Although not obvious at first sight, several parallels can be drawn between pregnancy andcancer. Many proliferative, invasive and immune tolerance mechanisms that supportnormal pregnancy are also exploited by malignancies to establish a nutrient supply andevade or edit the immune response of the host. The human placenta, of crucial importancefor pregnancy success, and its main cells, the trophoblast, share several features withmalignant cells such as high cell proliferation rate, lack of cell-contact inhibition andinvasiveness. Both in cancer and in pregnancy, the immune defense mechanisms,potentially threatening the survival of the tumor or the fetus, are progressively blunted oreven turned into tumor- or pregnancy-promoting players. Amongst immune mechanisms that are meant to protect the host from cancer and can be apotential threat to the fetus, the NKG2D receptor-ligand system stands out as the mostpowerful, stress-inducible “danger detector” system that comprises the activating NK cellreceptor NKG2D and its ligands, the MIC (MHC class I Chain-related proteins A and B)and ULBP (UL-16 Binding Proteins) families. It is the major cytotoxic mechanism in thebody promoting surveillance and homeostasis. In the present thesis we investigate theNKG2D receptor-ligand system in human early normal pregnancy and in theleukemia/lymphoma cell lines Jurkat and Raji and ask the questions “How is the NKG2Dreceptor-ligand system functioning in pregnancy and tumor? How is the danger of cytotoxicattack of the fetus avoided? Why is the immunosurveillance function compromised incancer patients?” We developed a method to isolate and culture villous trophoblast from early human normalplacenta and used it to study the NKG2D receptor-ligand system. We discovered that theNKG2D ligand families of molecules MICA/B and ULBP1-5 are constitutively expressedby the syncytiotrophoblast of the chorionic villi. Using immnunoelectron microscopy, westudied the expression of these molecules at the subcellular level and could show for thefirst time that they are preferably expressed on microvesicles in multivesicular bodies(MVB) of the late endosomal compartment and are secreted as exosomes. Exosomes arenanometer sized microvesicles of endosomal origin, produced and secreted by a great7variety of normal and tumor cells. The exosomes are packages of proteins and ribonucleicacids that function as “mail” or “messengers” between cells conveying different biologicalinformation. We isolated and studied exosomes from placental explant cultures. We foundthat they carry NKG2D ligands on their surface and are able to bind and down-regulate thecognate receptor on NK-, CD8+ and <img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Cgamma" /><img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Cdelta" />T cells. The down-regulation selectively causedimpairment of the cytotoxic response of the cells but did not affect their lytic ability asmeasured by perforin content and gene transcription. Thus, the NKG2D ligand-bearingexosomes suppress the cytotoxic activity of the cells in the vicinity of the placenta, leavingtheir cytolytic machinery intact, ready to function when the cognate receptor isrestored/recycled. These findings highlight the role of placental exosomes in the fetalmaternalimmune escape and support the view of placenta as an unique immunomodulatoryorgan. Next, we studied the expression and exosomal release of NKG2D ligands by tumor cellsusing the leukemia cell lines Jurkat and Raji as a tumor model. We found that NKG2Dligand-bearing exosomes with similar immunosuppressive properties as placental exosomesare constitutively secreted by the tumor cells, as a mechanism to blunt the cytotoxicresponse of the immune cells and thus protect themselves from cytotoxic attack by the host.Interestingly, we found that thermal- and oxidative stress up-regulates the exosomesecretion and the amount of exosome-secreted NKG2D ligands. Our results imply thattumor therapies that cause stress-induced damage, such as thermotherapy and stripping ofoxygen supply to the tumor, might have a previously unrecognized side effect causingenhanced exosome production and secretion, which in turn suppresses the natural antitumorimmune response and thus should be taken into account when designing an optimaltherapy of cancer patients. In conclusion, we describe a novel stress-inducible mechanism shared by placenta andtumors as an immune escape strategy. We found that placenta- and tumor-derived NKG2Dligand-bearing exosomes can suppress immune responses to promote the survival and wellbeing of the fetus or the tumor. Our work comprises an important contribution to theelucidation of the NKG2D ligand-receptor system and its mode of operation in the humanbody and opens new perspectives for designing novel therapies for infertility and cancer.

