888 resultados para Epithelial to mesenchymal transition


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The TNF family ligand ectodysplasin A (EDA) regulates the induction, morphogenesis and/or maintenance of skin-derived structures such as teeth, hair, sweat glands and several other glands. Deficiencies in the EDA - EDA receptor (EDAR) signalling pathway cause hypohidrotic ectodermal dysplasia (HED). This syndrome is characterized by the absence or malformation of several skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes, susceptibility to airways infections and crusting of various secretions. The EDA-EDAR system is an important effector of canonical Wnt signalling in developing skin appendages. It functions by stimulating NF-κB-mediated transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH), fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ) pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. In animal models of Eda-deficiency, soluble EDAR agonists can precisely correct clinically relevant symptoms with low side effects even at high agonist doses, indicating that efficient negative feedback signals occur in treated tissues. Hijacking of the placental antibody transport system can help deliver active molecules to developing foetuses in a timely manner. EDAR agonists may serve to treat certain forms of ectodermal dysplasia.

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A well circumscribed nodular mass discovered on routine chest ray examination, in the left inferior lobe of an otherwise healthy 49-year-old male. Histopathologically the lesion corresponded to a typical so called sclerosing hemangioma. The clinical and histopathological features are described. The sclerosing hemangioma of the lung is a rare benign tumor. Its histogenesis has not been explained yet. Following the electron-microscopic and immunohistochemical researches the opinions have been still unhomogeneous. Therefore, it is concluded that is a tumor of epithelial, endothelial, mesenchymal and even mesothelial origin. This study deals with this tumor, its immunohistochemical analysis points at its epithelial character.

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The central theme for this study is graduate employment and employability in European-wide discussion. In this study, the complex relationships between higher education and the world of work are explored from the vantage point of how individuals make use of the higher education system in their transition from education to employment. The variation among individual transition processes in nine European countries is analysed with the help of a comparable graduate survey. Countries in this study are Italy, Spain, France, Austria, Germany, the Netherlands, the United Kingdom, Finland, and Norway. The data used for the study is commonly known as the “CHEERS” or “Careers after Higher Education, A European Research Survey.” The data was collected in 1999. The study discusses the possibilities and limitations the higher education system has in supporting the initial education-to-work transitions of youth. The study also addresses problems with comparing national higher education systems in terms of enrolment and graduate employability. A central purpose for this study is to reflect on concerns about the prolongation of individual transitions with a framework that simultaneously considers both the graduate employability and the duration of the education-to-work transition process. The key concept for this study is the standard student/graduate; synonym concepts are the traditional and the conventional student/graduate. Standard graduates are relatively young individuals who are performing their initial transition from education to working-life and who complete the degree-earning process within the stipulated time frame. In all nine countries, standard graduates make up a considerable share of the student flow, passing from higher education to the labour markets. The share of standard graduates is by far the largest in France, where they comprise the overwhelming mass. The proportion of the standard graduates is the lowest in Italy, Finland, and Austria where approximately one in four graduates completed the process of higher education within the stipulated time frame. Of the nine countries compared, employability of the whole graduate population is the greatest in Norway, the UK, Finland, and the Netherlands. Compared with employability of the whole graduate population, variation among the countries is considerably reduced when reviewing the employability of only the standard graduates. Thereby, even though the ranking among countries remains largely unchanged, the variations among them are smaller when the duration of degree earning process is standardized. The study also discusses other ideal types of student careers (or transition processes) besides the standard student/graduate. Results of regression analyses indicate that that at the pan-European level analysis, the graduate labour markets are not heavily segmented in terms of the type of the individual transition process. When considering within-country differences between the graduates, the field of studies is clearly a more powerful explanatory variable than the type of the transition process. There are, nevertheless, clear indications that, irrespective of the country, chances of finding a high status job are, on the average, highest amongst those who graduate within the stipulated duration of the degree program and who thereby have experienced the standard student career, whereas, participating in working life while studying protects against unemployment after finishing one’s degree.

