Orientador: João Antonio Galbiatti / Banca: Carlos Eduardo Angeli Furlani / Banca: Emerson Fachini / Resumo: O desenvolvimento dos centros urbanos tem conduzido a um aumento desordenado na geração de resíduos e conseqüente poluição ambiental. Tendo em vista o potencial agronômico dos resíduos gerados pelas cidades, o presente trabalho teve por objetivo verificar a influência do composto de lixo (CL), composto de poda de árvore (CP) e substrato comercial (SC), associados a diferentes lâminas de irrigação no desenvolvimento de porta-enxerto (limão-cravo) de citros. O delineamento experimental adotado foi em blocos casualizados em um esquema fatorial 6x3, sendo seis diferentes combinações de substratos: S1 - 100% SC; S2 - 80% SC + 20% CP; S3 - 60% SC + 30% CP + 10% CL; S4 - 40% SC + 40% CP + 20% CL; S5 - 20% SC + 50% CP + 30% CL e S6 - 60% CP + 40% CL associados a três lâminas de irrigação: 50% (I1), 100% (I2) e 150% (I3) da evapotranspiração diária medida pelo atmômetro. Os parâmetros avaliados das plantas foram: altura, número de folhas, diâmetro do caule, matéria fresca aérea e matéria seca aérea. Os resultados permitiram concluir que a irrigação abaixo da evaporação medida pelo atmômetro causaram efeito negativo no desenvolvimento das plantas e que a reposição de água com 150% (I3) foi a que favoreceu o desenvolvimento. Os substratos S2, o qual se utilizou 80% de SC associado à 20% CP foi os que proporcionou melhor desenvolvimento dos porta-enxertos. Os substratos com porcentagem de composto de lixo superior a 30% mostraram-se inadequados para o desenvolvimento dos porta-enxertos / Abstract: The development of urban centers has led to an inordinate increase in the generation of waste and consequent environmental pollution. Considering the agronomic potential of the waste generated by cities, the present work objective was to check the influence of garbage compound (GC), pruning of tree (PT) and commercial substrate (CS), associated to different irrigation blades in the rootstocks (Rangpur Lime) citros development. The experimental delineation adopted was in random blocks in a fatorial scheme 6x3, being six different substrates combinations: S1 - 100% CS; S2 - 80% CS + 20% PT; S3 - 60% CS + 30% PT + 10% GC; S4 - 40% CS + 40% PT + 20% GC; S5 - 20% CS + 50% PT + 30% GC e S6 - 60% PT + 40% GC associated to different irrigation blades: 50% (I1), 100% (I2) e 150% (I3) of the daily evapotranspiration measured by the atmometer. The evaluated plants parameters were: height, leaves number, stem diameter, fresh matter and dry matter of the air part. The results allowed to conclude that the irrigation below the evaporation measured by the atmometer caused negative effect in the plants development and the water replacement with 150 % (I3) was the one that favored the development. The substrates S2, which is used 80% of SC associated with 20% CP was that the enhanced growth of the rootstocks. The substrates with garbage compound percentage superior to 30 % appeared unsuitable for the rootstocks development / Mestre

