Dans le but d'accéder à un radioimmunodosage simultané des 25-hydroxyvitamines D2 et D3, qui sont un bon indicateur de la quantité de vitamine D disponible dans l'organisme, 5 haptènes de la vitamine D de chaînons variables à fonction acide carboxylique terminale ont été préparés par hémisynthèse à partir de la chaîne latérale de la vitamine D2. Ces 5 haptènes ont été couplés à la sérum albumine bovine pour immuniser des souris, des rats et des lapins ou bien à l'histamine pour donner des traceurs radioactifs, marqués par l'iode (125I). Les animaux ont bien répondu en sécrétant des anticorps dirigés contre les deux 25-hydroxyvitamines D2 et D3 avec des reconnaissances presque identiques. Les cellules spléniques de 3 de ces rats ont pu être fusionnées avec un myélome de souris afin de les immortaliser. Deux hybridomes sécréteurs d'anticorps monoclonaux qui reconnaissent les deux vitamines similairement et ne croisent pas avec l'hormone 1α,25-dihydroxyvitamine D ont pu être sélectionnés.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 83-100).

Bakgrund: Vitamin D finns i två olika former, det animaliska D3 (kolekalciferol) och det vegetabiliska D2 (ergokalciferol). Det har rått olika åsikter bland läkarkåren och allmänheten om vilken av de två formerna som är mest potent för att höja 25(OH)D-statusen i blodet, det värde som mäts för att avgöra vitamin D-halten i kroppen. Då vitamin D-brist är vanligt förekommande bland befolkningen i Norden är det viktigt att veta vilken form som har bäst effekt och som därför bör användas för att behandla och förebygga vitamin D-brist. Det har även betydelse för veganer som inte äter det animaliska D3, där rekommendationen kanske behöver ändras. Syfte: Syftet med studien var att ta reda på om det finns någon skillnad i potensen av D2 respektive D3 för att höja 25(OH)D-statusen i blodet och i så fall, att hitta möjliga orsaker till denna skillnad. Metod: Sex relevanta vetenskapliga originalartiklar, som har undersökt effekten av D2 vs. D3 på 25(OH)D-statusen i blodet, hittades i databasen PubMed. Studierna genomfördes mellan 2008 och 2017. Studiedeltagarna var vuxna friska människor. Resultat: Fyra av studierna pekade på att D3 var mer effektivt än D2 för att höja 25(OH)D-statusen. En studie kom fram till att det inte fanns någon skillnad i potensen mellan D2 och D3 och en studie visade att D2 var mer effektivt jämfört med D3 när det gällde daglig behandling med låga doser men att D3 uppvisade bättre effekt vid behandling med höga doser med två eller fyra veckors avstånd. Slutsats: Majoriteten av studierna visade en bättre effekt av D3 än D2 för att höja 25(OH)D-nivåer i blodet. De blandade resultaten samt det begränsade antalet studier och deltagare gör att det inte är möjligt att kunna komma fram till en tydlig slutsats. / Background: Vitamin D comes in two different forms, D3 from animals (cholecalciferol) and D2 from plants (ergocalciferol). There has been different opinions among physicians and the general public about which of the calciferols is more potent to raise 25(OH)D-levels in the blood, which is the value that is measured to determine the vitamin D-status in the body. Since vitamin D deficiency is common among the people of the Nordic countries it is important to know which form has the best effect and should be used to treat and prevent vitamin D deficiency. Furthermore, it is relevant for vegans who do not eat the animalic D3, where recommendations might have to be changed. Aim: The aim of the study was to find out if there were differences in potency of D2 vs. D3 to raise 25(OH)D status in the blood and if so, to find possible explanations for those differences. Methods: Six relevant original articles that examined the effect of D2 vs. D3 on 25(OH)D status in the blood, were found in the database PubMed. The studies where published between the years 2008 and 2017. The participants were healthy adults. Results: Four of the studies suggested that D3 is more effective than D2 in order to raise the 25(OH)D status. One study concluded that there is no difference in the effectiveness of D2 vs D3 and one study showed that D2 is more effective than D3 when it comes to daily treatment but that D3 has a better effect than D2 when treatment happens on a two or four weekly basis with large doses. Conclusion: Most of the articles suggested a better effectiveness of D3 than D2 to raise 25(OH)D levels in the blood. However, besides the mixed results, the number of studies and participants was too small to come to a clear conclusion.

