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Joseph, Abdul Wahid. "Prospects for the reform of District Municipalities: the scope for manoeuvre." Thesis, University of the Western Cape, 2012. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_4515_1370947645.
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Joseph, A. W. "Prospects for the reform of district municipalities: the scope for manoeuvre." University of the Western Cape, 2010. http://hdl.handle.net/11394/2940.
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Traut, Michelle. "Recycled building materials : the likely impact on affordable housing in the Western Cape." Thesis, Peninsula Technikon, 2001. http://hdl.handle.net/20.500.11838/1057.
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Thesis (MTech (Built Environment))--Peninsula Technikon, 2001The construction industry globally, contributes between 18% and 24% of the GDP, and because of its labour intensive characteristics, contributes handsomely to total employment, forming important backward and forward linkages with the rest of the economy. Nevertheless, the extent and sophistication of these linkages crucially depend on the relative development of the construction industry relative to the overall economy. In the developing countries, these linkages are not very strong because of the use of informal materials, which is not commercialised and whose opportunity costs are often zero, and the huge imports of construction materials used in the modem sector of the economy. However, whether in the developed or developing economies, the construction industry is a major contributor to economic growth and development by providing the necessary infrastructure that facilitates production, consumption and recreational activities. In fulfilling these activities, the construction industry generates huge wastes of which only a tiny proportion are recycled and reused. However, in economies and countries where adequate and functional housing is a problem mainly due to lack of affordability, recycling and reuse of construction waste is a necessary prerequisite to enhancing housing affordability in these countries. This is the current situation that South Africa finds itself "''here because of its past history of 'apartheid', economic opportunities and amenities were denied to the blacks. There is nowhere that this deprivation is more pronounced than in the built environment sector where housing shortages and general disamenities prevail. High levels of unemployment further exacerbate the situation, - - which is a consequence of low skills and high illiteracy-rates. Thus, housing demand and supply by this group of the population are most likely, on the evidence available, to fall predominantly within the low-income housing category. Presently, all households falling into this category rely on financial assistance from the government to facilitate low-cost housing consumption because of pervasive poverty, which itself is due to the very high unemployment rate, illiteracy, lack of skills and general deprivation: a legacy of 'apartheid' policies enforced by previous government. The dilemma however is how to meet the huge housing demand within the limited resources available to the government on the one hand, and on the other, to satisfy such demand without compromising the environmental sustainability of the physical environment. Thus, the thesis aims to determine ways in which the construction industry could contribute to the sustainability of the carrying capacity of the biophysical environment and enhance social sustainability by facilitating affordability through the possible reductions to construction costs through recycling and reuse. By means of questionnaires and detailed interviews, underscored by a qualitative research approach, the potential of construction recycling and the possible contributions to environmental sustainability and housing affordability are determined. At completion, it is expected that this work will not only contribute to existing knowledge but would be of significance in terms of policy formulation to construction industry practitioners, central and local government policy makers, and other governmental and non-governmental organisations operating in the area of housing.
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Bazen, Stephen Laurence. "Minimum wage legislation : the likely impact on earnings, poverty and employment in the UK." Thesis, London School of Economics and Political Science (University of London), 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319349.
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Hamilton, Paul. "What is the likely impact of technology on the nature and future working environment of fine art printmaking?" Thesis, University of Ulster, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431547.
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Matsinhe, Tania Romana. "The likely impact of trade-related aspects of intellectual property rights (TRIPS) in Mozambique : the case of anti-malarial drugs." Master's thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/6990.
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Bibliography: leaves 94-99.Since 1994, there has been a lot of attention drawn on the World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) as the most important international instrument ever negotiated in this area. TRIPS establishes minimum universal standards in all areas of intellectual property and the intention is to implement these standards globally through a strong enforcement mechanism established in WTO. These standards affect pharmaceuticals, which many countries had previously excluded from patent protection in order to produce drugs at reduced prices and hence contribute to the improvement of public health. But now any Member State must comply with these minimum standards since failure to do so will result to the WTO dispute settlement system. No extensive review of the practical implications of the TRIPS Agreement has taken place at the global and national levels. The main objective of this paper is to examine the likely impact of this agreement on anti-malarial drugs in Mozambique. Given the persistence of the malaria epidemic in the country and the resistance to the drugs being utilized for this disease there is an acknowledged need for a new drug to eradicate the problem. The problem is that this new drug is likely to be under patent and this country has relied on generic drugs for all its existence and being a Member of the WTO Agreement they now have to wait until patents on the required drugs have expired or be submissive to the more expensive original brand. To accomplish this objective and to ascertain the end result of the above situation, past experiences were a major tool. By reviewing experiences of less developed countries in relation to patent protection and pharmaceuticals, some conclusions were made possible. In order to narrow down the conclusions drawn from these country experiences, a study was done in the Mozambican public sector by reviewing and analyzing the existing laws and regulations pertaining to pharmaceuticals and patent protection. This was done through questionnaires and interviews of the main stakeholders in this area. With this information the researcher was able to describe where Mozambique stands in relation to patents and how this might affect the pharmaceutical industry as a Member of the WTO agreement in the long run. This study therefore, relies heavily on secondary data.
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Lindstrand, Veronica. "Conflict Minerals : A Critical Assessment of the European Proposal on Conflict Minerals Due Diligence and Its Likely Impact on European Businesses." Thesis, Uppsala universitet, Juridiska institutionen, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-277879.
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Sarenmalm, Isabel. "Would you like your receipt? : Sustainability perspectives of consumer paper receipts." Thesis, Uppsala universitet, Institutionen för geovetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-296254.
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This report researches and analyses the sustainability perspectives of paper receipts, focusing on the economical, environmental and social aspects using a qualitative research method and by simultaneously drawing inspiration from the Sustainability Impact Assessment (SIA) model. The result section is conducted by using a literature review where a combination of previously used sources within my masters program is analysed and by reviewing articles and statistics in the search engine at the Uppsala University e-library database. The overall research purpose, to assess the sustainability of consumer receipts, is achieved by using the concept of sustainable development as the theoretical framework. This report suggests that there are some sustainability concerns with the current consumption of the traditional paper receipt, mainly in the context of environmental and social considerations. Three different alternatives to the traditional paper receipt are furthermore discussed as examples of potential routes forward. Two of the alternatives, electronic receipts and introducing a charge on paper receipts, are arguably the two most sustainable alternatives to regular paper receipts. The third alternative cannot be perceived as equally sustainable since “BPA/Bisphenol-free” receipts contain other chemicals equivalently hazardous to humans and the environment.
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Tefertiller, Alec. "Your Friends Like Our Brand: Social Impact, Capital, and Connections in Social Media Advertising." Thesis, University of Oregon, 2018. http://hdl.handle.net/1794/23100.
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Social media networks such as Facebook enable advertisers to embed social connection information within advertisements. The purpose of this study was to better understand how social cues in social media advertising contribute to consumers’ brand attitudes and purchase intentions. Two theoretical constructs guided the study: social impact theory and social capital theory. Social impact theory suggests that the number, relational strength, and immediacy of individuals exerting social influence determine its effectiveness. Social capital theory posits that our social networks are a product of the relational capital we have invested in them, with two forms of social capital: bonding and bridging. Bonding is associated with our intimate, "strong ties," and bridging is associated with our larger circle of acquaintances, or "weak ties." Using an experiment (N = 211), it was determined that while social context cues included in social media advertisements did influence brand attitudes, the strength and intensity of cues did not have an effect. Furthermore, bridging, strong-tie social capital positively moderated the relation between advertisement attitude and social media sharing of the advertisement as well as the relation between brand attitude and purchase intentions.
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Klazen, Tanya Chamel. "Analysing the likely impact of the new Namibia Investment Promotion Act 9 of 2016 on the flow of FDI into the country." Diss., University of Pretoria, 2017. http://hdl.handle.net/2263/64615.
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The purpose of this paper is to discuss and to anticipate the possible impacts Namibia’s New Investment Promotion Act (NIPA) may have on the flow of Foreign Direct Investment into the country. The aim is to highlight the researchers’ view that restrictive laws are harmful and deters investors. She maintains that NIPA be overhauled to create certainty and build investor confidence. Foreign direct investment is a significant part of every economy. It graces hosts with foreign revenue, technical know-how, technological spill overs, job creation, but to mention a few. The researcher also opines that liberal investment policies cannot be attributed to economic stagnation. The greatest evil in Africa is illicit financial flows, prompted by administrative corruption and the more. It is also noted throughout the paper that as Africans we need to focus on the proper implementation of domestic laws to see greater growth. This is where law-makers should direct their creative energies to. Liberal investment regimes are not the problem, but rather the ineffective implementation of those related laws and policies.Mini Dissertation (LLM)--University of Pretoria, 2017.
Centre for Human Rights
LLM
Unrestricted
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Ganster, Tina [Verfasser], Nicole [Akademischer Betreuer] Krämer, and Sonja [Akademischer Betreuer] Utz. ""Like" what you see? : The Impact of Facebook Likes against the Background of Conformity Goals and Self-Presentational Concerns / Tina Ganster. Gutachter: Sonja Utz. Betreuer: Nicole Krämer." Duisburg, 2015. http://d-nb.info/1067055215/34.
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Ganster, Tina [Verfasser], Nicole C. [Akademischer Betreuer] Krämer, and Sonja [Akademischer Betreuer] Utz. ""Like" what you see? : The Impact of Facebook Likes against the Background of Conformity Goals and Self-Presentational Concerns / Tina Ganster. Gutachter: Sonja Utz. Betreuer: Nicole Krämer." Duisburg, 2015. http://d-nb.info/1067055215/34.
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Breivik, Nicole L. "Compression of thick laminated composite beams with initial impact-like damage." Thesis, This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-09052009-040529/.