nÃo hà / Oxaliplatina (OXL) à a 3 geraÃÃo de agentes platinos com amplo espectro de atividade antitumoral. Exibe potente atividade citotÃxica, incluindo cÃncer colorretal, ovariano e pulmonar. Dentre os efeitos tÃxicos estÃo: laringoespasmo, nÃuseas, vÃmitos, fadiga e neuropatia perifÃrica, foco desse trabalho. Essa pesquisa objetivou desenvolver um modelo experimental para estudo da neuropatia sensitiva perifÃrica induzida por OXL em camundongos que sÃo animais geneticamente mais semelhantes ao ser humano, econÃmicos e dado a existÃncia de espÃcies diferentes para vÃrios fatores. O estudo foi aprovado pelo Comità de Ãtica em Pesquisa Animal da UFC (protocolo n 70/07). Camundongos Swiss machos (20-40g) foram tratados com OXL (1-4 mg/kg, EV) por 4 semanas paralelamente aos testes neuropÃticos utilizados para avaliar o desenvolvimento da neuropatia sensitiva e Rota Rod para verificar comprometimento motor. A hiperalgesia e alodÃnia tÃrmica foram avaliadas pelo teste de imersÃo da cauda (TIC) em Ãgua fria (4 ou 10ÂC) e em Ãgua aquecida (46 ou 42ÂC). O teste de hiperalgesia e alodÃnia mecÃnico (HPM; Von Frey) consistiu na estimulaÃÃo das patas traseiras com um sensor de forÃa (g) atà a sua retirada por um movimento de âflinchâ. Foi ainda verificado a aÃÃo analgÃsica da carbamezepina (CZP), oxcarbazepina (OZP), gabapentina (GABAP) e indometacina (INDO) no TIC Ãgua fria. Foi realizado a imunohistoquÃmica das patas traseiras dos animais em 24h e de 7 a 28 dias. Como resultados observou-se que no HPM houve uma diminuiÃÃo significativa (p<0,001) no limiar nociceptivo a partir do 14 dia atingindo o mÃximo na dose de 2mg/kg comparado ao grupo controle. No TIC 4ÂC houve uma diminuiÃÃo significativa (p<0,05) no limiar nociceptivo no 56 dia, no TIC alodÃnia pelo frio (10ÂC) foi observado uma diminuiÃÃo significativa (p<0,01) no limiar nociceptivo tambÃm no 56 dia, no TIC alodÃnia pelo quente (42ÂC) foi observado uma diminuiÃÃo significativa (p<0,05) no limiar nociceptivo a partir do 35 dia. Esses testes atingiram o mÃximo na dose de 1mg/kg comparados com o grupo controle e no TIC 46ÂC foi observado uma diminuiÃÃo significativa (p<0,01) no limiar nociceptivo a partir do 49 dia atingindo o mÃximo na dose de 1 e de 4mg/kg comparado ao grupo controle. No teste Rota Rod nenhuma variaÃÃo significativa foi observada em nenhum dos grupos, indicando a ausÃncia de comprometimento motor. O tratamento com CZP (0,3-30mg/kg), OZP (0,3-100mg/kg) e GABAP (6-54mg/kg) aumentou o limiar nociceptivo, indicando efeito analgÃsico e INDO (1-4mg/kg) nÃo demonstrou atividade analgÃsica nesse modelo. Na anÃlise da imunohistoquÃmica ficou comprovado que existe a participaÃÃo provÃvel de SP, CGRP e NMDA perifÃricos e nitrotirosina. Portanto, o uso de camundongos e do diferente mÃtodo de administraÃÃo da OXL (EV) pode ser utilizado em modelos futuros viabilizando o uso do fÃrmaco para tratamento do cÃncer, principalmente o colorretal, com todo o esquema terapÃutico, sem que a NSP interfira nas atividades de vida do paciente tratado. / Oxaliplatin (OXL) is a third-generation platinum-based chemotherapy with broad spectrum of anti-tumoral activity. Exhibt potent cytotoxic activity including against cancer colorectal, ovarian and lung cancer. Among the toxic effects are: laryngospasm, nauseas, vomiting, fatigue and peripheral neuropathy, focus of that work. That research planned to develop an experimental model for study of the peripheral neuropathy induced by OXL in mice that are animal genetically more similar to the human, economic and given the knockout species existence for several factors. The study was approved by the Committee of Ethics in Animal Research of the UFC (protocol n 70/07). Mice Swiss male (20-40g) were treated with OXL (1-4 mg/kg, EV) for 4 weeks in parallel to the neurophatic tests utilized for evaluate the development of the peripheral neuropathy and Route Rod for verify some motor compromise. To mechanical hyperalgesia and allodynia thermal were evaluated by the test of immersion of the tail (TIC) in cold water (4 or 10ÂC) and in water heated (46 or 42ÂC). The test of hyperalgesia and allodynia (HPM; Von Frey) consisted of the stimulation of the rear paws with a sensor of force (g) up to his retreat by a movement of "flinch". It was still verified the analgesic action of the carbamezepine (CZP), oxcarbazepine (OZP), gabapentin (GABAP) and indomethacin (INDO) in the TIC cold water. It was carried out to immunohistochemical of the hands paws of the animals in 24h and of 7 to 28 days. The results shows that in the HPM had a significant reduction (p<0,001) in the nociceptive threshold from the 14 day reaching the maximum one in the dose of 2mg/kg compared to the control group. In the TIC 4ÂC had a significant reduction (p<0,05) in the nociceptive threshold in the 56 day, in the TIC allodynia by the cold one (10ÂC) was observed a significant reduction (p<0,01) in the nociceptive threshold also in the 56 day, in the TIC allodynia by the hot one (42ÂC) was observed a significant reduction (p<0,05) in the nociceptive threshold from the 35 day. Those tests reached the maximum one in the dose of 1mg/kg compared with the control group and in the TIC 46ÂC was observed a significant reduction (p<0,01) in the nociceptive threshold from the 49 day reaching the maximum one in the doses of 1 and 4mg/kg compared to the control group. In the test Route Rod no significant variation was observed in no of the groups, indicating the absence of motor compromise. The handling with CZP (0,3-30mg/kg), OZP (0,3-100mg/kg) and GABAP (6-54mg/kg) increased the nociceptive threshold, indicating analgesic effect and INDO (1-4mg/kg) did not show analgesic activity in that model. In the analysis of the immunohistochemical was verified that exists the probable participation of SP, CGRP and NMDA peripheral and nitrotyrosine. Therefore, the use of mice and of the different approach of administration of the OXL (EV) can be utilized in future models making feasible the use of the drug for handling of the cancer, mainly the colorectal, with all the therapeutic plan without that to NSP interfere in the activities of the treated patient.

