibroblast input, epithelial cells migrated randomly and could not recover their integrity. All in all, we could demonstrate that fibroblasts are indispensable for epithelial integrity restoration under non-pathological conditions in a 2D coculture in vitro model. Given the physical role of fibroblasts on the epithelial tissue, in the fourth section of this thesis we aimed to develop an in vitro model that incorporated a lamina propria mimicking compartment, together with the epithelial tissue, all the while recapturing the native architecture. To do so, we employed an in-house developed 3D printing technology to fabricate flat and villus-like gelatine methacryloyl (GelMA)-PEGDA hydrogels. First, using flat hydrogels, embedded fibroblasts were shown to be viable, have proliferation capacity and spread over the hydrogel surface. Organoid-derived epithelial cells seeded on top could only grow and form monolayers when fibroblasts were embedded within the GelMA-PEGDA hydrogels. In villus-like hydrogels, fibroblasts not only migrated to and spread on the surface, but they preferentially located at the tips of the villus-like microstructures. Organoid-derived single cells seeded on top of grew mainly at the tips and bases of the hydrogels. In these cocultures, fibroblasts migrated to the regions where epithelial cells were growing, mainly the tips and the bases of the hydrogels. Finally, fibroblasts cocultured with epithelial cells had their nuclei more elongated than when cultured alone, indicating a physical communication between the two cell types. Overall, we developed an in vitro model that mimics the native tissue architecture and encompasses not only the epithelium but also the mesenchymal compartment. Through this platform, we have unveiled a bidirectional communication between epithelial cells and fibroblasts.[cat] Avui dia, el model in vitro estĂ ndard de l'intestĂ prim al camp del desenvolupament de fĂ rmacs encara consisteix en una monocapa de cèl¡lules cancerĂgenes sembrades sobre un substrat dur. Tot i els grans avenços que aquest model ha suposat, no recapitula de manera fidedigna la complexitat del teixit. Recentment sâha posat apunt el cultiu dâorganoids intestinals, estructures tridimensionals autoorganitzades que recapitulen moltes de les caracterĂstiques del teixit nadiu. Tot i això, presenten diverses limitacions: (i) en ser estructures tancades, l'accĂŠs a la part apical ĂŠs complicat; (ii) per crĂŠixer, necessiten estar dins una matriu altament heterogènia que dificulta poder establir gradients de factors bioquĂmics ben controlats; (ii) malgrat recapitular l'organitzaciĂł cel¡lular del teixit, no mimetitzen la seva arquitectura i (iv) no inclouen el compartiment âestromalâ (principalment fibroblasts), tot i que s'hagi demostrat ser essencial en el manteniment del nĂnxol de cèl¡lules mare.
Al llarg dâaquesta tesi sâhan desenvolupat diferents models que recapitulen moltes de les caracterĂstiques mencionades mĂŠs amunt. La primera secciĂł d'aquesta tesi ha tingut per objectiu reproduir lâarquitectura del teixit intestinal. Per això, hem adaptat una tècnica desenvolupada al nostre laboratori que es basa en fotolitografia per fabricar hidrogels de diacrilat de polietilè glicol (PEGDA) amb cavitats similar a les criptes intestinals. En la segona part, ens hem centrat en crear un model que permetĂŠs establir gradients bioquĂmics de factors del nĂnxol de cèl¡lules mare. En concret, hem desenvolupat un model in vitro que permet el cultiu de cèl¡lules epitelials derivades d'organoids en hidrogels amb unes microestructures que reprodueixen les vellositats intestinals sota lâefecte de gradients bioquĂmics fisiològicament rellevants. En la tercera part, hem desenvolupat un model que permet el co-cultiu de cèl¡lules epitelials derivades dâorganoids amb fibroblasts primaris aĂŻllats de lâintestĂ. A mĂŠs, a travĂŠs dâaquest model, hem pogut veure com els fibroblasts son essencials per a la migraciĂł de les cèl¡lules epitelials en un context no patològic. En la quarta i Ăşltima secciĂł dâaquesta tesi, hem incorporat el compartiment estromal en un model que tambĂŠ reprodueix lâarquitectura del teixit, establint doncs un co-cultiu de cèl¡lules epitelials i fibroblasts espacio-fisiològicament rellevant
Engineering in vitro models of the intestinal mucosa to study the role of the stroma on the epithelium
Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)[eng]
The standard in vitro model of the small intestine in the field of drug development still consists in a monolayer of cancer-derived cells seeded on a hard substrate. Despite the huge advances that this model has provided, it does not faithfully recapitulate the complexity of the native tissue. Recently, the long-term culture of primary intestinal epithelial cells has been achieved through intestinal organoids, self-organizing 3D structures retrieving many of the features of the native tissue. Yet, they still have some limitations: (i) they are closed structures whose apical side is difficult to access, (ii) to grow, they require to be embedded in a highly heterogeneous matrix where well-controlled gradients of biochemical factors cannot be established, (iii) despite recapitulating the native cell compartmentalization, they do not retrieve the dimensionality of the tissue and (iv) they do not include the stromal compartment (mainly fibroblasts), proven to be key to maintain the intestinal stem cell niche. Therefore, the general objective of this thesis is to contribute to the development of complex in vitro models of intestinal epithelium focusing on the incorporation of the input of the stroma.
