The purpose of this study was to describe mathematically the oxygen uptake kinetics during cycle ergometry, and to examine the effect of intensity on the kinetic responses within the severe domain. Sixteen volunteers performed a series of exercise tests at a range of intensities selected to elicit fatigue in ~3 to 10 min. A simple mono-exponential model effectively described the response across all intensities. There was a positive correlation between the response time and the time to fatigue, demonstrating that the maximal oxygen uptake was achieved faster at higher intensities within the severe domain. Models incorporating two components effectively described the responses only in tests lasting 8 min or more. It was concluded that there is a second, slow component in the oxygen uptake response only at the lower intensities within the severe domain.

Title of master thesis Determination of climbing specific maximal oxygen uptake during climbing with increasing inclination and constant speed. Work objectives To review the determination of climbing specific maximal oxygen uptake during climbing with increasing inclination and constant speed. Methods Twenty six climbers with climbing ability on UIAA scale from 4th to 10th degree were participated in this study. Maximal specific oxygen uptake was measured by climbing test, to exhaustion on climbing wall, where the inclination were changed from 95ř (105ř) to 135ř every three minutes. Speed of climbing was constant on 25 movements·min-1 . After a rest, the participants went a maximal running test on treadmill. There were evaluated relationships between climbing ability, inclination and cardiopulmonary variables. Results In maximal climbing test, climbers achived plato on value 40 ± 3,5 ml·kg-1 ·min-1 , without influence on climbing ability or inclination. The climbing ability most corelated with achived inclination r = 0,89 and heart rate r = 0,41. Our study confirmed disproportional rising of heart rate against oxygen uptake. Furthermore, there was a strong relationship to be found between ventilation per 1l oxygen to RER indicating specific breathing mechanism of advanced climbers. More demanding...

Nitrogen (N) fertilization due to atmospheric deposition (NDEP ) may explain some of the net carbon (C) sink (0.6-0.7 Pg y-1) in temperate forests, but estimates of the additional C uptake due to atmospheric N additions (∆C/∆N) can vary by over an order of magnitude (5 to 200 ∆C/∆N). High estimates from several recent studies [e.g. Magnani (2007), Nature 447 848-850], deriving ∆C/∆N from regional correlations between NDEP and measures of C uptake (such as eddy covariance -derived net ecosystem production, or forest inventory data) contradict estimates from other studies, particularly those involving 15N tracer applications added as fertilizer to the forest floor. A strong ∆C/∆N effect requires nitrogen to be efficiently acquired by trees and allocated to high C:N, long-lived woody tissues, but these isotope experiments typically report relatively little (~ 20 %) of 15N added is found above-ground, with less than 5 % of the total 15N applied found in wood. Consequently the high correlation-derived ∆C/∆N estimates are often attributed to co-variation with other factors across the range of sites investigated. However, 15N-fertilization treatments often impose considerably higher total N loads than ambient NDEP , while almost all exclusively only apply mineral 15N treatments to the soil, often in a limited number of treatment events over relatively short periods of time. Excessive N deposition loads can induce negative physiological effects and limit the resulting ∆C/∆N observed, and applying treatments to the soil ignores canopy nitrogen uptake, which has been demonstrated in numerous studies. As canopies can directly take up nitrogen, the chronic, (relatively) low levels of ambient NDEP inputs from pollution may be acquired without some of the effects of heavy N loads, with trees obtaining this N before it reaches the soil, allowing canopies to substitute for, or supplement, edaphic N nutrition. The strength of this effect depends on how much N uptake can occur across the canopy under field conditions, and if this extra N supplies growth in woody tissues such as the stem, as well as the canopy. Similarly, such mineral fertilizer isotope trace experiments are also unable to trace N in the decomposing litter and humus layers of the soil, which even under heavy NDEP loading contribute most of the N utilised for forest growth. Recent literature suggests that some organic (early decomposition) forms of N may be taken up by roots. If this litter N is not retained or distributed in the same way as mineral fertilizers, its contribution to plant nutrition and ∆C/∆N may need to be reassessed under nitrogen deposition. We tested some of these assumptions in the nursery and the field. In order to facilitate litter 15N tracing, we conducted an experiment injecting large trees with 15N-NH4NO3 to create 15N-labelled litter, tracing the applied isotope into a full harvest of the canopy. Such labelled litter substitute was used to replace the litter layer in a