917 resultados para internal and externalintegration


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Includes bibliography.

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Egg quality of semi-heavy laying hens fed on low protein diets (14.0% CP) and on different lysine levels is evaluated, while maintaining the same ratio of digestible amino acids / digestible lysine. Four hundred and twenty commercial strain Isa Brown laying hens, 28 weeks old, were divided into 42 experimental plots. A completely randomized design with six treatments and seven replicates was employed in four production cycles of 28 days each. Treatments comprised Control - 16.92% CP; 0.750% digestible lysine. Treatments 1 to 5, with CP levels 14% and digestible lysine levels 0.600, 0.675, 0.750, 0.825 and 0.900% respectively. Levels of Treatments 1 and 2 (0.546 and 0.640% digestible Met + Cys / 0.600 and 0.675% digestible lysine) provided smaller egg size. On the other hand, eggs had higher shell percentage when compared to control diet. When compared to other digestible amino acids, digestible lysine requirement may be estimated at 0.750% in a diet with 14% CP, which corresponds to the average daily intake of 876 mg dig. lysine hen-1 day-1 and 798 mg dig. Met + Cys hen-1 day-1, without jeopardizing performance and eggs' internal and external quality.

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The aim of this study was to analyze photosynthate partitioning in tomato photomorphogenic mutants at the ends of the vegetative (40 days after emergence [DAE]) and reproductive (69 DAE) stages and to determine its interaction with morphoanatomical aspects. The mutants aurea (au), phytochrome-deficient, high pigment-1 (hp1), light-exaggerated response, were studied along with the non-mutant Micro-Tom (MT) cultivar. The plants were analyzed at 40 and 68 DAE to identify photosynthate source organs and tissues as well as the target organs of remobilized photosynthate during the reproductive stage. The plants were evaluated for their internal and external morphology as well as the percentage of dry mass of their organs. Photosynthate allocation in the hp1 mutant occurred primarily in the roots and leaves, and allocation in the au mutant occurred primarily in fruits. The au mutant showed a high capacity for photosynthate remobilization to fruit during the reproductive stage, and the predominant sources of these remobilized photosynthates were the leaf spongy parenchyma, the root vascular cylinder and the marrow stem.

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The aim of this study was to evaluate the internal fit, marginal adaptation, and bond strengths of inlays made of computer-aided design/computer-aided manufacturing feldspathic ceramic and polymer-infiltrated ceramic. Twenty molars were randomly selected and prepared to receive inlays that were milled from both materials. Before cementation, internal fit was achieved using the replica technique by molding the internal surface with addition silicone and measuring the cement thicknesses of the pulpal and axial walls. Marginal adaptation was measured on the occlusal and proximal margins of the replica. The inlays were then cemented using resin cement (Panavia F2.0) and subjected to two million thermomechanical cycles in water (200 N load and 3.8-Hz frequency). The restored teeth were then cut into beams, using a lathe, for microtensile testing. The contact angles, marginal integrity, and surface patterns after etching were also observed. Statistical analysis was performed using two-way repeated measures analysis of variance (p<0.05), the Tukey test for internal fit and marginal adaptation, and the Student t-test for bond strength. The failure types (adhesive or cohesive) were classified on each fractured beam. The results showed that the misfit of the pulpal walls (p=0.0002) and the marginal adaptation (p=0.0001) of the feldspathic ceramic were significantly higher when compared to those of the polymer-infiltrated ceramic, while the bond strength values of the former were higher when compared to those of the latter. The contact angle of the polymer-infiltrated ceramic was also higher. In the present study, the hybrid ceramic presented improved internal and marginal adaptation, but the bond strengths were higher for the feldspathic ceramic.

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Brazil is the world's largest beef exporter with the world's largest commercial cattle herd; however, the production cycle needs to be more efficient to supply internal and external demands in the future. Feedlot operations are currently a reality for the Brazilian beef cattle industry; nonetheless the beef cattle industry in Brazil is still based on grass-fed animals in which the Nellore breed predominates. At some point this constitutes an important advantage for Brazilian beef exportations because some countries look for “natural beef.” Brazilian packing plants regulate the use of antibiotics, especially ionophores used as growth promoters, on farms certified to export beef to European countries. In addition, the use of any implant or beta-agonist for cattle is forbidden in Brazil. From 1970 to 2006, the Brazilian bovine herd increased at 2.04%/year, total pasture at 0.07%/year, area with cultivated pasture at 3.5%/year, and ratio of animals/hectare of total pasture at 1.97%/year, whereas the area with natural pasture decreased at 2.26%/year. These trends alleviate some of the pressure on Brazilian authorities with respect to deforestation of the Amazon forest. Although Brazil had the greatest growth rate of enteric methane emissions, it also had the greatest growth rate of beef production, resulting in Brazil having a negative growth rate (–1.82%/year) of methane emissions per unit of product (kilogram of methane/kilogram of beef).

