This dissertation is arranged in three parts which address issues concerning death and immortality. These issues all revolve around the temporal limit imposed by death. I have endeavoured to pose some questions which have relevance to a society clutching onto traditional notions of an afterlife despite its headlong thrust into a technologically advanced future where ethical confusions abound. In the first chapter I examine the metaphysics of the soul because postulating an afterlife is the conventional response to death anxiety. I have noticed that many people cling to hope of immortality without having any understanding of the metaphysical architecture of this hope. Consequently, from a philosophical perspective, I contrast arguments on the soul by Plato, Aristotle, Aquinas and Descartes. The second chapter emerges from a fascination with Epicurus's theory of living and, derivatively, of dying. It involves a comparison with (1) Aristotle's distinction between energeia (actuality) and kinesis (movement), and (2) the sybaritic hedonism of the Cyrenaics. Although the theme of this chapter is pleasure, it will be seen that pleasure lies embedded in the living project and is an important component in the drive for survival. In the third chapter I reflect on the meaning of life in conjunction with length of time lived. Here I compare the meaninglessness experienced by Leo Tolstoy (because his life is too short) and the meaninglessness experienced by the fictional character Elena Makropulos (because her life is too long). The Makropulos "case", both a play by Karel Capek and an opera by Leos Janacek, was introduced into the philosophical world by Bernard Williams.

Ames dwarf mice have a spontaneous homozygous Prophet of Pituitary Factor 1 (Prop1) loss-of-function mutation. The Prop1 mutation results in a lack of differentiation of lactotrophs, thyrotrophs, and somatotrophs in the anterior pituitary. Without these endocrine cell types, Ames dwarf mice have essentially no circulating levels of growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin, and exhibit downstream hormonal deficiencies including insulin-like growth factor 1 (IGF-1), 3’,3,5-triiodothyronine (T3), and thyroxine (T4). Ames dwarf mice are exceptionally long-lived (40% to over 60% depending on sex and diet). They are also extremely insulin sensitive, have a delayed incidence of cancer, and have improved energy metabolism. While the extended lifespan and the many characteristics of an extended healthspan have been known for some time in Ames dwarf mice, the revelation that dwarf mice have improved energy metabolism was less than a decade ago. This finding came about at the molecular level (improved efficiency of the electron transport chain) and at the whole-animal level (increased oxygen consumption and decreased respiratory quotient). To date, however, few studies have been directed at furthering our understanding of the possible mechanism(s) by which Ames dwarf mice have altered energy metabolism. The goal of the studies presented in this dissertation is to delineate these mechanisms and to lay the groundwork for future studies that broaden our understanding of the role(s) of energy metabolism in the aging process. Project 1 examines the effects of early-life T4 replacement therapy in Ames dwarf mice. Previous work established that life-long T4 replacement therapy shortens lifespan in Snell dwarf mice (these mice have endocrine deficits that are essentially identical to those of Ames dwarf mice), while short-term replacement therapy during the early postnatal period of Ames dwarf mice does not. We hypothesized that T4 replacement therapy causes transient impairment of energy metabolism, which is why long-term T4 replacement therapy shortens longevity, and short-term replacement therapy does not. Supporting our hypothesis, we showed that short-term T4 replacement therapy during the early postnatal period transiently impaired energy metabolism as measured by indirect calorimetry. Following early-life T4 replacement therapy, we also observed an accelerated rate of sexual development, as well as lasting effects on bone physiology. Project 2 continued our investigation of energy metabolism by examining a highly metabolic tissue: brown adipose tissue (BAT), which is responsible for non-shivering thermogenesis. Our laboratory has already demonstrated functional alterations in visceral adipose tissue of Ames dwarf mice, and given the altered energy metabolism of Ames dwarf mice, we hypothesized that BAT may also be functionally unique compared to their normal littermates. Supporting our hypothesis, we observed alterations in gene expression, relative weight, and histological structure of BAT in Ames dwarf mice. Moreover, surgical removal of the interscapular BAT depot resulted in a unique physiological response, where Ames dwarf mice lost adiposity in their subcutaneous, perirenal, and epididymal white adipose tissue depots, thus contrasting with normal mice that gained adiposity. Project 3 built upon the findings of our second study, where we continued to examine the role of non-shivering thermogenesis and core body temperature in Ames dwarf mice. To further understand the role of non-shivering thermogenesis in glucose homeostasis and energy metabolism, we housed a cohort of Ames dwarf mice and their normal littermates at room temperature (23˚C), and another cohort at thermoneutrality (for mice this is 30˚C). We found that Ames dwarf mice placed at thermoneutrality had impaired glucose homeostasis and energy metabolism. This is an important finding because we and others believe both of these metabolic processes are important factors for longevity. Taken together, these studies indicate that the improved energy metabolism in Ames dwarf mice is dependent upon several factors, including a loss of thyroid hormone signaling and improved non-shivering thermogenesis.