Sitka Spruce plantation (Picea sitchensis L. (Bong.)), where the fate of this 15N from litter decomposition in the soil system was compared against the fate of 15N in deposition. Similarly, in potted Sitka Spruce saplings, we used combination treatments of 15N-labelled litter, soil-targeted 15N-deposition, and canopy targeted 15N-deposition, investigating 15N return in different age classes of above and below ground biomass. We found that i) 15N recovery in canopies (needles and branches) in our injected trees was almost all of the injected 15N five months after injection, ii) canopy application of NDEP led to 60 % 15N return in above-ground parts of saplings compared to 21 % in soil applications and iii) a litter-derived 15N source was retained 55 % more in topsoil, and 36 % more in roots, than a similar deposition 15N source applied as mineral fertilizer. We discuss the implications of such findings in the context of 15N return in different plant organs and ecosystem pools, seasonal variation in N content, and overall inferences of a forest ∆C/∆N effect. Our results suggest that the total ∆C/∆N effect driven by a high N sequestration from canopy uptake in wood is ~ 114:1, more than double that of 15N tracer experiments but not as high as upper estimates from correlative studies, and that litter-derived organic N is better retained in trees and soils in excess of similar amounts of mineral 15N from deposition. Existing forest 15N-fertilization experiments could under-estimate the overall ∆C/∆N effect of atmospheric N deposition.

Les nanotechnologies sont en pleine expansion et leurs propriétés remarquables ouvrent la voie à des applications très variées intéressant la science des matériaux comme la nanomédecine. Cependant cet essor fulgurant doit s’accompagner d’interrogations justifiées sur les risques sanitaires pour l’homme et l’environnement compte tenu de leur potentielle toxicité biologique. Dans ce contexte le travail de cette thèse porte sur l’amélioration de la compréhension des mécanismes d’internalisation de particules au niveau cellulaire. Pour cela plusieurs types de micro- et nanoparticules fluorescentes de physico-chimie contrôlée (taille et groupements de surface) ont été synthétisés. Des contacts ont ensuite été établis avec une lignée cellulaire in vitro de macrophages (RAW 264.7) qui représente une cible préférentielle de l’organisme au niveau des moyens de défense. Différentes méthodologies de quantification en cytométrie en flux et fluorimétrie ont été développées dans le but de distinguer précisément les nanoparticules internalisées de celles adhérées au niveau des membranes. Des techniques complémentaires de microscopie confocale et MEB/MET ont été mises au point afin de mieux visualiser leur localisation intracellulaire. Enfin, pour nos diverses conditions expérimentales, une étude de l’activité biologique des particules a été évaluée sur la base des paramètres de réaction inflammatoire, d’altération membranaire et de stress oxydant. Ainsi, la première partie de ces travaux a concerné la mise au point d’une méthodologie de quantification de l’internalisation de particules fluorescentes microscopiques. Ensuite nous avons développé un modèle de nanoparticules doublement fluorescentes sensibles aux variations de pH permettant une quantification plus ciblée du processus de phagocytose. Enfin la dernière partie s’est attachée à étudier spécifiquement l’impact de la taille des nanoparticules sur leur internalisation. / Nanotechnologies are in full extension and the remarkable properties showed by nanomaterials pave the way for a variety of applications such as materials science or nanomedicine. However, this rapid expansion must be accompanied by justified interrogations about human’s health risks or impact on the environment because of their potential biological toxicity. In this context, this thesis aimed at improving the understanding of the cellular internalization mechanisms of particles. Different types of fluorescent micro- and nanoparticles with well-controlled physico-chemistry (size and surface groups) were synthesized. The contacts were established with an in vitro macrophage cell line (RAW 264.7), which represents the first line target cells in the human defense mechanisms. Different methodologies to accurately quantify and distinguish internalized nanoparticles from those just adhering to cell membranes were developed using flow cytometry and fluorimetry. Complementary confocal microscopy and SEM/TEM techniques were carried out to better visualize nanoparticles intracellular localization. Finally, for each experimental condition tested, the biological activity of the particles was evaluated in terms of inflammatory response, membrane alteration and oxidative stress. Thus, the first part of this work allowed the development of a methodology to quantify fluorescent microscopic particles internalization. Then a model of double fluorescent nanoparticles sensitive to pH variations was developed in order to quantify more precisely the phagocytic process. Finally the last part aimed at evaluating the impact of the size of the nanoparticles on their internalization.

