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Thesis submitted in fulfilment of the requirements for the degree of Magister Technologiae: Agriculture in the Faculty of Applied Sciences at the Cape Peninsula University of Technology / Conjugated linoleic acid (CLA), a fatty acid (FA) present in the meat and milk of ruminant animals, is considered a functional nutrient for humans. The interest in CLA is attributed to its many health benefits, such as having anti-carcinogenic, anti-atherogenic, anti-diabetic and anti-adipogenic effects. Dairy products are a rich natural source of CLA, and preliminary research indicates that the levels in milk can vary based on cattle breed and feeding system. The Fleckvieh is a popular dual-purpose breed recently introduced to the Western Cape. It is used in crossbreeding programs with Holstein and Jersey herds to increase fertility and beef production. Holstein and Jersey cattle are the two most common South African dairy breeds, but little information is available on the effect of crossbreeding on FA content and CLA levels in the milk. The primary objective of this study was to compare milk FA composition and CLA content of these two dairy breeds and their respective Fleckvieh crosses. A second objective was to investigate the effect of lactation stage on CLA levels. Jersey (J) and Fleckvieh x Jersey (F×J) cows were kept in a pasture-based system (PBS) for the duration of the study. Holstein (H) and Fleckvieh x Holstein (F×H) cows were housed in a feedlot system and fed a total mixed ration (TMR) for the duration of the study. The FA and CLA content of feeds from these two feeding systems were also analysed and compared. All cows used in the study were housed at the Elsenburg Research Farm of the Western Cape Department of Agriculture. Milk samples were collected every 35 days from the cows in each feeding group, starting 10 days after calving. Samples were kept in a freezer at -20 °C until laboratory analyses. The total number of milk samples collected was 1044. The milk FA composition and CLA in particular were determined by gas chromatography. Differences between groups were statistically analysed by two-way repeated measures of analysis of variance (ANOVA). Results show that milk CLA levels are higher in Fleckvieh-crossbred cows when compared to purebred cows. The higher CLA content of milk from Fleckvieh crossbred cows demonstrates the feasibility of using Fleckvieh bulls in South African crossbreeding programs, and are also an indication that genetic selection for increased CLA content is possible. The analysis of lactation stage showed that milk CLA is higher during late lactation. A comparison of feed samples from the two feeding systems revealed that pasture feeding resulted in higher omega-3 FA in milk. Key words: Conjugated linoleic acid, milk fatty acids profile, diet, breed, health benefits, Fleckvieh, Holstein, Jersey, diet, pasture based system, total mixed ration system,

A proposta geral do presente projeto consistiu na avaliação do desempenho, características de carcaça, bem como possíveis efeitos adversos, em frangos de corte alimentados com dietas contendo níveis crescentes de glicerina, resultante do processo de obtenção do biodiesel. Foram criados 1575 frangos de corte machos da linhagem comercial Cobb 500. Os pintos de um dia foram pesados e alocados de acordo com o peso médio em grupos de 45 aves distribuídas em 35 boxes. O delineamento experimental utilizado foi inteiramente casualizado, com cinco tratamentos (0; 2,5; 5; 7,5 e 10% de inclusão de glicerina bruta) e sete repetições. As dietas foram isonutritivas baseadas em milho, farelo de soja e óleo de soja. Em laboratório foi avaliado a concentração de glicerol, sódio, fósforo, potássio e metanol da glicerina bruta para correção na formulação das rações. Foi considerado o valor energético de 4100 kcal EMAn/kg para o glicerol puro. As variáveis de desempenho (peso vivo, ganho de peso, consumo de ração, conversão alimentar e viabilidade) foram monitoradas semanalmente e, aos 