Dopamine receptors belong to the G protein-coupled receptor (GPCR) superfamily and are classified into two families: D1-like (D1R and D5R) and D2-like (D2R, D3R and D4R), based on their ability to stimulate or inhibit adenylyl cyclase (AC). Classically, GPCRs (including D2R and D3R) are desensitized by the activation of the serine/threonine protein kinase C (PKC) upon phorbol-12-myristate-13-acetate (PMA) treatment. Previous studies demonstrate that while human D5R (hD5R) is also strongly desensitized upon PMA treatment, the human D1R (hD1R) undergo a robust PMA-induced sensitization. The aim of this PhD thesis was to explore how the canonical PKC- or phorbol ester-linked pathway can control the responsiveness of two similar GPCRs like hD1R and hD5R in an opposite fashion. Our data indicate that hD1R sensitization and hD5R desensitization are not mediated by a direct modulation of AC activity by PKC. Using a chimeric approach, we identified the third intracellular loop (IL3) as the key structural determinant controlling in an opposite manner the PMA-mediated regulation of hD1R and hD5R. To delineate the potential PKC phosphorylation sites, a series of mutation of serine (Ser) and threonine (Thr) located into IL3 of hD1R and hD5R were used. No hD1R mutation decreased the PMA-mediated sensitization. This suggests that hD1R phosphorylation is not required for PMA-induced sensitization. In contrast, our results indicate that PMA-mediated hD5R desensitization occurs through a hierarchical phosphorylation of Ser260, Ser261, Ser271 and Ser274. Notably, these hD5R mutants exhibited a PMA-induced sensitization, reminiscent of the PMA-induced hD1R sensitization. Additionally, using short hairpin RNAs (shRNAs), we showed that PKCε is the potentiating PKC while the desensitizing isoform is δ. Overall, our work suggests the presence or absence of specific Ser residues on IL3 of hD1-like receptors dictate if phosphorylation-dependent desensitization (through PKCδ) or phosphorylation-independent potentiation (via PKCε) will occur.

Background: The augmented whole body glucose uptake response to insulin during the postprandial state is described as meal-induced sensitization (MIS). MIS occurs when the presence of food in the upper gastrointestinal tract (GIT) activates two feeding signals (activation of hepatic parasympathetic nerves and elevation of hepatic glutathione level), and causes insulin to release hepatic insulin sensitizing substance (HISS), which stimulates glucose uptake in peripheral tissues. The impairment of HISS release results in the absence of meal-induced insulin sensitization (AMIS), causing progression to a cluster of metabolic, vascular, and cardiac dysfunction, which we refer to as components of the AMIS syndrome. Objectives: The objective of my doctoral research was to study the manipulation of the HISS-pathway, in age- and diet-induced AMIS models, with exercise ± antioxidants. Also, in a separate project I studied the signaling pathways involved with the HISS action in skeletal muscle. Methods: The 7-day voluntary running was used as exercise intervention to manipulate the HISS pathway in healthy and prediabetic rats. The interaction of an antioxidant cocktail, SAMEC (S-adenosylmethionine + vitamin E + vitamin C), with the effects of exercise on postprandial insulin response was studied. Moreover, in the signaling studies the insulin and 5'-adenosine monophosphate activated protein kinase (AMPK) pathways were examined to test their possible involvement with the HISS action in skeletal muscle. Results: Voluntary running-wheel exercise for 7 days increases the postprandial glucose uptake response to insulin in health and in prediabetes through enhancement/restoration of HISS action. Supplementation with SAMEC during 7 days of exercise does not either harm or add benefits to the positive effects of exercise on insulin sensitivity. Finally, the signaling studies indicate that HISS increases the rate of glycogen synthesis in muscle through an insulin/AMPK-independent pathway.