The III-V semiconductor compounds (i.e. In Ga As x 1-x , 1 x x InAs Sb - , In Ga Sb x 1-x and Al Ga As x 1-x ) have been studied using room temperature Raman spectroscopy. X-ray diffraction has been used as a complementary characterization technique. In this study all the III-V semiconductor compounds were grown by metal organic chemical vapour deposition (MOCVD) on GaAs and GaSb substrates. The layers were studied with respect to composition, strain variation and critical thickness. Raman spectroscopy has been employed to assess the composition dependence of optical phonons in the layers. The alloy composition was varied, while the thickness was kept constant in order to investigate compositional effects. A significant frequency shift of the phonon modes were observed as the composition changed. The composition dependence of the phonon frequencies were described by linear and polynomial expressions. The results of this study were compared with previous Raman and infrared work on III-V semiconductor compounds. Strain relaxation in InGaAs and InGaSb has been investigated by Raman and X-ray diffraction. Measurements were performed on several series of layers. For each series, the thickness was varied, while keeping the composition constant. For a given composition, the layer thicknesses were such that some layers should be fully strained, some partially relaxed and some fully relaxed. The Raman peak shifts and XRD confirm that a layer grows up to the critical thickness and then releases the strain as the thickness increases. Critical layer thickness values measured in this study were compared with published data, in which various techniques had been used to estimate the critical thickness.

A collection of poems.

This study aimed to examine how variable exposure to language statistical patterns affects reading behaviour, specifically, eye-movements during reading. The statistical patterns of language affect how individuals store, produce and comprehend language. When reading, individuals with greater linguistic proficiency typically have been shown to rely less on language statistical information compared to less proficient readers. Based on the Lexical Quality Hypothesis, however, it was hypothesized that spelling bias, a print-specific probabilistic cue, may only be utilized for representations with sufficient strengths of representation - through increased exposure to print in individuals, or through higher frequency of occurrence for individual words, since these individuals, and these words, would be expected to have representations of high quality in the reader’s mental lexicon. Undergraduate students with varying amounts of reading experience were presented with sentences containing English noun-noun compound words that varied in spelling bias, i.e. the probability of occurring in text either as spaced (window sill) or concatenated (windowsill). Linear mixed effect multiple regression models were fitted to the eye-movement data and demonstrated that compound words presented in their more supported format - i.e. the format with the highest bias, were read faster, but that this effect was modulated by reading experience, as measured by a test of exposure to print, as well as by word frequency. Only individuals with the most reading experience, and words with the highest frequencies benefited from this facilitatory effect of bias. This distributional property can thus be used during reading, but only when individuals' lexical representations are of sufficiently high quality. The results of this study thus suggest that future research considering the relationship between linguistic properties and reading must consider individual differences in reading skill and exposure. / Thesis / Master of Science (MSc)

