321 research outputs found
Endothelial and myointimal cell functions related to vascular inflammation and remodeling in Giant-Cell Arteritis: Contribution of interleukin-23p19, interleukin-35 and endothelin-1
Get PDFGiant cell arteritis (GCA) is vascular inflammatory disease frequently involving large and medium sized arteries. GCA pathogenesis is not completely characterized, although there is a well accepted general model based on the observation of the histopathology and supported by immunopathology studies. According to this model, CD4+T cells subsets (mainly Th1 and Th17) and macrophages are essential to orchestrate the amplification of pro-inflammatory cascades leading to chronic inflammation of the vessel wall. The main sites of entry of infiltrating leukocytes are the activated endothelial cells (EC) from the adventitial vasa vasorum. Importantly, the secretion of proteases by macrophages among others, promotes elastic lamina degradation and migration of leukocytes to the inner artery layers. Vascular smooth muscle cells (VSMC) have also an important role in GCA pathogenesis since, in this scenario; they acquire a pro-inflammatory phenotype by overexpressing adhesion molecules and pro-inflammatory cytokines, contributing to the persistence of inflammation. Inflammatory cell products, as well as vascular injury, trigger a vascular remodelling process which leads to the development of intimal hyperplasia and vascular lumen occlusion. VSMC acquisition of proliferative and migratory phenotype may contribute to vascular remodeling. Further investigation of molecules involved in GCA pathogenesis is needed in order to find new strategies to improve the current GCA treatment (glucocorticoids) since 50% of the patients relapse and 40% suffer form early (visual loss or stroke) or late (aortic aneurysm) complications derived from maladaptive vascular remodeling. For this reason, the aim of this doctoral thesis was to contribute knowledge to these GCA challenges by investigating new roles of two important molecules involved in the persistence of inflammation (IL-23p19 and IL-35) as well as a new role of endothelin 1 (ET-1) in GCA vascular remodeling.
The IL-12 superfamily of cytokines is composed by four heterodimeric cytokines: IL-12 (p40 + p19), IL-23 (p40 ad p19), IL-27 (p28 and Ebi3) and IL-35 (Ebi3 and p35). Regarding to these cytokines, we have demonstrated a dichotomy in the expression of p19 and p40 subunits suggesting a role for p19 independent from p40 heterodimerization. We observed that p19 but not p40 was induced by a pro-
inflammatory context in EC from the adventitial vasa vasorum of GCA specimens. Moreover, p19 was not secreted by stable p19-expressing EC suggesting an intracellular role. Our studies showed that p19 contributed to leukocyte attachment and transmigration by promoting overexpression of adhesion molecules ICAM-1 and VCAM-1. We also demonstrated that these effects were triggered by intracellular p19 binding to gp130 receptor, subsequently promoting phoshporylation and nuclear translocation of STAT3.
IL-35 cytokine was also investigated as a consequence of the previous observation that p35 (but not p40) was constitutively expressed by VSMC of GCA specimens. This dichotomy suggested that p35 may have and independent role from that derived from p40 heterodimerization or that p35 may have another partner to form a cytokine different from IL-12. Our results demonstrated that p35 dimerizes with Ebi3 subunit in order to form IL-35 in GCA specimens. Interestingly, we found that IL-35 was mainly produced by leukocytes and VSMC in the adventitial/media junctions of GCA lesions. In order to mimic this context, we used co-cultures of temporal artery-derived primary VSMC together with leukocytes which demonstrated that IL-35 expression in VSMC was increased by pro-inflammatory cytokines IL-1β, TNFα and IFNg. In addition, we have demonstrated a new role for this cytokine in VSMC. IL-35 interacts with gp130 in order to promote pro-inflammatory phenotype of VSMC. This is an important observation since, until present; IL-35 has been described as an anti-inflammatory cytokine involved in regulatory T cell (Treg) differentiation.
We previously reported that endothelin-1 (ET-1) and its receptors ETAR and ETBR are over-expressed in GCA lesions and GCA patients with ischemic complications have increased serum concentrations of ET-1. Although it has been observed that ET-1 may contribute to myofibroblast differentiation of fibroblasts, a crucial step in lung and skin fibrogenic diseases, the most investigated function of ET-1 in VSMC has been vascular tone regulation. In this thesis, we have demonstrated that ET-1 may contribute to vascular occlusion, by promoting the migration of VSMC through activation of the focal adhesion kinase (FAK)/Src and PI3K axis. In GCA lesions ET-1 was mainly produced by inflammatory cells and the interaction with PBMC increased ET-1 receptor expression by VSMC. ET-1 stimulated VSMC migration by inducing focal adhesion kinase (FAK) phosphorylation at Y397 permitting association with p85 subunit of PI3Kinase which co-localized with FAK at the cell protrusions of
migrating cells. Accordingly, inhibition of both FAK and PI3K abrogated ET-1 induced migration. Consistently, blockade of ETAR and ETBR with BQ123 and BQ788 antagonists inhibited ET-1 induced VSMC migration and VSMC outgrowth from cultured GCA-arteries.L’arteritis de cèl·lules gegants (ACG) és una malaltia inflamatòria crònica d’etiologia desconeguda que majoritàriament afecta les arteries de mitjà i gran calibre, entre elles l’artèria temporal. El tractament actual de l’ACG són els glucocorticoides tot i que el 50 % dels pacients recauen.