In the first section of this thesis, we successfully adapted an in-house developed photolithography-based technique to fabricate poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels with crypt-like cavities. Although the nature of the chemical reaction used yielded partially-crosslinked polymer trapped in the cavities, the fabricated hydrogels could be functionalized with collagen I and organoid-derived epithelial monolayers could be formed on top.
In the second section of this thesis, we have developed an in vitro model that allows the culture of organoid-derived cells on hydrogels with villus-like architecture under gradients of the ISC niche. The fabricated hydrogels showed native tissue-like elasticity and microstructures resembling those of the native villi. The mesh size of the hydrogels allowed the diffusion of the factors of the ISC niche through the hydrogel, which formed stable gradients along the villus vertical axis. An in silico model of protein diffusion through the hydrogel was developed to predict the profiles of the gradients of the factors of the ISC niche. Organoid-derived single cells seeded on collagen I-functionalized hydrogels formed complete monolayers. Only under gradients of the ISC niche factors, as opposed to uniform concentrations, the monolayers displayed native-like cell compartmentalization. Finally, organoid-derived cells cultured under gradients that promote more the proliferation showed faster growth dynamics but also a depletion of the proliferative pool. Altogether, these findings demonstrate that our villus-like 3D intestinal epithelial model retrieves native-like cell compartmentalization under appropriate gradients of ISC niche factors. The in vitro model presented here could be used to systematically screen gradients of factors, of particular interest those secreted by fibroblasts, and study the cellular response.
In the third section of this thesis, we aimed to study if intestinal fibroblasts have a physical role in epithelial cell migration under non-pathological conditions. Through the coculture of fibroblasts with intestinal organoids, we found that the paracrine signalling from the fibroblasts induced a cystic morphology in the organoids, whereas their physical presence triggered their expansion into 2D monolayers. This physical effect of fibroblasts leading the expansion of epithelial cells was also observed in a 2D engineered coculture in vitro model. Organoid-derived monolayers exposed to a cell-free space (gap) migrated directionally towards the gap and fully closed it. During this process, fibroblasts were found to also migrate but towards the monolayers, align perpendicularly to the migration front and produce equally oriented ECM proteins that might be used for epithelial cells to migrate directionally. Under only the paracrine signalling from fibroblasts, epithelial monolayers did not migrate that efficiently nor fully closed
the gaps. Under no fibroblast input, epithelial cells migrated randomly and could not recover their integrity. All in all, we could demonstrate that fibroblasts are indispensable for epithelial integrity restoration under non-pathological conditions in a 2D coculture in vitro model.