Background: Conventional chemotherapeutics target bulk tumour cells and generally leave cancer stem cell (CSC) populations unaffected. Recent literature characterized the presence and the role of CSC in several types of solid tumors, including colorectal cancer. Colorectal CSCs (CCSCs) display enhanced WNT/β-catenin pathway activity, sustaining self-renewal and tumor-initiating capacity. Thus, CCSCs are crucial for tumour recurrence and metastasis. As one of the main contributors to sustained self-renewal activity in CCSCs, enhanced formation of β-catenin/CBP complex is fostering transactivation of canonical WNT target genes such as c-myc. However, maintenance of healthy intestinal stem cells also dependents on the canonical WNT pathway. Thus, selective targeting CCSCs while sparring normal intestinal cells is still a significant challenge. Interestingly, Sam68 is a key mediator of the interaction between β-catenin and CBP. It has been reported as a “druggable” target to selectively disrupt β-catenin/CBP in CSCs. Indeed, CWP232228 successfully targets CSCs in AML by facilitating Sam68/CBP complex formation, and consequently lowering the abundance of β-catenin/CBP complexes. CWP232228 was clinically tested on multiple human cancers. Unfortunately, such clinical trials were halted due to unknown causes, and limited information was released on clinical safety and benefits. Consequently, developing more potent pharmacological modulators of Sam68/CBP complex formation is still highly relevant to eradicate CCSCs. Here we describe the discovery and characterization of a new CWP analog, known as YB-0158, which displays enhanced potency and neoplastic selectivity against CCSC. Methods and Results: Following the confirmation that ICG/CWP class of compounds bind to Sam68 in CSCs, I used in silico docking methods to screen for CWP analogs having high predicted affinity for Sam68 Cterminal proline-rich domain. Using high content imaging techniques, I confirmed our top candidate (YB-0158) as more potent vs. CWP parent molecule to compromise cell growth, to induce loss of pluripotency, and to increase Sam68 nuclear localization in a surrogate model of human CSCs. YB-0158 also displayed enhanced selective toxicity in colorectal cancer models vs. normal intestinal epithelium progenitor cells. Moreover, I confirmed that YB-0158 exert negative impact on cancer cell growth by inducing apoptosis and reducing proliferation. Lentiviral-based knockdowns explicitly displayed decrease in drug effectivity in the absence of Sam68, reinforcing the essential role of Sam68 mediating ICG-001/CWP response in CSCs. I demonstrated that Sam68 expression is enriched in tumor-initiating cell fractions derived from primary colorectal tumor tissues vs. bulk heterogeneous tumor organoids. Therefore, YB-0158 showed striking efficacy at supressing tumor-initiation activity in a patient-based serial organoid formation assay. Finally, YB-0158 eradicated CSCs activity in vivo as demonstrated by a syngeneic mouse-to-mouse serial transplantation assay. Conclusion: Overall, YB-0158 is a novel analog of CWP232228 with superior potency to target CCSCs activity through facilitation of Sam68 nuclear localization, thus reducing the interaction frequency between CBP and β-catenin.