No description available.

No description available.

Composite materials are widely used in temperature fluctuating environments, which make these materials highly prone to cracking. The cracking phenomenon is a result of high thermal stresses that are generated by the mismatch in properties of the composite constituents, particularly the mismatch in the thermal expansion coefficient. The main objective of this study is to understand the micromechanics of such a phenomenon. The problem has been investigated using the finite element method (FEM). The analyses were performed utilizing 3-D prism and axisymmetric models. Hexagonal fiber packing of unidirectional composites was considered. The dimensions of the models were assumed such that the models could provide sufficient information on the behavior near the free surface as well as the interior of fiber composites. Properties of the constituents were considered to be temperature dependent. The elasto-plastic and visco-elastic characteristics of the materials were also included. The transient thermal analysis of the models showed that, for most practical applications, the temperature gradient in the composite constituents has minor effects on the stresses generated. Therefore, several stress analyses were performed assuming a uniformly changing temperature throughout the composite. The elastic analysis of thermal stresses and deformations showed high radial and hoop stress concentrations occurring at the fiber end on the free surface. This is contrary to the shear-lag theorem, which assumes that these stress components are negligible. An overlapping hypothesis, based on the deformation of the fiber and matrix, is proposed to explain such high radial and hoop stresses. Using regular FEM elements, it was concluded that the stresses are singular in nature. The stress singularity was numerically investigated and found to be of the type r -á with á being dependent on the material properties but having a value close to 1/3. The elasto-visco-plastic behavior of composites was also analyzed. Large plastic strains were localized at the fiber end even for a small temperature change. Creep effects that were significant at elevated temperatures brought about some stress relaxation during the manufacturing process. Thermally induced stress concentration in composites can be controlled, to some extent, by changing the geometry of the free surface. The analysis of such effects indicated that reduction of the contact angle between the fiber and the matrix on the fire surface reduced the high radial and hoop stress magnitudes. Also, the influence of covering the free surface of the composite with a thin layer of matrix-like material was studied. The magnitudes of the radial and hoop stress components were substantially reduced. The case when the cover and the composite are made in separate stages (two-stage covering), was also studied. Based on the analysis, effective and practical ways of applying the cover are recommended. To verify the effects of the covering process, experiments were conducted on large-scale laboratory-made composite samples. The samples with the free surface covered with a thin layer of matrix-like material showed no trace of cracking or fiber/matrix debonding even after 1000 thermal cycles. On the other hand, in the samples without cover, exposed to identical thermal cycling, numerous matrix cracks and extensive fiber/matrix debonding were observed.

No description available.

Like all intertidal species, the barnacle Balanus glandula must cope with temperature and desiccation stress during daily low tide exposure. The increase in temperature at low tide leads to both increased metabolic rate and the potential for increased ATP demand. With its additional inhibition of oxygen intake, low tide thus has an energetic cost that is often reflected in an increase in oxygen consumption following resubmersion. As anthropogenically induced global climate change increases air and water temperatures, its cost might increase. B. glandula individuals were exposed to 4‑hour low tides with maximal temperatures of 18, 30, 35, and 38°C, and their oxygen consumption rates and behaviors were recorded for 4 hours upon resubmersion. It was found that aerial respiration could be measured, though aerial rates were only a fraction of aquatic rates. It was further found that relative aquatic oxygen consumption rates were not elevated following low tide for any temperatures. However, B. glandula individuals exposed to 35 and 38°C low tides remained active a significantly greater portion of time through the first and second hours of recovery, respectively. This indicates that a low tide stress effect is evident in B. glandula, but that it manifests not as an increase in the respiration rate when active, but rather as an increase in the overall activity time. Thus, with increasing global temperatures B. glandula will likely have increased energy needs. This might lead to range relocations, a drive to find new energy sources, and/or reallocations of energy budgets.