Made available in DSpace on 2014-06-11T19:26:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-28Bitstream added on 2014-06-13T20:34:28Z : No. of bitstreams: 1 vieira_mrs_me_botfca.pdf: 934932 bytes, checksum: 0d4804d6d955e5d2dde939bfc6d6770c (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A produção de flores de corte constitui uma atividade promissora, cuja comercialização exige técnicas de conservação que contribuem em manter a qualidade floral pós-colheita. A giberelina é um regulador vegetal que apresenta grande eficiência no crescimento, na indução de florescimento, na brotação, pode retardar a senescência, entre outros. Assim, o objetivo deste trabalho foi avaliar o efeito de baixas concentrações de ácido giberélico (GA3) aplicado a campo no crescimento da flor e qualidade pós-colheita de crisântemo cv. ‘Faroe’. As plantas foram pulverizadas aos 28 (vinte e oito) dias após o transplantio das mudas e a colheita programada com 95% das lígulas expandidas. Após a colheita, foram medidos os parâmetros: altura e diâmetro da haste, diâmetro da flor, comprimento da lígula, número de flores e tempo de reação (indução ao florescimento). Após a avaliação, as hastes foram armazenadas em câmara fria a temperatura de 10 °C e UR 95% durante 48 horas e levadas à temperatura ambiente. Após o periodo de armazenamento em câmara fria, foram comparadas com as hastes mantidas em temperatura ambiente e submetidas às seguintes análises: avaliação da senescência floral (escala de notas), consumo da solução do recipiente e medida do pH, ambas em intervalos de dois dias. A qualidade das hastes foi acompanhada pelas as análises bioquímicas (protéinas totais, carboidratos totais solúveis, atividade da peroxidase e poliaminas livres) no intervalo de quatro dias durante o tempo de vida de vaso. Apenas uma única aplicação de GA3 não teve interferência nas características fenotípicas em plantas de crisântemo cv ‘Faroe’, pelo menos em baixas concentrações, assim como não promoveram incremento na qualidade pós-colheita das flores. Não foi observado melhoria na qualidade das flores armazenadas... / The production of cut flowers is a promising commercial activity and its business demands conservation techniques that contribute to keep the post-harvested flower quality. Gibberellin is a growth regulator that is very efficient in the growth, flowering induction, budding, senescence delay, etc. Thus, the aim of this paper was to evaluate the effect of low concentrations of gibberellic acid (GA3) applied under field conditions on flower growth and post-harvest quality of chrysanthemums cv. ‘Faroe’. Application was carried out at 28 days after seedling transplanting and harvest was scheduled when 95% of ligulas were expanded. The following parameters were measured after harvest: stem height and diameter, flower diameter, ligula length, number of flowers and reaction time (flowering induction). After evaluation, the stems were stored in a cold chamber at 10° C and relative humidity of 95% for 48 hours and then taken to room temperature. Later they were compared to the stems kept at room temperature and submitted to the following analyses: flower senescence evaluation (score scale), solution consume, pH measurement, both at 2-day intervals. Stem quality was evaluated through biochemical analysis (total proteins, total soluble carbohydrates, peroxidase activity and free polyamines) at four-day intervals during the vase life. A single low concentration GA3 application has not interfered on phenotypic characteristics of chrysanthemum cv. ‘Faroe’ plants neither has improved post-harvested flower quality. There was not quality improvement of flowers stored in cold chamber after stem exposure to room temperature and flower senescence evaluation. In both treatments, stems presented a higher solution consume and pH varied during the vase life. Stems kept at room temperature showed great decreases in total protein content as well as in total soluble carbohydrate content in leaves and flowers of chrysanthemum cv. Faroe. There was an increase ...