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Bhattacharyya, Aritra. "Impact of the myeloid Krüppel-like factor 4 during pneumococcal pneumonia." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19302.
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Bakterielle Pneumonien sind weltweit eine der häufigsten Todesursachen und S. pneumoniae ist das häufigste klinische Isolat. Neutrophile Granulozyten gehören zur Klasse der myeloiden Zellen und sind eine wichtige Komponente der angeborenen Immunität gegen bakterielle Infektionen. Krüppel-like factor 4 (KLF4) spielt dabei nicht nur eine Rolle in der Differenzierung der Zellen des Immunsystems, sondern auch während der Infektion bei der Vermittlung inflammatorischer Signale in unterschiedlichen Zelltypen.
Diese Studie zeigt zum ersten Mal in vivo, dass myeloides KLF4 Einfluss auf den Krankheitsverlauf hat und die mit einer bakteriellen Pneumonie einhergehende Entzündungsreaktion reguliert. Die hier aufgeführten Ergebnisse demonstrieren, dass der Transkriptionsfaktor KLF4 während einer Pneumokokken Pneumonie in humanen und murinen neutrophilen Granulozyten induziert wird. Diese Induktion ist Zeit- und Dosisabhängig. Außerdem wird die Expression von myeloidem KLF4 durch die Autolyse von S. pneumoniae reguliert, aber nicht über Toll-like Rezeptor 2 (TLR2), TLR4 oder TLR9 vermittelt. Studien in einem Maus-Pneumonie Modell zeigen, dass myeloides KLF4 einen proinflammatorischen Phänotyp bewirkt. Mäuse mit einem KLF4 knockout (KLF4-/-) in myeloiden Zellen haben im Vergleich zu Wildtyp (KLF4+/+) Mäusen eine höhere Bakterienlast in Lunge, Blut und Milz. Obwohl die Produktion proinflammatorischer Zytokine (wie TNF-α, IL-1β und KC) in BALF und Plasma von KLF4-/- Mäusen geringer war, gab es keine Unterschiede bei der Zellrekrutierung in der BALF von KLF4-/- und KLF4+/+ Mäusen. Allerdings war die Zellrekrutierung im Blut der KLF4-/- Mäuse geringer als bei den KLF4+/+ Mäusen. Außerdem wurde eine erhöhte vaskuläre Permeabilität verbunden mit perivaskulären Ödemen und Pleuritis bei KLF4-/- Mäusen während der S. pneumoniae-induzierten Infektion beobachtet. Diese Mäuse erreichten auch eher die humanen Endpunkte als die vergleichbaren KLF4+/+ Mäuse.Bacterial pneumonia is one of the leading causes of death worldwide. Streptococcus pneumoniae is the most frequently isolated pathogen from clinical pneumonia samples. Neutrophils belong to the class of myeloid cells and forms an important component of this innate immune system against bacterial infections. Krüppel-like factor 4 (KLF4) has been reported to not only play a role in differentiation of cells of the immune system but also in mediating inflammatory signals in different kinds of host cells during infection. This study shows myeloid KLF4 has an impact on pneumococcal pneumonia outcome and regulates the inflammation associated with bacterial pneumonia in vivo in mice. The results presented in the work show that the transcription factor KLF4 is induced in human and mice neutrophils during pneumococcal pneumonia. The induction of KLF4 is time and dose dependent. Additionally, the expression of myeloid KLF4 is regulated by the autolysis of S. pneumoniae but is not mediated via Toll-like receptor (TLR) 2, TLR4 or TLR9. Studies using a mouse pneumonia model showed that myeloid KLF4 exhibits a pro-inflammatory phenotype. Mice with KLF4 knockout (KO) or KLF4-/- in myeloid cells had higher bacterial load in their lungs, blood and spleen in comparison to wildtype (WT) or KLF4+/+ mice. Although there was less pro-inflammatory cytokine (such as TNF-α, IL-1β and KC) production in the broncho-alveolar lavage fluid (BALF) and plasma of KLF4-/- mice yet there no differences in cell recruitment in the BALF of the KLF4-/- and KLF4+/+ mice. There was however less cell recruitment in the blood of KLF4-/- mice in comparison to KLF4+/+ mice. Additionally, an increased vascular permeability associated with perivascular edema and pleuritis was seen during Streptococcus pneumoniae-induced infection in KLF4-/- mice, which also reached earlier the human endpoints than the KLF4+/+ mice.
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Cassilhas, Ricardo Cardoso [UNIFESP]. "O impacto do exercício físico resistido na função cognitiva dos idosos." Universidade Federal de São Paulo (UNIFESP), 2007. http://repositorio.unifesp.br/handle/11600/23516.
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Previous issue date: 2007Associação fundo de Incentivo à Psicofarmacologia (AFIP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Objetivo: Este estudo teve como objetivo investigar, durante vinte e quatro semanas, o impacto do exercício físico resistido realizado com duas intensidades (moderada e alta) na função cognitiva dos idosos. Material e Métodos: sessenta e dois idosos sedentários entre 65 e 75 anos foram distribuídos aleatoriamente em três grupos (controle)/ N=23, experimental moderada (emoderada)/ N=19 e experimental alta (ealta)/ N=20. Antes e após o treinamento, os voluntários foram submetidos a avaliações físicas, sangüíneas, neuropsicológicas e ao perfil de humor. Resultados: Os grupos experimentais melhoraram a sua força muscular avaliada pelos testes de 1RM em relação ao grupo controle para todos os aparelhos, porém não mostraram diferença entre si. Além disso, o grupo ealta, em relação ao controle, aumentou a massa muscular e melhorou o desempenho nos testes números ordem direta, blocos de Corsi ordem inversa, semelhanças, recordação imediata do teste da figura complexa de Rey, item omissão do teste Toulouse, SF-36 (estado de saúde geral), POMS (tensão-ansiedade)/ (depressão) e (distúrbio total de humor). Este grupo também mostrou aumento na concentração sérica do IGF-1 em relação ao grupo controle. O grupo emoderada apresentou médias maiores em comparação com o controle, nos números ordem direta, blocos de Corsi ordem inversa, semelhanças, recordação imediata do teste da figura complexa de Rey, SF- 36 (estado de saúde geral)/ (vitalidade), POMS (tensão-ansiedade)/ (depressão)/ (raiva-hostilidade)/ (fadiga)/ (confusão mental) e (distúrbio total de humor). Também se observou para este grupo, aumento sérico do IGF-1 em comparação ao grupo controle. Conclusões: Após a intervenção, concluiu-se que o treinamento com exercício físico resistido promoveu uma melhora na função cognitiva dos idosos, mas, independente da intensidade do exercício físico resistido ter sido tipicamente moderada ou alta, a influência na função cognitiva foi igualmente benéfica.
Objective: This study aimed at investigating, for twenty-four weeks, the impact of resistance physical exercise performed at two intensities (moderate and high) on the cognitive function of the elderly. Material and Methods: sixty-two elderly individuals between 65 and 75 years old were randomly assigned to three groups: control (N=23), experimental moderate (emoderate, N=19) and experimental high (ehigh, N=20). The volunteers underwent blood tests, physical, neuropsychological and mood profile evaluations before and after the training. Results: The experimental groups showed greater improvement than the control group regarding muscular strength as evaluated by the 1RM tests in all the devices. They did not, however, show differences between each other. Moreover, when compared with the control group, the volunteers in the ehigh group increased their muscle mass and improved their performance in the tests of digit span forward, Corsi’s blocks backward, similarities, Rey’s complex figure immediate recall, omission item in the Toulouse’s test , SF-36 (general health state), POMS (tension-anxiety, depression and total mood disorder). That group also showed a higher increase in the seric concentration of IGF-1 when compared with the control group. The emoderate group presented higher means than the control group in the tests of digit span forward, Corsi’s blocks backward, similarities, Rey’s complex figure immediate recall, SF-36 (general health state, vitality), POMS (tension-anxiety, depression, anger-hostility, fatigue, mental confusion and total mood disorder). That group also showed a higher increase in the seric levels of IGF-1 when compared with the control group. Conclusions: After intervention, we concluded that the training with resistance exercise promoted improvement in the cognitive function of the elderly. Independently of the intensity of exercise having been moderate or high, its influence on the cognitive function of the elderly was equally beneficial.
BV UNIFESP: Teses e dissertações
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Pupjain, Srijan. "The impact of Toll-like receptors on antigen presentation by mouse macrophages." Thesis, University of Newcastle Upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491833.
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Toll-like receptors (TLRs) are a group of trans-membrane proteins playing important roles as pattern-recognition receptors (PRRs) of innate immunity that are mainly expressed on professional antigen presenting cells (APCs). Stimulation of APC with TLR ligands, a variety of Jnolecular components derived from microorganisms, triggers innate immunity and establishes adaptive immune responses. I studied the impact of TLR specific for bacterial components on antigen processing and presentation of protective antigen (PA) of B. anthracis by bone marrow macrophages from mice.
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Merkel, Steven Franklin. "Effects of Traumatic Brain Injury on Addiction-Like Behavior and Their Neuropathological Correlates." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/450997.
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PathologyPh.D.
Recent clinical and preclinical reports have identified traumatic brain injury (TBI) as an important risk factor affecting the development of substance use disorders (SUDs). Notably, these studies show that factors like age at the time of injury and TBI severity may increase the risk of substance abuse behavior post-TBI. Furthermore, radiological assessments in clinical TBI populations have observed neuropathology in select brain regions that form key neurocircuits that mediate drug reward and drug-seeking behavior. Therefore, the effects of TBI on the function of these brain structures may influence the risk of substance abuse behavior following brain injury. In order to test the effect of experimental TBI on substance abuse behavior, we utilized two premiere preclinical models: 1) the controlled cortical impact (CCI) model of experimental TBI and 2) a biased, three-phase, cocaine conditioned place preference (CPP) assay. Furthermore, we characterized the effect of experimental TBI on
Temple University--Theses
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Compte, Nathalie. "Impact of clinical factors on inflammaging and Toll-like receptors responses in old age." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209155.