Els mecanismes implicats en l’ACG s’han anat caracteritzant a partir d’observacions histopatològiques de l’artèria temporal així com a partir d’estudis immunopatològics. S’observa un clar infiltrat inflamatori format majoritàriament per limfòcits CD4+T i macròfags que van migrant des de l’adventícia fins a la íntima. La porta d’entrada d’aquest infiltrat es creu que podrien ser els petits vasos adventicials (vasa vasorum) que en condicions normals nodreixen l’artèria i, en canvi, en condicions patològiques s’observa una clara activació de les cèl·lules endotelials que els composen. Les cèl·lules infiltrants secreten citoquines i quimiocines encarregades de reclutar constantment més leucòcits donant lloc a la persistència de la inflamació en el teixit arterial. A més, aquestes cèl·lules també interaccionen amb altres components de la paret arterial com les cèl·lules muscular llises (VSMC) que també adquireixen un fenotip pro-inflamatori.
Per altra banda, en l’ACG també s’observa un important remodelat vascular patològic, majoritàriament degut al trencament de les làmines elàstiques de l’artèria i la migració cap a la llum vascular tant de l’infiltrat inflamatori com de les VSMC que adquireixen un fenotip més proliferatiu, migratori i productor de matriu extracel·lular que ajudarà a crear la hiperplàsia de la íntima, originant l’oclusió vascular.
Tenint en compte aquest context, en aquesta tesi doctoral s’han estudiat dues molècules implicades en la persistència de la inflamació. Per una banda, l’estudi de la subunitat p19 de la IL-23. En condicions pro-inflamatòries aquesta molècula podria actuar independentment de la dimerització amb la p40 per formar la IL-23 i podria intervenir desde el compartiment intracel.lular a traves d’una interacció directa amb gp130, en l’activació de les cèl·lules endotelials que formen el vasa vasorum adventicial, ajudant així al reclutament leucocitari. Per altra banda, l’estudi de la IL-35, expressada per les VSMC i els leucòcits infiltrants i no només per les cèl·lules T reguladores com s’havia descrit anteriorment. Hem observat i descrit per primera vegada, que la IL-35 també estaria involucrada en la persistència de la inflamació de l’ACG, induint un fenotip pro-inflamatori en les VSMC.
Pel que fa al remodelat vascular, hem estudiat l’endotelina (ET-1), que a través dels seus dos receptors (ETAR i ETBR) provocaria una inducció de la migració de les VSMC, tenint un rol essencial en la creació de la hiperplàsia de la íntima i la oclusió vascular
Historia de una mujer : album de cincuenta cromos /
Get PDFThe 50 full-page chromolithographs are signed on the stone by Planas, and bear the dates 1878-1880. The first plate is an added t.p. Captions in dialog beneath image.Mode of access: Internet.Centered on front free endpaper recto is armorial bookplate of Herce Alberto Lopez.Binding: textured blue cloth, quarter greenish-black leather, incorporating original front cover. Author and title gold-tooled on spine
Caracterização experimental do escoamento bifásico de uma mistura óleo e refrigerante em dutos de pequeno diâmetro
Get PDFDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Mecânica, Florianópolis, 2000.Diversos fenômenos que ocorrem no interior dos sistemas de refrigeração dependem da interação entre o óleo lubrificante e o fluido refrigerante. Uma boa miscibilidade entre óleo e refrigerante assegura o retorno do óleo para o compressor através da redução da sua viscosidade. Dentro do compressor o lubrificante é usado principalmente para selar vazamentos, para resfriar elementos quentes e para lubrificar partes deslizantes. O desempenho e a confiabilidade dos sistemas de mancais do compressor são fortemente afetados pela presença de refrigerante dissolvido no óleo. Isto ocorre devido ao desprendimento de refrigerante provocado por variações súbitas na temperatura e na pressão, o que origina uma mistura bifásica com densidade e viscosidade distintas das do lubrificante. Um conhecimento geral do escoamento da mistura óleo e refrigerante é crucial para o desenvolvimento de modelos de lubrificação, usados na análise e simulação de problemas de mecânica dos fluidos no interior de compressores. No presente estudo o escoamento de óleo lubrificante com desprendimento de refrigerante é explorado experimentalmente. Uma mistura de óleo saturado com refrigerante é forçada a escoar ao longo de dois tubos retos horizontais de diâmetro constante. Um tubo é usado para visualização do escoamento e no outro são realizadas medições de pressão e temperatura. Na entrada dos tubos o estado líquido prevalece e, à medida que o escoamento prossegue e conseqüentemente a pressão se reduz, ocorre o desprendimento de refrigerante devido à redução da solubilidade do fluido refrigerante no óleo lubrificante. Inicialmente observa-se uma pequena quantidade de bolhas, porém a população de bolhas cresce ao longo do escoamento, de modo que ao final dos tubos atinge-se escoamento em espuma. A visualização do escoamento permite a identificação dos regimes de escoamento bifásico experimentados