Azetidine is a four-membered nitrogen-containing heterocyclic ring that has recently received a great deal of attention as a molecular scaffold for the design and preparation of biologically active compounds. Structure-activity studies employing functionalized azetidines have led to the development of variety of drug molecules and clinical candidates encompassing a broad spectrum of biological activities. Herein, the synthesis a novel series of 3-aryl-3-arylmethoxyazetidines is described. Selected 3-aryl-3-arylmethoxyazetidines were evaluated for their binding affinity to multiple monoaminergic transporters for the potential treatment of methamphetamine addiction. It was discovered that this scaffold exhibits high binding affinity (nM) for both the serotonin and dopamine transporters. In addition, a new method was developed for the synthesis of 3,3-diarylazetidines. This new approach provides a facile and efficient method to synthesize a variety of diaryl heterocycles including 3,3-diarylazetidines, 3,3-diarylpyrrolidines, and 4,4-diarylpiperidines in moderate to good yields.

Hermeneutisk orättvisa är en orättvisa där en del av ens sociala erfarenheter görs obegripliga pågrund av ett hermeneutisk glapp i de kollektiva hermeneutiska resurserna. Följaktligen drabbas ett subjektav en objektiv svårighet i antingen 1) förstå sina sociala erfarenheter och/eller 2) kommunicerasina sociala erfarenheter. Fricker argumenterar för att det är ett strukturellt fenomen utan en individuellförövare. Därav uppkommer inte frågan om ansvar. Medina, å sin sida, argumenterar att ansvar uppkommeräven om det kan vara begränsat. I den här uppsatsen avser jag undersöka Medinas och Frickersståndpunkter för att utvärdera den större frågan om ansvar i förhållande till hermeneutisk orättvisa.Jag argumenterar, med Woomers begrepp misslyckat upptag, att Medina ger en bredare definitionav hermeneutisk orättvisa än Frickers ursprungliga definition. Vidare diskuterar jag Frickers och Medinasdelvis olika syn på ansvar. Jag argumenterar att individer kan hållas ansvariga för att bidra till hermeneutiskmarginalisering. Följt detta bär de något slags ansvar för att skapa möjligheten för att hermeneutiskaorättvisor kan existera. Med Goetzes distinktion mellan kognitiv och kommunikativ skadaav hermeneutisk orättvisa argumenterar jag vidare att individer trots allt kan hållas ansvariga i relationtill den kommunikativa skadan av orättvisan, men inte den kognitiva. Således håller jag delvis med bådeFricker och Medina. / Hermeneutical injustice is the injustice of having some part of ones social experiences unintelligibledue to a hermeneutical gap in the collective hermeneutical resources. Consequently, a subject suffersan objective difficulty in either 1) understanding his/her social experiences and/or 2) communicatinghis/her social experiences. Fricker argues that it is a structural phenomenon with no individual perpetrator.Hence, the question of responsibility does not arise. Medina, on the other hand, argues thatresponsibility does arise though it may be limited. In this paper my aim is to examine Medinas andFrickers position in order to evaluate the larger question of responsibility in relation to hermeneuticalinjustice. I argue, with Woomers notion of uptake failure, that Medina gives a wider definition of hermeneuticalinjustice than Frickers original definition. Furthermore I discuss their partially differentviews of responsibility. I argue that individuals can be held responsible for contributing to hermeneuticalmarginalization. They therefore bear some kind of responsibility for creating the possibility forhermeneutical injustices. With Goetzes distinction between the cognitive and communicative harm ofhermeneutical injustice I further argue that individuals can be held responsible in relation to the communicativeharm of the injustice, but not the cognitive. I therefore in some aspects agree with bothMedina and Fricker.