Previously, at Brunel University, two computer programs had been developed to facilitate the analysis of the diastolic material properties of the human left ventricle. These two computer programs consisted of; a finite element program, "XL1", which ran upon a Cray-1S/1000 and a post-processor and pre-processor, "HEART", which ran upon the Multics computer system. The computer program "HEART" produced the finite element model, which was then solved by "XL 1", and it also allowed for plotting the results in graphical form, The patient data was supplied by the Royal Brompton Hospital in the form of digitised cine-angiographic X-ray data plus pressure readings. The first stage was to transfer the two separate computer programs "HEART" and "XL 1" to the Sun Workstation system. The two programs were then combined to form a single package which can be used for the automated analysis of the patient data. An investigation into the effect that the elastic modulus ratio has upon the deformation of the left ventricle during diastole was performed. It was found that the effect is quite small and that using this parameter to match overall shape deformation would be extremely sensitive to the accuracy of the initial data. The main part of this work was the implementation of active cardiac contraction, by means of a thermal stress analogy, into the finite element program. This allows the systolic part of the cardiac cycle to be analysed. The analysis of the factors that affect cardiac contraction, including the material properties and boundary conditions was performed. This model was also used to investigate the effect that conditions such as ischaemia and the formation of scar tissue have upon the systolic left ventricle. The use of the thermal stressing analogy for cardiac contraction was demonstrated to mirror global and local deformation when applied to a realistic ventricular geometry.

Submitted by Nathália Faria da Silva (nathaliafsilva.ufv@gmail.com) on 2017-07-28T13:57:52Z No. of bitstreams: 1 texto completo.PDF: 1092273 bytes, checksum: 61189e2f9ff1c859ecd3bbb9a9959c9a (MD5) / Made available in DSpace on 2017-07-28T13:57:52Z (GMT). No. of bitstreams: 1 texto completo.PDF: 1092273 bytes, checksum: 61189e2f9ff1c859ecd3bbb9a9959c9a (MD5) Previous issue date: 2002-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Um sistema de medição e controle foi desenvolvido para o estudo de respostas fisiológicas de aves sujeitas a mudanças térmicas como meio de alívio de estresse térmico. O sistema faz o controle automático da temperatura (t a,SP ±0,2 oC) e da umidade relativa do ar (RH SP ±2 %); sendo que a velocidade do ar foi controlada manualmente (V SP ±0,1 m· s -1 ); e contínuo armazenamento das termografias (ex., temperatura superficial, t surf ) e da temperatura corporais (t b ) dos animais. As condições térmicas controladas na zona de ocupação animal (AZO) são atingidas pela operação de um pequeno túnel de vento (V = 0 to 1,5 m· s -1 ) colocado no interior de uma sala ambiental com t a e RH controlados (5,0 m comprimento × 3,5 m largura × 3,0 m altura). Os valores desejados de t a e RH foram alcançados por meio de aquecedores e umidificadores controlados em dois estágios via um módulo de controle e medição programável, e periféricos. Termografias (discernabilidade de 0.06°C) são adquiridas com uma camera infravermelho cuja operação é controlada remotamente por um PC. t b (±0.1°C) é armazenado em uma unidade de telemetria, sem a necessidade de intervenção cirurgica, que também é conectado a um PC. Em adição, um sistema de video tem sido usado para observar e arquivar os comportamentos do animal. A instrumentação desenvolvida foi usada em um experimento para ajustar equações empíricas para descrever as necessidades de molhamento parcial da superfície em galinhas poedeiras (Hy-Line W98, com 34 ± 1 semanas) sujeitas a condições de estresse térmico. A água necessária para limitar o aumento da temperatura superficial das galinhas foi expressada em termos de intervalo de aspersão (SI 10 , min) para uma dosagem constante (10 ml· aspersão -1 ) ou para uma taxa de evaporação (ER, ml.min -1 ) de água aspergida. As exposições térmicas consistiram de uma combinação fatorial de 3 temperaturas de bulbo seco (t db ) (35, 38 e 41 °C) x 2 temperaturas de ponto de orvalho (t dp ) (21,1 e 26,7 °C) x 3 velocidades do ar (V) (0,2, 0,7 e 1,2 m· s -1 ). As condições ambientais