43 dias de idade, 70 aves (14 aves/tratamento) foram sacrificadas para avaliação das características de carcaça e foi retirada também uma amostra da cama dos frangos de cada boxe para determinação de umidade. No período de 1 a 7 dias houve efeito linear positivo (P<0,05) para as variéveis: ganho de peso, consumo de ração e peso vivo, verificando-se que a inclusão de até 10% de glicerina na ração foi eficaz. No período de 1 a 21 dias ocorreu redução linear (P<0,05) da viabilidade, efeito cúbico (P<0,05) para o consumo de ração e efeito de quarto grau (P<0,05) para o ganho de peso e peso vivo, evidenciando melhores resultados de desempenho utilizando 5% de glicerina nas rações. No período total não houve efeito significativo para as variáveis de desempenho (P>0,05), embora verificado uma redução de 130 gramas no ganho de peso dos frangos alimentados com 10% de glicerina. Não houve efeito significativo para as características de carcaça (P>0,05), porém houve aumento linear (P<0,05) na umidade de cama dos frangos conforme a inclusão de glicerina na dieta. A inclusão de até 10% de glicerina na dieta até 7 dias e 5% nos períodos subsequentes, mostrou-se interessante na alimentação de frangos de corte. / The purpose of this work was to evaluate the effects of increasing levels of glycerin from biodiesel production in rations on the performance, carcass characteristics and moisture litter of broilers. The trial used 1575 Cobb male chicks. The chickens 1 day of age were weighed and allocated according to weight average to groups of 45 distributed in 35 pens in a completely randomized experimental design. Treatments were (0; 2,5; 5; 7,5 and 10%) glycerin inclusion with seven replicates per treatment. Was analyzed a contraction of glycerol, sodium, phosphorus, potassium and methanol from the crude glycerin in laboratory for formulate diets. Was considered the energy value of 4,100 kcal ME/ kg for the pure glycerol. The performance (liveweight, weight gain, feed intake, feed conversion and viability) were monitored weekly and at 43 days of age 70 broilers (14 broilers/ treatment) were sacrificed for evaluation of carcass characteristics. The moisture of the litter was analyzed in each pen. At seven days, it was found a positive linear effect (P<0.05) on weight gain, body weight and feed intake, verifying that the inclusion up to 10% glycerin in the diet was efficient. At 21 days, it was found a linear reduction (P<0.05) on viability, cubic effect (P <0.05) on feed intake and quartic effect (P <0.05) on weight gain and body weight. Results using 5% glycerin in diet showed better performance. At 42 days, there was no significant effect on the performance variables (P> 0.05), although a substantial reduction of 130 grams in weight gain was observed in broilers fed 10% glycerin. There was no significant effect on carcass characteristics (P> 0.05), but increased linear effect (P <0.05) was observed on litter moisture with the inclusion of glycerin in the diet. The inclusion of 10% of glycerin up to seven days and 5% after that was flexible in diets for broilers.

Foi avaliado o efeito do processamento do milho (PRC) e de diferentes teores de fibra insolúvel em detergente neutro proveniente de forragem (FDNf) no desempenho de bovinos. Posteriormente, foi estudado o efeito do PRC e da inclusão de polpa cítrica (PCtr) em substituição ao milho. Foram utilizados em cada experimento 112 bovinos machos não castrados da raça Nelore, com peso inicial de 384,1 ± 29,5 kg e 378,3 ± 21,3 kg respectivamente. O delineamento foi o de blocos completos casualizados em esquema fatorial 2x4. No primeiro experimento os dois PRC foram grão úmido ensilado (GU) e grão seco moído fino (MM) e os teores de FDNf foram 3, 8, 13 e 18% na MS. No segundo experimento foram utilizados os mesmo PRC (GU ou MM) e quatro teores de PCtr (0, 7, 14 e 21% na MS). No primeiro experimento, verificou-se efeito quadrático de FDNf para ganho de peso (P=0,01), sendo o ganho ótimo com inclusão de 13,0% de FDNf. Houve interação de PRC e FDNf (P=0,05) para