O diestro é a fase luteínica na cadela caracterizada pelo aumento de progesterona (P4) sérica na primeira metade e por flutuações de 17&#946;-estradiol (E2) na segunda metade. O corpo lúteo (CL) é uma glândula endócrina temporária, que passa por um processo de desenvolvimento, manutenção e regressão, atingindo atividade secretória plena quando sua formação está completa. A insulina é o hormônio anabólico essencial para a manutenção da homeostase de glicose e do crescimento e diferenciação celular, sendo secretado pelas células &#946; pancreáticas. A sinalização intracelular da insulina começa com a sua ligação a um receptor de membrana específico, o que desencadeia uma série de ações metabólicas. Sabe-se que uma das consequências desta ligação é a translocação de transportadores de glicose 4 (GLUT4; gene SLC2A4) para que ocorra a captação de glicose. Nosso grupo demonstrou a expressão de GLUT4 no corpo lúteo de cadelas, expressão esta regulada diferencialmente ao longo do diestro. A presença deste transportador levou-nos a hipotetizar que a insulina seja importante para regulação da função luteínica. Para testar tal hipótese, utilizamos imuno-histoquímica para localizar o receptor de insulina (RI) e outros fatores regulatórios (NFKB e IL6) de GLUT4 no CL canino durante o diestro (dias 10 a >70 pós-ovulação, po) e western blotting para quantificar estas proteínas; investigamos a expressão gênica dos fatores acima mencionados por PCR em tempo real; e por fim, analisamos os efeitos da insulina sobre a expressão gênica de RI e SLC2A4 em células luteínicas nos dias 20 e 40 po e também sobre a captação de glicose destas células. No presente estudo, observou-se que o corpo lúteo canino expressa as proteínas do RI, NFKB e IL6 de maneira distinta ao longo do diestro. A expressão do RNAm do RI apresentou maior expressão nos dias 20 e 70, e diminuição no dia 40. O NFKB apresentou maior expressão no dia 40, enquanto o IL6 apresentou maior expressão do dia 10 ao 40. Observou-se correlação negativa entre o gene RI e os níveis de insulina (r = -0,69; P = 0,006) e positiva com SLC2A4 (r = 0,89; P = 0,01) em todo o diestro, enquanto o IL6 correlacionou-se de maneira positiva com o RI apenas na primeira metade (r = 0,96; P <0,0001) e o NFKB, negativamente com o RI nos dias 30, 40 e 50 (r = -0,57 P <0,05). Após a adição de insulina no meio de cultivo, observou-se que as expressões gênicas de RI e SLC2A4 se comportaram de maneira oposta de acordo com a fase do diestro estudada: células do dia 20 po apresentaram um aumento desta expressão e do dia 40 um declínio. Por fim, através da 12 captação de glicose, observou-se que as células luteínicas caninas são capazes de responder à insulina, aumentando a captação na ordem de 4 vezes (basal: 2,05 ± 0,8; insulina: 5,73 ± 0,5; valor de P <0,01 em cpm/ug proteína; basal: 79,6 ± 35,3; insulina: 212,5 ± 34,5, valor de P <0,05 em cpm/106 células). Esses resultados apontam a insulina, bem como o IL6 e o NFKB como fatores importantes que desempenham um papel na função do CL canino e trazem o CL para o grupo de tecidos que respondem ao estímulo insulínico aumentando a expressão de GLUT4 e consequentemente a captação de glicose. Além disso, estes eventos parecem sofrer controle adicional pelos hormônios esteróides. / Diestrus is the luteal phase in dogs characterized by an increase in progesterone (P4) levels in the first half and fluctuations of 17&#946;-estradiol (E2) in the second half. The corpus luteum (CL) is a temporary endocrine gland, which undergoes a process of development, maintenance and regression, reaching full secretory activity when its formation is complete. Insulin is an anabolic hormone essential for the maintenance of glucose homeostasis, cell growth and differentiation, and is secreted by pancreatic beta cells. Intracellular signaling of insulin begins with its binding to a specific membrane receptor, which triggers a series of metabolic actions. It is known that one consequence of this connection is the translocation of glucose transporters 4 (GLUT4; gene SLC2A4) for glucose uptake. Our group demonstrated the expression of GLUT4 in the canine corpus luteum in a time-related manner throughout diestrus. The presence of this transporter led us to hypothesize that insulin is important for the regulation of luteal function. To test this hypothesis, we used immunohistochemistry to detect the