This research uses nonlinear Rayleigh surface waves to characterize stress corrosion cracking (SCC) damage in sensitized 304 Stainless Steel (304 SS). 304 SS is widely used in reactor pressure vessels and fuel pipelines, where a corrosive environment in combination with applied stress due to high internal pressures can cause SCC. SCC poses great risk to these structures as it initiates cracks late in the lifetime and often unexpectedly. The initiated microcracks grow and accumulate very quickly to form macroscopic cracks that lead to material failure. Welds and the nearby heat affected zones (HAZ) in the vessels and pipework are particularly affected by SCC as welding induces sensitization in the material. SCC damage results in microstructural changes such as dislocation movement and microcrack initiation that in the long term lead to reduced structural integrity and material failure. Therefore, the early detection of SCC is crucial to ensure safe operation. It has been shown that the microstructural changes caused by SCC can generate higher harmonic waves when excited harmonically. This research considers different levels of SCC damage induced in samples of sensitized 304 SS by applying stress to a specimen held in a corrosive medium (Sodium Thiosulfate). Nonlinear Rayleigh surface waves are introduced in the material and the fundamental and the second harmonic waves are measured. The nonlinearity parameter that relates the fundamental and the second harmonic amplitudes, is computed to quantify the SCC damage in each sample. The results obtained are used to demonstrate the feasibility of using nonlinear Rayleigh waves to characterize SCC damage.

Darbo tikslas – įvertinti dermatitu sergančių pacientų įsijautrinimą kontaktiniams alergenams ir su juo susijusius veiksnius. Darbo uždaviniai: 1. Nustatyti įsijautrinimo kontaktiniams alergenams dažnumą tarp dermatitu sergančių pacientų. 2. Įvertinti įsijautrinimo kontaktiniams alergenams dažnumo sąsajas su tiriamųjų amžiumi, lytimi ir profesija. 3. Nustatyti įsijautrinimo kontaktiniams alergenams klinikos ypatumus. 4. Įvertinti įsijautrinimo kontaktiniams alergenams sąsajas su atopiniu dermatitu, lėtine (-ėmis) kojos (-ų) opa (-omis) ir kitais veiksniais. Išvados: 1. Kontaktiniams alergenams įsijautrinę pusė dermatitu sergančių pacientų, dažniausiai – metalui nikeliui (17,1 proc.). Iš aromatinių medžiagų dažniausias yra įsijautrinimas Peru balzamui (8 proc.). Į pagrindinį alergenų rinkinį neįtrauktini retai (0,1 proc.) nustatyti alergenai: gumų medžiagos merkaptobenzotiazolas ir N-zopropil-N’-fenil-parafenilendiaminas. 2. Įsijautrinimas kontaktiniams alergenams jaunesniems nei 40 metų dermatitu sergantiems pacientams pasireiškia du kartus dažniau nei vyresniems, o moterims – du kartus dažniau nei vyrams. Žemės ūkio ir miškininkystės darbuotojai kontaktiniams alergenams įsijautrinę tris kartus dažniau nei kiti dirbantieji. Vertinant atskirus alergenus, jaunesni nei 40 metų pacientai dažniau nei vyresni yra įsijautrinę nikeliui, kobaltui ir kvaterniumui-15, o 40 metų ir vyresni – Peru balzamui, kanifolijai, aromatų mišiniui I, lanolinui, seskviterpenlaktonams ir... [toliau žr. visą tekstą] / The aim of the study: To evaluate contact sensitization and its associated factors in patients with dermatitis. The objectives of the study: 1. To determine the frequency of sensitization to contact allergens in patients with dermatitis. 2. To evaluate associations between the frequency of sensitization to contact allergens and age, sex and occupation in patients with dermatitis. 3. To determine clinical features of contact sensitization. 4. To evaluate associations between sensitization to contact allergens and atopic dermatitis, chronic leg ulcers and other factors. CONCLUSIONS 1.Half of the patients with dermatitis were sensitized to contact allergens, most frequently to metal nickel (17.1%). From the fragrances, bal¬sam of Peru was the most frequent contact allergen (8%). Rare allergens that should not be included in the baseline series are the substances present in the composition of rubber – mercaptobenzothiazole and N-isopropyl-N'-phenyl-p-phenylene diamine (IPPD). 2.Patients under 40 years of age are two times more frequently sensitized than the older ones. In women contact allergy is twice as more frequent as in men. Agricultural and forestry workers are sensitized to contact allergens three times as more often as other employees. What regards individual allergens, among patients under 40 years of age sensitization to nickel, cobalt and quaternium-15 is more prevalent than in the older ones. Among patients who are 40 years of age and over contact sensitization to... [to full text]