consumo de matéria seca (CMS) sendo que os maiores CMS foram obtidos com inclusões de 11,3 e 13,7% de FDNf para animais alimentados com MM e GU respectivamente. Em ambos os experimentos a eficiência alimentar (EA) foi melhor (P<0,01) para animais alimentados com GU em relação ao MM. Houve efeito quadrático de FDNf para peso de carcaça quente e fria (P=0,04), sendo as carcaças mais pesadas obtidas com 12,8% de FDNf na dieta. Foi observado efeito quadrático de FDNf para peso de gordura renal, pélvica e inguinal (P=0,04), sendo que a maior deposição ocorreu com inclusões de 12,5% de FDNf. Houve interação de PRC e FDNf para teor de amido fecal (AF; P<0,001). Animais alimentados com GU apresentaram teores médios de AF mais baixos (3% na MS) e independentes do teor de FDNf da dieta. Entretanto, animais recebendo dietas com MM apresentaram teores mais elevados de AF (13% na MS), que foi reduzido com o aumento do teor de FDNf. No segundo experimento, observou-se efeito de PRC (P<0,001) para CMS, que foi menor em animais alimentados com GU em relação aos MM. Houve efeito linear de PCtr no CMS (P<0,001), ocorrendo aumento no CMS com o aumento da inclusão de PCtr. Não houve efeito (P>0,05) de PRC e nem de PCtr para características de carcaça. O AF foi menor em animais alimentados com GU em relação ao MM (3,16 vs. 8,63% na MS, P<0,001). A exigência de FDNf para maior CMS foi dependente do método de PRC, sendo menor para o MM em relação ao GU (11,3 vs. 13,7% FDNf). A inclusão de aproximadamente 13% de FDNf parece ser adequada para maximizar o desempenho de bovinos Nelore em dietas contendo caroço de algodão. O GU melhora a EA e reduz as perdas fecais de amido. / The effect of corn processing (PRC) and different levels of neutral detergente fiber from forage (NDFf) on performance were evaluated in one experiment and the effects of PRC and different citrus pulp levels (PCtr) were evaluated in a second experiment. In each study 112 Nellore bulls were used with 384.1 ± 29.5 kg inicial body weight (iBW) for the first experiment and 378.3 ± 21.3 kg iBW for the second experiment. The animals were used in a randomized complete block design in a 2x4 factorial arrangement. The PRC methods evaluated were high moisture corn (HM) and finely ground corn (GC). The levels of NDFf evaluated were 3, 8, 13 e 18% in the DM. In the second trial the same two PRC (HM and GC) and four levels of PCtr were evaluated (0, 7, 14 and 21% in the DM). In the first experiment a quadratic effect of NDFf was observed (P=0.01) with peak gain at 13.0% of NDFf. There was an interaction between PRC and NDFf (P=0.05) for dry matter intake (DMI); peak DMI occurred with 11.3 and 13.7% NDFf for GC and HM respectively. In both experiments gain efficiency (GE) was better (P<0.01) for animals fed HM than GC. There was a quadratical effect of NDFf for hot and cold carcass weight (P=0.04), with maximum weights at 12.8% NDFf. A quadratical effect of NDFf for renal, pelvic and inguinal fat weight (P=0.04) was observed with the highest weights at 12.5% NDFf. There was an interaction between PRC and NDFf for fecal starch (FS; P<0.001). Animals fed HM diets presented no change in FS with different NDFf levels (3% in the DM). However, animals fed GC had higher average FS (13% in the DM), and there was a decrease in FS content with increasing NDFf percentage. In the second experiment, there was an effect of PRC (P<0.001) on DMI, with lower intakes for animals fed HM diets. There was a linear effect of PCtr (P<0.001) on DMI with increased intakes as a result of increasing PCtr in the diet. No effects were observed for PRC and PCtr for carcass traits. FS was lower in animals fed HM compared to GC (3.16 vs. 8.63% in the DM; P<0.001). The NDFf required to optimize DMI was dependent on method of PRC (maximum intake required 11.3 and 13.7% NDFf for GC and HM, respectively). The performance of Nellore bulls could be optimized with around 13% NDFf in diets with cottonseed. The high moisture corn improves gain efficiency and decreases starch fecal losses.

