Dissertations / Theses on the topic 'PyPy'

For the Python programming language there are several different interpreters and implementations. In this thesis project the performance regarding execution time is evaluated for four of these; CPython, Cython, Jython and PyPy. The performance was measured in a test suite, created during the project, comprised of tests for Python dictionaries, lists, tuples, generators and objects. Each test was run with both integers and objects as test data with varying problem size. Each test was implemented using Python code. For Cython and Jython separate versions of the test were also implemented which contained syntax and data types specific for that interpreter. The results showed that Jython and PyPy were fastest for a majority of the tests when running code with only Python syntax and data types. Cython uses the Python C/API and is therefore dependent on CPython. The performance of Cython was therefore often similar to CPython. Cython did perform better on some of the tests when using Cython syntax and data types, as it could therefore decrease its reliance to CPython. Each interpreter was able to perform fastest on at least one test, showing that there is not an interpreter that is best for all problems.
Det existerar flera olika implementationer och interpreterare för programmeringsspråket Python. I detta examensarbete evalueras prestandan avseende exekveringstid för fyra av dessa; CPython, Cython, Jython och PyPy. Prestandan mättes i en testsvit som skapades i detta projekt. Testsviten bestod av tester för Pythons dictionary, list, tuple, generator och objekt. Varje test kördes med bå de heltal och objekt som testdata med varierande problemstorlek. Varje test var implementerat i programmeringsspråket Python. För Cython och Jython implementerades ytterliggare en version av testerna som innehöll syntax och datatyper specifika för dessa interpreterare. Resultaten visade att Jython och PyPy var snabbast för en majoritet av testerna som endast använde sig av Pythons syntax och datatyper. Cython använder sig av Pythons C/API och är därför beroende av CPython. Prestandan av Cython var därför lik CPythons. Cython presterade bättre på vissa av testerna som utnyttjade Cythons syntax och datatyper, då den därmed kunde minska sitt beroende av CPython. Varje interpreterare lyckades prestera snabbast på minst ett test. Detta visar att det inte finns en interpreterare som är mest lämpad för alla problem.

Tämä kandidaatintutkielma käsittelee puhujalähtöisesti myönteisen ja kielteisen käskylauseen vaikuttavuutta puheen vastaanottajaan. Tutkielman aineisto on kerätty kyselytutkimuksella, ja sen informantteina toimivat yksityisen turvallisuusalan opiskelijat. Lähtökohtana on poliisilaissa (872/2011 § 6) määritellyt puhefunktiot neuvo, kehotus ja käsky, jotka koskevat myös yksityistä turvallisuusalaa. Tutkielma käsittelee myönteisen ja kielteisen imperatiivilauseiden erojen lisäksi muiden modaalisten lausetyyppien esiintyvyyttä turvallisuusalan kielenkäyttäjien ohjailevissa lausumissa. Lisäksi se yhdistelee modaalisten lausetyyppien ja puhefunktioiden suhdetta kyselyssä mitatuilla äänenvoimakkuuksien arvoilla. Tutkielma keskittyy puhujalähtöiseen analyysiin ja sen tavoitteena on olla hyödyksi fennistiikan lisäksi yksityiselle turvallisuusalalle. Analyysi on toteutettu kvantitatiivisilla ja kvalitatiivisilla menetelmillä. Tutkielman tulokset osoittavat, että kielteinen imperatiivilause on puhujan mielestä vaikuttavampi, mutta sitä käytetään kuitenkin vain vähän enemmän kuin myönteistä imperatiivilausetta. Tutkielma osoittaa myös, että kielenkäyttötilanteessa ohjaileva lausuma muodostetaan useimmiten muilla modaalisilla lausetyypeillä kuin imperatiivilauseella.

The prognosis for multiple myeloma (MM) and the activated B-cell subtype of diffuse large B-cell lymphoma (ABC DLBCL) is poor. Gene expression profiling studies have identified that the transcription factor, nuclear factor kappa B (NF-κB) is overexpressed and confers a poor prognosis in MM and ABC DLBCL. NF-κB regulates the transcription of genes involved in cell proliferation and survival. Thus, several groups have tried to identify and/or develop agents that target NF-κB to improve therapy and patient prognosis for MM and ABC DLBCL. Our laboratory has shown that the manganese porphyrin MnTE-2-PyP5+ inhibits NF-κB in a murine lymphoma cell culture model and enhances tumor cell death in combination with dexamethasone and cyclophosphamide, two agents that are routinely used to treat these neoplasms. MnTE-2-PyP5+ inhibits NF-κB by glutathionylating p65, a member of the NF-κB family. The objective of the following studies was to determine whether MnTE-2-PyP5+ enhances the chemotherapeutic response in human MM and ABC DLBCL cells that overexpress and depend on NF-κB for survival. The following studies demonstrate that MnTE-2-PyP5+ glutathionylates and inhibits NF-κB in human MM and ABC DLBCL cells. MnTE-2-PyP5+ also synergizes with several MM and DLBCL chemotherapeutics, including dexamethasone, cyclophosphamide, vincristine and bortezomib to enhance cell death. The data from these human cell lines will provide the basis for future studies to test MnTE-2-PyP5+ in animal models and for translating MnTE-2-PyP5+ to the clinic.

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O objetivo desta pesquisa é discutir a relação mítica de território étnico a partir do contexto das aldeias indígenas Guarani - Tekoá Ytu e Tekoá Pyau. Contribui de maneira salutar a reflexão da questão indígena no Brasil, pois envolve uma área de preservação permanente, expansão urbana e ocupação tradicional de direito originário. Adota concepção husserliniana na fenomenologia para avaliação da interação sujeito e natureza, bem como, de sua reprodução e reafirmação no espaço social que não o afasta da sua relação com o território. A pesquisa identifica os principais problemas que envolvem a área do Jaraguá (SP) com relação a população Guarani e como estes permanecem em área de espaço exíguo, conseguindo manter seus costumes e tradicionais em condições inóspitas, confrontando os dispositivos legais que regem o direito de posse sobrea terra no Brasil. Não obstante, traz o quadro exclusivo da aldeia indígena Tekoá Pyau, menor área indígena do Brasil que enfrenta ações de reintegração de posse, proibição de uso da área do Parque Estadual do Jaraguá, reserva florestal de Mata Atlântica, mas que ainda assim, firmam-se no espaço geográfico atribuindo lhe toda efetividade cultural e étnica
The aim of this study is to discuss the mythical relationship of ethnic territory from the context of Guarani indigenous villages - Tekoá Ytu and Tekoá Pyau; and thus contribute to the reflection of indigenous issues in Brazil, because it involves an area of permanent preservation, urban growth and traditional occupation of original right. It adopts husserliniana conception on phenomenology to evaluate the subject and nature interaction, as well as of its reproduction and reassertion in the social space which not departs from its relationship with the territory. The research identifies the main problems involving the Jaragua (SP) area regarding the Guarani population and how they remain in a limited space area, and managed to keep their old traditions in inhospitable conditions, comparing the legal mechanisms which govern the right of possession over land in Brazil. Nevertheless, provides the unique context of the Tekoá Pyau Indian village, smaller indigenous area in Brazil, which faces repossession actions, forbidding use of the Parque Estadual do Jaraguá area, a forest reserve of Atlantic Forest, but still, they set in the geographical space assigning it all the cultural and ethnic meaning

Orientadora: Bernadete Aparecida Caprioglio de Castro
Banca: Silvia Aparecida Guarnieri Ortigoza
Banca: Vilma Terezinha de Araújo Lima
Resumo: O objetivo desta pesquisa é discutir a relação mítica de território étnico a partir do contexto das aldeias indígenas Guarani - Tekoá Ytu e Tekoá Pyau. Contribui de maneira salutar a reflexão da questão indígena no Brasil, pois envolve uma área de preservação permanente, expansão urbana e ocupação tradicional de direito originário. Adota concepção husserliniana na fenomenologia para avaliação da interação sujeito e natureza, bem como, de sua reprodução e reafirmação no espaço social que não o afasta da sua relação com o território. A pesquisa identifica os principais problemas que envolvem a área do Jaraguá (SP) com relação a população Guarani e como estes permanecem em área de espaço exíguo, conseguindo manter seus costumes e tradicionais em condições inóspitas, confrontando os dispositivos legais que regem o direito de posse sobrea terra no Brasil. Não obstante, traz o quadro exclusivo da aldeia indígena Tekoá Pyau, menor área indígena do Brasil que enfrenta ações de reintegração de posse, proibição de uso da área do Parque Estadual do Jaraguá, reserva florestal de Mata Atlântica, mas que ainda assim, firmam-se no espaço geográfico atribuindo lhe toda efetividade cultural e étnica
Abstract: The aim of this study is to discuss the mythical relationship of ethnic territory from the context of Guarani indigenous villages - Tekoá Ytu and Tekoá Pyau; and thus contribute to the reflection of indigenous issues in Brazil, because it involves an area of permanent preservation, urban growth and traditional occupation of original right. It adopts husserliniana conception on phenomenology to evaluate the subject and nature interaction, as well as of its reproduction and reassertion in the social space which not departs from its relationship with the territory. The research identifies the main problems involving the Jaragua (SP) area regarding the Guarani population and how they remain in a limited space area, and managed to keep their old traditions in inhospitable conditions, comparing the legal mechanisms which govern the right of possession over land in Brazil. Nevertheless, provides the unique context of the Tekoá Pyau Indian village, smaller indigenous area in Brazil, which faces repossession actions, forbidding use of the Parque Estadual do Jaraguá area, a forest reserve of Atlantic Forest, but still, they set in the geographical space assigning it all the cultural and ethnic meaning
Mestre

Tiivistelmä. Tutkielman tarkoituksena on kuvata Oulun koulu-uimaopetuksen lisäopetusjärjestelmää ja sen toteuttamistapaa. Oulun kaupunki järjestää kaikille esikoululaisille sekä 1.–6. luokkalaisille maksutonta uimaopetusta. Jokainen luokka käy uimaopetuksessa yhden viikon jokaisena lukuvuotena. Tämän lisäksi heikkouimataitoisille sekä uimataidottomille järjestetään lisäuimaopetusta kesällä. Tutkimuksen tavoitteena on kuvata lisäuimaopetuksen järjestämismallia, tuoda esille sen vaikutuksia uimataitoon sekä perehtyä sen järjestämiseen liittyviin haasteisiin ja kehitysmahdollisuuksiin. Tutkimuksen teema oli Oulun koulu-uimaopetusjärjestelmän toimivuus. Tutkimuksen teoreettinen lähtökohta on uimaopetuksen tärkeys sekä sen esiintyminen perusopetuksen opetussuunnitelman perusteissa. Tutkielman teoria perustuu monipuolisesti suomalaiseen uimaopetukseen ja sen näkyvyyteen suomalaisen perusopetuksen opetussuunnitelmassa. Uimataidon opettamisen maininta opetussuunnitelmassa edellyttää kouluja, kaupunkeja ja kuntia tarjoamaan oppilaille uimaopetusta jokaisella luokka-asteella. Tapaustutkimuksen aineisto kerättiin haastattelemalla kahta esimiestä, yhtä vakituista uimaopettajaa ja kolmea kesäuimaopettajaa. Tutkimusaineisto koostui neljästä yksilöhaastattelusta sekä yhdestä parihaastattelusta. Aineisto analysoitiin aineistolähtöisellä sisällön analyysillä. Tutkimuksen tulokset osoittavat, että lisäuimaopetusta järjestetään pääsääntöisesti kesäisin. Lisäuimaopetuksella on havaittu olevan positiivisia vaikutuksia uimataitoon, mutta sen järjestämiseen liittyy myös monia haasteita. Lisäuimaopetuksen kehittämiseen nousi esiin monia kehittämismahdollisuuksia, joiden toteuttaminen vaatisi uudelleen resursointia sekä rakennemuutoksia. Esimerkiksi uusi uimahalli, seurayhteistyö ja lisäuimaopetuksen ajoituksen tarkoituksenmukaistaminen tehostaisivat lisäuimaopetusta Oulussa.

The developed world is currently in the grip of an obesity epidemic. As a result, there is much ongoing research into the development of an effective anti-obesity agent. Peptide YY (PYY) is a 36 amino acid gastro-intestinal hormone released post-prandially by L-cells in the gastro-intestinal tract in proportion to the calorie content of a meal. The predominant form of the hormone found in circulation is the truncated PYY(3-36). Administration of PYY(3-36) at physiological doses to humans has been shown to reduce food intake. However, due to enzymatic degradation these effects are short lived, reducing the hormone’s utility as an anti-obesity pharmaceutical agent. A series of analogues of PYY(3-36) were designed either with amino acid substitutions in specific parts of the peptide sequence and/or with chemical modifications to the native sequence with the aim of increasing resistance to enzymatic activity whilst retaining or even enhancing the peptide’s bioactivity. The analogues were tested for resistance to degradation by different proteolytic enzymes in comparison to natural PYY(3-36). Their affinity to the Y2 receptor, for which PYY(3-36) is a natural agonist was then investigated. Finally, the effects of peripheral administration of selected analogues on food intake in overnight fasted mice were investigated. These studies suggest that PYY(3-36) analogues may be a useful approach for the treatment of obesity, but further development work is required.