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The photosensitive molecule adsorption on titanium dioxide (TiO2) forms the so-called “dye sensitized TiO2” system, a typical organic/oxide heterojunction, which is of great interest in catalysis and energy applications, e.g. dye-sensitized solar cell (DSSC). Traditionally, the transition metal complex dyes are the focus of the study. However, as the fast development of the organic semiconductors and invention of new pure organic dyes, it is necessary to expand the research horizon to cover these molecules and concrete the fundamental understanding of their basic properties, especially during sensitization.In this work, we focus on two different photosensitive molecules: phthalocyanines and triphenylamine-based dyes. Phthalocyanines are organic semiconductors with symmetric macro aromatic molecular structures. They possess good photoelectrical properties and good thermal and chemical stability, which make them widely used in the organic electronic industries. Triphenylamine-based dyes are new types of pure organic dyes which deliver high efficiency and reduce the cost of DSSC. They can be nominated as one of the strong candidates to substitute the ruthenium complex dyes in DSSC. The researches were carried out using classic surface science techniques on single crystal substrates and under ultrahigh vacuum condition. The photosensitive molecules were deposited by organic molecular beam deposition. The substrate reconstruction and ordering were checked by low energy electron diffraction. The molecular electronic, geometric structures and charge transfer properties were characterized by photoelectron spectroscopy, near edge X-ray absorption fine structure spectroscopy and resonant photoelectron spectroscopy (RPES). Scanning tunneling microscopy is used to directly image the molecular adsorption.For phthalocyanines, we select MgPc, ZnPc, FePc and TiOPc, which showed a general charge transfer from molecule to the substrate when adsorbed on rutile TiO2(110) surface with 1×1 and 1×2 reconstructions. This charge transfer can be prevented by modifying the TiO2 surface with pyridine derivatives (4-tert-butyl pyridine (4TBP), 2,2’-bipyridine and 4,4’-bipyridine), and furthermore the energy level alignment at the interface is modified by the surface dipole established by the pyridine molecules. Annealing also plays an important role to control the molecular structure and change the electronic structure together with the charge transfer properties, shown by TiOPc film. Special discussions were done for 4TBP for its ability to shift the substrate band bending by healing the oxygen vacancies, which makes it an important additive in the DSSC electrolyte. For the triphenylamine-based dye (TPAC), the systematic deposition enables the characterization of the coverage dependent changes of molecular electronic and geometric structures. The light polarization dependent charge transfer was revealed by RPES. Furthermore, the iodine doped TPAC on TiO2 were investigated to mimic the electrolyte/dye/TiO2 interface in the real DSSC.The whole work of this thesis aims to provide fundamental understanding of the interaction between photosensitive molecules on TiO2 surfaces at molecular level in the monolayer region, e.g. the formation of interfacial states and the coverage dependent atomic and electronic structures, etc. We explored the potential of the application of new dyes and modified of the existing system by identifying their advantage and disadvantage. The results may benefit the fields of dye syntheses, catalysis researches and designs of organic photovoltaic devices. / QC 20111114

Identification of the complement C4d fragment in peritubular capillaries as a specific marker for antibody mediated rejection in renal transplantation revealed the critical role of antibodies in graft survival. In this thesis, I document the design and findings of studies performed to investigate the clinical impact of anti-HLA antibodies present before and/or after transplantation. Over time, the detection techniques for anti-HLA antibodies has evolved from the less sensitive complement-dependent lymphocytotoxicity (CDC) crossmatching (XM) to more sensitive solid phase assays such as Luminex®. Studies have been conducted to compare the predictive value of different antibody detection techniques. The first result chapter presents antibody specificity in positive CDC B-cell crossmatch (BXM), analysed with highly specific Luminex® assays. The study also investigates the predictive value of BXM in the general transplant population. I found that donor-specific anti-HLA antibodies (DSA) are only present