Orientador: Marcela Rocha de Oliveira Carrilho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T03:11:48Z (GMT). No. of bitstreams: 1 Malacarne-Zanon_Juliana_M.pdf: 636484 bytes, checksum: 6d6f6fb65dab84312134d942c458dc89 (MD5) Previous issue date: 2005 / Resumo: Este estudo avaliou o comportamento em água de sistemas adesivos com caráter hidrófilo diferentes. No primeiro estudo, a cinética de difusão da água foi avaliada a partir da mensuração da sorção, da solubilidade e do coeficiente de difusão da água em cada adesivo selecionado. Os materiais empregados foram: as resinas adesivas dos sistemas Clearfil SE (SE) e Scotchbond Multiuso (MP), e os adesivos simplificados Single Bond (SB) e Excite (EX). Cinco resinas experimentais com caráter hidrófilo estabelecido em função de seus respectivos parâmetros de solubilidade foram também avaliadas de modo que servissem como referência de materiais mais ou menos hidrófilos. Os materiais foram dispensados em matriz metálica e fotoativados por 40s (650mW/cm2). Para cada material, foram obtidos quinze espécimes em forma de disco (0,8mm x 5,8mm). Estes foram armazenados em câmara dessecante a 37°C até que não houvesse variação de sua massa seca (m1), aferida em balança analítica. Em seguida, dez destes foram armazenados em água destilada, e tiveram suas massas (m2), mensuradas após 1,2,3,4,5,6,7,14 e 28 dias, para avaliação da variação de massa ao longo do tempo. Ao final dos 28 dias, os espécimes foram novamente submetidos ao ciclo de dessecamento, para determinação da massa seca final (m3), e dos valores de sorção e solubilidade. Os cinco espécimes restantes foram também armazenados em água destilada, mas tiveram suas massas ¿úmidas¿ mensuradas em intervalos mais curtos para o cálculo do coeficiente de difusão da água em cada material. A composição e o caráter hidrófilo dos materiais influenciaram o trânsito de fluidos através dos mesmos. Dentre os adesivos comerciais, os sistemas mais hidrófilos (SB e EX) apresentaram valores de sorção, de solubilidade e de coeficiente de difusão da água significativamente maiores que dos adesivos menos hidrófilos (MP e SE) (p<0.05). Comportamento semelhante foi observado com a resina experimental mais hidrófila, R5. Com exceção da R1, todos os adesivos (comerciais e experimentais) apresentaram o maior aumento de massa no primeiro dia de armazenamento em água. Num segundo estudo, foi avaliado o efeito da armazenagem em água na resistência máxima à tração (RMT) dos adesivos comerciais referenciados. Para cada adesivo, foram obtidos 60 (±2) espécimes com área de secção transversal retangular de aproximadamente 1mm2. Estes foram armazenados em câmara dessecante a 37°C por 24 horas. Doze a treze espécimes de cada material foram submetidos ao ensaio de tração a 0,5mm/min tão logo foram removidos da câmara dessecante. Os demais foram armazenados em água destilada a 37°C e testados após 24h, 7 dias, 30 dias ou 180 dias. O armazenamento em água por 24h determinou a redução significativa da RMT de todos os adesivos (p<0,05). A armazenagem prolongada em água promoveu a queda dos valores de RMT apenas para o adesivo EX, após 180 dias (p<0,05). Com base nos resultados, é possível concluir que adesivos mais hidrófilos absorvem mais água num período mais curto de avaliação. A queda mais significativa nos valores de RMT ocorreu após as primeiras 24 horas de armazenamento em água, coincidindo com o período de maior absorção de água / Abstract: This study evaluated the effect of water storage on the kinetics of moieties diffusion and on the ultimate tensile strength of dental adhesives with different degree of hydrophilicity. In the first study, kinetics of moieties diffusion in commercial and experimental adhesives were evaluated using parameters as itswater sorption, solubility and water diffusion coefficient after ageing in distilled water. Four current dental adhesives were employed: the bonding resins of Clearfil SE Bond (SE) and Scotchbond Multi-Purpose (MP) systems, and the simplified ¿one-bottle¿ systems, Single Bond (SB) and Excite (EX). Five experimental resins with hidrophilicity recognizably different were used as reference. Specimen discs were prepared from each material by dispensing the uncured resin into a mould (5.8mm x 0.8mm). The specimens were placed in a desiccator at 37°C until a constant mass was obtained. After desiccation, the cured specimens were stored in distilled water and the kinetic of moieties diffusion was evaluated during the following times: 1,2,3,4,5,6,7,14 and 