How does a biological light sensor convert the energy of a photon through a sequence of structural changes to generate a biological signal? Photoactive Yellow Protein (PYP) isolated from the phototrophic bacterium Ectothiorhodospira halophila, a small water-soluble protein whose three-dimensional X-ray crystallographic structure has been determined to high resolution, serves as a paradigm for structural studies of the interaction of light and proteins. This blue light photosensor has been implicated in the negative phototactic response of these bacteria. PYP undergoes a cyclic series of absorbance changes upon illumination at its λ(max) of 446 nm. In its ground state, the anionic p-hydroxycinnamoyl chromophore of PYP is covalently bound as a thiol ester to Cys69, buried in a hydrophobic pocket, and hydrogen bonded via its phenolate oxygen to Glu46 and Tyr42. The chromophore becomes protonated in the photobleached state (I₂) after it undergoes trans-cis isomerization, which results in breaking of the H-bond between Glu46 and the chromophore and partial exposure of the phenolic ring to the solvent. To gain an in-depth understanding of these interactions at the molecular level, the active site of the protein and the chromophore structure was modulated via site-directed mutagenesis and incorporation of variant chromophores. The structural, optical, kinetic and thermodynamic properties of several such altered proteins have been investigated and presented in this dissertation. Interestingly, Glu46Asp and Glu46Ala mutations demonstrated dual photoactive species as a result of a pH driven color transition. Met100Ala was the first PYP mutant to exhibit properties of an optical switch. The unique properties of PYP and its mutant forms may eventually permit their use in optical devices for switching, memory, computing and holographic applications. Early stages of the photocycle were characterized using picosecond and femtosecond ultrafast transient absorption spectroscopy. These time-resolved spectroscopic studies have revealed the presence of two new intermediates. The time constants for formation and decay of these intermediates have now been resolved and the structural and mechanistic aspects of these results are discussed. Recently, PYP was proposed as a structural prototype for the PAS domain superfamily. PYP/PAS domains therefore form an important structural motif for biological signaling.

Le neuropeptide y (npy), neurotransmetteur et le peptide yy (pyy), hormone secretee par les cellules endocrines de l'intestin inhibent la lipolyse sur des adipocytes isoles canins et humains. Ces effets récemment découverts au laboratoire nous ont conduit a caractériser le récepteur impliques. Dans le tissu adipeux de chien, il s'agit d'un récepteur au pyy appartenant au sous-type y2, d'un poids moléculaire apparent de 62 kda et couple a des protéines gi. Les effets antilipolytiques du npy et du pyy et le nombre de ces récepteurs ont également été détermines dans le tissu adipeux d'animaux de laboratoire et de rongeurs hibernants (loir, lerot et gerboise). Parmi ces espèces, un puissant effet inhibiteur du npy et pyy n'a été retrouve que chez le lerot. La seconde partie des recherches a été consacrée à l'adipocyte humain. Le tissu adipeux humain a la particularité de présenter une heterogeneite fonctionnelle selon sa localisation anatomique. Ainsi, le nombre de récepteurs au pyy et alpha2-adrenergiques est plus important dans le tissu adipeux sous-cutané que dans un dépôt profond. Ces différences se retrouvent également dans les effets antilipolytiques induits par le pyy et l'adrénaline. De plus, l'expression des récepteurs alpha2-adrenergiques est fortement corrélée a celle des récepteurs au pyy. Le rôle et la contribution relative de chacun de ces systèmes antilipolytiques restent à définir

Peptide YY (PYY) is a hormone produced by the enteroendocrine L cells in the gut. It is also expressed in the pancreatic islets and brainstem. PYY is secreted from the L cells in proportion to caloric intake and is involved in the regulation of satiety and energy homeostasis. The physiological role of PYY in the pancreatic islets and brainstem is not clear. In order to investigate the physiological role of PYY-expressing cells, I used a transgenic mouse model in which diphtheria toxin receptor (DTR) is expressed downstream of the PYY promoter. This enabled ablation of the PYY-expressing cells following administration of diphtheria toxin (DT) in adult mice. Intraperitoneal administration of DT at a dose of 40ng/g resulted in a significant loss of colonic, pancreatic and brainstem PYY (> 95%). Interestingly, ablation of PYY-expressing cells resulted in a significant loss of pancreatic insulin and hence severe hyperglycaemia in adult mice. In vitro administration of DT in cultured islets resulted in a significant dose-dependent loss of insulin, PYY and glucagon content. Immunohistochemical distribution of DTR was shown to be limited to the periphery of the islet, where PYY is also expressed. These experiments suggest that a product of the PYY-expressing cells may provide a paracrine factor essential for beta cell viability. Replacement of PYY using twice-daily subcutaneous injection of a long-acting PYY analogue (X-PYY) prevented the development of diabetes and reduced the loss of pancreatic insulin content. Administration of the analogue also reduced insulin loss in streptozotocin-treated mice. These studies suggest that PYY may be an important signal for beta cell maintenance. These findings have important implications for identifying novel therapies for prevention of beta cell loss in diabetes mellitus.

Whether increasing meal frequency leads to greater body weight loss, better appetite control and higher levels of PYY remains to be determined. The purpose of this study is to investigate the effect of high MF (HMF) on body weight loss, appetite and PYY in healthy obese men and women. Sixteen obese individuals were randomized to an 8-week equicaloric energy restriction (-700 kcal/day) that either consisted of HMF (3 meals/day and 3 snacks/day; age= 34.63+/-9.50 y and BMI=37.1+/-4.6 kg/m 2) or low MF (LMF) (3 meals/day; age=36.3+/-7.4 y and BMI=34.8+/-4.0 kg/m2). Baseline energy needs were determined with indirect calorimetry. Appetite (VAS) and body composition (DEXA) were assessed before and after weight loss. Body weight was significantly decreased in both groups (p<0.001), but no significant difference was found between conditions (p>0.05). Significant higher levels of fullness at time 120min and at time 300min was noted for the LMF group (p< .05). PYY levels were comparable across conditions and remained unchanged over the intervention. These findings suggest that increasing MF under conditions of equicaloric energy restriction does not increase weight loss. Further, no favorable effects of increased MF on appetite and on PYY levels were noted.

Le peptide yy (pyy), le neuropeptide y (npy) et le polypeptide pancreatique (pp) sont des peptides de 36 acides amines composant une famille structurale appelee pp-fold. Parmi leurs nombreux effets, le pyy et le npy sont consideres comme les plus puissants inhibiteurs des secretions hydro-electrolytiques de l'intestin grele. En 1986, un recepteur presentant une affinite legerement superieure pour le pyy que pour le npy a ete decouvert et defini comme recepteur preferant le pyy. Ce recepteur du pyy est exprime quasi exclusivement dans le compartiment cryptique de l'epithelium du grele, lieu des secretions hydro-electrolytiques intestinales. Parmi les cinq recepteurs y actuellement clones (y 1, y 2, y 4, y 5, y 6), et mediant les effets des peptides de la famille du pyy/npy/pp, trois sont aptes a lier le pyy et le npy. Dans le but d'identifier le(s) recepteur(s) responsable(s) des effets intestinaux du pyy, nous avons couple diverses approches. Une etude par rt-pcr nous a permis de localiser les sous-types y 2, y 4 et y 5 au niveau des cryptes du jejunum de rat. Le recepteur y 4 etant clairement oriente vers la liaison du pp, les sous-types y 2 et y 5, restaient donc les sous-types candidats pour medier les effets antisecretoires intestinaux du pyy. Dans un deuxieme temps, une comparaison des profils pharmacologiques de ces recepteurs avec le recepteur preferant le pyy, nous a permis de constater d'une part des differentes significatives avec y 5, et d'autre part une similitude avec le sous-type y 2. En couplant des approches fonctionnelles du sous-type y 2 (production d'ampc, mouvements ioniques), mais egalement physiologiques (secretions d'eau in vivo), nous arrivons a la conclusion que le recepteur y 2 est responsable des effets du pyy sur l'intestin de rat, et que ce recepteur serait le recepteur preferant le pyy precedemment decrit. Le clonage du recepteur y 2 intestinal de rat montre qu'il est a 100% identique avec son homologue present dans le cerveau.

This thesis explores the roles of the gut hormones Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) in the modulation of human brain reward pathways utilising functional magnetic resonance imaging (fMRI). PYY and GLP-1 are co-released post-prandially and both have been shown to reduce appetite and inhibit food intake when administered to humans. They have the potential to be developed into anti-obesity therapies, with the expectation that low-dose combination therapy may provide more effective weight loss and limited side effects. There are currently no safe and effective medications available to treat obesity, and yet this global health crisis continues unabated. In this context, a study of the mechanisms by which gut hormones exert their anorectic effects, may guide the rational development of new drugs. To date, the effects of GLP-1 alone and the ways in which PYY and GLP-1 combine to modulate brain activity in humans are unknown. This thesis contains a set of functional MRI experiments designed to determine these effects in healthy, fasted, normal-weight human subjects. Results are compared with the changes in brain activation patterns observed physiologically following a meal. For the first time in humans, I have demonstrated that, in conjunction with a comparable effect on lunchtime energy intake, combined infusion of PYY3-36 and GLP-17-36amide to fasted subjects results in a similar modulation of brain activity as observed following a large breakfast. This supports the proposal that these hormones are major physiological mediators of satiety in humans. Both the fed state and the administration of anorectic gut hormones to fasted subjects, reduces activation in multiple brain reward regions in response to visual food-cues. This confirms that circulating gut hormones modulate the hedonic processing of food. The lack of any obvious differential activation pattern between PYY3-36 and GLP-17- 36amide raises the possibility that they act at corticolimbic structures via a final common pathway.

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Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná
The Type 2 Diabetes Mellitus, as well as the metabolic syndrome (MS), is a multifactorial and metabolic disorder that now presents itself as a worldwide pandemic with effects on morbidity and mortality, possibly as a result of the mismatch between biological and cultural evolution of man. Was the object of research of this study to analyze the tissue expression of incretin hormones glucagon Pepitide Like-1 (GLP1) and Pepitide YY (PYY3-36), to identify and quantify L cells along the gastrointestinal tract in patients with DM2 subjected to adaptative gastroenteromentectomia with intestinal bipartition (Partial Duodenal Switch - DSP). The study was approved by the Ethics Committee of UEPG and patients informed and educated about the research objectives. The volunteer group consisted of 7 patients aged between 35 and 65 years, body mass index> 25 kg/m2 with T2DM on dietary treatment and medication for a minimum of 2 years and with difficulty on glycemic control and hypertriglyceridemia associated. Samples were obtained from the intestinal mucosa (jejunum and ileum) of DSP in patients undergoing preoperative and postoperative condition of fasting for 12 hours (three and twelve months respectively), through incisional biopsy. These biopsies were designed to test immunohistochemistry, qRT-PCR (Quantitative Real Time PCR) and Western Blott. The results were consistent and indicate a very significant differential expression between the state of pre-and postoperative tests for qRT-PCR (p = 0.1669) and Western Blot (p = 0.1569). Immunohistochemistry also showed low significance (p = 0.0043) of immune marked L cells for the same patients under the same conditions. These data can be interpreted in light of the fast imposed on patients. In addition the results are unprecedented for the immunostaining of L-cells of the human gastrointestinal tract, the data indicate that these cells have basal secretion for GLP-1, even after 12 hours without feed stimulation. In addition, the patients showed normalization of blood glucose levels in the post-surgery, suggesting metabolic improvement. It was also found that the number of L cells marked increases in density along the gastrointestinal tract toward the distal portion of the ileum (p = 0.0409). With these results it was possible to identify, locate and investigate different levels of expression and secretion from intestinal L cells in patients with DM2 and subjected to surgical control.
Diabetes mellitus do tipo 2 (DM2), assim como a Síndrome Metabólica (SM), é uma desordem metabólica e multifatorial que atualmente se apresenta como pandemia mundial com reflexos na morbimortalidade, possivelmente em decorrência do descompasso entre a evolução biológica e cultural do homem. Foi objeto de investigação do presente estudo analisar a expressão tecidual dos hormônios incretínicos Glucagon Like Pepitide-1 (GLP1) e Pepitide YY (PYY3-36), visando identificar e quantificar células L ao longo do trato gastrointestinal, de pacientes portadores de DM2 submetidos a gastroenteromentectomia adaptativa com bipartição intestinal (Duodenal Switch Parcial - DSP). O trabalho foi aprovado pelo Comitê de Ética da UEPG e os pacientes informados e esclarecidos sobre os objetivos da pesquisa. O grupo de voluntários foi composto de 7 pacientes com idade entre 35 e 65 anos, Índice de Massa Corporal > 25 Kg/m2, com DM2 em tratamento dietético e medicamentoso por um período mínimo de 2 anos e com dificuldade de controle glicêmico e hipertrigliceridemia associada. Foram obtidas amostras da mucosa intestinal (jejuno e íleo) dos pacientes submetidos à DSP no pré-operatório e no pós-operatório em condição de jejum de 12 horas (três e doze meses, respectivamente), através de biópsia incisional. Estas biópsias foram destinadas aos ensaios de Imunohistoquímica, qRT-PCR (Quantitative Real Time PCR) e Western Blott. Os resultados obtidos foram congruentes e apontam uma expressão diferencial pouco significativa entre o estado de pré- e pós-operatório para os ensaios de qRT-PCR (p=0,1669) e Western Blott (p=0,1569). A imunohistoquímica mostrou também baixa significância (p=0,0043) de células L imuno marcadas para os mesmos pacientes, nas mesmas condições. Estes dados podem ser interpretados a luz do jejum imposto aos pacientes. Além dos resultados serem inéditos para a imunomarcação de células L do trato gastrointestinal humano, os dados obtidos indicam que estas células apresentam secreção basal para GLP-1, mesmo após 12 horas sem estímulo alimentar. Em adição, os pacientes apresentaram normalização dos níveis de glicemia no estado pós-operado, sugerindo melhora metabólica. Foi ainda constatado que o número de células L marcadas aumenta em densidade ao longo do trato gastrointestinal em direção à porção mais distal do íleo (p=0,0409). Com estes resultados foi possível identificar, localizar e investigar diferentes níveis de expressão e secreção das células L intestinais em pacientes portadores de DM2 e submetidos a controle cirúrgico.