<p>The C-O single bond is found in numerous functional motifs including carboxylic acids,</p> <p>alcohols, and ethers. These compounds represent ideal precursors towards C-X (X = C, H, or heteroatom) bond formation due to their inherent stability and abundance in nature. As such, synthetic chemists continue to develop new technologies for the transformation of these precursors into biologically useful targets such as amides and amines. However, due to the stability of the C-O single bond, accessing such targets remains a consistent challenge. The activation of the carboxylic acids towards peptide synthesis has been facilitated through various coupling agents, including organoboron and transition metal catalysts. However, coupling agents can generate stochiometric, difficult-to-remove, toxic waste by-products.</p> <p>Organoboron/transition metal catalyzed condensations offer a more atom economical approach but suffer from varying degrees of optical erosion and poor sustainability. Phosphonium-based deoxyaminative technologies provide access to amines from alcohols via a phosphorus oxygen double bond formation driving force, but possesses a narrow nucleophilic nitrogen source scope, and poor atom economy. Transition metal/enzyme catalyzed “hydrogen borrowings” represent atom economical deoxyaminative alternatives. Still, their respective use of costly metals, and multiple enzymatic cascade steps severely limit the sustainability and scope of such protocols.</p> <p>An ambient deoxyamidation of carboxylic acids and deoxyamination of alcohols was</p> <p>developed through the use of N-haloimides activated by triphenylphosphine. Such</p> <p>technologies were found to possess broad functional tolerance and formed C-N bonds via a</p> <p>coupling to free amines, and the direct installment of the imide motif. Mechanistic experiments suggest that such transformations take place via the in situ generation of two separate phosphonium reactive species. </p>

<p> An investigation of flabelliformine, an alkaloid obtained from Lycopodium flabelliforme, led to the establishment of its structure. </p> <p> A study of the mass spectra of annotine (a minor alkaloid present in Lycopodium annotinum) and several of its derivatives in combination with degradative work gave support to a total structure proposed previously for the alkaloid.</p> <p> A synthetic approach to the Lycopodium alkaloids was considered. 1-Carbomethoxy-3-methyl-7-methoxybicyclo [3.3.1] non-3-en-9-one, a compound which appeared suitable as an intermediate in the synthesis, was prepared in low yield. The difficulty encountered in the purification of this compound, coupled with the low yield in which it was obtained, indicated the impracticality of this approach to a total synthesis of a Lycopodium alkaloid.</p> / Thesis / Doctor of Philosophy (PhD)

<p> A brief review of the rhenium-chlorine system is presented and a method to determine rhenium:chlorine atom ratios by neutron activation analysis is described. An infrared cell which is useful for highly re-active vapours at temperatures up to 400°C is also described. The compound claimed to be rhenium hexachloride is shown to be rhenium oxytetrachloride and a reliable preparation of β-rhenium tetrachloride is discovered. The hexachlororhenate(V)ion and several complexes containing rhenium(V), rhenium(VI) and rhenium(VII) are prepared. Chemical and physical evidence is used to predict structures of some of the above compounds.</p> / Thesis / Doctor of Philosophy (PhD)

<p> In six conditioned suppression experiments with rats, two conditioned stimuli (CSs) were individually trained and then tested as a compound. In one set of experiments, the suppressing effect of the compound was greater than that of either CS presented alone. This result is referred to as compound summation. In a second set of experiments, the suppressing effect of the compound was less than that of the "stronger" suppressing individual CS. This result is referred to as compound attenuation. The combination of summation and attenuation makes it possible to determine whether CSs with unknown properties are weakly excitatory (i.e., weak suppressors) or inhibitory (i.e., conditioned characteristics that are opposite the excitatory suppressing effect). If an unknown CS is tested in compound with a second CS known to be excitatory, summation indicates that the unknown stimulus is excitatory, while attenuation indicates that the unknown stimulus is inhibitory. In a final set of experiments, this compound test procedure was used to examine extinction and differential conditioning as inhibitory training procedures. Extensive extinction of a previously trained CS, even far beyond the point at which suppression vanished, was found to be an ineffective inhibitory training procedure. Rather, compound tests showed that the stimulus retained excitatory properties. Differential conditioning was found to be a very effective inhibitory training procedure, regardless of whether presentations of a previously trained CS and shock, shook alone, or the previously trained CS - alone accompanied the unreinforced CS undergoing inhibitory conditioning. These findings are discussed in terms of current theories of conditioning and unresolved issues surrounding the acquisition and maintenance of inhibitory properties.</p> / Thesis / Doctor of Philosophy (PhD)