in one third of positive BXM and are associated with poor outcomes. The novel finding is that >80% of the DSA detected by BXM are complement-fixing IgG₁ and IgG₃ subclasses. Transplant glomerulopathy (TG) is type of chronic renal graft rejection. The pathogenesis of TG is unclear. In the second result chapter, I report risk factors and involvement of anti-HLA antibodies in the development of TG. This study shows that glomerular rejection, delayed graft function, HLA presensitization and DSA have a univariate effect on TG development. Multivariate analysis revealed that DSA are an independent predictor of TG, after adjustment for other risk factors. I have further investigated the role of BXM in a unique, well-matched, highly sensitized patient group transplanted under the national renal exchange programme. I compared Luminex® antibody analysis with BXM in predicting transplant outcomes. In highly sensitized patients, DSA are found in two thirds of positive BXM. In univariate analyses, BXM is associated with humoral rejection whereas DSA defined by Luminex® are associated with total and all rejection types. The major finding is that, by multivariate analysis, DSA defined by Luminex® are an independent predictor of total and humoral rejection, but BXM are not. These interesting findings are reported in the third result chapter. Studies reported in this thesis define the clinical significance of anti-HLA antibodies in renal transplant outcomes. Method comparison studies provide useful information on antibody specificity and their impact on graft survival. Collectively, a better understanding of alloantibodies associated with graft rejection and limitation of antibody detection methods may facilitate donor selection and choice of immunosuppressants, and consequently improve transplant outcomes. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1379925 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2010

Orientador : Sonia Regina Albano de Lima / Banca : Maria Lucia Senna Machado Pascoal / Banca : Felisberto Sabino da Costa / Resumo: A presente dissertação é o resultado de uma pesquisa-ação realizada no IA-UNESP, pelo aluno Alexandre Cintra Leite Ruger intutulada "A percursão corporal como proposta de sensibilização musical para atores e estudantes de teatro", com a orientação da Profa. Dra. Sonia Regina Albano de Lim. Teve como objetivo refletir e avaliar a prática de ensino do mestrando sob o ponto de vista pedagógico, artístico musical e científico no curso de extensão oferecido para os alunos de primeiro ano do curso de licenciatura em artes cênicas coordenado pela Profa. Dra. Carminda Mesdes André e na preparação musical do grupo teatral Atrás do Grito, com direção de Osvaldo Anzolin, ambos do IA-UNESP. Foi importante para a pesquisa observar se a prática docente desenvolvida pelo mestrando nos cursos realizados seria um meio eficaz para sensibilizar alunos de artes cênica. O trabalho científico justificava-se na ausência quase que completa de um ensino musical sensibilizatório parfa os estudantes da área de cênicas. Os resultados pretendidos com essa prática docente concentrava-se na hipótese de que o trabalho de sensibilização musical propiciaria aos alunos de artes cênicas, um aguçar da percepção musical e rítmica, trazendo-lhes maior desenvoltura corporal e expressividade em cena. A fundamentação teórica da pesquisa estabeleceu-se a partir de uma revisão bibliográfica que se concentrou em três pontos básicos: o corpo e o ensino musical, a compreensão do binômio corpo-mente e o ensino musical nas artes cênicas como meio de desenvolvimento da expressividade e da conscientização corporal. O mestrando flundamentou sua práticac de docência e a pesquisa em alguns ensinamentos de Emmile Jacques-Dalcroz, Carl Orff, Edgard Willens Murray Schafer e no trabalho de percussão corporal desenvolvido pelo grupo Barbatuques. ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This thesis is the result of a research-action carried through in IA-UNESP, by the researcher Alexandre Cintra Leite Ruger called "The Body Percussion proposed as musical sensitization for the actors and theater students", with the orientation of Profa. Dra. Sonia Regina Albano de Lima. The objective is to reflect and to evaluate the way of teaching of the researcher under the pedagogical, artistic-musical and scientific points of views in the extension course offered for the pupils of the firs year of the licentiate cours in scenic arts, coordinated by Profa. Dra. Carminda Mesdes André and in the musical preparation of the theatrical group Atrás do Grito, with Osvaldo Anzolin direction, both of the IA-UNESP. It was important for the research to