Submitted by (edna.saturno@ufrpe.br) on 2017-02-15T12:33:27Z No. of bitstreams: 1 Jose Mario Baracho de Franca.pdf: 1060458 bytes, checksum: 5843154b02f16dc4ab5f2c5eaf2e0798 (MD5) / Made available in DSpace on 2017-02-15T12:33:27Z (GMT). No. of bitstreams: 1 Jose Mario Baracho de Franca.pdf: 1060458 bytes, checksum: 5843154b02f16dc4ab5f2c5eaf2e0798 (MD5) Previous issue date: 2003-08-04 / The growth of tilapia, Oreochromis spp, were evaluated in a intensive culture, from march to June 2003, through the use of twelve 5 m3 cages located at Açude Poço da Cruz (Ibimirim-PE). The experiment was designed to contain three treatments, according to the strains (Nilotica, Vermelha and Chitralada) and four replicates. Tilapia juveniles averaging 58.28, 18.74 and 63.62g, respectively, for each strain were stocked in randomly cages in a density of 600 juveniles/cage. A extruded commercial ration with 36% crude protein was used during the first 19 days, another with 32% for the subsequent 63 days and another one with 28% for the last 14 days of growout phage. Fish growth was followed through fortnightly measurements with approximately 5% of fish population. The main water quality variables were measured during the culture (temperature = 28.25 ± 0.65ºC, pH = 7.63 ± 0.38 and dissolved oxygen = 5.48 ± 0.98 mg/L) maintained adequate to the fishculture. Growth and production data were differents (P≤0.05) among treatments. Nilotica strain grew better than Chitralada than Vermelha, with respectively growth daily of 5.72, 4.60 and 3.23g/day. The final weight and weight gain were higher (P≤0.05) forNilotica (607.71g and 549.43g) than for Chitralada (504.23g and 440.61g) and Vermelha (328.79g and 335.05g). In this culture system it was possible to maintain a reasonable biomass in the cages since the final biomass were 268.68, 271.62 and 177.38Kg/cage, respectively for Nilotica, Chiralada and Vermelha. This represent a biomass of 6.99, 7.63 and 2.25Kg/m3, respectively for each strain. The feed conversion ratio was 1.85 for Nilotica, 1.77 for Chitralada and 1.86 for Vermelha strains. In spite of the fast growth, Nilotica strain showed a lower survival (73.71%) in relation with Vermelha strain, which presented the highest survival (91.29%) and lowest yield. These results shows that the tilapia Chitralada and Nilotica have a good performance for this type of culture are recommended for cage culture in a commercial scale. / O crescimento de três linhagens de tilápias, Oreochromis spp, em cultivo intensivo, de março a junho de 2003, utilizando doze tanques-rede de 5 m3, instalados no Açude Poço da Cruz (Ibimirim-PE). O experimento foi delineado para conter três tratamentos, utilizando-se as tilápias Nilótica, Vermelha e Chitralada, com quatro repetições. Juvenis de tilápia com peso médio de 58,28, 18,74 e 63,62 g, respectivamente, para os tratamentos Nilótica, Vermelha e Chitralada foram estocados aleatoriamente nos tanques-rede numa densidade de 600 juvenis/tanque-rede. Uma ração comercial extrusada com 36% de proteína bruta foi usada durante os 19 dias iniciais, outra com 32% para os 63 dias subseqüentes e uma com 28% para os últimos 14 dias da fase de engorda. Foi acompanhado o crescimento dos peixes com amostragens quinzenais, de aproximadamente 5% de população. As principais variáveis de qualidade de água medidas durante o cultivo (temperatura = 28,25 ± 0,65ºC; pH = 7,63 ± 0,38 e oxigênio dissolvido = 5,48 ± 0,98mg/L) mantiveram-se adequadas para o cultivo de peixes. Os dados de crescimento e produção foram diferentes (P≤0,05) entre os tratamentos. A tilápia Nilótica apresentou maior crescimento (5,72 g/dia) em relação à Chitralada (4,60 g/dia) e a Vermelha (3,23 g/dia). O peso final e ganho de peso foram maiores (P≤0,05) para Nilótica (607,71g e 549,43g) que para Chitralada (504,23 e 440,61g) e a Vermelha (328,79g e 335,05g). Neste sistema de cultivo foi possível manter uma biomassa razoável, sendo registrada uma biomassa final de 268,68; 271,62 e 177,38 Kg/tanque-rede, respectivamente, para as tilápias Nilótica, Chitralada e Vermelha, o que correspondeu a 6,99, 7,63 e 2,25Kg/m3 para as respectivas linhagens. A conversão alimentar foi de 1,85 para Nilótica, 1,77 para Chitralada e 1,86 para a Vermelha. Apesar do melhor crescimento da Nilótica, constatou-se uma menor sobrevivência (73,71%) em relação à linhagem Vermelha (91,29%), que apresentou baixo rendimento de cultivo. Diante dos resultados constata-se um melhor desempenho para as tilápias Nilótica e Chitralada, sendo portanto recomendadas para o cultivo comercial em tanques-rede.