Ever since the late 1950's, context-free grammars have played an important role within the field of linguistics, been a part of introductory courses and expanded into other fields of study. Meanwhile, data visualization in modern web development has made it possible to do feature rich visualization in the browser. In this thesis, these two developments are united, by developing a browser based app, to write context-free grammars, parse sentences and visualize the output. A user experience study with usability-tests and user-interviews is conducted, in order to investigate the possible benefits and disadvantages of said visualization when writing context-free grammars. The results show that data visualization was limitedly used by participants, in that it helped them to see if sentences were parsed and, if a sentence was not parsed, at which position parsing went wrong. Future improvements on the software and studies on them are proposed as well as the expansion of the field of data visualization within linguistics. / Ända sedan det sena 1950-talet har kontextfria grammatiker spelat en viktig roll hos lingvistiska teorier, används i introduktionskurser och expanderats till andra forskningsfält. Samtidigt har datavisualisering inom modern webbutveckling gjort det möjligt att skapa innehållsrik visualisering i webbläsaren. I detta examensarbete förenas dessa två utvecklingar genom utvecklandet av en webbapplikation, gjord för att skriva kontextfria grammatiker, parsa meningar och visualisera utdatan. En användarbarhetsstudie utförs, bestående av användartest och användaintervjuer, för att undersöka möjliga fördelar och nackdelar av visualisering i skrivandet av kontextfria grammatiker. Resultaten visar att data visualisering användes på ett begränsat sätt av deltagarna, i den meningen att det hjälpte dem att se om satser kan parsas och, om en sats inte blir parsad, se på vilket stället parsning misslyckades. Framtida förbättringar av applikationen och studier av dem föreslås samt en utbyggnad av data visualisering inom lingvistik.

Visualizations, web technologies and mobile devices are subjects which are trending nowadays in the world of technology and many research projects are tackling different issues. The originality of the thesis is in the aspect of bringing all these mentioned subjects together and providing findings that will help web designers when implementing visualizations for mobile phones. The thesis explores the use of web technologies for the visualization of complex data for mobile devices, both looking at the technical state of the art and capabilities, and at the difference in information needs for users in a mobile usage context. The first part deals with an in-depth research of the existing projects that deal with similar issues, analyzing the official documentation of the technologies and the community of developers. The other part of the research is focused on providing insights on the required changes for adapting to the needs of mobile device users by doing a usability testing on a specific visualization. The results provide information valuable for adapting visualizations, such as font sizes, color combinations, animation complexity and data simplicity. The use case that is used for feeding the visualizations with data belongs to the domain of eco visualizations, in particular dealing with sustainable food consumption.

This thesis documents the development of a web-application attacking the problem of visualization of co-authorship networks. The visualization encompasses several views.Each of them shows different aspects of the data which is loaded from Academic Archive Online (DiVa), a library system which holds all publications released in the Linnaeus University.  To detect relationships among authors, a new interactive layout for Node-Link Diagrams was developed which shows publications, authors and corresponding organizations (faculties, departments) in a radial manner. This Network-View is connected to another view showing the attributes (year, type) of the publications. In development, particular emphasis was placed on a rich support of user interaction in order to equip the user with a tool that allows graphical and explorative analysis of the underlying data.

The effects of parathyroid hormone (PTH), prostaglandins (PGE1, PGE2, PGF2a), cAMP, cAMP-analogues, phosphodiesterase (PDE) inhibitors and la (OH) D3 on bone resorption and associated cellular process have been studied in a bone organ culture system using half- calvaria from 6-7 day-old mice. Bone resorption was assessed by determining the release of calcium (Ca2+), inorganic phosphate (Pi) and 45Ca from the calvarial bones to the culture media. The release of lysosomal enzymes was studied by analysing the activities of β-glucuronidase, β-N-acetyl- glucosaminidase, β-galactosidase and p-nitrophenyl phosphatase in bone expiants and culture media. The release of non-lysosomal enzymes was followed by assaying the activities of lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in the expiants as well as the media. In addition glucose consumption and lactate production was registered. The findings may be summarized as follows: 1. cAMP and PDE-inhibitors have the capacity to inhibit the initial stages of spontaneous as well as PTH- PGE1- and PGE2-stimulated bone resorption. 2. cAMP and PDE-inhibitors produce after a lag period, or a period of reduced bone resorption, a stimulatory effect on bone resorption. 3. There is a significant correlation between bone resorption and lysosomal enzyme release both as regards the inhibitory and stimulatory effect of cAMP. 4. PGE2 and la (OH) D3 increase the release of lysosomal enzymes in parallel with bone resorption. 5. Bone resorption stimulated by cAMP and PGE2 is associated with increased glucose consumption and lactate production, while la (OH) D3 promotes bone resorption without any change with regard to these parameters of glucose metabolism. It is concluded that the initial stages of bone resorption stimulated by PTH, PGE1 and PGE2 is medited by cAMP-independent mechanisms, but that this nucleotide may be an intracellular mediator of these hormones of later stages of bone resorption. It is suggested that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts. The observations further support the concept that lysosomal enzyme release is intimately associated with bone resorption. Finally it is concluded that increased lactate production seems to be related to bone resorption stimulated by agents which increase the level of cAMP (PTH, PGE2, dbcAMP), but that it is not an indispensible part of the mechanism by which the osteoclasts solubilize bone mineral. / digitalisering@umu.se