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The incorporation of the Spanish university system into the European Higher Education Areahas brought about a series of adaptations. Among the recommendations is the inclusion ofan external training period in a company, which has resulted in significant changes in thedegree syllabus in order to balance the theoretical and practical education required by thestudents. This new framework has been legally confirmed by the Spanish Government and, inthe case of the University of Barcelona, by the publication of internal guidelines. Takingadvantage of this new opportunity to adapt the Pharmacy degree to real-world problems inindustry, the Dean’s team of the Faculty of Pharmacy, with the support of the Facultyadministrative staff and the Students Advisory Service, have assumed the challenge ofincluding a new subject in the syllabus entitled Training in Companies.In parallel, a new activity has been set up to ensure that the students choose the mostsuitable company department/job for them and to help them pass the company interview.Under the name of Passport to a Profession, a series of ten explanatory talks has beenscheduled every academic year. These talks deal with a broad range of topics aimed atproviding the students with the basic tools they will need to make the most of a companytraining period and to make headway in the professional world when they finish theirdegree. In addition, three Faculty of Pharmacy-Pharmaceutical company workshops and tworound-table conferences have been held in the last two years in order to bring the universityand industry together. Notably, the project to provide students with company training isexpanding on an international level, with two to three undergraduate students contractedevery year by a United Kingdom-based multinational pharmaceutical company.The statistical data of the whole process has been analysed for a more in-depthunderstanding of the activity and to improve the programme.

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The purpose of this dissertation is to examine the dynamics of the socio-technical system in the field of ageing. The study stems from the notion that the ageing of the population as a powerful megatrend has wide societal effects, and is not just a matter for the social and health sector. The central topic in the study is change: not only the age structures and structures of society are changing, but also at the same time there is constant development, for instance, in technologies, infrastructures and cultural perceptions. The changing concept of innovation has widened the understanding of innovations related to ageing from medical and assistive technological innovations to service and social innovations, as well as systemic innovations at different levels, which means the intertwined and co-evolutionary change in technologies, structures, services and thinking models. By the same token, the perceptions of older people and old age are becoming more multi-faceted: old age is no longer equated to illnesses and decline, but visions of active ageing and a third age have emerged, which are framed by choices, opportunities, resources and consumption in later life. The research task in this study is to open up the processes and mechanisms of change in the field of ageing, which are studied as a complex, multi-level and interrelated socio-technical system. The question is about co-effective elements consisting of macro-level landscape changes, the existing socio-technical regime (the rule system, practices and structures) and bottom-up niche-innovations. Societal transitions do not account for the things inside the regime alone, or for the long-term changes in the landscape, nor for the radical innovations, but for the interplay between all these levels. The research problem is studied through five research articles, which offer micro-level case studies to macro-level phenomenon. Each of the articles focus on different aspects related to ageing and change, and utilise various datasets. The framework of this study leans on the studies of socio-technical systems and multi-level perspective on transitions mainly developed by Frank Geels. Essential factors in transition from one socio-technological regime to another are the co-evolutionary processes between landscape changes, regime level and experimental niches. Landscape level changes, like the ageing of the population, destabilise the regime in the forms of coming pressures. This destabilization offers windows for opportunity to niche-innovations outside or at fringe of the regime, which, through their breakthrough, accelerate the transition process. However, the change is not easy because of various kinds of lock-ins and inertia, which tend to maintain the stability of the regime. In this dissertation, a constructionist approach of society is applied leaning mainly to the ideas of Anthony Giddens’ theory of structuration, with the dual nature of structures. The change is taking place in the interplay between actors and structures: structures shape people’s practices, but at the same time these practices constitute and reproduce social systems. Technology and other material aspects, as part of socio-technical systems, and the use of them, also take part in the structuration process. The findings of the study point out that co-evolutionary and co-effective relationships between economic, cultural, technological and institutional fields, as well as relationships between landscape changes, changes in the local and regime-level practices and rule systems, are a very complex and multi-level dynamic socio-technical phenomenon. At the landscape level of ageing, which creates the pressures and triggers to the regime change, there are three remarkable megatrends: demographic change, changes in the global economy and the development of technologies. These exert pressures to the socio-technical regime, which as a rule system is experiencing changes in the form of new markets and consumer habits, new ways of perceiving ageing, new models of organising the health care and other services and as new ways of considering innovation and innovativeness. There are also inner dynamics in the relationships between these aspects within the regime. These are interrelated and coconstructed: the prevailing perceptions of ageing and innovation, for instance, reflect the ageing policies, innovation policies, societal structures, organising models, technology and scientific discussion, and vice versa. Technology is part of the inner dynamics of the sociotechnological regime. Physical properties of the artefacts set limitations and opportunities with regard to their functions and uses. The use of and discussion about technology, contributes producing and reproducing the perceptions of old age. For societal transition, micro-level changes are also needed, in form of niche-innovations, for instance new services, organisational models or new technologies, Regimes, as stabilitystriven systems, tend to generate incremental innovations, but radically new innovations are generated in experimental niches protected from ‘normal’ market selection. The windows of opportunity for radical novelties may be opened if the circumstances are favourable for instance by tensions in the socio-technical regime affected by landscape level changes. This dissertation indicates that a change is taking place, firstly, in the dynamic interactionbetween levels, as a result of purposive action and governance to some extent. Breaking the inertia and using the window of opportunity for change and innovation offered by dynamics between levels, presupposes the actors’ special capabilities and actions such as dynamic capabilities and distance management. Secondly, the change is taking place the socio-technological negotiations inside the regime: interaction between technological and social, which is embodied in the use of technology. The use of technology includes small-level contextual scripts that also participate in forming broader societal scripts (for instance defining old age at the society level), which in their turn affect the formation of policies for innovation and ageing. Thirdly, the change is taking place by the means of active formation of the multi-actor innovation networks, where the role of distance management is crucial to facilitate the communication between actors coming from different backgrounds as well as to help the niches born outside the regime to utilise the window of opportunity offered by regime destabilisation. This dissertation has both theoretical and practical contributions. This study participates in the discussion of action-oriented view on transition by opening up of the socio-technological, coevolutionary processes of the multi-faceted phenomenon of ageing, which has lacked systematic analyses. The focus of this study, however, is not on the large-scale coordination and governance, but rather on opening up the incremental elements and structuration processes, which contribute to the transition little by little, and which can be affected to. This increases the practical importance of this dissertation, by highlighting the importance of very tiny, everyday elements in the change processes in the long run.