insulin receptor (IR) and possible regulatory factors (IL6 and NFKB) of GLUT4 in canine CL during diestrus (days 10 to > 70 after ovulation, po) and western blotting to quantify these proteins. In addition, we investigated the gene expression of the above mentioned factors by real-time PCR and analyzed the effects of insulin on IR and SLC2A4 gene expression in canine luteal cells at days 20 and 40 po and also on glucose uptake by these cells. Canine CL differentialy expressed RI, NFKB and IL6 during diestrus. The IR expression was higher on days 20 and 70, with and decreased at day 40. NFKB expression was higher on day 40 and IL6 increased on days 10 to 40 po. It was observed a negative correlation between IR expression and insulin levels (r = -0.69 P = 0.006) and positive with SLC2A4 (r = 0.89, P = 0.01) throughout diestrus. IR was positively correlated with IL6 only in the first half of diestrus (r = 0.96, P <0.0001), while it was negatively correlated with NFKB on days 30, 40 and 50 (r = -0.57 P <0.05). After insulin treatment, RI and SLC2A4 expressions behave differently according to the diestrus phase: on day 20, they increased and on day 40 they declined. Finally, we could observe through glucose uptake method that canine luteal cells are able to respond to insulin stimuli, increasing glucose uptake by approximately four folds (basal: 2.05 ± 0.8; insulin: 5.73 ± 0.5 cpm / ug protein, P < 0.01; basal: 79.6 ± 35.3; insulin: 212.5 ± 34.5 cpm/106 cells, P < 0.05). These results point towards a regulatory function 14 exerted by insulin, IL6 and NFKB in the canine CL and place this organ among the insulin sensitive ones, which respond to insulin stimuli increasing GLUT4 expression and glucose uptake. Moreover, these events seems to undergo a further control by steroid hormones.

As atividades antrópicas desenvolvidas nas ultimas décadas têm alterado o ciclo natural dos nutrientes, o que traz efeitos negativos às aos recursos hídricos. Os crescentes problemas com a eutrofização nesses ambientes têm aumentado os casos de florescimento de cianobactérias, que podem trazer riscos aos ecossistemas e comprometer a saúde da população. Em reservatórios, esses efeitos são ainda mais indesejáveis tendo em vista que acumulam água para múltiplos usos. Em vista desse quadro, torna-se importante o estudo da relação dos nutrientes com a comunidade fitoplanctônica. Geralmente os estudos de controle da eutrofização por restrição de nutrientes se atentam apenas à restrição do fósforo. O conhecimento sobre os efeitos das diferentes fontes nitrogenadas em reservatórios tropicais/subtropicais é praticamente inexistente. Para investigar a importância do amônio, nitrato e ureia como fontes de nitrogênio para o fitoplâncton em reservatórios tropicais com diferentes graus de trofia, foram realizadas 4 coletas nos reservatórios de Itupararanga (supereutrófico) e Barra Bonita (hipereutrófico) em dois pontos na coluna de água (profundidades referentes a 50 e 10% da radiação solar fotossinteticamente ativa na subsuperfície). As taxas de assimilação obtidas nessa pesquisa foram relativamente maiores que em trabalhos semelhantes devido à grande biomassa fitoplanctônica em Itupararanga e em Barra Bonita. As taxas de assimilação foram maiores na estação chuvosa, em Barra Bonita que em Itupararanga e, na primeira profundidade. As estratégias de assimilação de nitrogênio foram relacionadas à composição da comunidade fitoplanctônica. Em Itupararanga a comunidade apresentou domínio da cianobactéria Cylindrospemospsis raciborskii e mostrou-se bem adaptada à assimilação de amônio, nitrato e ureia, sendo o amônio a forma nitrogenada preferida, seguido de nitrato e ureia. Em Barra Bonita, a comunidade apresentou domínio da cianobactéria Microcystis aeruginosa durante a estação chuvosa, e ausência de dominância na estação seca. A mudança na composição da comunidade resultou numa maior afinidade pelo nitrato. A intensidade luminosa teve efeito positivo na assimilação da ureia. As cianobactérias parecem bem adaptadas à assimilação de qualquer fonte de nitrogênio disponível, e parte do sucesso desse grupo em reservatórios subtropicais pode ser atribuído a esta característica. / Human activities in the last decades are altering the natural nutrient cycles, with damaging repercussions to the water sources. The growing eutrophication problems are increasing cyanobacterial