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Le vieillissement s’accompagne d’une altération globale des fonctions physiologiques notamment celles de l’immunité :on parle « d’immunosénescence ». Ce processus se traduit entre autre par l’installation d’un état inflammatoire chronique caractérisé par une augmentation des taux sériques de cytokines telles que l’interleukine(IL)-6 et des protéines de la phase aigüe. Cet état proinflammatoire serait incriminé dans le déclin des fonctions physiologiques, la fragilité et les syndromes gériatriques. Par ailleurs, les maladies cardiovasculaires, la dépression et l’infection chronique par le Cytomégalovirus (CMV) sont également associés à un état inflammatoire chronique. La prévalence de ces comorbidités étant importante chez les patients gériatriques, ces maladies pourraient donc contribuer à l’association observée entre marqueurs de l’inflammation et les syndromes gériatriques.Les infections représentent un problème majeur en gériatrie. Les cellules du système immunitaire inné jouent un rôle important dans les défenses contre les agents pathogènes. La reconnaissance de ceux-ci par les cellules dendritiques, les macrophages ou les monocytes fait intervenir une série de molécules telles que les récepteurs de la famille Toll (TLR). Certains travaux suggèrent que la fonction des cellules de l’immunité innée pourrait être perturbée chez les individus âgés mais ces données restent controversées.
Dans ce travail, nous souhaitons aborder les hypothèses suivantes :
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Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Winek, Kirsten M. "Writing Like a Lawyer: How Law Student Involvement Impacts Self-Reported Gains in Writing Skills in Law School." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1557486361911544.
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Chancellor, Tommy Neal. "Impact of body condition on plasma leptin and insulin-like growth factor-I concentrations in stallions and geldings." [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1035.
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Klein, Kendyl M. "Why Don't I Look Like Her? The Impact of Social Media on Female Body Image." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/cmc_theses/720.
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The purpose of this paper is to understand and criticize the role of social media in the development and/or encouragement of eating disorders, disordered eating, and body dissatisfaction in college-aged women. College women are exceptionally vulnerable to the impact that social media can have on their body image as they develop an outlook on their bodies and accept the developmental changes that occurred during puberty. This paper provides evidence that there is a relationship between the recent surge in disordered eating and high consumption of social media. I examine the ways in which traditional advertising has portrayed women throughout history, as well as analyze the ways in which this depiction of the female ideal has helped shaped society’s perspectives about beauty and increased the rate of disordered eating among college aged females. Further, this analysis assesses the ways in which the thin ideal as portrayed in advertising encourages women to look a certain, unrealistic way. I also consider various social psychological theories to explain how women in society form their perceptions with a combination of what they see in the media as well as what they see in their friends and family. I demonstrate that social networking sites (SNS) have similar effects on young women as advertising and other forms of mass media do. Therefore, I will argue that SNS, as a combination of real life and a personalized form of advertising, can potentially have the same, yet amplified, consequences. Indeed, I argue that the ubiquitous and enduring nature of social media websites result perhaps in a wider and more detrimental impact to the body image concerns of college aged women than advertising or the media generally.
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Brencicova, Eva. "Investigating the impact of ovarian carcinoma ascites on Toll-like receptor mediated dendritic cell activation." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/investigating-the-impact-of-ovarian-carcinoma-ascites-on-tolllike-receptor-mediated-dendritic-cell-activation(f38c549c-0831-49be-9fe2-9229c221f66b).html.
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In this study, we investigate the impact of ovarian carcinoma associated ascites on dendritic cell (DC) activation by Toll-like receptor (TLR) agonists in vitro. DC have the potential to instigate a tumour-specific adaptive immune response, but their ability to induce differentiation of naïve lymphocytes into effector cells in lymphoid tissues is dependent on their activation status. Here, we examine whether DC activation by TLR agonists is impeded by ovarian carcinoma environment and if so, how these effects can be alleviated. Our results show that ascites reduces the TLR-mediated up-regulation of the co-stimulatory molecule CD86 and partially inhibits the production of the pro-inflammatory cytokines interleukin-6 (IL-6), IL-12 and tumour necrosis factor α (TNFα) in monocyte-derived DC from healthy donors. We further observe an impaired T cell stimulatory capacity of monocyte-derived DC upon activation with TLR agonists in the presence of ascites, indicating that their function as antigen-presenting cells is affected by the immunosuppressive factors. Selective neutralization of IL-10 and prostaglandin E2 (PGE2) in vitro alleviates the suppressive effects of ovarian carcinoma associated ascites. However, our results show that autocrine IL-10 contributes to the observed suppression. The role of autocrine PGE2 is yet unclear, as we have no indication that this protein is produced by TLR-activated monocyte-derived DC. We have established and present here an elegant method to dissect the relative contributions of ascites-derived versus autocrine IL-10 and PGE2, and experiments to this effect are ongoing. The findings of this study can enhance the understanding of the ovarian carcinoma environment and its influence and relevance in the context of DC-based vaccines and other immunotherapeutic intervention strategies in ovarian carcinoma.
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Salisbury, Lauren E. "The Impact of Course Management Systems Like Blackboard on First Year Composition Pedagogy and Practice." University of Findlay / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=findlay1432220779.
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Kanthilatha, H. G. "Development and validation of a psychological screening tool to assess pre-enlistment psychological factors likely to impact on military well-being and performance in the context of the Sri Lankan military." Thesis, University of Hull, 2017. http://hydra.hull.ac.uk/resources/hull:16478.
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Military personnel who are directly involved in war face its most harmful consequences. However, research suggests that personality differences and characteristics might mitigate or exacerbate the impact on individual responses to war-related experiences. These characteristics could be either risk or protective factors. The current study aimed to develop and validate a psychological screening tool to assess pre-enlistment personality factors which can contribute to the well-being of military personnel and determine whether this tool can predict variables related to military well-being and performance. Two main studies were conducted to achieve these aims. Firstly, a cross-sectional descriptive survey was conducted with 960 junior military officers representing triforces in Sri Lanka for scale development and validation. A tool was developed combining Resilience Scale (RS25), Dispositional Resilience Scale (DRS15), and Mental Toughness Questionnaire (MTQ48). This tool was validated through EFA and CFA processes adopting a split sample cross validation method and resulting a scale with 42 items which was named as the “Resilience Inventory for Military (RIM)”. These 42 items comprised two factors. One consisted of 20 resilience items, the other consisted of 22 mental toughness items. Both subscales in this scale demonstated good validity and reliability levels. Secondly, a longitudinal study was carried out with 92 Cadet trainees to determine whether this scale can predict the turnover intention of the trainees, newcomer adjustment of trainees, training satisfaction,training performance and their general mental health condition. The results demonstrated that those who score high on the RIM scale have a greater adjustment, good level of mental health, are less likely to exibhit turnover intention and more satisfied with the training. The findings can help Sri Lankan military forces identify the most resilient candidates for military service and minimise negative behaviour outcomes among military personnel. Also, this research suggests how mental toughness, hardiness and resilience relate together. This approach might also be of use elsewhere in South Asia.
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Russell, Christopher David. "Single nucleotide polymorphisms in bovine chemokine and toll-like receptors : impacts on disease susceptibility and productivity in dairy cattle." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13201/.
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Bovine mastitis is recognised worldwide as the most important and costly disease affecting dairy cattle. The reduction of herd mastitis rates is crucially needed to improve animal welfare and profitability, and lessen the reliance on antibiotics. Single nucleotide polymorphisms (SNPs) within genes that have a critical role in the innate immune response, such as Toll-like receptors (TLRs) and the chemokine receptors CXCR1 and CXCR2, could impact on establishment and progression of intramammary infection, and therefore influence an animal’s susceptibility to disease. The genetic selection of animals with favourable TLR and CXCR1/2 mutations, with no impact on production traits, could be incorporated into dairy breeding programmes. In order to investigate any associations with clinical mastitis (CM) incidence and milk quality and quantity, this study identified and analysed SNPs alongside actual CM and production data from a Holstein-Friesian herd. This revealed 46 SNPs, 9 of which are novel, within boTLR1/4/5, boCD14, boCXCR1 and boCXCR2; selected SNPs were then tested for association with CM. This is the first report of boTLR1 SNPs and a non-coding boCXCR1 SNP that associate significantly with susceptibility to CM. Favourable linkage of reduced CM with increased milk fat and protein was observed, indicating selection for these markers would not be detrimental to milk quality. Furthermore, this study provides evidence that some of these SNPs underpin functional variation in bovine TLR1 and CXCR1, and possibly underlie an immunological mechanism for disease susceptibility. SNPs in boTLR1 and boCXCR1 were significantly associated with impaired transcript levels in milk somatic cells. In addition boTLR1 SNPs associated with impaired cytokine responses from cell populations when exposed to ligand or heat-killed mastitis-causing bacteria. The potential impact of boTLR1 variation on the immune response to Staphylococcus aureus is demonstrated, and this has implications for boTLR1-mediated immune responses to other pathogens.
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Sales, Maria Lilian. "Impacto dos polimorfismos Pro249Ser do toll-like receptor-6 e Asp299Gly do toll-like receptor-4 sobre a estrutura ventricular esquerda em pacientes hipertensos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309924.