Main aim of this work is to evaluace the financial situation of STUDENT AGENCY s.r.o. from 2006 to 2010 with the help of financial analysis. Another goal of this thesis is to find main indicators, which has the ability to influence key results of the company. Last goal is to find restrictions, which can limit this key results and find shortcomings, where should company focus on.

O objetivo deste estudo foi avaliar a qualidade da glicerina produzida no Brasil e o seu efeito no valor de energia metabolizável e na digestibilidade para frangos de corte, bem como avaliar o desempenho e qualidade de carne, estudando os possíveis efeitos adversos e determinando o melhor nível de inclusão a ser adotado com segurança. Na primeira etapa foram coletadas 10 amostras de glicerina de diferentes fontes e origens para a análise da composição. Em seguida, foram selecionadas 4 glicerinas de composições contrastantes para a determinação da energia metabolizável e digestibilidade em ensaios de metabolismo com 200 frangos de corte durante o período de 21 a 29 dias de idade, através do método de coleta total de excretas. Na segunda etapa, as aves foram submetidas ao um delineamento inteiramente ao acaso, com 6 tratamentos e 6 repetições de 45 aves cada. Os tratamentos constituíam de uma ração controle e 5 rações com 2,5; 5,0; 7,5; 10,0 e 12,5% de glicerina, sendo que a glicerina utilizada foi a que apresentou melhor composição química e energia metabolizável de 3145 kcal/kg. A umidade da cama foi analisada aos 28, 35 e 40 dias de idade. Aos 40 dias de idade foram sacrificadas 6 aves por tratamento para determinação do rendimento de carcaça e partes, além de coleta do músculo do peito, perna e fígado. Nos músculos do peito e da perna foram realizadas as análises de qualidade de carne. Também foram determinados a composição centesimal e perfil de ácidos graxos da gordura no músculo do peito. As energias aparente metabolizável corrigida para o balanço de nitrogênio das glicerinas foram de 3145, 5026, 2828 e 2892 kcal/kg. Para o desempenho das aves o aumento do nível de glicerina na dieta até 10% não afetou negativamente, somente com a inclusão de 12,5% de glicerina houve piora no peso (P<0,05) para o período de 40 dias de idade. Não houve efeito significativo para o rendimento de carcaça e partes (P>0,05). Não foram encontradas diferenças (P>0,05) para a composição centesimal e perfil de ácidos graxos na gordura. Aos 35 e 40 dias de idade foram encontrados aumento no teor de umidade da cama (P<0,05) com a inclusão de 10 e 12,5% de glicerina. Não foram encontrados alterações nos fígados das aves com os maiores níveis de inclusão. Os resultados sugerem que dietas contendo a inclusão de até 5% não causam nenhum efeito negativo para as aves e cama. / The objective of this study was to evaluate the quality of the glycerin produced in Brazil and its effect on the value of metabolizable energy and digestibility, the performance and meat quality of broilers, studying the possible adverse effects and determining the best level of inclusion to be adopted safely. In the trial were collected 10 glycerin samples from different sources and analysis of the composition. In the following section, we selected four contrasting glycerins compositions for the determination of metabolizable energy and digestibility in metabolism trials with 200 broiler chickens during the 21-29 days of age, by the method of total excreta collection. In the second trial, the birds were subjected to a completely randomized design with 6 treatments and 6 replicates of 45 birds each. The treatments were a control diet and five diets with 2.5, 5.0, 7.5, 10.0 and 12.5% glycerin, and glycerin was used with the best chemical composition and metabolizable energy 3145 kcal / kg. The litter moisture was analyzed at 28, 35 and 40 days old. At 40 days of age were sacrificed 6 birds per treatment for determination of carcass yield and parts, and collection of the breast muscle, leg and liver. In the muscles of the chest and leg were performed the analyzes of meat quality. We also determined the composition and profile of fatty acid in breast muscle. The apparent metabolizable energy corrected for nitrogen balance of glycerins were 3145, 5026, 2828 and 2892 kcal / kg. For the performance of the birds increased level of glycerin in the diet up to 10% did not affect negatively only with the inclusion of 12.5% glycerin worsened in weight (P <0.05) for the period of 40 days old. There was no significant effect on carcass yield and parts (P> 0.05). There were no differences (P> 0.05) for the composition and profile of fatty acids in fat. At 35 and 40 days of age were found increase in moisture content of the bed (P <0.05) with the inclusion of 10 and 12.5% glycerin. No changes were found in the livers of the birds with the highest levels of inclusion. The results suggest that diets containing the inclusion of up to 5% do not cause any negative effects for the broilers, meat quality and litter