Le peptide yy (pyy) est une hormone de 36 acides amines, liberee par les cellules endocrines de l'intestin. Le neuropeptide y (npy) est un neuropeptide ubiquitaire de l'organisme. Les deux peptides presentent une grande homologie de sequence. Le ppy et le npy sont consideres comme les plus puissants inhibiteurs des secretions hydroelectrolytiques de l'intestin grele. En 1986, notre equipe a decouvert un nouveau recepteur liant le pyy et le npy mais preferant le pyy. Ce recepteur intestinal du pyy est couple negativement a la production d'ampc, inhibant l'effet des activateurs physiologiques de ce systeme, comme le peptide intestinal vasoactif (vip). Notre etude a consiste, d'une part, a determiner la localisation du recepteur du pyy le long de l'axe crypto-villositaire de l'epithelium intestinal; d'autre part, a caracteriser les proprietes structurales et moleculaires du recepteur pyy en solution, etape preliminaire pour sa purification. Nous avons ainsi montre que le recepteur du pyy est exprime quasi exclusivement dans le compartiment secretoire cryptique ou il induit une forte inhibition du systeme de production de l'ampc. Les techniques de filtration sur gel et d'ultracentrifugation en gradient de saccharose, ont montre que le recepteur est une glycoproteine monomerique de masse moleculaire de 44 kda. Ces observations nous ont amenes a etudier l'expression d'un autre recepteur couple negativement a la production d'ampc dans l'epithelium de l'intestin grele de rat: le recepteur alpha#2-adrenergique. Comme le recepteur du pyy, le recepteur alpha#2-adrenergique se distribue quasi-exclusivement dans le compartiment cryptique du jejunum de rat. Ces resultats sont en accord avec le role secretoire des cellules cryptiques. Par contre, le recepteur du vip est exprime de maniere homogene dans l'axe crypto-villositaire. Par ailleurs, l'etude de l'expression des proteines transductrices gi et gs dans l'axe crypto-villositaire a mis en evidence une expression divergente des proteines g au cours de la differenciation epitheliale de l'intestin grele de rat. Ainsi, il n'existe pas de correlation entre l'expression des recepteurs du pyy, alpha#2-adrenergique, du vip et les proteines g auxquelles ils sont couples

Commonly, teacher evaluations function as summative appraisal mechanisms of teacher performance and effectiveness, as accountability measures and assurances of quality instruction to educational stakeholders. Recently, greater interest in the potential for evaluations to contribute to improvements in teaching and learning has emerged. The use of professional teaching standards and evaluation rubrics represents a significant advance in the design of evaluation tools and procedures. Continuing implementation challenges however, means the potential for evaluations to notably enhance teachers’ professional development is far from realized within many educational contexts. The traditional focus on the individual within evaluations also fails to recognize the collaborative work of teaching teams and to capitalize on the potential of teachers to support improvement in each other’s practice. This inquiry explored the circumstances under which evaluations might promote professional development at the individual level and within teaching teams. The study is located within an international school, which utilizes the International Baccalaureate Primary Years Program curriculum. The research question driving the inquiry was; how can teachers and principals within IB PYP schools achieve a focus on professional development and systematic learning within teacher evaluation? An Instructional Rounds protocol was employed to promote a focus on professional development within this qualitative case study. Fullan’s Change Theory guided the implementation and analysis of change in the form and function of evaluations within the school. Findings suggest viable and valuable professional learning can be incorporated into and supported during evaluations. A structured process, incorporating greater frequency of feedback, check-ins, dialogue and collaborative work between supervisors and teachers is needed to produce the monitoring mechanism and sustained gentle pressure necessary to support on-going professional learning. Redefining and broadening concepts of improvement, of involved leadership and professional development is important. Limited focus on specific goals and connecting peers with similar goals encourages commitment to improvement efforts.

Einleitung/ Zielstellung Zusätzlich zur Gammastrahlung emittiert 99mTc ca. 5 niederenergetische Auger-Elektronen mit Reichweiten von wenigen Nanometern im Gewebe. Diese haben für die nuklear-medizinische Diagnostik keine Bedeutung. Es wird jedoch über eine therapeutische Nutzung diskutiert, wofür eine Anreicherung der Auger-Elektronen-Emitter in einem strahlensensitiven Zellkompartiment erforderlich ist. Ziel der Arbeit war es, verschiedene [99mTc]Tc-Radiopharmaka hinsichtlich ihres Uptakeverhaltens, der subzellulärer Verteilung und des Retentionsverhaltens in vitro zu untersuchen, sowie die mutmaßlich durch den Auger-Effekt hervorgerufene Radiotoxizität der [99mTc]Tc-markierten Radiopharmaka zu vergleichen und die gewonnenen Ergebnisse in Hinblick auf potentielle extranukleäre strahlensensitive Targets zu interpretieren. Material und Methode Durchgeführt wurden die Versuche im ersten Abschnitt der Arbeit an Natrium-Iodid-Symporter (NIS)-positiven FRTL-5-Schilddrüsenzellen. Von [99mTc] Pertechnetat ([99mTc]TcO4-), [99mTc]TcO4- nach Vorinkubation von Perchlorat ([99mTc]TcO4-/ ClO4-), [99mTc]Tc-Hexakis-2-Methoxyisobutylisonitril ([99mTc]Tc-MIBI), [99mTc]Tc-Hexamethyl-Propylenaminoxim ([99mTc]Tc-HMPAO) und [99mTc]TcO4- nach Vorinkubation von Zinn-Pyrophosphat (Sn- PYP/ [99mTc]TcO4-) wurden die intrazelluläre Radio¬nuklid¬aufnahme und die subzelluläre Verteilung untersucht. Basierend auf den Ergebnissen dieser Versuche wurde die mittlere absorbierte Zellkerndosis kalkuliert. Zur Beurteilung der strahlenbiologischen Wirkung wurde das klonogene Zellüberleben mit der Anzahl residualer gH2AX-Foci (DNA-Schaden) verglichen und die Wirkung der [99mTc]Tc Tracer auf den Zellzyklus von FRTL-5-Zellen untersucht. Im zweiten Abschnitt der Arbeit wurde an EGFR-positiven A431-Zellen die radiotoxische Wirkung in Abhängigkeit von der intra¬zellulären Lokalisation von [99mTc]Alexa(488)-C225-Cyclooctin-Dpa-Tc(CO)3 ([99mTc]Tc-C225), [99mTc]Tc-HMPAO und [99mTc]TcO4- auf das klonogene Zellüberleben untersucht. Ergebnisse und Diskussion Aufgrund verschiedener Uptakemechanismen zeigte jedes der untersuchten [99mTc]Tc-Radiopharmaka Unterschiede im zeitlichen Verlauf der Uptakekinetik. Durch Blockierung des NIS durch ClO4- konnte eine intrazelluläre Aufnahme von [99mTc]TcO4- verhindert werden, wogegen durch Vorinkubation mit Sn-PYP die zelluläre Aufnahme von [99mTc]TcO4- um das 22-fache gesteigert wurde. [99mTc]Tc-MIBI und [99mTc]Tc-HMPAO wurden aufgrund ihrer lipophilen Eigenschaften unabhängig vom NIS passiv in die Zelle transportiert. Die Untersuchung der intrazellulären Verteilung ergab für [99mTc]Tc-HMPAO und Sn-PYP/ [99mTc]TcO4- eine vergleichbar hohe Anreicherung in der Membran/Organellen-Fraktion sowie in der Zellkernfraktion. Von [99mTc]TcO4- und [99mTc]Tc-MIBI wurde die Hauptaktivität in der Zytosol-Fraktion und nur geringe Anteile in der Membran/Organellen-Fraktion sowie in der Zellkernfraktion nachgewiesen. In guter Übereinstimmung zur subzellulären Verteilung zeigten Sn-PYP/ [99mTc]TcO4- und [99mTc]Tc-HMPAO eine fast vollständige, hingegen [99mTc]Tc-MIBI und [99mTc]TcO4- nur eine geringe Retention. Aufgrund der genannten Unterschiede wurde bei gleicher inkubierter Aktivitätskonzentration folgende Reihenfolge der resultierenden Zellkerndosis ermittelt: [99mTc]TcO4- < [99mTc]Tc-MIBI < [99mTc]Tc-HMPAO < Sn-PYP/ [99mTc]TcO4-. [99mTc]TcO4- und [99mTc]Tc-HMPAO zeigten eine ähnliche Wirkung auf das klonogene Zellüberleben und auf den Zellzyklus. Jedoch bewirken sie eine wesentlich stärkere Reduzierung des Überlebens und einen stärkeren G2-Arrest als [99mTc]Tc-MIBI und Sn-PYP/ [99mTc]TcO4-, wobei [99mTc]Tc-MIBI bei allen drei untersuchten biologischen Endpunkten die geringste Wirkung zeigte. Bei einer vergleichbaren Reduktion des Zellüberlebens von [99mTc]TcO4- und [99mTc]Tc-HMPAO induzierte [99mTc]Tc-HMPAO lediglich die Hälfte der gH2AX-Foci im Vergleich zu [99mTc]TcO4-. Die trotz geringerem DNA-Schaden vergleichbare radiotoxische Wirkung zeigte, dass das klonogene Zellüberleben nicht allein vom DNA-Schaden abhängt. Daraus folgt, dass es außer der Kern-DNA noch weitere strahlensensitive Kompartimente gibt, die durch [99mTc]Tc-HMPAO stärker geschädigt wurden als von den anderen untersuchten [99mTc]Tc Tracern. Ein mögliches extranukleäres strahlensensitives Target ist die Zellmembran, so dass im zweiten Teil der Arbeit zur Überprüfung der Radiosensitivität der Zellmembran die radiotoxische Wirkung von [99mTc]Tc-C225 an EGFR-positiven A431-Zellen untersucht wurde. [99mTc]Tc-C225 wurde über den EGFR und [99mTc]Tc-HMPAO aufgrund seiner Lipophilie durch Diffusion intrazellulär aufgenommen. [99mTc]TcO4- dagegen zeigte keine intrazelluläre Aufnahme in die NIS-negativen Zellen und wurde als Referenz für eine extrazelluläre Bestrahlung verwendet. [99mTc]Tc-C225 wies nach einstündiger Inkubation eine Membranbindung von lediglich 10 % auf, die im Laufe von 24 h auf 1,9 % absank. Dies zeigte, dass [99mTc]Tc-C225 rasch in den A431-Zellen internalisiert wurde und dass nur bei sehr kurzen Inkubationszeiten von einer spezifischen Zellmembranmarkierung gesprochen werden kann. [99mTc]Tc-HMPAO ging keine Bindung an die Zellmembran ein. Weiterhin wurde bei der Inkubation steigender Aktivitäts- und Antikörperkonzentrationen von [99mTc]Tc C225 eine Sättigung des EGFR beobachtet, woraus eine wesentlich geringere Zellkerndosis als bei Inkubation von [99mTc]Tc-HMPAO resultierte. Im Vergleich des klonogenen Zellüberlebens zeigten [99mTc]Tc-C225 und [99mTc]Tc-HMPAO bei gleicher Zellkerndosis keine Unterschiede in der radiobiologischen Wirkung. Somit konnte lediglich eine Verstärkung der radiotoxischen Effekte von [99mTc]Tc-C225 an A431-Zellen im Vergleich zur ausschließlich extrazellulären Verteilung von [99mTc]TcO4- gezeigt werden. Schlussfolgerung Die Untersuchung der radiotoxischen Wirkung von [99mTc]Tc-C225 ermöglichte bei den angewendeten Versuchsbedingungen keine Rückschlüsse auf die Strahlensensitivität der Zellmembran. Weiterführende Arbeiten zur Entwicklung eines 99mTc-markierbaren spezifischen Membranmarkers wären notwendig, um klären zu können, ob die Zellmembran ein ähnlich strahlensensitives Target wie die nukleäre DNA ist. Dosimetrische Betrachtungen an den als Modellsystemen dienenden FRTL-5- und A431-Zellen deuten darauf hin, dass aufgrund ungenügender Anreicherung eine therapeutische Wirkung der Auger-Elektronen im Tumorgewebe eher unrealistisch ist. Damit sollte aus gegenwärtiger Sicht die klinische Anwendung von 99mTc auf den diagnostischen Einsatz beschränkt bleiben. Jedoch könnte 99mTc als Auger-Elektronen-Emitter bei spezifischer Anreicherung in definierten Zellkompartimenten als Nano-Tool zur Erforschung der Strahlensensitivität einzelner Zellbestandteile eingesetzt werden
Introduction In addition to gamma radiation, 99mTc emits approximately 5 low energy Auger and internal conversion electrons per decay, resulting in high ionization density proximal to the radionuclide’s decay position. Low-energy Auger electrons with path lengths of only nanometers cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. To achieve a radiobiological effect, an intracellular accumulation and distribution in relevant cell compartments of the Auger electron emitter is required. Aim The aim of the thesis was the comparison of different [99mTc]Tc-labeled compounds concerning their intracellular uptake, subcellular distribution and retention in vitro. Furthermore the radiotoxicity caused by the Auger effect has to be investigated. Material and Methods The intracellular radionuclide uptake, subcellular distribution (ProteoExtract®-Kit) and retention of [99mTc] pertechnetate ([99mTc]TcO4-), [99mTc]TcO4- after pre-incubation of perchlorate ([99mTc]TcO4-/ClO4-), [99mTc]TcO4- after pre-incubation of stannous pyrophosphate ([99mTc]TcO4-/Sn-PYP), [99mTc]Tc-hexamethyl-propylene-aminoxime ([99mTc]Tc-HMPAO) and [99mTc]Tc-hexakis-2-methoxyisobutylisonitrile ([99mTc]Tc-MIBI) were quantified in sodium-iodide symporter (NIS)-positive rat thyroid FRTL-5 cells. Basing on these results the mean absorbed nucleus dose was calculated. Radiotoxicity was investigated using phosphorylated histone H2AX (gH2AX foci), clonogenic cell survival and cell cycle analyzes. Additionally the radiotoxicity of [99mTc]Alexa(488)-C225-Cyclooctin-Dpa-Tc(CO)3 ([99mTc]Tc-C225) was compared with the one of [99mTc]TcO4- and [99mTc]Tc -HMPAO depending on the subcellular distribution in EGFR-positive A431 cells. Results and Discussion For the analyzed [99mTc]Tc-labeled compounds we detected differences in the time courses of the uptake kinetics caused by different uptake mechanisms into the FRTL-5 cells. The radionuclide uptake of [99mTc]TcO4- was blocked in the presence of perchlorate and increased by a factor of approximately 22 after pre-incubation of Sn-PYP. The lipophilic complexes [99mTc]Tc-MIBI and [99mTc]Tc-HMPAO crossed the cell membrane through passive transport via diffusion. The compartmental analysis indicated that [99mTc]Tc-HMPAO and [99mTc]TcO4-/Sn-PYP revealed a comparable high uptake in the nucleus and in the membrane/organelle fraction. [99mTc]TcO4- and [99mTc]Tc-MIBI were preferentially distributed in the cytosol, with lower amounts of the accumulated activity in both the membranes/organelles and the nucleus compared with the other compounds. In good agreement with the subcellular distribution [99mTc]Tc-HMPAO, [99mTc]TcO4-/Sn-PYP showed a nearly complete retention and [99mTc]TcO4-, [99mTc]Tc-MIBI a low retention. Due to the differences mentioned above the following sequence of the calculated mean nucleus dose for identical activity concentrations was determined: [99mTc]TcO4- < [99mTc]Tc-MIBI < [99mTc]Tc-HMPAO < Sn PYP/ [99mTc]TcO4-. [99mTc]TcO4- and [99mTc]Tc-HMPAO caused a similar reduction of the cell survival and a dose dependent G2-arrest. [99mTc]Tc-MIBI and Sn-PYP/ [99mTc]TcO4- are both less radiotoxic in terms of the estimated nucleus dose compared with [99mTc]TcO4- and [99mTc]Tc-HMPAO. Despite the similar effect on the cell survival [99mTc]Tc-HMPAO induced only half of the residual gH2AX foci than [99mTc]TcO4-. These findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response, which may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. A possible extra-nuclear radiosensitive target is the cell membrane. That’s why the aim of the second part of the thesis is the investigation of the radiosensitivity of the cell membrane. Therefore the radiotoxic influence of [99mTc]Tc-C225 was analyzed at EGFR-positive A431 cells. [99mTc]Tc-C225 was taken up over the EGFR and the lipophilic [99mTc]Tc-HMPAO was transported via diffusion over the cell membrane. In contrast, [99mTc]TcO4- did not show any intracellular uptake into the NIS-negative cells and therefore was used as extracellular reference. An incubation of [99mTc]Tc-C225 for one hour resulted to a membrane binding of only 10 %, which was reduced to 1.9 % after 24 hours. This demonstrated a fast internalization into A431-cell. Therefore only in the case of a very short incubation time [99mTc]Tc-C225 leads to a specific targeting of the cell membrane. [99mTc]Tc-HMPAO did not bind to the cell membrane. Furthermore the incubation of increasing concentrations of activity and antibody resulted in a saturation of the EGFR, leading to a significant lower nucleus dose in comparison to the incubation of [99mTc]Tc-HMPAO. Concerning the clonogenic cell survival no differences in the radiotoxicity of [99mTc]Tc-C225 and [99mTc]Tc-HMPAO were observed for equal nucleus dose. Thus only an amplification of the radiotoxic effects of [99mTc]Tc-C225 in comparison to the extracellular distribution in A431 cells of 99mTc-pertechnetate was observed. Conclusion The investigation of the radiotoxic effect of [99mTc]Tc-C225 did not allow any conclusions about the radiosensitivity of the cell membrane under the given experimental conditions. For clarifying if the radiosensitivity of the cell membrane is comparable to the one of the nucleus DNA further experiments for the development of a [99mTc]Tc-labeled specific target for the cell membrane are necessary. On the basis of the dosimetric considerations of the FRTL-5 cells and A431 cells used as model systems it can be concluded that because of an insufficient accumulation a therapeutic radiotoxic effect of the Auger electrons is not realistic. Therefore the clinical use of 99mTc should be limited to the diagnostics. Nevertheless specific accumulated Auger electrons of 99mTc could be applied in the field of investigation as nano-tools for the subcellular analysis of radiotoxicity