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Orientador: Wilson Nadruz JúniorTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Estudos experimentais revelaram que a inibição de componentes da via de sinalização celular regulada pelos Toll-Like Receptors (TLRs) pode atenuar a hipertrofia cardíaca em animais submetidos à sobrecarga pressora. O objetivo deste estudo foi investigar a influência dos polimorfismos Asp299Gly do TLR4 e Pro249Ser do TLR6 sobre a estrutura do ventrículo esquerdo (VE) em indivíduos hipertensos. Foram estudados 443 pacientes por meio de avaliação clínica, laboratorial e ecocardiográfica, enquanto que os polimorfismos foram detectados por reação de polimerase em cadeia/enzima de restrição. Ademais, monócitos obtidos de sangue periférico de pacientes hipertensos foram estimulados in vitro com LPS (agonista de TLR4) e zimosan (agonista de TLR6) e a produção de interleucina-6 e fator de necrose tumoral-alfa (TNF-alfa) foi avaliada de acordo com a presença da variante Asp299Gly do TLR4 e Pro249Ser do TLR6. Mulheres que carregavam o alelo TLR4 299Gly apresentaram menor espessura de parede posterior do VE, menor espessura de septo, menor índice de massa do VE e reduzida prevalência de hipertrofia cardíaca. Mulheres homozigotas para TLR6 249Ser apresentaram menor espessura da parede do VE e menor espessura relativa da parede do VE em relação às mulheres com os genótipos Pro/Ser e Pro/Pro. Estes achados foram confirmados por análise de regressão linear múltipla, que incluiu idade, pressão arterial sistólica e diastólica, índice de massa corpórea, menopausa, diabetes mellitus e uso de antihipertensivos como fatores confundidores. Por fim, estudos funcionais in vitro revelaram que monócitos de homens e mulheres que apresentaram o alelo TLR4 299Gly tiveram menor produção de interleucina-6 após estímulo com LPS e a presença do alelo TLR6 249Ser em homozigose esteve associada a uma menor produção de interleucina-6 e TNF-alfa após estímulo com zimosan apenas nos monócitos extraídos de mulheres hipertensas. De maneira geral, esses dados sugerem que pode haver uma interação entre gêneros, polimorfismos dos receptores Toll-like e fenótipo do VE em indivíduos hipertensos. Sob esta perspectiva, estudos longitudinais são necessários para avaliar o impacto destes polimorfismos sobre o risco cardiovascular em mulheres hipertensas
Abstract: Experimental studies have shown that inhibition of components of cell signaling pathway regulated by Toll-Like Receptors (TLRs) can reduce cardiac hypertrophy in animals subjected to pressure overload. The aim of this study was to investigate the influence of the polymorphisms TLR4 Asp299Gly and TLR6 Pro249Ser on the structure of the left ventricle in hypertensive subjects. We studied 443 patients by clinical, laboratory and echocardiographic, while polymorphisms were detected by the polymerase chain / restriction enzyme. Moreover, monocytes obtained from peripheral blood of hypertensive patients were stimulated in vitro with LPS (TLR4 agonist) and zymosan (TLR6 agonist) and the production of interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) was assessed according to the presence of the Asp299Gly variant of TLR4 and Pro249Ser of TLR6. Women who carried the TLR4 299Gly allele had lower posterior wall thickness, thinner septum, a lower rate of left ventricular mass and reduced prevalence of cardiac hypertrophy. Women homozygous for TLR6 249Ser had lower posterior wall thickness and relative wall thickness, compared to women with the genotype Pro/Ser and Pro/Pro. These findings were confirmed by analysis of multiple linear regression that included age, systolic and diastolic blood pressure, body mass index, menopause, diabetes mellitus and use of antihypertensive drugs as confounding factors. Finally, in vitro functional studies revealed that monocytes from men and women who harbored the TLR4 299Gly allele had lower production of interleukin-6 after stimulation with LPS and the presence of homozygous 249Ser allele was associated with a lower production of Interleukin-6 and TNF-alpha after stimulation with zymosan only in monocytes hypertensive women. These data suggest that there may be an interaction between gender, polymorphisms of Toll-like receptors and ventricular phenotype in hypertensive subjects. In this regard, longitudinal studies are needed to assess the impact of these polymorphisms on the cardiovascular risk of hypertensive women
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Venturini, Nicolas. "Experimental Broadband Signal Reconstruction for Plate-like Structures." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amslaurea.unibo.it/20470/.
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In the Structural Health Monitoring (SHM) field, the Acoustic Emission (AE) technique is a passive method by which damage is localized and identified by capturing Lamb Waves (LW) signals propagating in a plate-like structure. The reconstruction of emitted signals from damage at the source location constitutes one of the main challenges faced by the SHM community. Recently, the application of a Frequencies Compensation Transfer Function (FCTF) has been used to reconstruct narrowband and broadband signals through a hybrid experimental and numerical Time Reversal (TR) process on aluminum plates.
This study aims to reconstruct through experimental methods different types of narrowband and broadband signals on different plate-like structures making use of FCTF. In particular, Hanning Window (HW) and numerical broadband signals have been reconstructed for aluminum and steel plates. The results obtained in this study show how the FCTF method can be applied to different types of materials in plate-like structures. Moreover, the FCTF method has been applied on real broadband signals emitted by the Pencil Lead Break (PLB) technique and Rock Impact (RI) test. These last results prove that the FCTF method is able to compensate for the frequency changes on a single wave packet. Such results are fundamental, as they open the possibility to reconstruct any type of source signals emitted by any damage type.
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Oosterhof, Chris Anne. "Impact of Depressogenic-and Antidepressant-like Challenges on Monoamine System Activities: in vivo Electrophysiological Characterization Studies." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34230.
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Introduction: major depressive disorder is a common psychiatric disorder associated with high economic cost, severe human suffering, and low remission rates. Imbalanced neurotransmission of the monoaminergic serotonin (5-HT), dopamine (DA) and norepinephrine (NE) systems is implicated in this disorder. However, the etiology underlying this presumed imbalance and the mechanism by which antidepressant strategies restore this imbalance requires further exploration. Accordingly, the present work assessed the effects of depressogenic and antidepressant-like conditions on these systems.
Methodology: Electrophysiological extracellular single unit recordings from 5-HT, DA, NE, and hippocampal pyramidal neurons were obtained in adult male chloral hydrate anaesthetized Sprague-Dawley rats. Effects on relevant receptors were characterized using established electrophysiological and/or pharmacological strategies. Prenatal stress was used to model depressogenic-like conditions. The effects on monoamine systems of asenapine and brexpiprazole, two atypical antipsychotics with antidepressant potential, were characterized after acute (brexpiprazole) and sustained administration. These sustained regimens resulted in clinically relevant blood plasma levels.
Results: Prenatal stress exposure altered monoamine system activities but did not produce detrimental effects on behavior. Asenapine and brexpiprazole had unique effects on the activities of monoamine systems. Unlike other antipsychotics, both agents did not produce a cessation of the firing of dopamine neurons in the ventral tegmental area, thereby providing novel insights in the role of this system in the treatment of mood disorders. Furthermore, both agents enhanced the tonic activation of postsynaptic 5-HT1A receptors, similarly to the effects of all antidepressant strategies.
Conclusion: Prenatal stress altered the activities of 5-HT, NE and DA neurons. Since these central changes were obtained in animals displaying normal behavior, they presumably reflect adaptations to depressogenic-like conditions. The characterization of asenapine and brexpiprazole contributed to a further understanding of their mechanisms of action. Together, these studies provide insight in neural substrates presumably relevant to the antidepressant response.
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Alkawar, Abdulrhaman Mohammed Mohammed. "Insulin-like growth factor-1 (IGF-1) impacts p53-regulated gene products in UVB-irradiated human keratinocytes and skin epidermis." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1588119867567084.
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Payne, Alison Jane. ""It has hit us like a whirlwind" : the impact of commercial television advertising in Britain 1954-1964." Thesis, Birkbeck (University of London), 2016. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.720360.
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The Chairman of the advertising agency, Foote, Cone and Belding, claimed that the launch of the new advertising medium of commercial television, in 1955, was a ’whirlwind’ for his industry. New disciplines, new techniques, and new relationships with the production industry had to be established, and existing campaigns in press had to be transferred to television, an advertising medium that London agencies had no experience with. Also, for the first time, agencies had to work within a regulatory process established by legislation, and policed by the Independent Television Authority. The Authority was tasked with a public service remit to protect citizens both as viewers of television and the consumers of branded goods. The acceptance of viewers, of the commercials on this new television channel. was central to the concerns of both the advertising industry and the regulator. To identify the extent of the impact of commercial television advertising, on the advertising industry, advertising regulation and the viewers, this thesis draws on contemporary research carried out by the BBC, archival material from the regulatory authority and the representative organisations of the advertising industry, and the trade press, and combines this with new interviews with practitioners, working in the advertising and television industries, from 1954-1964. Using material from advertising archives, the thesis also examines the advertising of one important category of advertised goods, washing powders, to identify how the advertising agencies evolved their clients’ advertising, from press, to the new advertising medium of television.
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Contreras, Daimer Mauthsud Leovan Ospina. "Angle of attack impact in the aerothermodynamics of a hypersonic vehicle with surface discontinuity-like a cavity." Instituto Nacional de Pesquisas Espaciais (INPE), 2017. http://urlib.net/sid.inpe.br/mtc-m21b/2017/04.12.00.58.