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Ambitious energy targets set by EU put pressures to increase share of renewable electricity supply in this and next decades and therefore, some EU member countries have boosted increasing renewable energy generation capacity by implementing subsidy schemes on national level. In this study, two different change approaches to increase renewable energy supply and increase self-sufficiency of supply are assessed with respect to their impacts on power system, electricity market and electricity generation costs in Finland. It is obtained that the current electricity generation costs are high compared to opportunities of earnings from present-day investor’s perspective. In addition, the growth expectations of consumptions and the price forecasts do not stimulate investing in new generation capacity. Revolutionary transition path is driven by administrative and political interventions to achieve the energy targets. Evolutionary transition path is driven by market-based mechanisms, such as market itself and emission trading scheme. It is obtained in this study that in the revolutionary transition path operation of market-based mechanisms is distorted to some extent and it is likely that this path requires providing more public financial resources compared to evolutionary transition path. In the evolutionary transition path the energy targets are not achieved as quickly but market-based mechanisms function better and investment environment endures more stable compared to revolutionary transition path.

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Tämä työ tutkii ja tarkastelee transitio-kokeilua ravinnetaloudessa. Transitio-kokeilu on toimintatutkimusprojekti, joka toteutetaan systeemisen muutoksen ajattelun mukaisesti alhaalta ylöspäin. Ravinnetalous määritetään tarkemmin työn kautta sekä analysoidaan monitaso-perspektiivin näkökulmasta. Ravinnetalous on terminä varsin tuntematon ja tarvitsee enemmän tunnettavuutta laajemman yleisön edessä. Transitio-areenan ja transitio-visioiden kehittäminen ovat työn keskipisteessä, koska ne ovat tärkeimpiä vaiheita transition alkuvaiheessa. Joukko sidosryhmätoimijoita osallistuu transitio areenaan sekä visioiden jatkokehittelyyn. Visio(t) luodaan ensisijaisesti backcasting-menetelmällä, jota myös täydennetään tavanomaisella ennustamisella. Backcasting- menetelmä on osin osallistava ja siinä käytetään ravinteiden planeettarajoja kvantitatiivisina pääperiaatteina, minkä tuloksena myös visiot ovat osin kvantitatiivisia. Transitio areenan kokoaminen ja fasilitointi aiheuttavat hankalia kysymyksiä, jotka tarvitsevat jatko-tutkimusta. Alhaalta-ylöspäin organisoitu transitio-arena houkuttelee niche-toimijoita, mutta epäonnistuu sitouttamaan julkisen vallan toimijoita. Toimintamallin voimasuhteet, politiikka ja transition vakiinnuttaminen tulisivat olla jatko-toimenpiteinä niin tutkimuksessa kuin toiminnassakin.