Introdução: A prevalência de doenças crônicas tem crescido em decorrência do aumento da obesidade nos últimos anos. Peptídeos secretados pelo trato gastrointestinal, como o peptídeo semelhante ao glucagon 1 (GLP-1) e o peptídeo YY (PYY), exercem papel fundamental no controle da ingestão alimentar, pois levam informações acerca dos nutrientes ingeridos até o sistema nervoso central, possuindo efeitos anorexígenos e/ou orexígenos. Tanto GLP-1 quanto PYY são produzidos pelas células-L do íleo distal e cólon, sendo liberados após a ingestão alimentar. Além do efeito incretina produzido pelo GLP-1, ambos os peptídeos apresentam implicações no controle do apetite, o qual reflete na redução do peso corpóreo. Objetivos: Demonstrar um aumento na secreção de GLP-1 e PYY após sobrecarga oral de diferentes tipos de lipídios, comparados à controle negativo (água) e positivo (glicose). Métodos: Foi realizado um estudo experimental controlado em ratos Wistar, distribuídos em 4 grupos de acordo com a sobrecarga oral: grupo MUFA (óleo de oliva); grupo SAT (banha suína); grupo GLUC (glicose) e grupo CONT (água), foram avaliadas as concentrações séricas de GLP-1 ativo e PYY3-36 nos tempos: 0, 15, 30, 60 e 120 minutos. As sobrecargas foram isovolumétricas e isocalóricas, com exceção do grupo controle. Resultados: Houve pico de secreção do GLP-1 pós-sobrecarga no grupo MUFA no ponto 120’ vs CONT e GLUC (p≤0,001) e no ponto 30’ quando comparado ao seu baseline. Também observou-se pico de secreção de PYY no grupo MUFA vs CONT no ponto 30’ (p=0,015); no ponto 60’ vs CONT e GLUC (p=0,019) e no ponto 120’ vs CONT e SAT (p=0,02). A carga secretada do PYY foi maior no MUFA quando comparada ao CONT (p=0,04). Verificou-se forte correlação entre os níveis basais e AUC’s do GLP-1 e PYY (r=0,57; (p= 0,02); r=0,39; (p≤0,001)). A proporção GLP-1/PYY apresentou um coeficiente médio de 3,77 (±2,04). O grupo MUFA evidenciou níveis menores de glicose e maiores de insulina no ponto 15’, enquanto SAT mostrou níveis maiores de glicose e menores de insulina neste ponto, porém, sem diferença significativa. Conclusão: A sobrecarga oral de fontes de ácidos graxos monoinsaturados promoveu um pico de secreção do GLP-1 de forma rápida e no que diz respeito ao PYY, o pico foi mais sustentado. Estudos adicionais são necessários, a fim de se avalir o efeito de fontes distintas de lipídeos da dieta sobre a secreção destes peptídeos e seus efeitos na saciedade.
Background: The increased prevalence of chronic diseases has risen due to obesity. Gut peptides, such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), play an important role controlling food intake in response to a meal. GLP-1 exerts the known incretin effect stimulating the release of insulin in a glucosedependent manner. Besides its insulinotropic effects, it is well established that GLP-1 slows gastric emptying, and also inhibits inappropriate glucagon release, additionally improves satiety. Both PYY and GLP-1 are produced by L cells of the distal ileum and colon. Objective: Demonstrate an increased secretion of PYY and GLP-1 after oral overload of different types of lipids, compared to negative (water) and positive (glucose) control. Methods: We conducted a controlled experimental study in Wistar rats, divided into 4 groups according to oral overload: MUFA group (olive oil), SAT group (lard:), carbohydrates group (glucose) and CONT group (water), It was evaluated the serum concentration of active GLP-1 and PYY3-36 in the times: 0, 15, 30, 60 and 120 minutes. Overloads were isovolumetric and isocaloric, but the control group. Results: It was verified a higher peak secretion of GLP-1 in MUFA group at 120' after overload vs. CONT and carbohydrates (p ≤ 0.001) and at 30' when compared to its baseline (p=0,01). It was shown a higher secretion peak of GLP-1 after MUFA overload at time 120’ vs CONT e GLUC (p≤0,001) and at time 30’ when compared to its baseline. It was also verified a PYY release peak in MUFA vs CONT at time 30’ (p=0,015); 60’ vs CONT e GLUC (p=0,019) and 120’ vs CONT e SAT (p=0,02). PYY release load presented higher in MUFA group when compared to CONT (p=0,04). A strong correlation was seen between baseline PYY and GLP-1 (r=0,57; p= 0,02) as their AUC’s (r=0,39; p≤0,001). GLP-1/PYY proportion release presented a mean coefficient of 3, 77(±2,04).Conclusion: monounsaturated fatty acids promoted a release peak of GLP-1 in a faster manner and concerning PYY this peak was more sustained. Further studies are necessary to evaluate whether distinct diet fatty acids can ameliorate these gut peptides release and their role on satiety.

This diploma thesis is focused on the description and implementation of the API wrapper application, which works on top of computational core ibp bioinformatics. The first half of the thesis is focused on the summary of basic knowledge in the field of DNA research, as well as the specification of the problem and description of selected technologies. The other half deals with the actual implementation, distribution, and evaluation of application applicability on specific DNA sequences.

Obesity and type 2 diabetes (T2D) are associated with insulin resistance and increased levels of inflammation markers, suggesting activation of the immune system. However, the link between this so called ??low-grade inflammation?? and insulin resistance is poorly understood. In this thesis we aimed to investigate the direct effects of insulin on immune cells, and if these effects are changed in the setting of insulin resistance. We showed that insulin has anti-inflammatory effects by shifting T cell differentiation into a T helper type 2 phenotype. This effect was lost in insulin resistant subjects, which resulted in a more pro-inflammatory T helper type 1 cell hyperpolarisation. We also demonstrated that the Th1/2 balance is related to the degree of insulin resistance, and varies accordingly in clinical models of increasing or decreasing insulin resistance. Furthermore, we demonstrated that in a very early stage of pre-diabetes, where normal glucose tolerance and insulin sensitivity are still preserved, we cannot detect any immune activation, but we see a blunted food response of the appetite suppressant hormone PYY. Whilst this could put subjects at risk for further weight gain and development of obesity and T2D, we also demonstrated for the first time that PYY itself has strong anti-inflammatory properties, and that a deficiency in PYY could result in promoting a pro-inflammatory environment. In summary, we could demonstrate strong evidence that both, insulin and PYY are potent anti-inflammatory hormones which modulate immune function, and the observed deficiency in these hormones could contribute to further increase in inflammation and disease progression. Further work is indicated in this area to better understand the sequence and mechanism of immune activation, which may open up new therapeutic avenues for prevention and treatment of T2D.