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The study described in this dissertation was undertaken with the purpose to investigate the impact of discontinuities present on the surface of hypersonic space vehicles. With this perspective in mind, computational simulations of a non-reacting rarefied hypersonic flow over a flat plate with a cavity have been performed by using the Direct Simulation Monte Carlo method. Simulations provided a comprehensive description about the nature of the flowfield structure and the aerodynamic surface properties on the cavity resulting from changes in the length-to-depth (L/H) ratio and changes in the angle of attack of the oncoming flow. A detailed description of the flowfield properties (velocity, density, pressure and temperature) and aerodynamics surface properties (number flux, heat transfer, pressure and skin friction) were obtained by a numerical method that properly account for non-equilibrium effects in the transition flow regime. Results for a cavity defined by L/H ratio of 1, 2, 3 and 4, and flow with angle of attack of 10, 15 and 20 degrees, were compared to those of a flat plate without a cavity with zero-degree angle of incidence and with a flat plate at incidence. The analysis showed that the flow topology inside the cavity, composed by recirculation regions, depended on the L/H ratio as well as on the angle of attack, for the conditions investigated. For L/H < 3 a single vortex core was formed, and filled entirely the cavity. In contrast, for L/H of 3 and 4, two vortices were formed inside the cavity, at the vicinity of the backward and forward faces. The analysis also showed that, for the L/H = 4 case, the flow topology inside the cavity corresponds to that of a ${''}$closed cavity${''}$ in the continuum flow regime for 10-degree angle of incidence, and similar to an open cavity for the others angles of attack investigated. In addition, it was found that the maximum values for the heat transfer, pressure and skin friction coefficients inside the cavity took place on the cavity forward face. It was also found that, maximum values for heat transfer coefficient inside the cavities increased with increasing the angle of attack $\alpha$. However, it was observed that these maximum values are smaller than those observed in a flat-plate without a cavity for the corresponding angle of attack. Consequently, in terms of pressure, the presence of the cavity on the vehicle surface can not be ignored in the vehicle design.O estudo descrito nesta dissertação foi realizado com o propósito de investigar o impacto de descontinuidades presentes na superfície de veículos espaciais hipersônicos. Em busca deste propósito, simulações computacionais de um escoamento hipersônico rarefeito não-reativo sobre uma cavidade foram realizadas usando-se o método Direct Simulation Monte Carlo. As simulações forneceram informações detalhadas sobre a natureza da estrutura do escoamento, propriedades primárias e propriedades aerodinâmicas, em função de mudanças na razão comprimento-profundidade (L/H) da cavidade, e mudanças no ângulo de ataque do escoamento incidindo sobre a cavidade. Uma descrição detalhada, das propriedades primárias (velocidade, massa específica, pressão e temperatura) e das quantidades aerodinâmica na superfície (transferência de calor, pressão e atrito), foi obtida por um método numérico que leva em conta adequadamente os efeitos de não-equilíbrio no regime de transição. Os resultados, para cavidades definidas por L/H de 1, 2, 3 e 4, com ângulos de ataque do escoamento de 10, 15 e 20 graus, foram comparados com os de uma placa plana sem/com a presença de cavidade sem/com incidência. A análise mostrou que a topologia do escoamento dentro da cavidade, composta por regiões de recirculação,dependeu da razão L/H bem como do ângulo de ataque do escoamento, para as condições investigadas. Para L/H < 3, observou-se a formação de um único vórtice ocupando inteiramente a cavidade. Para cavidade com L/H =3 e 4, dois vórtices foram formados dentro da cavidade, nas vizinhanças das faces a montante e a jusante da cavidade. A análise também mostrou que, para uma cavidade com L/H = 4 e 10 graus de incidência, a estrutura do escoamento dentro da cavidade correspondeu aquela de uma cavidade fechada , conforme definido para um escoamento no regime do contínuo. Por outro lado, para L/H = 4 e maiores ângulos de incidência, a estrutura do escoamento correspondeu aquela de uma cavidade aberta , para os ângulos de ataque investigados. Outrossim, verificou-se que os valores máximos para os coeficientes de transferência de calor, pressão e coeficiente de atrito ocorreram na superfície a montante do escoamento dentro da cavidade. Verificou-se também que, os valores máximos para o coeficiente de transferência de calor dentro da cavidade aumentaram com o aumento do ângulo de ataque $\alpha$. Todavia, esses valores máximos foram menores do que aqueles observados sobre uma placa plana sem cavidade com incidência. Como resultado, em termos de pressão, a presença da cavidade sobre a superfície do veículo não pode ser ignorada no projeto do veículo.
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Roylance, Christina. "Treating Objects like Women: The Impact of Terror Management and Objectification on the Perception of Women's Faces." Thesis, North Dakota State University, 2014. https://hdl.handle.net/10365/27428.
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According to terror management theory, humans are threatened by the awareness of death and counter this threat by investing in cultural systems that make them feel like they are more than mortal animals. Based on this proposition, it has been argued that women's bodies pose a unique existential threat, as they remind humans of their similarity to other biological organisms. However, no research thus far has examined how death awareness impacts perceptual assessments of women. The current study examined the effect of heightened death-awareness on perceptions of women's faces, utilizing face-morphing techniques that create a range of artificial-to-real faces. Results indicated that following a death-awareness induction, participants perceived artificial female faces as less artificial, but not necessarily more attractive. MS did not predict perceptions of male faces. These results suggest that existential concerns about death have an impact on perceptual assessments of women.
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Boivin, Audrey. "Rôle des récepteurs Toll-like dans la régénérescence d'axones périphériques lésés. Impacts sur la dégénérescence Wallérienne et la récupération des fonctions locomotrices." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24983/24983.pdf.
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Rosenberger, Karen [Verfasser]. "The impact of Toll-like receptor activation on neuroinflammation and neurodegeneration in the central nervous system / Karen Rosenberger." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/1078505322/34.
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Weinlich, Ricardo. "Regulação do CD95L por PGE2 e seu impacto na morte de linfócitos T." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-19112008-171500/.
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Células apresentadoras de antígeno (APCs) controlam as respostas de linfócitos T por múltiplos mecanismos, que incluem a expressão de moléculas co-estimuladoras, a produção de citocinas e outros mediadores. Estes mecanismos exercem influência não só na proliferação, diferenciação e polarização dos linfócitos T, mas também interferem na sobrevivência destas células. No presente trabalho, foi demonstrado que fator(es) solúvel(eis) produzido(s) por APCs ativadas via receptores do tipo Toll (TLRs) suprimem a morte induzida por ativação (AICD) de linfócitos T. Este efeito foi observado em APCs não estimuladas, porém foi significativamente maior após estimulação das APCs com lipopolissacarídeo (LPS). Através do uso de diferentes camundongos nocautes, foi mostrado que a produção do fator protetor induzida por LPS é dependente da via de TLR4/MyD88 e independente de TLR2 e CD14. Este fator foi identificado como prostaglandina E2 (PGE2) e foi demonstrado que os sobrenadantes derivados de APC e a PGE2 sintética bloqueiam a expressão de CD95L em linfócitos T estimulados via TCR/CD3. A inibição da expressão de CD95L reduz tanto a AICD como a morte de macrófagos, alvos do ataque citotóxico dos linfócitos T ativados. Foi demonstrado também que, ao invés de bloquear a via do CD95, a PGE2 potencializa a morte induzida por anticorpos anti-CD95 agonistas. Os receptores de PGE2, EP2 e EP4, parecem ser os responsáveis por mediar os efeitos supressores da PGE2 na AICD, já que a estimulação farmacológica destes receptores mimetiza o efeito protetor da PGE2 e seus respectivos antagonistas interferem com a proteção conferida pelos sobrenadantes de APCs e pela PGE2 sintética. A ativação do EP2 e do EP4 age sinergicamente na ativação das vias dependentes da PKA e de EPAC, que contribuem para a inibição da AICD. Por fim, a ativação dos principais fatores de transcrição envolvidos com a expressão de CD95L (NFAT, AP-1 e NF-kB) não é bloqueada por PGE2. Por outro lado, PGE2 induziu a expressão de ICER, um repressor transcripcional, através da ativação de CREB. Em conjunto, estes resultados indicam que as APCs podem modular os níveis de expressão de CD95L através da secreção de PGE2 em resposta ao LPS, através de uma via dependente de TLR4 e MyD88, com conseqüências tanto para a morte de linfócitos T quanto para a sua própria sobrevivência.Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. In this present work, it was demonstrated that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD). This effect was observed in non-stimulated APCs, but it was significantly increased after lipopolysaccharide (LPS) treatment. Using different KO mice, it was found that the LPS-induced protective factor is dependent on TLR4/MyD88 and independent of TLR2 and CD14. The protective factor was identified as prostaglandin E2 (PGE2) and it was shown that both APC-derived supernatants and PGE2 prevented CD95L upregulation in T cells in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T cell killing of target macrophages. It was also demonstrated that instead of blocking CD95 pathway, PGE2 enhanced T cell death induced by agonistic anti-CD95 antibodies. The PGE2 receptors, EP2 and EP4, appear to be involved in AICD suppression since pharmacological stimulation of these receptors mimics the protective effect on T cells and their respective antagonists interfere with the protection induced by either APCs derived or synthetic PGE2. The engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and exchange protein directly activated by cAMP pathways to prevent AICD. Finally, the activation of the main transcription factors involved in CD95L expression (NFAT, AP-1 and NF-kB) is not avoided by PGE2. On the other hand, PGE2 induces the expression of ICER, a transcriptional repressor of CD95L, through CREB activation. Taken together, these results indicate that APCs can regulate T-cell levels of CD95L by releasing PGE2 in response to LPS through a TLR4/MyD88-dependent pathway, with consequences for both T cell and their own survival.