Over the past few years there has been an extensive growth in data traffic consumption devices. Billions of mobile data devices are connected to the global wireless network. Customers demand revived services and up-to-date developed applications, like real-time video and games. These applications require reliable and high data rate wireless communication with high throughput network. One way to meet these requirements is by increasing the number of transmit and/or receive antennas of the wireless communication systems. Massive multiple-input multiple-output (MIMO) has emerged as a promising candidate technology for the next generation (5G) wireless communication. Massive MIMO increases the spatial multiplexing gain and the data rate by adding an excessive number of antennas to the base station (BS) terminals of wireless communication systems. However, building efficient algorithms able to decode a coherently or non-coherently large flow of transmitted signal with low complexity is a big challenge in massive MIMO. In this dissertation, we propose novel approaches to achieve optimal performance for joint channel estimation and signal detection for massive MIMO systems. The dissertation consists of three parts depending on the number of users at the receiver side. In the first part, we introduce a probabilistic approach to solve the problem of coherent signal detection using the optimized Markov Chain Monte Carlo (MCMC) technique. Two factors contribute to the speed of finding the optimal solution by the MCMC detector: The probability of encountering the optimal solution when the Markov chain converges to the stationary distribution, and the mixing time of the MCMC detector. First, we compute the optimal value of the “temperature'' parameter such that the MC encounters the optimal solution in a polynomially small probability. Second, we study the mixing time of the underlying Markov chain of the proposed MCMC detector. We assume the channel state information is known in the first part of the dissertation; in the second part we consider non-coherent signal detection. We develop and design an optimal joint channel estimation and signal detection algorithms for massive (single-input multiple-output) SIMO wireless systems. We propose exact non-coherent data detection algorithms in the sense of generalized likelihood ratio test (GLRT). In addition to their optimality, these proposed tree based algorithms perform low expected complexity and for general modulus constellations. More specifically, despite the large number of the unknown channel coefficients for massive SIMO systems, we show that the expected computational complexity of these algorithms is linear in the number of receive antennas (N) and polynomial in channel coherence time (T). We prove that as $N \rightarrow \infty$, the number of tested hypotheses for each coherent block equals $T$ times the cardinality of the modulus constellation. Simulation results show that the optimal non-coherent data detection algorithms achieve significant performance gains (up to 5 dB improvement in energy efficiency) with low computational complexity. In the part three, we consider massive MIMO uplink wireless systems with time-division duplex (TDD) operation. We propose an optimal algorithm in terms of GLRT to solve the problem of joint channel estimation and data detection for massive MIMO systems. We show that the expected complexity of our algorithm grows polynomially in the channel coherence time (T). The proposed algorithm is novel in two terms: First, the transmitted signal can be chosen from any modulus constellation, constant and non-constant. Second, the algorithm decodes the received noisy signal, which is transmitted a from multiple-antenna array, offering exact solution with polynomial complexity in the coherent block interval. Simulation results demonstrate significant performance gains of our approach compared with suboptimal non-coherent detection schemes. To the best of our knowledge, this is the first algorithm which efficiently achieves GLRT-optimal non-coherent detections for massive MIMO systems with general constellations.