foram expressas como 18 combinações de déficit de vapor de pressão do ar (VPD air ) x V. ER foi diretamente proporcional ao produto VPD air · V . As relações podem servir como a base para a otimizar o sistema de resfriamento superficial intermitente para alívio de estresse térmico em galinhas criadas em gaiolas. Ademais, um índice de desconforto térmico (TDI) foi derivado com base nas respostas fisiológicas, temperatura superficial (t surf ) e temperatura corporal (t b ), de galinhas sujeitas a exposições térmicas. Com base no aumento da t b aos 50 min de exposição térmica (Δt b,50 ), um TDI foi relacionado ao VPD air e a V da seguinte forma: TDI = -15.17 + 18.62 (t db ) n – 0.92 · (VPD air · V ) n . Usando TDI, quatro zonas de desconforto térmico (segura, alerta, perigo e fatal) foram definidas para as várias combinações de condições térmicas. Um modelo teórico de transferência de calor e massa em regime transiente também foi proposto para predizer Δt b,50 em função das condições ambientais, das condições fisiológicas das aves e do nível de molhamento (β). O modelo proporciona uma ferramenta conveniente e interativa para determinar Δt b,50 nas galinhas submetidas ou não ao molhamento superficial para t db variando de 35 a 38 °C. / A control and measurement system was developed for studying physiological responses of poultry to thermal challenges and means of thermal stress relief. The system features automatic control of air temperature (t a,SP ±0.2 oC) and relative humidity (RH SP ± 2 %); manual setting of air velocity (V SP ± 0.1 m· s -1 ); and continuous recording of thermographs (i.e., core body temperature (t b ) of the animal. surface temperature, t surf ) and The controlled thermal conditions in the animal-occupied zone (AOZ) are achieved through operation of a small wind tunnel (V = 0 to 1.5 m· s -1 ) inside a t a - and RH-controlled environmental room (5 m L × 3.5 m W × 3.0 m H). Target t a and RH values are achieved by controlling auxiliary heaters and humidifiers in two stages via a programmable measurement and control module and peripherals. Thermographs (0.06°C discernability) are acquired with an infrared (IR) imager whose operation is remotely controlled by a PC. Core body temperature (t b , ±0.1°C) is recorded with a surgery-free telemetric sensing unit that is also interfaced with a PC. In addition, a video monitoring system is used to observe and archive animal behaviors. The instrumentation developed was used in an experiment to establish empirical equations to describe the need of partial surface wetting for cooling laying hens (Hy-Line W-98, 34 ±1 wk old) subjected to a range of thermal stress conditions. The thermal exposures consisted of a factorial combination of 3 dry bulb temperatures (t db ) (35, 38 and 41 °C) × 2 dew point temperatures (t dp ) (21.1 and 26.7 ° C) × 3 air velocities (V) (0.2, 0.7 and 1.2 m· s - ). The environmental conditions were expressed as 18 combinations of air vapor pressure deficit (VPD air ) × V. The water necessary to limit hen surface temperature from rising was expressed in terms of sprinkle interval (SI 10 , min) for a constant spray dosage (10 ml· spray -1 ) or evaporation rate (ER, ml· min -1 ) of the sprayed water. ER was directly proportional to VPD air · V . The relationships may serve as the basis for optimizing an intermittent partial surface cooling system for thermal stress relief of caged layers. Also from the study, a thermal discomfort index (TDI) was derived based on physiological responses, surface temperature (t surf ) and core body temperature (t b ) of the control (non-cooled) hens. Based on t b rise after 50 min of thermal exposure (Δt b,50 ), TDI related to VPD air and V as: TDI = -15.17 + 18.62 (t db ) n – 0.92· (VPD air · was V ) n . Using TDI, four zones of thermal discomfort (safe, alert, danger, and fatal) were defined for various combinations of thermal conditions. Furthermore, theoretical transient heat and mass transfer model was proposed to predict Δt b,50 as a function of environmental conditions, physiological responses of the hens and surface wetness level (β). The model provides a convenient, interactive tool for determining Δt b,50 on wetted and non-wetted hens for t db ranging from 35 to 38 °C.