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Bauermann, Fernando Viçosa. "Emergência do grupo de pestivírus hobi-like e impacto no diagnóstico e controle do vírus da diarréia viral bovina." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/4083.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe genus Pestivirus is composed by four important pathogens of livestock: bovine viral diarrhea virus 1 and 2 (BVDV-1 and BVDV-2), classical swine fever virus (CSFV) and border disease virus (BDV) of sheep. An emerging group of pestivirus temptatively called as HoBi-like, BVDV-3, or atypical pestiviruses was first detected and characterized in Europe from a fetal bovine serum (FBS) lot originated in Brazil. HoBi-like viruses share genetic and antigenic similarities with BVDV species. The present thesis is composed by studies that address the emergence of this virus group and its potential impact on BVDV diagnostic and control. Monoclonal antibody binding demonstrated the existence of conserved regions within epitopes in the glycoprotein Erns and the non-structural protein NS2/3 among the pestiviruses species (BVDV-1; BVDV-2; e HoBi-like), whereas high degree of divergence was detected in glycoprotein E2. These findings suggest that panpestiviruses diagnostic tests may rely on the Erns and NS2/3 proteins, and pestiviruses specific species diagnostic tests should target the E2 glycoprotein. The threshold for detection of HoBi-like virus using commercial BVDV antigen capture ELISA was statistically similar to BVDV detection. On the other hand, two BVDV antibody detection ELISA kits failed to detect at least 20% of animals harboring antibodies against HoBi_D32/00. Thus, it is obvious the need for the development of specific diagnostic tests to HoBi-like viruses. Likewise, it was verified that vaccines containing strains of BVDV-1 and BVDV-2 inactivated or modified live (MLV) virus generate suboptimal protection against HoBi-like viruses. Higher levels of protective antibodies against HoBi-like virus were verified using MLV. Nevertheless the geometric mean titer for HoBi-like was 12.9, while 51.1 and 23.5 for BVDV-1 and BVDV-2, respectively. In addition to low levels of protective antibodies, seroconversion was verified in 68% of animals to HoBi-like virus, although reached 100% and 94% against BVDV-1 and BVDV-2, respectively. Regarding to the diagnostic and control of pestiviruses, the trade of FBS may poses as an important route for dissemination of agents contaminating this product. Composed by a homogenate of serum from hundreds to thousands of fetuses, pestiviruses screening in FBS lots are potentially an important source of information regarding the presence and/or dissemination of these viruses in the region where samples were originated from. Therefore, FBS lots originated in North American countries and processed in the United States of America (USA) or Europe were tested. While several lots were detected as positive for BVDV, none of the lots manufactured in the USA were detected as positive for HoBi-like viruses or antibodies against it. However, two FBS lots processed in Europe were positive for HoBi-like viruses, suggesting that the contamination did occur during the pooling or package of these samples in Europe. These results strongly indicate the need for international rules regarding certification of FBS origin, employment of certified diagnostic tests and measures to avoid contamination of FBS during the manufacturing process. Was also verified the need to include specific tests to detect HoBi-like viruses in the FBS quality control routine. Briefly, the studies here presented demonstrated that the available BVDV diagnostic tests frequently fail in detecting HoBi-like viruses and/or differentiate between HoBi-like virus and BVDV species. In addition, the detection of animal harboring antibodies against HoBi-like using commercial diagnostic tests is unreliable. Likewise, in-vitro studies demonstrated that the cross protection against HoBi-like viruses in serum of animals immunized against BVDV-1 and BVDV-2 is limited. Therefore, the detection and control of this emergent group of viruses require the development of specific diagnostic tests and vaccines.
O gênero Pestivirus é composto por quatro espécies virais: vírus da diarréia viral bovina tipos 1 e 2 (BVDV-1 e BVDV-2), vírus da peste suína clássica (CSFV) e vírus da doença da fronteira (BDV). Um novo grupo de pestivírus, provisoriamente denominado de HoBi-like, BVDV-3, ou pestivirus atípicos foi inicialmente identificado na Europa em uma amostra de soro fetal bovino (SFB) importada do Brasil. O vírus (ou grupo de vírus) HoBi-like possui similaridades ao nível genético e antigênico com o BVDV. A presente tese apresenta trabalhos de avaliação do impacto da emergência deste novo grupo de vírus no diagnóstico e controle do BVDV. Utilizando anticorpos monoclonais, verificou-se maior reatividade cruzada entre as espécies de pestivírus (BVDV-1; BVDV-2; e HoBi-like) em epitopos da glicoproteína Erns e proteína não-estrutural NS2/3, comparando com epitopos da glicoproteína E2. Assim, sugere-se que testes panpestivírus devem ser direcionados às proteínas Erns e NS2/3, enquanto testes específicos podem explorar diferenças existentes na glicoproteína E2. Por meio de um teste comercial de ELISA de captura de antígeno, verificou-se que o limiar de detecção do vírus HoBi_D32/00 é estatisticamente similar ao do BVDV. Entretanto, dois kits de ELISA para a detecção de anticorpos contra o BVDV falharam em detectar ao menos 20% dos animais soropositivos para HoBi_D32/00. Sugere-se a necessidade de reformular os testes diagnósticos para BVDV ou desenvolvimento de testes específicos. Da mesma forma, verificou-se que vacinas para BVDV-1 e BVDV-2 contendo antígenos inativados ou atenuados produzem uma proteção cruzada fraca contra o vírus HoBi-like. Os melhores resultados de proteção foram verificados com o uso de vacina viva atenuada, entretanto, o título médio geométrico (GMT) contra vírus HoBi-like foi de 12,9, enquanto para o BVDV-1 e BVDV-2 foram respectivamente, 51,1 e 23,5. Somado aos baixos títulos de anticorpos, a soroconversão verificada para o vírus HoBi-like foi de 68% dos animais, enquanto 100% e 94% para BVDV-1 e BVDV-2, respectivamente. Relacionado ao diagnóstico e controle dos pestivírus, o comércio de SFB possui papel relevante na disseminação de agentes infecciosos. Composto por um homogeneizado do soro de centenas a milhares de fetos bovinos, lotes de SFB possuem alto potencial para a identificação de pestivírus circulantes na região de origem dos animais abatidos. Assim, foram testados lotes de SFB originados na América do Norte e manufaturados nos EUA ou na Europa. Apesar de vários lotes estarem contaminados com BVDV, não foi evidenciada a presença do vírus HoBi-like ou de anticorpos específicos em lotes produzidos nos EUA. Entretanto, foi detectada a presença do agente em dois lotes manufaturados na Europa, indicando a possibilidade de contaminação dessas amostras durante o processo de pooling e embalagem na Europa. Demonstra-se imprescindível a criação de regras internacionais relacionadas à certificação de origem do SFB, a implementação de testes padrão para a detecção de agentes, e adoção de medidas que impeçam a contaminação do produto durante o processamento. Verificou-se também a necessidade de incluir testes específicos para os vírus HoBi-like na rotina de testes utilizada para certificação de qualidade do SFB. Em resumo, os resultados demonstraram que os testes diagnósticos para BVDV frequentemente falham em detectar o vírus HoBi-like ou em diferenciar BVDV de HoBi-like vírus. Testes comerciais para detecção de anticorpos contra BVDV não detectam eficientemente animais expostos ao vírus HoBi-like. Da mesma forma, estudos in-vitro demonstram que a proteção cruzada contra o vírus HoBi-like conferida a animais vacinados para BVDV é limitada. Assim, medidas de detecção e controle para pestivírus devem incluir testes diagnósticos e vacinas específica para o vírus HoBi-like.
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Johansson, Jenny. "The Impact of Growth Hormone and Gamma-Hydroxybutyrate (GHB) on Systems Related to Cognition." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185631.
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Drug dependence is a serious and increasing problem in our society, especially among adolescents. The use of the large variety of substances available can result in a range of physiological and psychological adverse effects on individuals and negative consequences on the society overall. Several different types of drugs induce neurotoxicological damages, which in turn can generate impairment in for example the reward system and affect cognitive parameters. The drug gamma-hydroxybutyrate (GHB) is usually considered a harmless compound among abusers, but has now shown to be highly addictive. Furthermore, GHB can cause memory impairments in both humans and animals. On the contrary, growth hormone (GH) and its main mediator insulin-like growth factor 1 (IGF-1) have recently been suggested to improve memory and learning in several studies. The hormones exhibit certain neuroprotective capabilities and have also previously been demonstrated to reverse opioid induced apoptosis in hippocampal cells. These effects and the fact that GHB is shown to increase GH secretion, which attracted considerable attention among body builders, led us to initiate studies on GHB and its impact on relevant systems in the central nervous system (CNS). Thus, the main purpose of the present investigation was to elucidate some of the underlying mechanisms that could account for the effects exerted by GH and GHB in the CNS. We found that a) GH affects the density and functionality of GABAB-receptors and opioid receptors in the male rat brain, b) GHB induces cognitive deficits and down-regulates GABAB-receptors, c) GHB treatment creates an imbalance between the endogenous opioids Met-enkaphalin-Arg6Phe7 (MEAP) and dynorphin B and increases the levels of MEAP in regions of the brain that are associated with drug dependence, and d) GHB affects the expression of IGF-1 receptors but not the plasma levels of IGF-1. In conclusion, the present work demonstrates that GH interacts with both opioid and GABAB-receptors in the male rat CNS and that GHB has an impact on brain regions associated with cognition and the development of dependence. These observations may be of relevance in many aspects related to addiction and might be translated into humans.
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Bhandari, Anita [Verfasser]. "Impact of cigarette smoke exposure on the airway epithelium of Drosophila melanogaster to model COPD-like phenotypes / Anita Bhandari." Kiel : Universitätsbibliothek Kiel, 2019. http://d-nb.info/1181096731/34.
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Handschuh, Juliane [Verfasser]. "The interaction of Kv1.3 with Dlg-like MAGUKs and its impact on calcium signaling in activated T cells / Juliane Handschuh." Magdeburg : Universitätsbibliothek, 2017. http://d-nb.info/1128726475/34.
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Bhattacharyya, Aritra [Verfasser], Stefan [Gutachter] Hippenstiel, Regine [Gutachter] Hengge, and Andreas [Gutachter] Meisel. "Impact of the myeloid Krüppel-like factor 4 during pneumococcal pneumonia / Aritra Bhattacharyya ; Gutachter: Stefan Hippenstiel, Regine Hengge, Andreas Meisel." Berlin : Humboldt-Universität zu Berlin, 2018. http://d-nb.info/1185668357/34.
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Kella, Greta. "What? Do I look like this? : A qualitative study of mirrors’ impact on contemporary dance pedagogy students’ experiences of themselves." Thesis, Stockholms konstnärliga högskola, Institutionen för danspedagogik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uniarts:diva-351.