pela mistura. As distribuições de pressão e temperatura são medidas ao longo do escoamento e a partir delas o título e a fração de vazio são estimados. O principal objetivo deste trabalho é melhorar a compreensão deste complexo escoamento para permitir a elaboração de modelos físicos e matemáticos com o intuito de explorar a mecânica de fluidos no interior de componentes do compressor.Several phenomena occurring inside refrigerating systems depend on the interaction between the lubrication oil and the refrigerant working fluid. Regarding the refrigeration cycle, good miscibility of oil and refrigerant assure easy return of the circulating oil to the compressor through the reduction of the oil viscosity. Inside the compressor the lubricant is mainly used for leakage sealing, cooling of hot elements and lubrication of sliding parts. In the compressor bearing systems the presence of refrigerant dissolved in the oil greatly influences the performance and reliability of the compressor due to the outgassing resulting from sudden temperature and pressure variations. This causes the formation of a two-phase mixture with density and viscosity strongly affecting the lubricant characteristics. A general understanding of the oil-refrigerant mixture flow is crucial in developing lubrication models to be used in analysis and simulation of the fluid mechanics inside the compressor. In the present work the lubrication oil flow with refrigerant outgassing is explored experimentally. A mixture of oil saturated with refrigerant is forced to flow in two straight horizontal tubes of constant diameter. One tube is used for flow visualization and the other is instrumented for pressure and temperature measurements. At the tubes inlet, liquid state prevails and as flow proceeds the pressure drop reduces the gas solubility in the oil and outgassing occurs. Initially a small amount of bubbles is observed and eventually the bubble population reaches a stage where foaming flow is observed. The flow visualization allowed identification of the two-phase flow regimes experienced by the mixture. Pressure and temperature distributions are measured along the flow and from that mixture quality and void fraction were estimated. The main motivation for this work is to improve the understanding of this complex flow to construct physical and mathematical models for exploring the fluid mechanics within the compressor parts
Historia de las bibliotecas populares en la Argentina entre 1870 y 1955: Antecedentes bibliográficos
Get PDFEl artículo revisa la bibliografía disponible sobre las bibliotecas populares en la Argentina (1870 y 1955). A través de un análisis de los textos, se establece un periodización tentativa: por un lado, se destaca una fase genética (1870-1895), dentro de la cual se gestaron estos establecimientos y alcanzaron, con dificultades, ciertos niveles aceptación social; por otro, se extiende una etapa de expansión y disputa (1895-1955), donde las bibliotecas populares se afirman definitivamente en el campo de las instituciones culturales del país. Entre las principales conclusiones, se indica que las investigaciones realizadas hasta la fecha no agotan la temática. Por último, y en base a los indicios disponibles, se establecen algunos principios de análisis que permitan auxiliar la tarea heurística de futuras indagacionesIn this article the author presents a literature review on the evolution of popular libraries in Argentina organized in two time periods: i) the genesis phase (1870-1895), when these establishments were created and struggled to gain social acceptance, and ii) the expansion and dispute phase (1895-1955) when popular libraries succeed to become a consolidated cultural institution in the country. The author also presents principles of analysis to assist the heuristic labor of future inquiriesFil: Planas, Javier. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina
Paranoia and Hope: The Art of Juan Batlle Planas and its Relationship to the Argentine Technological Imagination of the 1930s and 1940s
Get PDFabstract: The creative works of artist and poet Juan Batlle Planas (1911-1966)—a figure relatively unknown outside of Argentina—have long been understood as enigmatic and solitary experiments in surrealism. This essay, through a combination of formal analysis and cultural history, examines his collage series and paintings made in the 1930s and 1940s—especially his Paranoid X-ray series—to argue that these works are representative of a broader set of urban cultural responses in Argentina to the struggles of economic recession, political uncertainty brought by military rule of the 1930s, and tidal waves of (mis)information spread by mass mediated news sources. In particular, my analysis expands on Beatriz Sarlo’s theory of the “knowledge of the poor,” a term she uses to indicate the prominence of professional science, pop psychology, and crackpot inventions in Buenos Aires’s working class and middle class cultures of the 1920s and 1930s. By placing Batlle Planas’ work in this historical context, this essay reveals how Batlle Planas’ eclectic interests in Freudian psychology, Tibetan Buddhism, crystallized minerals, and the bizarre healing theories of Wilhelm Reich correlate with the growing technological imagination inspired by Argentina’s mass media, which in the early decades of the 20th Century circulated a surrealistic jumble of cultural information across Latin America