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Poucos organismos são aptos a suportar o alto estresse provocado pelas variações de temperatura e alta dessecação na faixa superior da região entremarés de costões rochosos, sendo um deles o cirripédio Chthamalus. Apesar da sua resistência, vivem constantemente próximos ao seu limite de tolerância fisiológica, o que pode influenciar suas populações. O objetivo deste estudo foi caracterizar as flutuações das populações de Chthamalus spp. na faixa superior da região entremarés em quatro costões rochosos na Baía da Ilha Grande entre 2002 e 2012, relacionando estas variações com os fatores ambientais temperatura do ar, temperatura superficial marinha e precipitação, verificando o potencial destes organismos como indicadores de variações climáticas. Para isso foram investigadas a temperatura do ar e precipitação a partir de dados da estação meteorológica de Angra dos Reis e temperatura da superfície do mar a partir de imagens de satélite (MODIS/AQUA), além das porcentagens de cobertura de Chthamalus spp. a partir de amostragens sazonais. Em geral o estudo indica que as populações foram influenciadas pelas variáveis biológicas recrutamento e competição intraespecífica. Foram verificadas grandes diferenças entre as populações nos costões rochosos estudados. A estação C1, apresentou altas coberturas de cirripédios jovens e adultos ao longo de praticamente todo o período de estudo. Na estação C2 ocorreram as maiores variações, enquanto nas estações C3 e C4 ocorreram coberturas menores e variações menos proeminentes. Estas diferenças provavelmente estiveram ligadas às características físicas de cada costão rochoso. Os anos de 2003 e 2010 foram caracterizados como de altas temperaturas (temperaturas do mar e do ar) quando comparados com os demais anos de estudo. Estes anos foram ainda caracterizados pela ocorrência do fenômeno El Niño, com altas anomalias térmicas, o que indica que este fenômeno climático influenciou as temperaturas da região. Nestes mesmos anos as coberturas de Chthamalus spp. foram relativamente baixas, o que indica que o estresse térmico afetou as populações deste cirripédio. Pode-se inferir através deste estudo que as populações de Chthamalus spp. sofrem influência direta dos fatores ambientais investigados, sendo com isso um potencial indicador de mudanças climáticas. / Few organisms are able to withstand high stress caused by temperature variations and high desiccation in the upper limit of the intertidal zone of rocky shores, as the barnacle Chthamalus. Despite their resistance, these organisms constantly live near their physiological tolerance limit, which influence their populations. The aim of this study was to characterize the fluctuations of Chthamalus spp. populations in the upper zone of four intertidal rocky shores in Ilha Grande Bay between 2002 and 2012, relating these changes to the environmental factors of air temperature, sea surface temperature and precipitation, verifying the potential of these organisms as indicators of climatic variations. For that the air temperature and precipitation were investigated using data from the meteorological station of Angra dos Reis and sea surface temperature from satellite images (MODIS/AQUA), in addition to the coverage percentages of Chthamalus spp. from seasonal samplings. In general the study indicates that populations were influenced by the biological variables recruitment and intraspecific competition. Large differences were found between the fluctuations on the rocky shores studied. The station C1, showed high coverage of barnacles and young adults throughout almost the entire period of study. At the station C2 occurred the largest variations, while in C3 and C4 stations have ocurred the smaller coverages and less prominent variations. These differences were probably related to the physical characteristics of each rocky shore. The years 2003 and 2010 were characterized as high temperature yeras (temperatures of sea and air) when compared to the other years of study. These years were also characterized by the occurrence of El Niño, with high thermal anomalies, indicating that this climatic phenomenon influenced the temperatures in the region. In these same years the coverage of Chthamalus spp. were relatively low, indicating that heat stress affected the populations of this cirripédio. Is possible infer from this study that the cirripédio Chthamalus spp. is under direct influence of environmental factors investigated, being, with that, a potential indicator of climate change.