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The purpose of this study was to describe how mirrors affect contemporary dance pedagogy students’experiences of themselves. Empirical material was collected through semi-structured interviews with four dance pedagogy students at the School of Dance and Circus, and analyzed with the help of post-humanistic perspective and Lacanian mirror stage theory. The results suggest that mirrors are active agents that participate in several things, for example they create an evaluating gaze, objectification, alienation from the subject as a unity, experience of two-dimensional bodies and distraction. The results also suggest that the mirrors actively create afront and direction, and therefore they shield dancers from sensing their ‘inner selves’ as well as others in theroom, time and space. The feeling of success and mood affect the way dancers feel about their mirror images and themselves. In summary, this study stresses that the mirror, an object, is active and agentic, instead of thinking that the dancer is the only active part in the dancer-mirror relationship.
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Mabilia, Greta. "Like Me : An exploration into the impact of social media on our mental well-being from a speculative design perspective." Thesis, Linnéuniversitetet, Institutionen för design (DE), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-76572.
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What impact do social media have on mental well-being and how can design become a tool for increasing awareness among users? To interact on social media means to find new ways of seeking a sense of belonging, of being part of a society that can validate our existence and attribute value to what we decide to share. But what happens when there is a gap separating the ways in which we create value and sense of selfworth online and offline? How does it impact our mental well-being and the capacity to become a productive element of our society? Like Me is a speculative design project that explores the gap between the virtual and the real, while researching how it impacts our mental well-being and sense of self-worth in society. This Bachelor’s thesis delves into this topic through design methods and visual communication, resulting in a short fictional film about a speculative scenario. The aim of this research is to raise a discussion about embracing what is to come, finding a new sense of awareness to improve our impact on social sustainability. KEYWORD
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Orwick, Ogden Sherri L. "Agent for Interactive Student Assistance: A Study of an Avatar-Based Conversational Agent's Impact on Student Engagement and Recruitment at BGSU's College of Technology." Bowling Green State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1319804597.
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Silva, Fernanda Gaisler da. "Impacto da obesidade no trofismo cardíaco em camundongos C57BL/6 e FVB/NJ: participação da resposta inflamatória e dos receptores Toll-like." reponame:Repositório Institucional da UFABC, 2017.
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Orientadora: Profa. Dra. Marcela Sorelli Carneiro RamosTese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biossistemas, 2017.
As doencas cardiovasculares correspondem ao maior risco de morte subita em todo o mundo, a populacao mundial tem se tornado cada vez mais sedentaria e junto as doencas cardiovasculares outros problemas de saude publica aumentam como a obesidade e diabetes mellitus. Os gastos com a saude publica aumentam muito devido a maior incidencia de doencas associadas ao sedentarismo, obesidade, tabagismo, estresse, hipertensao arterial entre outros. Especificamente a obesidade e considerada uma epidemia mundial, que esta associada aos habitos alimentares e sedentarismo, e esta amplamente relacionada ao fator de risco cardiovascular como hipertensao arterial, resistencia insulinica, dislipidemia e diabetes mellitus, que favorecem o processo aterosclerotico e a ocorrencia de eventos cardiovasculares. Ha uma maior prevalencia de hipertensao arterial em individuos obesos e presenca de hipertrofia cardiaca, que e a maior condicao de morbimortalidade cardiovascular. Trata-se de uma doenca cronica relacionada a eventos pro-inflamatorios com acao de diversas citocinas e quimiocinas alem de hormonios envolvidos na resposta imunologica inata. Os receptores Toll-Like fazem parte da Resposta Imunologica Inata e estao presentes em diversos tecidos, incluindo o coracao. Quando ativados desencadeiam uma resposta intracelular, ativando fatores transcricionais, como NF-kB, que leva a transcricao genica de citocinas inflamatorias: IL-6, TNF-¿¿, INF-gama, IL-1. Algumas doencas cardiovasculares sao antecedidas por inflamacoes sistemicas ou locais, demonstrando que as citocinas sao responsaveis por modular o trofismo cardiaco. Diante do exposto, uma analise mais completa envolvendo obesidade e processos inflamatorios com o risco cardiovascular se faz necessaria para a compreensao de moleculas e vias de sinalizacao, reguladas nessa patologia. O presente estudo tem como objetivo avaliar a contribuicao dos fatores inflamatorios na hipertrofia cardiaca induzida por modelo experimental de obesidade. Para tanto, foram utilizados camundongos C57Bl/6 e camundongos FVB/NJ submetidos ao tratamento com dieta rica em gordura contendo 23% proteina, 35,5% carboidrato e 35,9% gordura e foram comparados aos grupos chow (controle) submetidos a dieta composta por 19% de proteina, 56% de carboidrato, 3,5% de gordura por 68 dias de tratamento. Os animais C57Bl/6 apresentaram maior ganho de peso em relacao aos FVB/NJ ao final dos 68 dias de dieta High Fat. O aumento de colesterol serico, insulina, glicemia, epiWAT (epididymal white adipose tissue) foi maior nos animais C57Bl/6. As duas linhagens apresentaram Heart Weight/Body Lenght e Heart Weight/Tibia Lenght maior em relacao ao grupo Chow, ou seja, grupo controle. Atraves da tecnica de Q-PCR os niveis de mRNA dos marcadores moleculares de hipertrofia cardiaca foram avaliados, e o marcador alfa-actina mostrou-se aumentado na linhagem C57Bl/6 enquanto o marcador ANF (atrial natriuretic factor) mostrou-se aumentado na linhagem FVB/NJ, quando comparados aos seus respectivos grupos chow. Os genes TLR2, TLR4, TNF-¿¿, IL-6, MyD88 e NF-kB tambem foram avaliados. A expressao genica de TLR2, MyD88 e NF-kB mostrou-se diminuida nos animais FVB/NJ submetidos a dieta rica em gordura quando comparados aos animais controle. Na linhagem C57Bl/6, observou-se aumento na expressao genica de TNF-¿¿ e NF-kB. A inducao da obesidade promoveu maior ganho de peso na linhagem C57Bl/6 acompanhado de maior adiposidade abdominal e no tecido epididimal, essa linhagem apresentou maior sensibilidade a insulina e maiores niveis de colesterol na dieta High Fat em relacao a linhagem FVB/JN. Houve remodelamento cardiaco em ambas linhagens e a expressao genica de citocinas inflamatorias foi mais evidente na linhagem C57Bl/6, tambem apresentando maior expressao genica de NF-kB. A linhagem FVB/NJ apresentou diminuicao na expressao de MyD88 e NF-kB na dieta High Fat. Com base nos resultados obtidos verificamos que os camundongos C57Bl/6 mostraram-se mais suscetiveis a dieta enquanto a linhagem FVB/JN mostrou-se mais resistente.
Cardiovascular diseases correspond to an increased risk of worldwide sudden death, the world population has become increasingly sedentary and with cardiovascular diseases other public health problems increase such as obesity and diabetes mellitus. Expenditures on public health increase greatly due to a higher incidence of diseases associated with sedentarism, obesity, smoking, stress, hypertension among others. Obesity specifically is considered a worldwide epidemic, which is associated with eating habits and sedentary lifestyle, and is largely related to cardiovascular risk such as hypertension, insulin resistance, dyslipidemia and diabetes mellitus, which favor the atherosclerotic process and occurrence of cardiovascular events. There is a higher prevalence of hypertension in obese and presence of cardiac hypertrophy, which is a higher cardiovascular morbidity and mortality condition. It is a chronic disease related to pro-inflammatory events with the action of various cytokines and chemokines in addition to hormones involved in the innate immune response. Toll-like receptors are part of the innate immune response and are present in several tissues including the heart. When activated trigger an intracellular response, activating transcriptional factors such as NF-kB, which leads to the genetic transcription of inflammatory cytokines: IL-6, TNF- á, IFN-gamma, IL-1. Some cardiovascular diseases are antecedents of systemic or local inflammations, demonstrating that cytokines are responsible for modulating cardiac trophism. In summary, a more complete analysis involving obesity and inflammatory processes with cardiovascular risk to understand molecules and signaling pathways regulated in this pathology are needed. The present study aims to evaluate the contribution of inflammatory factors in cardiac hypertrophy induced by the experimental model of obesity. For this, C57Bl/6 mice and FVB/NJ mice submitted to a high fat diet containing 23% protein, 35.5% carbohydrate and 35.9% fat were compared to the Chow (control) groups submitted to a chow diet containing 19% protein, 56% carbohydrate, 3.5% fat for 68 days of treatment. The C57Bl/6 animals presented greater weight gain in relation to FVB/NJ at the end of 68 days of high fat diet. Serum cholesterol, insulin, glycemia, epiWAT (epididymal white adipose tissue) increased in C57B1/6 animals. Both strains presented Heart Weight/Body Lenght and Heart Weight/Tibia Lenght higher than the Chow group. mRNA levels of cardiac hypertrophy molecular markers were evaluated through Q-PCR technique, and the alpha-actin marker was shown to be increased in the C57B1/6 lineage while the ANF (atrial natriuretic factor) marker was shown to be increased in the FVB/NJ lineage, when compared to their respective chow groups. TLR2, TLR4, TNF-á, IL-6, MyD88 and NF-kB genes were also evaluated. Gene expression of TLR2, MyD88 and NF-kB were decreased in FVB / NJ animals submitted to a high fat diet when compared to control animals. There was an increase in the gene expression of TNF-á and NF-kB in C57Bl/6 lineage. The induction of obesity promoted greater weight gain in the C57Bl/6 mice followed by a greater abdominal and epididymal adiposity, this lineage presented higher insulin sensitivity and higher cholesterol levels in the High Fat diet when compared to the FVB/JN lineage. There was cardiac remodeling in both lineages and inflammatory cytokines gene expression were more evident in the C57Bl/6 mice, also presenting a greater gene expression of NF-kB. The FVB/NJ mice showed decreased expression of MyD88 and NF-kB on the High Fat diet. Based on the results, we found that the C57Bl/6 mice were more susceptible to the High Fat diet than the FVB/JN strain.