Le vieillissement croissant de la population canadienne aura une incidence, dans les ann??es ?? venir, sur les risques de fractures ost??oporotiques et autres pathologies de l'os. Parmi ces risques, les fractures avec pertes osseuses pr??sentent des d??fis consid??rables et causent un lourd fardeau ??conomique. La soci??t?? Ost??oporose Canada estime que plus de 30 milliards de dollars seront d??pens??s pour le traitement de l???ost??oporose et de leurs fractures associ??es d???ici 2018. La m??thode de comblement des pertes osseuses standard actuelle, soit l'autogreffe, est limit??e et pr??sente des risques pour le patient. ?? titre d'alternative, deux strat??gies ont ??t?? jusqu'?? maintenant ??tudi??es: les syst??mes de lib??ration de facteurs de croissance (?? growth factor delivery systems ??, GFDS) et le d??veloppement de mat??riaux biomim??tiques. Ces deux strat??gies ont comme point commun l'utilisation de facteurs de croissance ost??og??niques comme les prot??ines morphog??n??tiques osseuses (BMPs), telles la BMP-2 (r??f??rence commerciale) et la BMP-9. Malgr?? leur effet important, les BMPs restent couteuses ?? produire. Le laboratoire de N. Faucheux a d??velopp?? un peptide (pBMP-9) d??riv?? de la BMP-9 qui poss??de un effet ost??og??nique d??montr??, mais dont les m??canismes d???action et le comportement en syst??me de lib??ration restent ?? ??tre ??tudi??s. Les objectifs de ce projet de recherche ont donc port?? sur l?????tude du comportement de cellules osseuses pr??ost??oblastes murins (MC3T3-E1) face ?? ces facteurs de croissance ainsi que sur le suivi et la mod??lisation des cin??tiques de lib??ration du pBMP-9 ?? partir d???une matrice de collag??ne, utilis??e actuellement en clinique. Le m??moire poss??de ainsi trois volets. Le premier volet de ces travaux a consist?? ?? faire une revue de la litt??rature sur le processus de r??g??n??ration osseuse endochondrale afin de bien comprendre le r??le jou?? par les facteurs de croissance et cerner les d??fis de conception d???un GFDS utilis?? en r??g??n??ration osseuse. Les nouvelles approches de GFDS ont ??t?? revues en d??tail ainsi que les principaux mod??les math??matiques d??velopp??s et appliqu??s aux mol??cules th??rapeutiques. Cette revue de la litt??rature a ??t?? publi??e dans Journal of Controlled Release. Le second volet de ces travaux s???est pench?? sur l?????tude et la mod??lisation math??matique des cin??tiques de lib??ration du pBMP-9 ?? partir d???hydrogels de collag??ne. Les r??sultats exp??rimentaux ont men?? ?? la r??daction d???un article qui vient d?????tre accept?? dans la revue Journal of Controlled Release. Cette ??tude consistait ?? ??valuer les m??canismes de transfert de masse impliqu??s dans la lib??ration pour diff??rentes concentrations de pBMP-9 ?? partir d'hydrogels de collag??ne. Les cin??tiques de lib??ration ont ??t?? mod??lis??es et ont montr?? la pr??sence d'interactions importantes entre le pBMP-9 et les fibres de collag??ne. Le troisi??me volet a consist?? ?? d??terminer l'effet dose de la BMP-9 et de la BMP-2 sur la capacit?? des MC3T3-E1 ?? se diff??rencier en pr??sence ou en absence de s??rum de veau foetal (?? foetal bovine serum ??, FBS). Ces travaux ont conduit ?? la r??daction d???un article qui vient d?????tre accept?? dans la revue Tissue Engineering Part A. La BMP-9 ??tant jusqu'alors mal comprise, l'??tude s'est pench??e sur cette prot??ine tout en ayant comme objectif de transposer les connaissances au pBMP-9. Les r??sultats ont d??montr?? que les m??canismes d'action de la BMP-9 ??taient tr??s diff??rents de ceux de la BMP-2 en pr??sence de FBS. Les r??sultats ont ??galement permis d'??tablir que, ?? l'instar de la BMP-2, la pr??sence de FBS potentialise fortement l'effet ost??og??nique de la BMP-9. Cet effet a d???ailleurs pu ??tre r??cr???? par l???IGF-2. Les conclusions de ce travail favoriseront le d??veloppement de syst??mes de lib??ration ost??og??niques plus efficaces.