Introdução: O PYY é um peptídeo regulador da saciedade produzido pelas células intestinais em resposta à chegada intraluminal de nutrientes. Objetivos: O presente estudo objetivou avaliar o efeito de sobrecargas agudas de gorduras saturadas (SAT) e monoinsaturadas (MUFA) na secreção aguda de PYY em ratos Wistar normais e após insulinorresistência induzida por dieta hiperlipídica. Métodos: Em experimento controlado, ratos Wistar foram submetidos a uma dieta altamente gordurosa (HFD) (55% de gordura) por 19 semanas (n=15) ou à dieta normal (GC) pelo mesmo tempo (ração ad libitum) (n=15). Ao final de 14 semanas foi realizado um experimento cross-over onde foi avaliada a resposta secretória de PYY sérico nos tempos basal e 60 minutos após sobrecarga oral lipídica isovolumétrica, por meio de gavagem, ajustadas para o peso, administrada de forma aleatória, em dias diferentes, constituídas por ácidos graxos saturados (SAT-banha de porco) ou monoinsaturados (MUFA-óleo de oliva) ou água (CONT). Diferenças entre médias e grupos foram avaliadas por meio de ANOVA de medidas repetidas e associação por regressão linear simples. Resultados: Em relação ao PYY, no grupo com dieta normal, ambas sobrecargas MUFA e SAT elevaram a resposta secretória de PYY significativamente em relação aos seus respectivos basais: MUFA-Basal 2,18 (± 0,24) vs. MUFA-60min 2,30 (± 0,26) pg/ml e SAT-basal 2,21 (± 0.25) pg/ml vs. SAT- 60min 2,29 (± 0,22) pg/ml ANOVA múltiplas entradas p= 0,019 intragrupos; entretanto, sem diferença entre grupos MUFA e SAT (ANOVA múltiplas entradas entre-grupos p= 0,314). No grupo HFD por outro lado, a sobrecarga SAT reduziu o PYY: SAT-basal 2,16 (± 0.21) pg/ml vs. SAT-60min 2,11 (± 0,30) pg/ml (p= 0,01,intragrupos) enquanto a sobrecarga MUFA manteve o mesmo aumento MUFAbasal 2,15pg/ml vs. MUFA-60min 2,22 (± 0.22) pg/ml. p=0,019 (intragrupos). A administração de água (CONT) também reduziu o PYY em relação ao basal, tanto com na dieta normal (p= 0,0091) como na dieta (HFD) (p= 0,0091), mas sem diferença entre os grupos (p= 0,7433). Conclusão: Em ratos Wistar, as sobrecargas lipídicas, tanto de MUFA como de gordura saturadas, aumentam agudamente a secreção de PYY. Entretanto, em ratos Wistar tornados insulinorresistentes através de uma dieta altamente rica em gordura saturada, a mesma sobrecarga de gordura saturada perde a capacidade de estimular os níveis de PYY, enquanto à resposta ao MUFA segue preservada. Esta resposta paradoxal a gorduras saturadas poderia representar um dano celular causado pela insulinorresistência ao tecido intestinal interferindo no aparato secretor de PYY em resposta a este nutriente. Estudos no tecido intestinal precisam ser realizados para identificar possíveis fatores envolvidos e suas implicações no controle da saciedade pelo PYY em indivíduos insulinorresistentes.
Background: PYY is a gut peptide released by L-cells from the intestine after a meal. Objective: The present study aimed to evaluate the effect of acute overloads of saturated fatty acids (SAT) and monounsaturated fatty acids (MUFA) on PYY release in normal and diet induced insulin resistant wistar rats. Methods: a nineteen weeks experiment was conducted with 30 wistar rats that were allocated into two groups: high fat diet (HFD group) (n=15) with diet composition of 55% of lard and 45% standard chow and control group (CG) (n=15). Both groups received water and food ad libitum. Later a cross-over experiment was conducted to evaluate PYY secretory response 60 minutes after two different lipid overloads (SAT-lard; MUFAolive oil) and water (CONT), adjusted by weight, all isovolumetric and lipids were isocaloric, randomly administered in different days. Mean differences were analyzed by repeated measures ANOVA and association by simple linear regression. Results: Both MUFA and SAT overloads significantly increased PYY release in the CG in comparison with baselines: MUFA-Baseline 2,18±0,24 vs. MUFA-60min 2,30±0,26pg/ml and SAT-baseline 2,21±0.25pg/ml vs. SAT-60min 2,29±0,22 pg/ml ANOVA multiple entry p=0,019 intra-group, however without difference between MUFA and SAT (ANOVA multiple entry inter-group p=0,314). In the other hand, HFD SAT overload significantly decreased PYY release: SAT-baseline 2,16±0.21 pg/ml vs. SAT-60min 2,11±0,30 pg/ml (p=0,01,intra-group) while MUFA overload was able to keep the increase on PYY release MUFA-baseline 2,15pg/ml vs. MUFA-60min 2,22±0.22 pg/ml. p=0,019 (intra-group). Water overload (CONT) also reduced PYY release in comparison with baseline in both CG (p=0,0091) and HFD (p=0,0091), without difference between them (p= 0,7433). Conclusion: MUFA and SAT overloads increase PYY release after 60 minutes in normal wistar rats. However, when became high fat diet induced insulin resistant the SAT overload looses the capacity to stimulate PYY release, while MUFA response keeps preserved. This paradoxal finding to saturated fatty acids could indicate a cellular damage caused by insulin resistance in the intestinal tissue which compromises PYY secretory apparatus in response to this nutrient. Studies in the intestinal tissue must be conducted in order to identify possible factors involved and its implications in satiety signals PYY mediated in insulin resistance individuals.

El síndrome de Prader-Willi (SPW) es la causa de obesidad genética más frecuente. Está provocado por una falta de expresión de los genes de la región cromosómica 15q11-13. Adémas de desarrollar una obesidad mórbida, asocian retraso mental, una facies característica, hipogonadismo hipogonadotropo y déficit de hormona de crecimiento.
El control de la ingesta y del peso corporal es un proceso complejo en el que intervienen señales periféricas que informan sobre la adiposidad del organismo y otras que se producen en el tracto gastrointestinal que producen saciedad como el péptido YY (PYY). Por otra parte, la ghrelina, secretada en su mayoría por el estómago, estimula la ingesta. Finalmente, la adiponectina, fabricada en el tejido adiposo, y algunas proteínas relacionadas con la inflamación intervienen también en la regulación del metabolismo.
En esta tesis se estudian ghrelina, PYY, adiponectina y proteínas relacionadas con la inflamación (IL-6, IL-18, PCR, C3 y TNF-alfa) tanto en ayunas como tras la ingesta de una dieta líquida estándar en pacientes adultos con SPW y se compara con sujetos obesos de igual índice de masa corporal y sujetos con normopeso.
La ghrelina en ayunas fue superior en los pacientes con SPW. Tras la ingesta, la concentración de ghrelina disminuyó en los tres grupos pero en los pacientes con SPW, el descenso fue menos marcado, de forma que el área bajo la curva (AUC) de ghrelina fue superior en estos pacientes comparado con los sujetos obesos.
La concentración de PYY en ayunas fue inferior en los pacientes con SPW que en los otros dos grupos y, tras la ingesta, ascendió de forma menos marcada, a diferencia de lo observado en los sujetos obesos y con normopeso, en los que se produjo un pico de PYY a los 60 minutos. La concentración de PYY fue inversamente proporcional a la ghrelina en ayunas y al AUC de ghrelina, pudiendo además considerarse un predictor de esta última. El incremento de PYY tras la ingesta se correlacionó negativamente con el descenso de ghrelina en los pacientes con SPW en los minutos 60 y 120.
La concentración de adiponectina en ayunas fue inferior en los pacientes con SPW respecto a los sujetos con normopeso, pero superior a la de los sujetos obesos. No se observó ningún cambio en las concentraciones de adiponectina tras la ingesta ni en el grupo de sujetos obesos ni en el grupo con normopeso. Se observó un descenso del 13% en la adiponectina en el minuto 240 en el grupo con SPW. El AUC de adiponectina fue similar en los tres grupos.
Los sujetos obesos, con o sin SPW, mostraron concentraciones superiores en ayunas de algunos marcadores de inflamación comparado con el grupo de sujetos con normopeso. Además, comparado con los sujetos obesos, los pacientes con SPW mostraron concentraciones superiores de C3, IL-18, IL-6 y PCR, indicando que presentan aún un mayor grado de inflamación. No se observaron cambios tras la ingesta de ninguna de la proteínas de inflamación, de forma que persistieron elevadas aquellas que ya lo estaban en ayunas. La concentración de IL-18 se correlacionó negativamente con la testosterona en los varones con SPW. En conclusión, la hiperghrelinemia observada en los pacientes con SPW podría estar relacionada con una disminución de la concentración de PYY. La obesidad que acompaña al SPW, cursa con concentraciones de adiponectina y proteínas relacionadas con la inflamación superiores a los observados en la obesidad esencial.
Prader-Willi syndrome (PWS) is considered as one of the most common causes of genetic obesity in humans. The characteristic clinical features include neonatal hypotony, mental retardation, behavioural abnormalities and excessive appetite with progressive massive obesity. The aim of the study was to investigate fasting and postprandial ghrelin, peptide YY, adiponectin and inflammation-related proteins levels in PWS patients as compared to obese and lean subjects and whether they could contribute to the pathogenesis of obesity in this syndrome. We studied 7 patients with PWS, 16 obese patients and 42 lean subjects for the fasting study. From this group, we evaluated 7 patients with PWS, 7 age-sex-BMI-matched obese non-PWS and 7 age-sex-matched lean subjects before and after the administration of 750 Kcal of a standard liquid meal. Fasting ghrelin levels were higher in PWS than in the other two groups. Fasting PYY levels were lower in patients with PWS than in lean subjects but similar to those in obese subjects. The postpradial decrease in ghrelin concentrations was lower in PWS as compared to the other two groups. PYY response after the meal was blunted in patients with PWS, but not in the other two groups. Fasting PYY levels correlated negatively with fasting ghrelin levels and with ghrelin AUC and they were the only predictor for ghrelin AUC. The increase in PYY correlated negatively with the decrease in ghrelin in times 60 min and 120 min in PWS. Fasting plasma adiponectin levels were lower in PWS than in lean subjects but higher than in obese patients. After the meal, adiponectin concentrations mildly decreased in PWS at time point 240 min, while in obese and lean subjects no changes were observed. However, the adiponectin AUC was similar in all three groups. Compared to non-PWS, PWS subjects showed higher plasma concentrations of CRP, C3, IL-18 and IL-6 that persisted postprandially elevated for CRP, C3 and IL-18. TNF-alpha did not differ between the three groups. These results were independent from IGF-1 levels, HOMA index, and BMI. In male subjects with PWS, testosterone levels correlated to IL-18.

The G-protein coupled receptors (GPCRs) comprise the largest family of receptors in humans and other vertebrates. They are embedded in the cell membrane and are activated by many different signaling molecules. Activation modulates cellular signal transduction pathways and influences many physiological processes. Therefore the GPCRs are important as targets for numerous drugs. The receptors for NPY (neuropeptide Y) belong to GPCRs of Class A (rhodopsin-like). NPY and its related peptides PYY and PP are involved in the regulation of appetite, blood pressure and many other processes. They share a common structure and interact with the receptors Y1, Y2, Y4 and Y5 in mammals, and, in addition, Y7 and Y8 in amphibians and bony fishes. This thesis is focused on the human Y2 receptor, known to reduce appetite, by investigating the importance of thirteen amino acid residues for ligand binding. Mutagenesis followed by functional expression and receptor binding was conducted. During the course of this work several new GPCR crystal structures have been resolved, thereby improving the receptor modeling in papers I-III. The major finding is that even though the Y1 and Y2 receptors have evolved from a common ancestor, their points of ligand interaction differ and have thus changed during evolution. In general, the positions investigated resulted in milder changes in the ligands’ affinities for Y2 compared to Y1. These findings were incorporated in the design of new Y1 and Y2 receptor models, leading to improved understanding of how such divergent receptors, sharing only 30 percent sequence identity, can still interact with the same ligands. Notably, several of the mutations introduced in Y2 resulted in increased affinity. A novel NPY receptor gene named Y2-2 was identified in the genomes of zebrafish and medaka. This brings the number of zebrafish NPY receptors to seven. The binding characteristics of zebrafish Y2-2 differed from zebrafish Y2 mainly in the interaction with NPY13-36 and the antagonist BIIE0246. In conclusion, these results increase our understanding of ligand interactions with GPCRs and will be useful for refinement of ligand-receptor models for future development of receptor subtype-selective drugs.