28 days. Shorter time intervals were used to calculate diffusion coefficient. After the 28 days, water sorption and solubility related to the entire period of storage were determined. Resin composition and hydrophilicity influenced water sorption, solubility and kinetics of moieties diffusion of both the commercial and experimental resins. Between commercial adhesives, the most hydrophilic systems (SB and EX) showed water sorption, solubility and diffusion coefficient values significantly greater than the least hydrophilic materials (SE and MP). The most hydrophilic experimental resin, R5, showed the highest values of water sorption, solubility and diffusion coefficient. Except for resin R1, all materials (commercial and experimental) presented the greatest mass gain at the first day of water storage. In a second study, the effect of water storage on the ultimate tensile strength (TS) of the same commercial was evaluated. I-shaped specimens were prepared by pouring the adhesives mentioned above into a brass mould. The adhesives were light-cured, removed from the mould and stored in a desiccator at 37°C for 24 hours. Afterwards, twelve to thirteen specimens of each adhesive were tested under tension at 0.05 mm/min, while the remaining specimens were stored in distilled water for 24 hours, 7, 30 and 180 days, before testing. In contrast to dry storage, water immersion produced significantly lower values of UTS for all materials (p<0.05), within the first 24 hours of storage. For the adhesives SE, MP and SB no significant changes in the UTS were observed along the whole period of ageing in water. However, a significant reduction in the UTS was detected after 180 days of water storage for the EX system (p<0.05). Based on the results brought about with these two studies, it can be concluded that more hydrophilic dental adhesives absorb more water within a short period of storage. The greatest decrease in UTS occurred after 24 hours of water storage; period in which was also observed the greatest amount of water uptake. Prolonged water storage had a detrimental effect on the UTS of the EX system, one of the most hydrophilic adhesives employed in the study / Mestrado / Materiais Dentarios / Mestre em Materiais Dentários

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A great deal of time, money, and effort can be expended on hiring community college presidents without any assurance that they will remain in their new positions a substantial amount of time. Building on decades of literature reporting the continuing decrease of presidential longevity, this study examined the methods most successful in selecting presidents with relatively greater longevity and what relationship exists between the type of presidential search used and the length of tenure. An original 18-question survey was e-mailed to 904 community college and two-year institution presidents to capture information about both current and previous presidencies. Participants returned 224 valid responses for a response rate of 24.8%. Results of a generalized linear model (GLM) yielded a statistically significant result showing a positive relationship between the variable Q7STDT1(type of presidential searches in current position) and length of tenure of selected candidates (F = 3.41, p = .006).No significant relationship was found between the selection process used in the immediately previous presidential positions and selected candidates’ longevity in those positions. Information from this study can be used to decide what types of selection process should be used and to indicate further topics of inquiry in this area.

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Yes / Living longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic. / A.R.V., M.W., and T.E. were supported by the US Army Research Office (W911NF-19-1-0235). L.S., M.W., and T.E. were supported by the United Mitochondrial Disease Foundation (PI-19-0985). L.S. was also supported by the University of Exeter Jubilee Scholarship. M.C., N.J.S., and T.E. were supported by the UK Space Agency (ST/R005737/1). N.J.S. and T.E. were supported by BBSRC (BB/N015894/1). S.A.V. was supported by NASA (NNX15AL16G). N.J.S. was supported by grants from NASA [NSSC22K0250; NSSC22K0278] and acknowledges the support of the Osteopathic Heritage Foundation through funding for the Osteopathic Heritage Foundation Ralph S. Licklider, D.O., Research Endowment in the Heritage College of Osteopathic Medicine.

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