O presente trabalho de pesquisa foi conduzido em uma granja de integração da empresa Cooperfrango e Frigorífico Cooperfrango, situados em Descalvado / SP, e no Centro de Pesquisa e Desenvolvimento de Carnes do Instituto de Tecnologia de Alimentos-ITAL, Campinas / SP. A fase experimental foi realizada no período de 25 de fevereiro a 03 de março de 2005, e as avaliações de qualidade de carcaça e carne se estenderam até o mês de maio de 2005. O escopo dessa investigação foi avaliar o efeito de um suplemento vitamínico (contendo vitamina D3 combinada com polifenóis) na dieta hídrica de frangos, nas características de qualidade da carcaça (hematomas, escoriações e fraturas) e carne (cor, textura, pH, perda por cocção e capacidade de retenção de água). Foi utilizado um total de 13.000 frangos do mesmo sexo, idade, linhagem genética, submetidos às mesmas condições de manejo. As aves foram divididas em dois grupos, um grupo controle (em que não se utilizou vitamina na água de beber) e outro grupo teste, no qual foi utilizado 128,2 UI de vitamina D3 combinada com 0,5 ppm de polifenóis (hidroxicinamatos e hidroxibenzoatos) durante os 7 dias que antecederam o abate. As aves foram transportadas e abatidas em condições comerciais. Para verificar a incidência de fraturas, contusões, hematomas e lesões de pele, foram amostradas 300 carcaças, avaliadas conforme metodologia proposta pelo departamento de agricultura americano (USDA). As características de qualidade da carne avaliadas no músculo pectoralis major em 65 amostras /grupo constituíram o pH, temperatura, cor, capacidade de retenção de água, textura e perda por cocção. Não houve diferenças significativas em relação ao pH, capacidade de retenção de água, textura e cor. Houve maior perda na cocção no grupo teste. No entanto, os resultados de classificação de carcaça foram favoráveis ao grupo teste, pois este apresentou mais amostras com classificação A (77,66% contra 62,18% do grupo controle), demonstrando que os animais tratados com vitamina D3 e polifenóis apresentaram menos hematomas e fraturas, causadas por estresse antes do abate. / The present work was lead in commercial poultry integration from Cooperfrango and their slaughterhouse, located in Descalvado- São Paulo State - Brazil. The analysis was conduced in the Center of Research and Development of Meats of the Institute of Food Technology in Campinas - São Paulo - Brazil. The experimental phase was carried through the period between February 25th and March 3rd in 2005. Evaluations of carcass quality and meat quality had extended until May of 2005. The target of this inquiry was to evaluate the effect of a vitamin complex supplementation (D3 vitamin combined with polyphenols) added in a drinking water for poultry, in the characteristics of carcass quality (skin excoriations, hematomas and fractures) and meat quality (color, texture, pH, cooking loss and capacity of water retention). It was used 13,000 chickens of the same sex, age, genetic ancestry and submitted to the same conditions of handling. The birds had been divided in two groups, a control group (where vitamin in the water was not used to drink) and another tested group which was used 128,2 UI of D3 vitamin combined with 0,5 ppm of polyphenols (hydroxicinamates and hydroxibenzoates) during the 7 days before slaughter. The birds were carried, transported and killed using commercial conditions. To verify and evaluate the incidence of fractures, bruises, hematomas and skin injuries, 300 carcasses were collected following the methodology proposal for the American Department of Agriculture (USDA). The characteristics of meat quality were evaluated in the muscle pectoralis major using 65 samples per group and the measures was pH, temperature, color, capacity of water retention, texture and loss for firing. There were no significant differences in pH, capacity of water retention, texture and color. The tested group had greater cooking loss. However, the results of carcass quality were worst in control group. The tested group presented more samples with classification A (77.66% against 62.18% of the control group), demonstrating that the animals supplemented with D3 vitamin and polyphenols had less hematomas and fractures caused for stress before slaughter.