The number of operations for morbid obesity is rising fast. We have examined aspects of postoperative physiology and results after bariatric surgery. The pH in the proximal pouch after Roux-en-Y gastric bypass (RYGBP) was investigated with catheter-based and wire-less technique. Gastric emptying, PYY-levels in the fasting state and after a standardized meal was evaluated after biliopancreatic diversion with duodenal switch (DS). A clinical trial was undertaken, comparing DS to RYGBP in patients with BMI>48. Main outcome variables were safety and long-term weight results as well as abdominal symptoms and laboratory results. Patients with stomal ulcer had significantly lower pH in their proximal gastric pouch as compared to asymptomatic control subjects. Long-time pH measurements with the wire-less BRAVO-system were feasible and demonstrated pH<4 in median 10.5% of the time in asymptomatic post-RYGBP patients. After DS, the T50 of gastric emptying was 28±16 minutes. PYY-levels were higher after DS than in age-matched control subjects. BMI-reduction was greater after DS (24 BMI-units) than after RYGBP (17 BMI-units) in median 3.5 (2.0-5.3) years after surgery (p<0.001). Fasting glucose and HbA1c levels were lower one and three years after DS as compared to RYGBP. On the other hand, DS-patients reported having more diarrhea and malodorous flatus. This thesis has resulted in deepened knowledge. Acid produced in the proximal pouch is an important pathogenetic factor in the development of stomal ulcer after RYGBP. However, symptom-free patients have an acidic environment in the proximal Roux-limb as well. After DS, gastric emptying is fast, but not instantaneous, and PYY-levels are high. DS results in superior weight reduction and better glucose control as compared to RYGBP in patients with BMI>48. We believe that DS has a place in surgical treatment of the super-obese, even though symptoms of diarrhea and malodorous flatus are more common after DS.

HIV prevention programs in schools are acknowledged as one of the best prospects for controlling the world HIV epidemic. Epidemiological evidence indicates that deaths world-wide from AIDS are yet to peak. Although HIV notifications and AIDS deaths in the total Australian population have decreased', there has been an increase in rates in the Australian Indigenous population. There is also some evidence of complacency in HIV prevention vigilance in Australia which indicates a need for continued focus on prevention programs. The knowledge levels, attitudes toward HIV risk, and risk-taking behaviours of young Australians place them at risk of exposure to HIV. Appropriate prevention programs can be delivered to these vulnerable young people through the school setting. Programs delivered in schools have been shown to have a positive effect and teachers are vital to the delivery of these education programs. Without appropriate training, however, teachers may not optimise the outcomes of these programs. While it would be desirable for teachers to be trained in HIV prevention education in pre-service training this has not been the case in Western Australia (WA). When there is not an opportunity for pre-service training, professional development programs can be implemented to provide additional training required by teachers. Traditionally this professional development has been provided through workshops. These face-to-face delivery methods, however, do not always adequately serve the needs of all teachers, and in particular the needs of teachers in rural and remote areas. In an attempt to address the needs of these teachers, alternate methods of professional development delivery may be appropriate. The aim of this study was to test an alternate method of delivery.The study designed, disseminated and evaluated the implementation of a flexible learning professional development program for teachers of HIV education. The program was based on print-based distance learning, supported by a video and tutors. Five objectives were developed for the study. These objectives were: Objective One - To determine factors associated with teachers' enrolment in the Protect Yourself Program (PYP). Objective Two - To determine the association between factors related to entry characteristics, social integration, external attribution, academic integration and incompatibility and amount of PYP completed. Objective Three - To determine the association between amount of PYP completed and factors related to the teaching of HIV lessons. Objective Four - To examine the context in which intervention and comparison group teachers were operating for this study. Objective Five - To evaluate the process of teacher recruitment to PYP, satisfaction with the flexible learning methodology, satisfaction with the PYP materials and completion of PYP. A comprehensive theoretical framework was constructed to guide the development of the empirical study and the professional development program, as little evidence was found in the literature of similar empirically evaluated studies. This framework incorporated: Adult Learning Theory; the Model of Student Progress; the PRECEDEPROCEED Model; the Health Promoting Schools Framework; Diffusion of Innovation and the Communication Behaviour Change Model. The study was conducted in two parts. Firstly, an exploratory study was conducted which provided a basis upon which to implement the second, larger empirical study.A quasi-experimental study design was implemented due to restrictions placed upon the study by the WA Department of Health, the funding agency. The study sample was made up of teachers from government and independent, primary and second schools in WA. In total, 126 teachers were recruited to the intervention group and enrolled in the professional development program, and 128 to the comparison group, who completed some of the evaluation instruments, but did not participate in a professional development program. The professional development intervention program incorporated four comprehensive work modules, which were delivered in print form. A video and tutorial support supplemented the print materials. To evaluate the professional development program, seven instruments were developed. From these instruments five categories of variables were created, namely demographic, contextual, teacher characteristics, process and dependent. These variables were developed as single item variables, scales or indices. Quantitative data were analysed using the Statistical Package for the Social Sciences and a combination of univariate, bivariate, and multivariate techniques (logistic regression and analysis of covariance) were conducted. Qualitative data were analysed for themes. A binary logistic regression was conducted to evaluate Objective One: to determine factors associated with teachers’ enrolment in PYP. The analysis identified four factors which were associated with enrolment in PYP.The teachers most likely to enrol in PYP had no pre-service training in health education and did not consider themselves to be a specialist or coordinator of health education. The majority of program participants had been teaching health education for between three and seven years and displayed a high level of acceptance of the flexible learning methodology. Objective Two: to determine the association between factors related to entry characteristics, social integration, external attribution, academic integration and incompatibility and amount of PYP completed was evaluated using a nominal logistic regression analysis with the intervention group sample only. Completion of the PYP program by participants was related to circumstances which were often beyond the control of the program, such as events occurring in a teacher’s personal life. However, teachers who showed a preference for flexible learning were found to be more successful in completing the program. The effects of PYP were measured by Objective Three: to determine the association between amount of PYP completed and factors related to the teaching of HIV lessons. Three of the six factors considered by this objective returned a significant association with program dose. Teacher perceived access to HIV education resources was found to be positively related to the dose of materials a participant completed.Participants who completed a high dose of the program considered HIV resources to be relatively easier to access than participants completing a low dose. Teachers who completed a high dose of PYP reported being more comfortable to teach HIV lessons than teachers completing a mid dose. In addition, intervention group teachers showed a significant change in comfort with their ability to teach HIV lessons and specified HIV topics to Years 8, 9, and 10 classes and intervention group teachers of Year 8 students thought the HIV topics were less important for this level of students. The final variable to show a significant change over time when dose of the program was considered was teacher sexual conservativeness. Both high and mid dose participants reported being less sexually conservative than low or no dose participants from pre to midtest. The context of the teachers participating in the PYP study was investigated through Objective Four: to examine the context in which intervention and Comparison group teachers were operating for this study. Two factors were found to be associated with gender, six with school location and eleven with level of teaching. These associations provided important contextual information for interpreting the findings of the study. Objective Five evaluated the process of teacher recruitment to PYP, satisfaction with the flexible learning methodology, satisfaction with the PYP materials and completion of PYP. The recruitment strategies implemented for PYP were effective in having teachers from government and independent schools in WA recruited to PYP.However, more than 90% of the intervention group were from government schools. Schools encouraged more than one teacher from a school to enrol, with nine primary schools, four district high schools, one community high school, one secondary college, four senior high schools and one combined independent primary and high school enrolling more than one teacher in the program. The flexible learning methodology was reported to be suitable for the needs of teachers who enrolled in PYP, as they felt comfortable with the learning methodology and appreciated the opportunity to choose when and where they completed the program. The opportunity for face-to-face contact, however, was still preferred by some teachers. The materials within the program were considered to be appropriate and useful. The writing style and activities were well received and the efforts of the tutors were welcomed by the majority of the intervention group. One third of teachers who enrolled in PYP completed at least some of the materials, but less than 10% completed the entire program. The most frequent suggestions made for increasing program completion rates were to set dates for completion of the program modules and to allow time release to complete the program. At baseline, this research showed that teachers considered it important for their students to have access to HIV education, but many of these teachers did not feel comfortable providing HIV education for their students.As positive effects were observed in the PYP program of impact of program dose on factors affecting the implementation of HIV education, it would appear that flexible learning professional development was a suitable alternative to face-to-face professional development. Teachers' acceptance of flexible learning professional development as an alternate methodology, however, appears to be in its infancy and will require more empirical research. Future research, study design improvements and intervention design improvements can be informed by the following recommendations. Future research Recommendation 1: There be more rigorous investigation of flexible learning as a methodology for provision of professional development for teachers of health education. Recommendation 2: The status of claiming credit for professional development toward postgraduate qualifications for teachers continue to be investigated. Recommendation 3 : Further research be undertaken to evaluate available technologies and their acceptance by teachers as a delivery method for flexible learning professional development. Study design improvements Recommendation 4: design limitations of the PYP study. Future research be designed to overcome the study Intervention design improvements Recommendation 5: The findings of the PYP study and suggestions made by PYP participants be used to improve future health education professional development programs.

Abstract Parasites are an inseparable part of the life of wild birds. They may cause morbidity, mortality or reduction in fecundity. Parasite distribution in hosts is typically not uniform and many host factors (e.g. age) may affect the pattern of distribution. Under certain conditions, parasites even have the potential to regulate the host population. The grouse species of Finnish forests — the capercaillie Tetrao urogallus , the black grouse Lyrurus tetrix and the hazel grouse Tetrastes bonasia — harbour several species of intestinal helminth parasites. The populations have fluctuated in cyclic manner but the mechanisms behind the cycles are largely unknown. I studied the interactions of forest grouse and their intestinal helminth parasites by using intestinal samples collected by hunters in five game management districts during eight years (1995–2002). The most common parasite species in the samples was the nematode Ascaridia compar. Also, three species of cestodes (Skrjabinia cesticillus, Paroniella urogalli and Hymenolepis sp.) were found. Large size, male gender and age over 1 year were connected with an increased probability and intensity of A. compar infection. Juvenile grouse were commonly infected with cestodes while in adults infections were quite rare. The influence of inbreeding on the susceptibility to parasite infections was studied in the capercaillie by analysing microsatellite heterozygosity. The less heterozygous birds were more likely to be infected with A. compar and were more intensely infected suggesting negative influence of inbreeding on parasite resistance. An indirect negative effect of parasites was found by comparing bags hunted with a trained dog or without a dog. Grouse infected by cestodes were significantly more common in the dog-assisted bag. Thus, cestode infection seemed to make grouse more vulnerable to canine predation. The interaction between grouse population dynamics and parasites was studied by analyzing the grouse densities obtained from annual wildlife counts and parasite indices. A. compar was most common and most abundant in the years of grouse population decline. The grouse population growth rate was negatively correlated with the annual mean abundance of A. compar. Relative survival but not breeding success decreased as the abundance of A. compar increased. The findings suggest that A. compar influences the dynamics of Finnish grouse even though regular cyclic dynamics are no longer evident
Tiivistelmä Loiset kuuluvat erottamattomana osana luonnonvaraisten lintujen elämään. Ne voivat aiheuttaa sairautta, kuolleisuutta tai hedelmällisyyden alentumista. Tyypillisesti loiset ovat levinneet isäntäpopulaatioon epätasaisesti ja monet isännän ominaisuudet (esim. ikä) vaikuttavat levinneisyyteen. Tietyissä oloissa loiset voivat jopa säädellä isäntäpopulaatiotaan. Suomalaiset metsäkanalinnut — metso Tetrao urogallus, teeri Lyrurus tetrix ja pyy Tetrastes bonasia — ovat useiden suolistoloismatolajien isäntiä. Metsäkanapopulaatiot ovat vaihdelleet syklisesti, mutta syklejä aiheuttavat mekanismit ovat yhä tuntemattomia. Tutkin metsäkanalintujen ja niiden suolistoloisten välisiä vuorovaikutuksia käyttäen metsästäjien vuosina 1995–2002 viidestä eri riistanhoitopiiristä keräämiä suolistonäytteitä. Yleisin loislaji näytteissä oli kanalintusuolinkainen, Ascaridia compar. Myös kolme heisimatolajia (Skrjabinia cesticillus, Paroniella urogalli ja Hymenolepis sp.) todettiin. Suuri koko, koirassukupuoli ja yli yhden vuoden ikä olivat yhteydessä suurempaan kanalintusuolinkaistartunnan todennäköisyyteen ja voimakkuuteen. Nuorilla (alle 1 v.) linnuilla heisimadot olivat yleisiä, kun taas aikuisilla tartunnat olivat varsin harvinaisia. Sisäsiittoisuuden vaikutusta loistartuntaherkkyyteen tutkittiin metsolla mikrosatelliittiheterotsygotian perusteella. Vähemmän heterotsygoottiset metsot olivat todennäköisemmin ja voimakkaammin suolinkaisten infektoimia, mikä viittaa sisäsiittoisuuden negatiiviseen vaikutukseen loisten vastustuskykyyn. Loisten epäsuora haitallinen vaikutus havaittiin, kun verrattiin koiran kanssa ja ilman koiraa metsästettyä lintusaalista. Heisimadot olivat selvästi yleisempiä linnuilla, jotka oli metsästetty koiran kanssa kuin ilman koiraa metsästetyillä. Heisimatotartunta näytti siis altistavan metsäkanoja koiraeläinten saalistukselle. Metsäkanalintu- ja loispopulaatioiden välistä vuorovaikutusta tutkittiin analysoimalla vuosittaisia metsäkanatiheyksiä ja loisten runsautta. Kanalintusuolinkainen oli yleisimmillään ja runsaimmillaan metsäkanatiheyden laskuvuosina. Metsäkanapopulaation vuosittainen kasvuvauhti korreloi negatiivisesti kanalintusuolinkaisen vuosittaisen runsauden kanssa. Suhteellinen elossasäilyvyys laski kanalintusuolinkaisen runsauden lisääntyessä, mutta lisääntymistuloksen suhteen ei ollut samaa ilmiötä. Löydökset viittaavat siihen, että kanalintusuolinkaisella on vaikutusta suomalaisten metsäkanalintukantojen vaihteluihin, vaikka syklisiä kannanvaihteluja ei enää havaitakaan