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Travail dirigé présenté à la Faculté des études supérieures et postdoctorales en vue de l’obtention du grade de Maîtrise ès sciences (M. Sc.) option expertise-conseil en soins infirmiers

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Le TDAH persiste jusqu’à l’âge adulte dans la majorité des cas. Les jeunes ayant un TDAH sont plus à risque de sous-performance et de décrochage scolaires. Ils présentent également des déficits organisationnels, tel qu’une difficulté à planifier et compléter leurs devoirs. Sans interventions appropriées, ils sont à risque de difficultés importantes au secondaire. La présente étude vise à évaluer l’effet d’une intervention multimodale, Projet TRANSITION, sur l’engagement et le rendement scolaires des jeunes ayant un TDAH. L’échantillon était composé de 47 familles, réparties aléatoirement entre un groupe participant à l’intervention et un groupe contrôle. A la fin de secondaire 1, les jeunes ayant participé ou non à l’intervention ne se distinguent pas quant à la qualité de leur engagement scolaire (cognitif, affectif, comportemental). À la fin du secondaire 1, il n’y a pas de différence significative entre les groupes au niveau des difficultés en lecture ou mathématiques rapportées par le jeune ou le parent, de l’écart à la moyenne de la classe selon le bulletin, et du rendement scolaire par rapport aux autres élèves de leur classe rapporté par le jeune. Cependant, les parents perçoivent que les jeunes ayant participé à l’intervention présentent un meilleur rendement scolaire par rapport aux autres élèves de leur classe en comparaison aux jeunes du groupe contrôle.

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Rapport de stage présenté à la Faculté des sciences infirmières en vue de l'obtention du grade de Maître ès sciences (M.Sc.) en sciences infirmières option expertise-conseil en soins infirmiers

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Dues à leur importance croissante dans la dégénérescence musculaire, les mitochondries sont de plus en plus étudiées en relation à diverses myopathies. Leurs mécanismes de contrôle de qualité sont reconnus pour leur rôle important dans la santé mitochondrial. Dans cette étude, nous tentons de déterminer si le déficit de mitophagie chez les souris déficiente du gène Parkin causera une exacerbation des dysfonctions mitochondriales normalement induite par la doxorubicine. Nous avons analysé l’impact de l’ablation de Parkin en réponse à un traitement à la doxorubicine au niveau du fonctionnement cardiaque, des fonctions mitochondriales et de l’enzymologie mitochondriale. Nos résultats démontrent qu’à l’état basal, l’absence de Parkin n’induit pas de pathologie cardiaque mais est associé à des dysfonctions mitochondriales multiples. La doxorubicine induit des dysfonctions respiratoires, du stress oxydant mitochondrial et une susceptibilité à l’ouverture du pore de transition de perméabilité (PTP). Finalement, contrairement à notre hypothèse, l’absence de Parkin n’accentue pas les dysfonctions mitochondriales induites par la doxorubicine et semble même exercer un effet protecteur.

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We developed a nanoparticles (NPs) library from poly(ethylene glycol)–poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a “micelle-like” or “polymer nano-aggregate” structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to “polymer nano-aggregate” particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.

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High styrene rubber ionomers were prepared by sulfonating styrene–butadiene rubber of high styrene content (high styrene rubber) in 1,2-dichloroethane using acetyl sulfate reagent, followed by neutralization of the precursor acids using methanolic zinc acetate. The ionomers were characterized using X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), dynamic mechanical analysis (DMA), and also by the evaluation of mechanical properties. The FTIR studies of the ionomer reveal that the sulfonate groups are attached to the benzene ring. The NMR spectra give credence to this observation. Results of DMA show an ionic transition (Ti) in addition to glass–rubber transition (Tg). Incorporation of ionic groups results in improved mechanical properties as well as retention of properties after three cycles of processing

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Cows in severe negative energy balance after calving have reduced fertility, mediated by metabolic signals influencing the reproductive system. We hypothesised that transition diet could alter metabolic status after calving, and thus influence fertility. Multiparous dairy cows were assigned to four transition groups 6 weeks pre-calving and fed: (a) basal control diet (n = 10); (b) basal diet plus barley (STARCH, n = 10); (c) basal diet plus Soypass (high protein, HiPROT, n = 11); or (d) no transition management (NoTRANS, n = 9). All cows received the same lactational diet. Blood samples, body weights and condition scores (BCS) were collected weekly. Fertility parameters were monitored using milk progesterone profiles and were not affected by transition diet. Data from all cows were then combined and analysed according to the pattern of post-partum ovarian activity. Cows with low progesterone profiles had significantly lower insulin-like growth factor-I (IGF-I) and insulin concentrations accompanied by reduced dry matter intakes (DMIs), BCS and body weight. Cows with prolonged luteal activity (PLA) were older and tended to have lower IGF-I. Analysis based on the calving to conception interval revealed that cows which failed to conceive (9/40) also had reduced IGF-I, BCS and body weight. Fertility was, therefore, decreased in cows which were in poor metabolic status following calving. This was reflected in reduced circulating IGF-I concentrations and compromised both ovarian activity and conception. There was little effect of the transition diets on these parameters. (C) 2003 Elsevier Science Inc. All rights reserved.