Made available in DSpace on 2014-06-11T19:33:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-13Bitstream added on 2014-06-13T18:45:28Z : No. of bitstreams: 1 carvalho_fb_dr_botfmvz.pdf: 1116788 bytes, checksum: 71d1b92cc308a1f5ab29263d440e0716 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Universidade Estadual Paulista (UNESP) / O experimento teve por objetivo determinar o efeito da temperatura ambiente e da idade da ave sobre o valor energético do milho. Foram utilizados 288 pintos de corte da linhagem Cobb distribuídos em delineamento experimental inteiramente casualizado com esquema de parcelas subdivididas no tempo, sendo as três temperaturas de criação (fria: 18ºC; termoneutra: 25ºC e quente: 33ºC) as parcelas e as três idades de avaliação (inicial: 11 a 14; crescimento: 25 a 28 e final: 39 a 42 dias) as subparcelas, com seis repetições de seis aves cada. A ração basal para o experimento foi formulada à base de milho e farelo de soja e a dieta teste obtida com substituição de parte da ração basal pelo alimento teste: 40% do milho + 60% da ração basal. Foram calculados os coeficientes de metabolizabilidade aparente e verdadeira da matéria seca, do nitrogênio, do extrato etéreo da dieta teste e os valores de energia metabolizável aparente e verdadeira (EMA e EMV); e corrigidas pelo balanço de nitrogênio do milho (EMAn e EMVn), em kcal/kg, com base na matéria natural. Foram encontrados valores médios de EMAn do milho, para aves criadas em temperatura fria, termoneutra e quente de 3322, 3279 e 3233 kcal/kg, respectivamente, e para as fases de criação inicial, crescimento e final de 3215, 3218 e 3400 kcal/kg, respectivamente. Os valores de energia metabolizável do milho, os balanços e os coeficientes de metabolizabilidade dos nutrientes da dieta teste aumentam com a idade do frango de corte, porém as energias metabolizáveis do milho não foram afetadas pela temperatura ambiente. Os balanços e os coeficientes de metabolizabilidade dos nutrientes da dieta teste foram reduzidos em estresse por calor para aves na fase de crescimento e final / The aim of this study was to evaluate the effects of environmental temperature and age of broilers chicks on energy value of corn. Two hundred and eighty-eight Cobb chicks were distributed in a complete randomized design with a splitplot arrangement with six replication of six chicks each, the main plots were the three temperatures (cold: 18°C; thermoneutral: 25°C and hot: 33°C) and age was the secondary plot (initial: 11 to 14, growing: 25 to 28 and final: 39 to 42 days). The basal diet was based on corn and soybean meal. The test diet was produced by replacing the basal diet for test food: 40% of corn + 60% of the basal diet. The coefficient of apparent and true metabolizability of dry matter, nitrogen, ether extract of the test diet and apparent and true metabolizable energies (AME and TME) of corn were calculated and energy values were corrected for nitrogen balance (AMEn and TMEn) of corn, in kcal/kg, as fed basis. The mean values of AMEn observed for broilers chicks in cold, thermoneutral and hot temperature of 3322, 3279 and 3233 kcal/kg, respectively, and the phases initial, growing and final of 3215, 3218 and 3400 kcal/ kg, respectively. The metabolizable energy values of corn, the balance and coefficients of metabolizability of the nutrients of the test diet increased with the age of broiler; however the metabolizable energies were not affected by environmental temperature. The balance and coefficients of metabolizability of the nutrients of the test diet were decreased by heat stress for broiler in the growing and final phase