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Wolchok, Emma Justine. ""It feels like this massive weight" : the impact of stigma on health care experiences as described by people with Borderline Personality Disorder." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50365.
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People with Borderline Personality Disorder (BPD) often experience numerous mental and physical health issues, and consequently interact with health care professionals on a regular basis. There is a pervasive negative attitude towards people with BPD amongst health care professionals, as people with BPD are perceived as attention seeking, manipulative, hostile, and willfully resistant to treatment. This stigma influences the way people with BPD are treated by professionals. The current body of literature about the experiences of people with BPD in the health care system focuses exclusively on the mental health care system. The research reviewed in this study sought to answer the question: How do people with BPD describe interactions with health care professionals when accessing care for physical health issues? This paper reports findings from interviews with five people living with BPD. Although these participants did not describe unpleasant or stigmatizing experiences in health care specifically, they reported feeling stigmatized in general due to their diagnosis, and these experiences of stigma influenced the way they access health care. The data gathered from these participants have several implications for service delivery to people with BPD.Arts, Faculty of
Social Work, School of
Graduate
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Jumaa, Joell. "The impact of caffeine on gene expression in the brain and plasma corticosterone concentrations in rats with varying degrees of anxiety like behaviour." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-445629.
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Anxiety disorders are the most common psychiatric disorders worldwide and are associated withcomorbidity and morbidity. Although there are several therapeutic drugs for this mental condition,there is a need to develop alternative treatments as treatment response differ between patients.Meanwhile, many researchers suggest a link between mental diseases and adenosinergic signaltransduction regulation in the central nervous system (CNS). The adenosine receptor antagonist,caffeine, have been of interest in these studies as some hypotheses suggest its role in modulatinganxiety-like behaviour. The aim with this study was to measure the gene expression of A2aR, A1R,D2R and C-fos and corticosterone plasma levels in rats, after acute injection with caffeine (50 mg/kg)in three rat groups: low/intermediate/ high anxiety-like behaviour groups. We used qPCR and ELISAto conduct this study. In amygdala, a significant increase of A1R was observed in the low anxietygroup compared with the control group. The same group also showed a significant increase incorticosterone plasma levels. As a result of our findings, the adenosine receptor antagonist caffeinemay play a role in the regulation of certain genes and hormones involved in anxiety, further suggestinga role of the adenosine receptor system in anxiety disorders.
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Matti, Albert I. "Impact of in vitro embryo culture on the expression of insulin like growth factors and their receptors in the sheep heart in late gestation /." Title page and abstract only, 2005. http://web4.library.adelaide.edu.au/theses/09SB/09sbm4441.pdf.
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Barbar, Saber Davide. "Impact de la ventilation mécanique sur la réponse inflammatoire médiée par les Toll-like receptors 2 et 4 dans un modèle de pneumopathie bactérienne." Thesis, Dijon, 2014. http://www.theses.fr/2014DIJOS039/document.
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Introduction: La pneumonie associée à la ventilation mécanique (VM) est fréquente chez les patients ventilés. L’étirement cyclique (EC) induit par la VM pourrait amorcer le poumon vers une réponse inflammatoire en cas d'exposition à des bactéries. Les Toll-like Receptors (TLR) reconnaissent les bactéries et déclenchent l'immunité. La VM pourrait moduler l'expression des TLR et leur réactivité aux agonistes. Le décubitus ventral (DV) réduit l’étirement du poumon. Méthodes: Les niveaux de TLR2 et la réponse à ses agonistes ont été mesures dans des cellules pulmonaires soumises à un EC, et dans un modèle de lapin ventilé. Une stimulation ex vivo du sang total prélevé sur lapins ventilés a été réalisée. Une pneumonie a été induite chez des lapins soumis à VM et maintenus en décubitus dorsal ou tournés en DV. Résultats: L’EC des cellules ainsi que des poumons de lapins augmente les niveaux de TLR2 et la réponse inflammatoire à ses agonistes. La VM et l’exposition du poumon à des agonistes TLR2 induisent synergiquement des lésions. Chez des lapins avec pneumonie sous VM la clairance bactérienne pulmonaire est réduite, la probabilité de bactériémie et le taux des cytokines circulantes augmentés. Le sang total provenant d'animaux sous VM libère de grandes quantités de cytokines après stimulation. Le DV est associe à des niveaux plus faibles de concentrations bactériennes et d'inflammation. Conclusions: La VM sensibilise le poumon aux ligands bactériens de TLR2, modifie la clairance bactérienne pulmonaire, favorise les lésions pulmonaires et de l'inflammation. La surexpression de TLR2 induite par l’EC pourrait expliquer ces différences. Le DV pourrait avoir un effet protecteurIntroduction: Ventilator-associated pneumonia is common in patients subjected to mechanical ventilation (MV). Cyclic stretch subsequent to MV could prime the lung toward an inflammatory response if exposed to bacteria. Toll-like receptors (TLRs) recognize pathogens thus triggering immunity. MV could modulate TLRs expression and responsiveness to agonists. The prone position (PP) reduces lung stretch.Methods:TLR2 levels and response to the TLR2 ligands were measured in human pulmonary cells submitted to cyclic stretch, and either spontaneously breathing (SB) or MV rabbits. Ex vivo stimulation of whole blood taken from SB or MV rabbits was performed.Enterobacter aerogenes pneumonia was induced in rabbits subjected to MV and kept supine or turned to the PP. Results: Cyclic stretch of human cells as well as rabbitsÕ lung increased both TLR2 levels and inflammatory response to its agonist. MV and airways exposure to TLR2 ligands acted synergistically in causing lung injury.A decrease of lung bacterial clearance and a greater likelihood of bacteremia were observed in MV rabbits with S. aureus pneumonia. Circulating cytokines rose significantly only in these animals. MV induced TLR2 spleen overexpression. Whole blood obtained from MV animals released larger amounts of cytokines after stimulation. PP was associated with lower levels of bacterial concentrations and inflammation. Conclusions: MV sensitizes the lung to bacterial TLR2 ligands, alters lung bacterial clearance, promotes lung injury and inflammation. Both pulmonary and peripheral blood stretch-induced TLR2 overexpression could account at least in part for such differences. The PP could be protective
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Kitai, Takeshi. "Impact of New Development of Ulcer-Like Projection on Clinical Outcomes in Patients With Type B Aortic Dissection With Closed and Thrombosed False Lumen." Kyoto University, 2013. http://hdl.handle.net/2433/174823.
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Benoit, Simon. "Impact of the administration of α-casozepine, a benzodiazepine-like peptide from bovine αs1-casein, and of a proteolysis fragment on neural activity in mice." Thesis, Université de Lorraine, 2017. http://www.theses.fr/2017LORR0345/document.
Full textAbstract:
L’α-casozépine (α-CZP) est un décapeptide porteur des propriétés anxiolytiques de l’hydrolysat trypsique de caséine αs1 bovine. Différentes propriétés ont pu rapprocher ce peptide de la famille des benzodiazépines, les anxiolytiques les plus prescrits. Cependant, certaines différences, dont notamment une absence d’effets secondaires, permettent aussi de distinguer l’α-CZP des benzodiazépines. Bien que de nombreux éléments laissent penser qu’une action centrale reste l’hypothèse principale du mécanisme d’action de l’α-CZP, aucune régulation de l’activité de zones cérébrales n’avait été montrée jusqu’à présent. Ce travail de thèse aura donc pu montrer que les propriétés anxiolytiques de l’α-CZP sont associées à une modification de l’activité cérébrale chez la souris, après une unique injection intrapéritonéale, dans différentes régions impliquées dans la régulation de l’anxiété, notamment l’amygdale, la formation hippocampale, le noyau accumbens et certains noyaux de l’hypothalamus et du raphé. De plus, ces modifications de l’activité cérébrale ne sont pas exactement les mêmes que celles observées avec le diazépam, une benzodiazépine de référence, ni de celles obtenues avec YLGYL, un peptide dérivé de l’α-CZP, bien qu’il existe des similitudes dans le comportement de l’animal suite aux différents traitements effectués. Enfin, il a été démontré qu’une situation anxiogène est indispensable pour révéler cet effet central. L’ensemble de ce travail aura permis d’avancer dans la compréhension du mode d’action d’un peptide alimentaire ayant des effets positifs sur le comportement et les émotions de son consommateurΑ-casozepine (α-CZP) is a decapeptide that mediates the anxiolytic-like properties of the tryptic hydrolysate of bovine αs1-casein. Different properties of α-CZP leads to consider this peptide close to the benzodiazepine family, the most commonly used anxiolytic molecules. In contrast, other results suggest a distinct mode of action between α-CZP and benzodiazepines, especially the fact that the peptide does not have side effects. Although a central action remains the main hypothesis of the mode of action of α-CZP, no regulation of the brain activity has been shown before. The work achieved in this thesis displayed the fact that the anxiolytic-like properties of α-CZP, after a single intraperitoneal injection of the peptide, are associated with a modulation of cerebral activity in several regions linked to anxiety regulation in mice brains, such as the amygdala, the hippocampal formation, the accumbens nucleus and some nuclei of the hypothalamus or raphe. Besides, these modulations of neural activity are not exactly the same as those obtained after an injection of diazepam, a reference benzodiazepine, or YLGYL, a derivative of α-CZP, even though observed behaviours are similar. Eventually, it has been demonstrated that an anxiety-inducing situation is needed to trigger the central effects of α-CZP. This work allowed a better understanding of the mode of action of a bioactive peptide from alimentary origin that has a positive action on its consumer’s mood and behaviour