Reseña de Coll-Planas (2012) La carne y la metáfora. Una reflexión sobre el cuerpo en la teoría queer
No full textThe article presents a review of the book “La carne y la metáfora” (Flesh and Metaphor) by Gerard Coll-Planas (Editorial UOC, 2012), in which the author critiques the way in which queer theory has been interpreted in recent years by some sectors of this movement in Spain, paying particular attention to the way of understanding the body and its relationship with sex/gender identities. To this end, Coll-Planas explains the main ideas of this theoretical framework, as well as the most recurrent critiques of it. In his journey, he uses different narrative techniques that invite the reader to immerse themselves in the Internet to learn about some specific cases that exemplify the way we relate to the body today, or how it is mistreated or abused because of prevailing homophobia. In conclusion, Coll-Planas proposes the politicization of dependence, vulnerability, and death.El artículo presenta una reseña del libro «La carne y la metáfora», de Gerard Coll-Planas (Editorial UOC, 2012), en el cual el autor expone sus críticas a la manera en que han sido interpretados en los últimos años los planteamientos de la teoría queer por algunos sectores de este movimiento en España, poniendo especial atención a la manera de entender el cuerpo y su relación con las identidades de sexo/género. Para ello, Coll-Planas explica las ideas principales de este marco teórico, así como las críticas más recurrentes que se le plantean. En su recorrido, utiliza diferentes técnicas narrativas que invitan al lector a sumergirse en Internet para conocer algunos casos concretos que ejemplifican la forma en que hoy nos relacionamos con el cuerpo, o de cómo éste es maltratado o vejado por culpa de la homofobia imperante. Como conclusión, Coll-Planas propone la politización de la dependencia, la vulnerabilidad y la muerte
Elementary popular libraries. Nationalism, immigration and library policy during the 1910s
No full textFil: Planas, Javier. Universidad Nacional de La Plata; Argentina.Fil: Planas, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.En la década de 1910 la Comisión Protectora de Bibliotecas Populares de la Argentina elaboró una política de expansión del campo denominada bibliotecas populares elementales. El objetivo era consolidar una política cultural de afirmación del sentimiento nacional, contra los dilemas que, en la perspectiva oficial, habían generado la inmigración y las ideologías de izquierda. Para reconstruir y comprender el modo en que se construyó un diagnóstico de la realidad bibliotecaria y se produjo una estrategia como respuesta, se estudia el libro de actas del organismo, sus publicaciones y otros documentos de interés. Tres aspectos constituyen las variables de análisis principales: (a) las características generales de la propuesta; (b) los argumentos políticos, culturales y sociales que la justificaron; (c) las realizaciones que tuvo entre 1912 y 1921. Entre las conclusiones, se destaca la voluntad estatal por vertebrar el campo bibliotecario argentino y, a partir de él, participar en la formación de los ciudadanos.In this article the author presents a study of the Elementary Popular Libraries created in Argentina during the 1910s, with the aim of consolidating a cultural policy of affirmation of national sentiment as a means of confronting the dilemmas caused by immigration and left-wing ideologies. Three aspects constitute the main variables of analysis: (a) the general characteristics of the proposal; (b) the political, cultural and social arguments that justified it; (c) its achievements between 1912 and 1921. Among the conclusions, the will of the State to intervene and model the Argentine library field stands out
Sistema diédrico. Caras planas
No full textEste vídeo forma parte del MOOC "El lenguaje de la Ingeniería", módulo de Dibujo técnico. https://mooc.upc.edu
Sistema diédrico. Caras planas
No full textEste vídeo forma parte del MOOC "El lenguaje de la Ingeniería", módulo de Dibujo técnico. https://mooc.upc.edu
Solid-Phase Synthesis of Cyclic Depsipeptides Containing a Tyrosine Phenyl Ester Bond
No full textThe first solid-phase
strategy for the synthesis of cyclic depsipeptides
containing a phenyl ester linkage in their structure is described.
The key steps of the synthesis were the formation of the phenyl ester
bond and the on-resin head-to-side-chain cyclization. The amino acid
configuration significantly influenced the formation and the stability
of the cyclic depsipeptides. The presence of a l-Tyr1 and a d-Tyr7 led to the most stable sequences
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