The regulation of glucagon-like peptide-1 and peptide YY hormone levels are regulated based on different influential factors, but primarily levels are dependent upon ingested food content. As meals today become more fat-enriched, there is greater requirement for evaluation of these hormones that regulate insulin and satiety levels within the body. We have shown that the gene expression transcript production of glucagon-like peptide-1 and peptide YY are modulated by different concentrations, and times of short-chain fatty acids and long-chain fatty acids. Although the peptide hormone levels have the influential physiological role on effector tissue, the regulation of these hormones begins at the transcript levels. Recent research indicates that glucagon-like peptide-1 and peptide YY hormones are altered in response to different free-fatty acids. The present investigation generally demonstrated an overall decrease in both hormones after chronic exposure to fatty acids. Intestinal secretin tumor cell line (STC-1 cells) was used as a representative for intestinal L-cells. Quantitative real-time PCR analysis was used to determine the changes in RNA transcripts. Overall, there was a decrease in the 3-hour timeline, which continued to decrease in the 16-hour and 24-hour timelines for glucagon-like peptide-1. Peptide YY transcript expression in 3-hours increased significantly after exposure to propionate, a significant decrease after exposure to acetate, and no significant increase or decrease after exposure to butyrate. However, there was a significant decrease in peptide YY once reaching 24-hour exposure. It was determined there is a threshold for different concentrations of free-fatty acids to influence glucagon-like peptide-1 and peptide YY production, which was present in the different concentrations of butyrate. Lastly, exposure to both concentrations of linolenic acid caused a significant decrease in glucagon-like peptide-1 and peptide YY.

HIV prevention programs in schools are acknowledged as one of the best prospects for controlling the world HIV epidemic. Epidemiological evidence indicates that deaths world-wide from AIDS are yet to peak. Although HIV notifications and AIDS deaths in the total Australian population have decreased', there has been an increase in rates in the Australian Indigenous population. There is also some evidence of complacency in HIV prevention vigilance in Australia which indicates a need for continued focus on prevention programs. The knowledge levels, attitudes toward HIV risk, and risk-taking behaviours of young Australians place them at risk of exposure to HIV. Appropriate prevention programs can be delivered to these vulnerable young people through the school setting. Programs delivered in schools have been shown to have a positive effect and teachers are vital to the delivery of these education programs. Without appropriate training, however, teachers may not optimise the outcomes of these programs. While it would be desirable for teachers to be trained in HIV prevention education in pre-service training this has not been the case in Western Australia (WA). When there is not an opportunity for pre-service training, professional development programs can be implemented to provide additional training required by teachers. Traditionally this professional development has been provided through workshops. These face-to-face delivery methods, however, do not always adequately serve the needs of all teachers, and in particular the needs of teachers in rural and remote areas. In an attempt to address the needs of these teachers, alternate methods of professional development delivery may be appropriate. The aim of this study was to test an alternate method of delivery.
The study designed, disseminated and evaluated the implementation of a flexible learning professional development program for teachers of HIV education. The program was based on print-based distance learning, supported by a video and tutors. Five objectives were developed for the study. These objectives were: Objective One - To determine factors associated with teachers' enrolment in the Protect Yourself Program (PYP). Objective Two - To determine the association between factors related to entry characteristics, social integration, external attribution, academic integration and incompatibility and amount of PYP completed. Objective Three - To determine the association between amount of PYP completed and factors related to the teaching of HIV lessons. Objective Four - To examine the context in which intervention and comparison group teachers were operating for this study. Objective Five - To evaluate the process of teacher recruitment to PYP, satisfaction with the flexible learning methodology, satisfaction with the PYP materials and completion of PYP. A comprehensive theoretical framework was constructed to guide the development of the empirical study and the professional development program, as little evidence was found in the literature of similar empirically evaluated studies. This framework incorporated: Adult Learning Theory; the Model of Student Progress; the PRECEDEPROCEED Model; the Health Promoting Schools Framework; Diffusion of Innovation and the Communication Behaviour Change Model. The study was conducted in two parts. Firstly, an exploratory study was conducted which provided a basis upon which to implement the second, larger empirical study.
A quasi-experimental study design was implemented due to restrictions placed upon the study by the WA Department of Health, the funding agency. The study sample was made up of teachers from government and independent, primary and second schools in WA. In total, 126 teachers were recruited to the intervention group and enrolled in the professional development program, and 128 to the comparison group, who completed some of the evaluation instruments, but did not participate in a professional development program. The professional development intervention program incorporated four comprehensive work modules, which were delivered in print form. A video and tutorial support supplemented the print materials. To evaluate the professional development program, seven instruments were developed. From these instruments five categories of variables were created, namely demographic, contextual, teacher characteristics, process and dependent. These variables were developed as single item variables, scales or indices. Quantitative data were analysed using the Statistical Package for the Social Sciences and a combination of univariate, bivariate, and multivariate techniques (logistic regression and analysis of covariance) were conducted. Qualitative data were analysed for themes. A binary logistic regression was conducted to evaluate Objective One: to determine factors associated with teachers’ enrolment in PYP. The analysis identified four factors which were associated with enrolment in PYP.
The teachers most likely to enrol in PYP had no pre-service training in health education and did not consider themselves to be a specialist or coordinator of health education. The majority of program participants had been teaching health education for between three and seven years and displayed a high level of acceptance of the flexible learning methodology. Objective Two: to determine the association between factors related to entry characteristics, social integration, external attribution, academic integration and incompatibility and amount of PYP completed was evaluated using a nominal logistic regression analysis with the intervention group sample only. Completion of the PYP program by participants was related to circumstances which were often beyond the control of the program, such as events occurring in a teacher’s personal life. However, teachers who showed a preference for flexible learning were found to be more successful in completing the program. The effects of PYP were measured by Objective Three: to determine the association between amount of PYP completed and factors related to the teaching of HIV lessons. Three of the six factors considered by this objective returned a significant association with program dose. Teacher perceived access to HIV education resources was found to be positively related to the dose of materials a participant completed.
Participants who completed a high dose of the program considered HIV resources to be relatively easier to access than participants completing a low dose. Teachers who completed a high dose of PYP reported being more comfortable to teach HIV lessons than teachers completing a mid dose. In addition, intervention group teachers showed a significant change in comfort with their ability to teach HIV lessons and specified HIV topics to Years 8, 9, and 10 classes and intervention group teachers of Year 8 students thought the HIV topics were less important for this level of students. The final variable to show a significant change over time when dose of the program was considered was teacher sexual conservativeness. Both high and mid dose participants reported being less sexually conservative than low or no dose participants from pre to midtest. The context of the teachers participating in the PYP study was investigated through Objective Four: to examine the context in which intervention and Comparison group teachers were operating for this study. Two factors were found to be associated with gender, six with school location and eleven with level of teaching. These associations provided important contextual information for interpreting the findings of the study. Objective Five evaluated the process of teacher recruitment to PYP, satisfaction with the flexible learning methodology, satisfaction with the PYP materials and completion of PYP. The recruitment strategies implemented for PYP were effective in having teachers from government and independent schools in WA recruited to PYP.
However, more than 90% of the intervention group were from government schools. Schools encouraged more than one teacher from a school to enrol, with nine primary schools, four district high schools, one community high school, one secondary college, four senior high schools and one combined independent primary and high school enrolling more than one teacher in the program. The flexible learning methodology was reported to be suitable for the needs of teachers who enrolled in PYP, as they felt comfortable with the learning methodology and appreciated the opportunity to choose when and where they completed the program. The opportunity for face-to-face contact, however, was still preferred by some teachers. The materials within the program were considered to be appropriate and useful. The writing style and activities were well received and the efforts of the tutors were welcomed by the majority of the intervention group. One third of teachers who enrolled in PYP completed at least some of the materials, but less than 10% completed the entire program. The most frequent suggestions made for increasing program completion rates were to set dates for completion of the program modules and to allow time release to complete the program. At baseline, this research showed that teachers considered it important for their students to have access to HIV education, but many of these teachers did not feel comfortable providing HIV education for their students.
As positive effects were observed in the PYP program of impact of program dose on factors affecting the implementation of HIV education, it would appear that flexible learning professional development was a suitable alternative to face-to-face professional development. Teachers' acceptance of flexible learning professional development as an alternate methodology, however, appears to be in its infancy and will require more empirical research. Future research, study design improvements and intervention design improvements can be informed by the following recommendations. Future research Recommendation 1: There be more rigorous investigation of flexible learning as a methodology for provision of professional development for teachers of health education. Recommendation 2: The status of claiming credit for professional development toward postgraduate qualifications for teachers continue to be investigated. Recommendation 3 : Further research be undertaken to evaluate available technologies and their acceptance by teachers as a delivery method for flexible learning professional development. Study design improvements Recommendation 4: design limitations of the PYP study. Future research be designed to overcome the study Intervention design improvements Recommendation 5: The findings of the PYP study and suggestions made by PYP participants be used to improve future health education professional development programs.

The purpose of this study is to determine what alternative forms of assessments are being practiced in a public school with an international programme and to explore the teachers` attitudes towards the use of alternative assessment procedures. Various assessment models and strategies have been investigated and discussed, as pre¬senting a part of the educational practice in the primary classrooms that engage the International Baccalaureate/ Primary Years Programme at the elementary school level (age range 6-11) in the years 0-5.

While defining my research problem, I have started from hypothesis that practicing of alternative assessment has an important positive role in the international schools supporting, promoting and improving student learning.

International schools are facing both challenging and complexity of assessment pro¬cess while striving to apply both national and international programs` recom¬menda¬tions concerning the testing.

Alternative forms of assessments are being used in conjunction with other forms of assessment, such as standardised tests, in order to assess both student perfor¬mance and the intentions of the International Baccalaureate/ Primary Years Pro¬gramme.

This paper investigates what alternative assessment practices (portfolio, perfor¬mance assessment, Exhibition, self-assessment) are being applied and used in the same school where the standardised tests are also being applied and used (text book tests, teacher-made tests, local and national test).

The hypothesis was supported and the study findings suggest that various types of assessments are needed to be utilized in order to fairly evaluate students` needs as well as that alternative assessment has an important positive role meeting individual student’s needs supporting a process of learning.

Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.

Today new programming languages proliferate, but many of them suffer from poor performance and inscrutable semantics. We assert that the root of many of the performance and semantic problems of today's languages is that language implementation is extremely difficult. This thesis addresses the fundamental challenges of efficiently developing high-level managed languages. Modern high-level languages provide abstractions over execution, memory management and concurrency. It requires enormous intellectual capability and engineering effort to properly manage these concerns. Lacking such resources, developers usually choose naive implementation approaches in the early stages of language design, a strategy which too often has long-term consequences, hindering the future development of the language. Existing language development platforms have failed to provide the right level of abstraction, and forced implementers to reinvent low-level mechanisms in order to obtain performance. My thesis is that the introduction of micro virtual machines will allow the development of higher-quality, high-performance managed languages. The first contribution of this thesis is the design of Mu, with the specification of Mu as the main outcome. Mu is the first micro virtual machine, a robust, performant, and light-weight abstraction over just three concerns: execution, concurrency and garbage collection. Such a foundation attacks three of the most fundamental and challenging issues that face existing language designs and implementations, leaving the language implementers free to focus on the higher levels of their language design. The second contribution is an in-depth analysis of on-stack replacement and its efficient implementation. This low-level mechanism underpins run-time feedback-directed optimisation, which is key to the efficient implementation of dynamic languages. The third contribution is demonstrating the viability of Mu through RPython, a real-world non-trivial language implementation. We also did some preliminary research of GHC as a Mu client. We have created the Mu specification and its reference implementation, both of which are open-source. We show that that Mu's on-stack replacement API can gracefully support dynamic languages such as JavaScript, and it is implementable on concrete hardware. Our RPython client has been able to translate and execute non-trivial RPython programs, and can run the RPySOM interpreter and the core of the PyPy interpreter. With micro virtual machines providing a low-level substrate, language developers now have the option to build their next language on a micro virtual machine. We believe that the quality of programming languages will be improved as a result.