bloom occurrences and the environmental and health risks associated. In reservoirs, those effects are even more undesirable, due to its waters multipurpose. Therefore, understanding the relations between nutrients and phytoplankton community is needed. Overall, eutrophication control efforts are focus on phosphorus restriction. Little is known on the effects the available nitrogen sources on tropical/subtropical reservoirs primary production. To investigate the importance of ammonium, nitrate and urea to the phytoplankton in subtropical reservoirs with different trophic states, four field campaignes were conducted between October/2013 and June/2014. The water was collected in two points (depths corresponded to 50 e 10% of the surface\'s solar radiation). The uptake rates observed in the work were relatively higher than most similar works, presumably due to the high phytoplanktonic biomass in Itupararanga and Barra Bonita. The uptake rates were higher in the rain season, in the shallower depths and in Barra Bonita than Itupararanga. The uptake also differ among the reservoirs: In Itupararanga, the phytoplankton community was dominated by the cyanobacteria Cylindrospemospsis raciborskii dominance, and was well adapted to the use of ammonium, nitrate and urea (with ammonium been the favorite N source). In Barra Bonita, the phytoplankton community was dominated by the cyanobacteria Microcystis aeruginosa in the rain season and showed no dominance in the dry season. The shift in the phytoplankton community seamed to increase its affinity to nitrate uptake. The light intensity was correlated with urea uptake only. The cyanobacteria ability to use any given nitrogen source can be a key factor to its success.

O consumo máximo de oxigênio (VO2máx), o limiar ventilatório (LV), ponto de compensação respiratória (PCR) e a economia de corrida (EC) são importantes variáveis fisiológicas associadas com a aptidão aeróbia em corrida. Acredita-se que o polimorfismo da enzima conversora de angiotensina (ECA) possa estar influenciando nos valores dessas variáveis. Contudo, essa relação causal não tem sido amplamente estudada durante a corrida. Dessa forma, o objetivo do presente trabalho foi investigar a associação entre os genótipos da ECA e o VO2máx, LV, PCR e EC mensuradas durante a corrida em esteira. Cento e cinquenta (n = 150) voluntários fisicamente ativos realizaram os seguintes testes: a) teste incremental máximo para determinação do VO2máx, LV e PCR; b) dois testes de velocidade constante (10 km/h e 12 km/h) em esteira para determinação da EC. Os genótipos apresentaram a frequência de: II = 21% ; ID = 52% e DD = 27%. Os resultados apresentaram uma tendência dos indivíduos com o genótipo II apresentarem maiores valores do VO2máx (p = 0.08), bem como a análise do efeito prático apresentou um possível efeito benéfico desse genótipo. No entanto, não foi constatada diferença entre os valores do LV, PCR, e EC entre os indivíduos. Esses resultados sugerem que o genótipo II da ECA pode estar influenciando nos valores da variável máxima relacionada com o consumo de oxigênio / The maximal oxygen uptake (VO2máx), ventilatory threshold (VT), respiratory compensation point (RCP), and running economy (RE) are important variables associated with running aerobic fitness. However, the influence of Angiotensin Converting Enzyme (ACE) polymorphism on these variables determined in running has not been largely investigated. Therefore, the present study aimed to investigate the relationship between ACE genotypes and maximal oxygen uptake, respiratory compensation point, and running economy measured in running. One hundred and fifty (n = 150) physically active young men performed the following tests: a) a maximal incremental treadmill test to determine VO2máx and RCP, b) two constant-speed running test (10 km.h-1 and 12 km.h-1) to determine the RE. The genotype frequency were II = 21 %; ID = 52 %; DD = 27 %. There were a likely beneficial effect and a tendency for the participants with ACE II genotype to have higher VO2max values than DD or ID genotypes (p = 0.08) and the smallest worthwhile effects show a beneficial effect. There were not associations between the genotypes for RCP and RE. These findings suggest that II ACE genotype would influence in maximal variable correlated with oxygen consumption

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