La capacit?? de r??g??n??ration des foies de mammif??res est consid??rable. Suite ?? une h??patectomie partielle, les h??patocytes entrent de fa??on synchrone dans un ??tat de prolif??ration dans lequel ils quittent simultan??ment la phase G0 pour entrer en phase G1. Nous nous sommes int??ress??s aux changements ??pig??n??tiques et transcriptionnels qui surviennent durant ce processus. Pour ce faire, nous avons g??n??r?? des donn??es de ChIP-seq pour diff??rents temps suivant cette chirurgie pour : - la polym??rase II (pol II), - la polym??rase III (pol III), - les marqueurs ??pig??n??tiques H3K4me3 et H3K36me3, - ainsi que le cofacteur de transcription HCF-1. Ces donn??es nous ont permis de suivre et d???explorer les modifications dans la transcription et les changements ?? travers le g??nome durant la r??g??n??ration h??patique. La chromatine a ??t?? pr??par??e ?? partir de huit points dans le temps diff??rents suivant l'h??patectomie partielle (1h, 10h, 20h, 28h, 36h, 44h, 48h et 60h). Les ??chantillons ont ??t?? s??quenc??s avec la technologie dite "paired-end" (chaque fragment donne lieu ?? deux lectures de 50 ou 100 nucl??otides, une pour chaque bout) permettant la localisation pr??cise et la longueur exacte de chaque fragment s??quenc?? sur le g??nome. En moyenne, 225 millions de s??quences ont ??t?? obtenues pour chaque ??chantillon, puis cartographi??es sur le g??nome murin (C57BL6/J, assemblage MGSCv37/mm9, juillet 2007). De fa??on consistante avec une synchronisation robuste du cycle de division cellulaire, les patrons de transcription des g??nes du cycle cellulaire (par exemple, les cdks et les cyclines) r??v??lent un ??tat actif ou inactif bien d??fini qui corr??le avec l'activit?? attendue du g??ne. Nous avons effectu?? une premi??re analyse globale de l'occupation par la pol II ?? travers les diff??rents points dans le temps et avons identifi?? 9 423 g??nes montrant un changement significatif dans la fixation de la polym??rase au promoteur. En groupant les g??nes ayant un profil similaire, nous avons remarqu?? une concordance significative entre le point dans le temps du cycle cellulaire pendant lequel la pol II est pr??sente de fa??on maximale au promoteur des g??nes et la fonction qui leur est reli??e. Nous continuons d???explorer g??ne par g??ne, les variations au niveau des marqueurs ??pig??n??tiques, en fonction du profil de fixation de la pol II. Aucune analyse n???a cependant encore d??but?? en ce qui concerne la pol III et le facteur de transcription HCF-1. L'analyse continue de la transcription des g??nes du cycle de division cellulaire durant ce processus de r??g??n??ration h??patique vous sera pr??sent??e.