碩士
國立臺灣大學
資訊工程學研究所
95
Java language is a typical object-oriented computer language. Programmers have gotten convenience in container declaration and usage since generics was supported by JDK5.0. As a result of using generalization to implement the generics support of new Java compiler. There could be difference between the source code and the real semantic in its class file. Java core reflection is also incomplete. The primal reason is that Java Virtual Machine doesn’t support parameterized type. In this thesis we bring up a light weight solution for parameterized type checking at runtime. It can also support runtime parameterized type reflection. This solution can work without modifying Java Virtual Machine.

In my thesis I deal with the pollen of allergenic plants, the origin and proces of allergy to plant pollen and the inclusion of these topics in the teaching of plant biology in high schools. In the theoretical part I focus on topic of pollen allergy. First, I generally describe allergy and its origin, causes of allergic diseases, environmental factors and the development of allergic disease. I also briefly address the naming and registration of allergens and I also mention the so-called cross-allergy. Great emphasis is placed on pollen allergy, which is devoted to a larger unit, divided into individual subchapters dealing with the physiological function of the nose, followed by an allergic reaction of type I, an allergic reaction that occurs on the nasal mucosa. Furthermore, subchapters mentioning the classification of allergic rhinitis, diagnosis and pharmacotherapy, including additions to the drug groups used in the treatment of pollen allergy. Another larger unit is devoted to the structure of the plant's blossom as a source of allergen, which includes the anatomy of the blossom parts and a description of the pollen grain. The anatomical description of the blossom is followed by a practical part, first created by a tabular overview with selected allergenic plants. Each plant causing the allergy...

7 Abstract The thesis is focused on the pollen of selected allergenic plants. Thesis is structured into two parts., pollination and fertilization , development of the pollen grain , its structure and chemical composition. The end of the theoretical part, dedicated to allergies, is divided into subsections dealing with First, teoretical part describes the flower and its morphology, discusses the pollen grain, stamen anatomical structure immunity and allergies, naming and registration of allergens and cross- pollen allergy . The practical part contains an analysis of curriculum for students of secondary schools. An integral part of the work is a survey of teachers in secondary schools, in which method of questioning was used. The aim of this questioning was to determine the presence of solved issue in terms of representation of pollen and pollen allergens in textbooks for secondary schools , as well as the inclusion of this issue in the official curriculum, under the National Programme for the Development of Education in the Czech Republic. Based on the results of a questionnaire survey of secondary school teachers, teaching materials have been developed in the form of two worksheets for teaching botany and guidance on laboratory exercises in plant biology.

Peptide YY (PYY) is a gut-derived hormone that is renowned for its effects on satiety. Reduced satiety in obese people has been attributed to low fasting and postprandial PYY levels. However, it has not been determined whether low PYY levels are the cause or the outcome of obesity. Moreover, the long-term role of PYY in regulating energy balance is unclear. Results presented in this thesis, using PYY-deficient mice (PYY-/-) and PYY transgenic mice (PYYtg) highlight that PYY indeed has an important role in regulating energy balance and glucose homeostasis in vivo. PYY knockout mice became obese with ageing or high-fat feeding linked to a hyperinsulinemic phenotype associated with hypersecretion of insulin from isolated pancreatic islets. These findings suggested that PYY deficiency may be a predisposing factor for the development of obesity and type 2 diabetes. On the other hand, PYYtg mice exhibited decreased adiposity and increased metabolism under high-fat feeding. Furthermore, PYYtg/ob mice had improved glucose tolerance and decreased adiposity. These latter studies suggested that high circulating PYY levels may protect against the development of obesity and type 2 diabetes. Interestingly, both animal models support PYY as an important regulator of the somatotropic axis. These preliminary findings prompted investigations in understanding whether low PYY levels may be a predisposing factor for the development of obesity and type 2 diabetes in human subjects. In a population of healthy human subjects that had a predisposition to the development of type 2 diabetes and obesity, fasting PYY levels were lower than in normal subjects. Moreover, low fasting PYY levels strongly correlated with decreased insulin sensitivity and high levels of fasting insulin. Collectively, these findings suggest that low circulating levels of PYY could contribute to increased adiposity, insulin resistance and type 2 diabetes. Therefore determination of PYY levels may be a method of detecting whether people are predisposed to becoming obese and insulin resistant. This work also suggests that treatments that enhance circulating PYY levels may be protective in the development of obesity and type 2 diabetes.

In Schizosaccharomyces pombe mitosis is initiated when Cdc25 tyrosine phosphatase dephosphorylates Cdc2 (Cdk1) and in turn Cdc2 kinase phosphorylates mitotic targets. Cdc2 is thought to phosphorylate and further activate Cdc25, forming a positive feedback loop between the two for robust entry into mitosis. Pyp3 tyrosine phosphatase is essential in the absence of Cdc25. Its role is thought to be in directly dephosphorylating Cdc2 under these conditions. Pyp3 also presents a link between cell division and growth. It interacts physically and genetically with the mRNA cap-binding protein eIF4E and is thought to play the same role as mammalian 4E-binding proteins. Pyp3 has a consensus TOS motif potentially enabling nutritional input from the TOR pathway into translation regulation. Since known 4E-BPs are not phosphatases, Pyp3 may act as a 4E-binding protein independently of its phosphatase activity. Evolutionarily conserved Cdc2 phosphorylation sites in Cdc25 were substituted to non-phosphorylatable Ala, or to Glu as a phosphomimic. The T89E phosphomimic mutation creates an activated allele of Cdc25, cdc25-89w. It has a dominant semi-wee phenotype due to accelerated entry into mitosis. Pyp3 was mutagenized to remove the function of the phosphatase active site and also the putative TOS motif. The Pyp3 active site is essential for its role in cell cycle initiation. It is also essential for the genetic interaction with eIF4E, tif1. Removal of a putative Pyp3 TOS motif affects the Pyp3 localization to cytoplasmic foci following co-overexpression of eIF4E. Similar localization occurs in response to heat stress. These results make important contributions to the understanding of mitotic initiation, and link between cell growth and division.
Thesis (Master, Biology) -- Queen's University, 2013-09-12 14:40:40.384

abstract: This research investigates teachers' understanding of and feelings about transdisciplinary education and the International Baccalaureate's Primary Years Programme (PYP) as utilized by two remote schools in the province of Papua, Indonesia on the island of New Guinea. A goal of transdisciplinary education is to make learning through inquiry authentic, broad, student-centered, and relevant to the real world. In this study I examine educators’ perspectives of how transdisciplinary education is manifested in the two different and yet related elementary schools. Both schools are supported by a multinational mining company. One school is for expatriate students and the language of instruction is English. The second school, which is for Indonesian students, follows the Indonesian National Curriculum of 2013, with instruction delivered in the Indonesian language by Indonesian teachers. A single expatriate superintendent oversees both schools. Teacher experience, teacher PYP experience, implications of the PYP framework, cultural implications of the location, and demographics of the school stakeholders were considerations of this research. To acquire data, homeroom teachers, specialist teachers (music, art, physical education, and language), administrators, and PYP coordinators completed a survey and were interviewed. Additional data were collected through document examination and observation. A broad range of experience with transdisciplinary education existed in both schools, contributing to some confusion about how to implement the PYP framework and varying conceptions of what constitutes transdisciplinary education. Principles of the PYP were evident in curriculum documents and planning and discussed by the teachers in both schools. Educators at the expatriate school identified with the international-mindedness and approaches to learning in the PYP. Educators at the national school valued to character education elements of the PYP, which they viewed as consistent with Indonesian principles of pancasila. The mission and vision statements of the schools in this study aligned with the PYP in different ways. Challenges faced by educators in these schools are acquisition of professional development, experienced teachers and teaching materials due to the remote location of the schools. While transdisciplinary education was described, it was not necessarily implemented. The findings of this study suggest that transdisciplinary education is a mindset that takes time, experience, and commitment to implement.
Dissertation/Thesis
Doctoral Dissertation Music Education 2019

Trabalho de Projeto do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
ResumoIntrodução: O excesso de peso e obesidade são, atualmente, um grave problema de saúde pública. Os mecanismos do controlo do apetite envolvem sinalização cerebral, gastrointestinal e do tecido adiposo. É sugerido ainda que mediadores libertados perifericamente, como o Peptídeo Semelhante ao Glucagon-1 (GLP-1) e o Peptídeo tirosina-tirosina (PYY), induzam alterações relevantes a nível central.O objetivo deste trabalho é reunir informação da literatura cientifica atual acerca dos efeitos centrais mediados pela secreção periférica de GLP-1 e PYY, relacionando-os com o controlo do apetite. Métodos: A revisão bibliográfica baseou-se na pesquisa de artigos publicados na base de dados PubMed desde 2011 até à atualidade, incluindo artigos publicados em anos anteriores. Foram ainda consultados livros do foro da Endocrinologia.Resultados e Discussão: GLP-1 e PYY são libertados pelas células L intestinais e ligam-se aos seus recetores no gânglio inferior do nervo vago, estabelecendo por esta via uma das formas de comunicação com o tronco cerebral e hipotálamo.O PYY 3-36, formado a partir da clivagem de PYY 1-36 pela enzima dipeptidil peptidase 4 (DPP-4), atravessa livremente a barreira hematoencefálica, atuando preferencialmente nos recetores Y2 no núcleo arqueado (ARC) do hipotálamo, conduzindo a inibição dos neurónios produtores de neuropeptídeo Y (NPY) e ativação dos neurónios pró-opio melanocortina (POMC), tendo como resultado final a redução do apetite. Pode também atuar por ativação do núcleo do trato solitário (NTS), após sinalização do trato gastrointestinal pelo nervo vago.Já o GLP-1, poderá ter influência no apetite por 3 vias: ativação do NTS pelo nervo vago após sinalização sensorial do trato gastrointestinal, ativação do NTS pelo nervo vago após sinalização neuronal proveniente da região hepatoportal ou acesso ao SNC através de falhas na barreira hematoencefálica como a área postrema (AP) e o órgão subfornical. Os neurónios do NTS, projetam-se para os núcleos ARC e núcleos paraventriculares (PVN), induzindo a perda de apetite.Considerações Finais: A administração periférica de GLP-1 e PYY 3-36 está associada a uma ação central no sentido da redução do apetite, corroborando a sua importância na modulação do peso corporal e a sua modulação no tratamento da obesidade.Uma das perspetivas futuras mais promissoras é a investigação recorrendo a ressonância magnética funcional (fRMN), no sentido de objetivar as zonas em que estes peptídeos atuam centralmente, possibilitando uma melhor compreensão dos mecanismos inerentes e o eventual desenvolvimento de novas estratégias terapêuticas.Palavras-chave: Peptídeo YY, Peptídeo Semelhante ao Glucagon-1, Apetite e Efeitos Centrais.
AbstractIntroduction: Overweight and obesity are a public health problem. Appetite regulation involves brain, gastrointestinal and adipose tissue signaling. There is some evidence suggesting that the brainstem is an important site of action for peripheral Glucagon-Like Peptide-1(GLP-1) and Peptide tyrosine-tyrosine (PYY).This dissertation aimed to review the current knowledge of the central effects induced by peripheral secretion of GLP-1 and PYY on appetite control. Methodology: A review of the published literature through research using PubMed interface was conducted, to select references since 2011 until now, including some articles published in previous years selected by cross-reference. Endocrinology books were also consulted.Results and Discussion: GLP-1 is secreted together with PYY by L intestinal cells and trigger their receptors located at the lower ganglion of the vagus nerve, thereby reaching brainstem and hypothalamus.Dipeptidyl peptidase-4 (DPP-4) cleaves PYY 1-36 forming PYY 3-36. PYY 3-36 is believed to cross the blood-brain barrier and binds with high affinity to the Y2 receptors on arcuate nucleus (ARC) within the hypothalamus, leading to appetite suppression by the inhibition of neuropeptide Y (NPY) neurons and activation of proopiomelanocortin (POMC) neurons. This peptide can also act through the vagus nerve, which transmits information from the digestive tract to the nucleus tractus solitarius (NTS).GLP-1 has effect on appetite through 3 pathways: activation of the NTS by the vagus nerve after sensorial signaling of the digestive tract, activation of the NTS by the vagus nerve after hepatoportal signaling and access to SNC through permeable areas in the blood-brain barrier such as area postrema (AP) and subfornical organ. NTS neurons project to the ARC and paraventricular nucleus (PVN), inducing loss of appetite. Final Remarks: Peripheral GLP-1 and PYY 3-36 are associated with central effects that suppress appetite, suggesting that their action may be modulated in the treatment of obesity. In the future, research using functional magnetic resonance imaging (fRMN), may be used in order to establish, more specifically, the central targets of these peptides, making possible the development of new therapeutic strategies. Keywords: Peptide YY, Glucagon-Like Peptide-1, Appetite and Central Effects