observe if the teaching developed by the resarcher in the courses would be an efficient way to sensetize pupils of scenic arts. The scientific work was justified by the almost complete absence of a sensitizing musical education for the students of scenic arts. The intended results with this teaching were concentrated in the hypothesis that the work of musical sensitization would propiatiate the pupils of scenic arts, to sharpen the musical and rhytimic perception , briging bigger body nimbleness and expressiveness in scene. The research theoretical grounding was established from a bibliographical revision that concentred in three basic points: the body and musical education, the understanding of the binominal body-mind and musical education in the scenic arts as a mean of development of the expressiveness and the body awareness. The resarcher based his way lof teaching of the resarch on some techiniques of Emmile Jacques-Dalcroze, Carl Orff, Edgard Willens Murray Schafer and tin the work of body developed bye the Gorup Barbatuques. ...(Complet abstract, access undermentioned eletronic adress) / Mestre

Magister Philosophiae - MPhil / This qualitative study was conducted from June to November 2009, using designed questionnaires for sixty three (63) registered students and five (5) HIV program staff .The main reason for this study was to understand the underlying factors for why students may utilize or may not utilize the available HIV services on campus. The willingness of students to express their views was a positive finding in this study. Majority students who answered the questionnaires were quite aware of these HIV services. They also agreed that services provided are good. The study also found out that females utilized these services more than males and majority of students learnt of the HIV services from the HIV programs pamphlets and website thus indicating that the HIV program at UWC is function. However the research study also found out that the though students are aware of these services few utilize them and majority are females thus leaves a question why males do not utilize. / South Africa

abstract: Intermittent social defeat stress produces vulnerability to drugs of abuse, a phenomena known as cross-sensitization, which is proceeded by a corresponding upregulation of ventral tegmental area (VTA) mu-opioid receptors (MORs). Since VTA MORs are implicated in the expression of psychostimulant sensitization, they may also mediate social stress-induced vulnerability to drugs of abuse. Social stress and drugs of abuse increase mesolimbic brain-derived neurotrophic factor (BDNF) signaling with its receptor, tropomyosin-related kinase B (TrkB). These studies examined whether VTA MOR signaling is important for the behavioral and cellular consequences of social stress. First, the function of VTA MORs in the behavioral consequences of intermittent social defeat stress was investigated. Lentivirus-mediated knockdown of VTA MORs prevented social stress-induced cross-sensitization, as well as stress-induced social avoidance and weight gain deficits. Next it was examined whether VTA MOR expression is critical for stress-induced alterations in the mesocorticolimbic circuit. At the time cross-sensitization was known to occur, lentivirus-mediated knockdown of VTA MORs prevented stress-induced increases in VTA BDNF and its receptor, TrkB in the nucleus accumbens (NAc), and attenuated NAc expression of delta FosB. There was no effect of either stress or virus on BDNF expression in the prefrontal cortex. Since social stress-induced upregulation of VTA MORs is necessary for consequences of social stress, next activity dependent changes in AKT, a downstream target of MOR stimulation associated with sensitization to psychostimulant drugs, were investigated. Using fluorescent immunohistochemical double labeling for the active form of AKT (pAKT) and markers of either GABA or dopamine neurons in the VTA, it was determined that social stress significantly increased the expression of pAKT in GABA, but not dopamine neurons, and that this effect was dependent on VTA MOR expression. Moreover, intra-VTA inhibition of pAKT during stress prevented stress-induced weight gain deficits, while acute inhibition of VTA pAKT blocked the expression of cross-sensitization in subjects that had previously exhibited sensitized locomotor activity. Together these results suggest that social stress upregulates MORs on VTA GABA neurons, resulting in AKT phosphorylation, and that increased VTA MOR-pAKT signaling may represent a novel therapeutic target for the intervention of substance abuse disorders. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2015