Orientador: Danielle Goveia / Resumo: Estudos epidemiológicos mostram que uma parcela significativa da população mundial, independente de idade, etnia e localização geográfica, apresenta baixos níveis séricos de vitamina D3. Neste contexto, a incorporação da vitamina D3 em novos sistemas de liberação de fármacos, como os sistemas transdérmicos, têm sido apontados como alternativa para a administração deste medicamento. A extração da nanocelulose de fibras vegetais e sua utilização na fabricação de insumos da área da saúde tem se destacado na medicina, pois apresenta propriedades como biocompatibilidade, biodegradabilidade e baixa toxicidade. A celulose tem um longo histórico de aplicações na área da saúde, agindo como mediador na liberação controlada de fármacos, mas sua utilização nanoestruturada em membranas, como sistema de liberação local de fármacos ainda é um desafio. Neste estudo foi desenvolvida uma membrana, pela técnica de “casting”, de nanocelulose extraída do linter de algodão e vitamina D3 acrescidos dos componentes, álcool polivinílico, glicerina e tween 80. A nanocelulose e as membranas foram caracterizadas por microscopia eletrônica de varredura de alta resolução (MEV-FEG), espectroscopia no infravermelho com transformada de Fourier (FT-IR), teste de tração no dinamômetro e a cinética de liberação do fármaco por espectroscopia molecular no ultravioleta visível (UV-Vis). A membrana apresentou reprodutibilidade na síntese, ótimas propriedades físicas como flexibilidade, transparência e elasticidade,... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Epidemiological studies show that a significant portion of the population has low serum vitamin D3 levels, regardless of age, ethnicity and geographical location. In this context, the incorporation of vitamin D3 in new drug delivery systems, such as transdermal systems, has been suggested as an alternative for the administration of this drug. The extraction of nanocellulose from plant fibers and its use in the manufacture of health inputs has been highlighted in medicine, as it has properties such as biocompatibility, biodegradability and low toxicity. Cellulose has a long history of healthcare applications, acting as a mediator in controlled drug release, but its nanostructured use in membranes as a local drug delivery system is still a challenge. In this study a membrane was developed by casting technique of nanocellulose extracted from cotton linter and vitamin D3 plus the components, polyvinyl alcohol, glycerin and tween 80. Nanocellulose and membranes were characterized by high scanning electron microscopy. resolution (SEM-FEG), Fourier transform infrared spectroscopy (FT-IR), dynamometer tensile test and drug release kinetics by visible ultraviolet molecular spectroscopy (UV-Vis). The membrane showed reproducibility in synthesis, excellent physical properties such as flexibility, transparency and elasticity, as well as adequate resistance for biomedical applications. Through the FT-IR it was observed the presence of all active components in the sample, without structura... (Complete abstract click electronic access below) / Mestre

The D3 dopamine receptor (D3R) belongs to D2-class of dopamine receptors (DARs) and is involved in emotion, movement, and reward. D3R dysfunction has been reported in some neuropsychiatric disorders such as addiction, cognitive deficits, depression, schizophrenia, and Parkinson’s disease. Genetic studies have shown two polymorphic variants of the D3R gene resulting from substitution of serine to glycine at position nine of the amino terminus. Isoform 5 of adenylyl cyclase (AC5) is one of the nine transmembrane bound ACs in the brain and myocardium. Previous studies in rats have shown that AC5 is expressed in the striatum, nucleus accumbens and olfactory tubercle and at lower levels in islands of Calleja, where the D3R is also expressed. Previous studies showed that although D2R and D4R inhibit ACs activity in different cell types, inhibition of ACs by D3R is weak and often undetectable. It has been shown that D3R selectively inhibits AC5 activity in human embryonic kidney 293 (HEK293) cells co-transfected with D3R and AC5. Co-expression of D3R and AC5 in brain regions which are major coordinators of normal and pathological movement, and the selective inhibition of AC5 activity by D3R raise the possibility of a functional link between AC5 and D3R in the modulation of signal transduction and trafficking. I hypothesized that AC5 plays a unique role in modulation of D3R trafficking and signaling pathways through interaction between D3R and AC5. Herein, I demonstrated an interaction between D3R and AC5 in vivo and in vitro using reciprocal co-immunoprecipitation/immunoblotting (co-IP/IB) assays. Interestingly, DA may facilitate the formation of protein complex between D3R and AC5 in vitro. Radio ligand binding assays revealed that heterodimerization of D3R polymorphic variants with AC5 does not change ligand binding affinity and expression of the D3R. Furthermore, taking advantages of GloSensor assays, selective inhibition of AC5 activity by D3Ser9 and D3Gly9 has been shown following activation by DA and quinpirole. Using ELISA studies showed that AC5 promotes cell surface expression and total expression of D3Ser9 and D3Gly9. Moreover, ELISA results suggested that AC5 facilitates DA-induced D3Ser9 endocytosis in dynamin and β-arrestin 2 dependent process, while having no effect on D3Gly9 polymorphic variant. The results also revealed that AC5 attenuates heterologous (PKC-induced) internalization of D3Ser9, while it does not have any effect on D3Gly9 heterologous internalization. My results also displayed a complex formation between D3R, AC5 and, β-arrestin 2 under basal and DA stimulation conditions, which emphasize the role of β-arrestin 2 in D3R signal transduction. Overall, a new regulatory mechanism for D3R has been suggested. My results suggested that complex formation between both D3R polymorphic variants with AC5 can regulate signaling and trafficking properties of D3R without changing the binding affinity of the receptor. These data will be meaningful for understanding of diseases and developing treatment strategies.