Given the physical role of fibroblasts on the epithelial tissue, in the fourth section of this thesis we aimed to develop an in vitro model that incorporated a lamina propria mimicking compartment, together with the epithelial tissue, all the while recapturing the native architecture. To do so, we employed an in-house developed 3D printing technology to fabricate flat and villus-like gelatine methacryloyl (GelMA)-PEGDA hydrogels. First, using flat hydrogels, embedded fibroblasts were shown to be viable, have proliferation capacity and spread over the hydrogel surface. Organoid-derived epithelial cells seeded on top could only grow and form monolayers when fibroblasts were embedded within the GelMA-PEGDA hydrogels. In villus-like hydrogels, fibroblasts not only migrated to and spread on the surface, but they preferentially located at the tips of the villus-like microstructures. Organoid-derived single cells seeded on top of grew mainly at the tips and bases of the hydrogels. In these cocultures, fibroblasts migrated to the regions where epithelial cells were growing, mainly the tips and the bases of the hydrogels. Finally, fibroblasts cocultured with epithelial cells had their nuclei more elongated than when cultured alone, indicating a physical communication between the two cell types. Overall, we developed an in vitro model that mimics the native tissue architecture and encompasses not only the epithelium but also the mesenchymal compartment. Through this platform, we have unveiled a bidirectional communication between epithelial cells and fibroblasts.[cat] Avui dia, el model in vitro estĂ ndard de l'intestĂ prim al camp del desenvolupament de fĂ rmacs encara consisteix en una monocapa de cèl¡lules cancerĂgenes sembrades sobre un substrat dur. Tot i els grans avenços que aquest model ha suposat, no recapitula de manera fidedigna la complexitat del teixit. Recentment sâha posat apunt el cultiu dâorganoids intestinals, estructures tridimensionals autoorganitzades que recapitulen moltes de les caracterĂstiques del teixit nadiu. Tot i això, presenten diverses limitacions: (i) en ser estructures tancades, l'accĂŠs a la part apical ĂŠs complicat; (ii) per crĂŠixer, necessiten estar dins una matriu altament heterogènia que dificulta poder establir gradients de factors bioquĂmics ben controlats; (ii) malgrat recapitular l'organitzaciĂł cel¡lular del teixit, no mimetitzen la seva arquitectura i (iv) no inclouen el compartiment âestromalâ (principalment fibroblasts), tot i que s'hagi demostrat ser essencial en el manteniment del nĂnxol de cèl¡lules mare.
Al llarg dâaquesta tesi sâhan desenvolupat diferents models que recapitulen moltes de les caracterĂstiques mencionades mĂŠs amunt. La primera secciĂł d'aquesta tesi ha tingut per objectiu reproduir lâarquitectura del teixit intestinal. Per això, hem adaptat una tècnica desenvolupada al nostre laboratori que es basa en fotolitografia per fabricar hidrogels de diacrilat de polietilè glicol (PEGDA) amb cavitats similar a les criptes intestinals. En la segona part, ens hem centrat en crear un model que permetĂŠs establir gradients bioquĂmics de factors del nĂnxol de cèl¡lules mare. En concret, hem desenvolupat un model in vitro que permet el cultiu de cèl¡lules epitelials derivades d'organoids en hidrogels amb unes microestructures que reprodueixen les vellositats intestinals sota lâefecte de gradients bioquĂmics fisiològicament rellevants. En la tercera part, hem desenvolupat un model que permet el co-cultiu de cèl¡lules epitelials derivades dâorganoids amb fibroblasts primaris aĂŻllats de lâintestĂ. A mĂŠs, a travĂŠs dâaquest model, hem pogut veure com els fibroblasts son essencials per a la migraciĂł de les cèl¡lules epitelials en un context no patològic. En la quarta i Ăşltima secciĂł dâaquesta tesi, hem incorporat el compartiment estromal en un model que tambĂŠ reprodueix lâarquitectura del teixit, establint doncs un co-cultiu de cèl¡lules epitelials i fibroblasts espacio-fisiològicament rellevant
Relation between the and nuclear matrix elements revisited
We show that the dominant Gamow-Teller part, , of the nuclear
matrix element governing the neutrinoless decay is related to the
matrix element governing the allowed two-neutrino
decay. That relation is revealed when these matrix elements are expressed as
functions of the relative distance between the pair of neutrons that are
transformed into a pair of protons in the decay. Analyzing this
relation allows us to understand the contrasting behavior of these matrix
elements when and is changed; while changes slowly and
smoothly, has pronounced shell effects. We also discuss the
possibility of phenomenological determination of the
and from them of the values from the
experimental study of the strength functions
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