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Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 +/- A 3 years) and young group (n = 21, 23 +/- A 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

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Aldolase has emerged as a promising molecular target for the treatment of human African trypanosomiasis. Over the last years, due to the increasing number of patients infected with Trypanosoma brucei, there is an urgent need for new drugs to treat this neglected disease. In the present study, two-dimensional fragment-based quantitative-structure activity relationship (QSAR) models were generated for a series of inhibitors of aldolase. Through the application of leave-one-out and leave-many-out cross-validation procedures, significant correlation coefficients were obtained (r(2) = 0.98 and q(2) = 0.77) as an indication of the statistical internal and external consistency of the models. The best model was employed to predict pK(i) values for a series of test set compounds, and the predicted values were in good agreement with the experimental results, showing the power of the model for untested compounds. Moreover, structure-based molecular modeling studies were performed to investigate the binding mode of the inhibitors in the active site of the parasitic target enzyme. The structural and QSAR results provided useful molecular information for the design of new aldolase inhibitors within this structural class.

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The humoral immune response is dependent on the formation of antibodies. Antibodies are produced by terminally differentiated B cells, plasma cells. Plasma cells are generated either directly from antigen challenged B cells, memory cells or from cells that have undergone the germinal center (GC) reaction. The GC is the main site for class switch, somatic hypermutation and generation of memory cells. Different factors, both internal and external, shape the outcome of the immune response. In this thesis, we have studied a few factors that influence the maturation of the humoral response. We have studied how age affects the response, and we show that responses against thymus dependent antigens (TD) are more affected than responses to thymus independent (TI) antigens, in concordance with the view that the T cell compartment is more affected by age than the B cell compartment. Furthermore, we demonstrate that priming early in life have a big influence on the immune response in the aged individual. Priming with a TI form of the carbohydrate dextran B512 (Dx) induces a reduction of IgG levels in later TD responses against Dx. We have evaluated possible mechanisms for this reduction. The reduction does not seem to be caused by clonal exhaustion or antibody mediated mechanisms. We also showed that the reduced TD response after TI priming can be induced against another molecule than Dx. With the hypothesis that TI antigens induce a plasma cell biased maturation of the responding B cells, we examined the presence of Blimp-1, a master regulator of plasma cell differentiation, in GCs induced by TD and TI antigen. Blimp-1 was found earlier in GCs induced by TI antigen and the staining intensity in these GCs was stronger than in TD antigen induced GCs, indicating that plasma cells might be continuously recruited from these GCs. B cells undergoing the GC reaction are thought to be under a strict selection pressure that removes cells with low affinity for the antigen and also cells that have acquired self-reactivity. We investigated the effect of apoptotic deficiencies on the accumulation of somatic mutations in GC B cells. In mice lacking the death receptor Fas, lpr mice, the frequency of mutations was increased but the pattern of the mutations did not differ from wild type mice. In contrast, mice over-expressing the anti-apoptotic protein Bcl-2, had a lowered frequency of mutations and the mutations introduced had other characteristics.

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Theory of aging postulates that aging is a remodeling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades. Thus , stress response and adaptation mechanisms play a fundamental role in the aging process where the capability of adaptating effects, certainly, also is related the lifespan of each individual. A key gene linking aging to stress response is indeed p21, an induction of cyclin-dependent kinase inhibitor which triggers cell growth arrest associated with senescence and damage response and notably is involved in the up-regulation of multiple genes that have been associated with senescence or implicated in age-related . This PhD thesis project that has been performed in collaboration with the Roninson Lab at Ordway Research Institute in Albany, NY had two main aims: -the testing the hypothesis that p21 polymorphisms are involved in longevity -Evaluating age-associated differences in gene expression and transcriptional response to p21 and DNA damage In the first project, trough PCR-sequencing and Sequenom strategies, we we found out that there are about 30 polymorphic variants in the p21 gene. In addition, we found an haplotpype located in -5kb region of the p21 promoter whose frequency is ~ 2 fold higher in centenarians than in the general population (Large-scale analysis of haplotype frequencies is currently in progress). Functional studies I carried out on the promoter highilighted that the ―centenarian‖ haplotype doesn’t affect the basal p21 promoter activity or its response to p53. However, there are many other possible physiological conditions in which the centenarian allele of the p21 promoter may potentially show a different response (IL6, IFN,progesterone, vitamin E, Vitamin D etc). In the second part, project #2, trough Microarrays we seeked to evaluate the differences in gene expression between centenarians, elderly, young in dermal fibroblast cultures and their response to p21 and DNA damage. Microarray analysis of gene expression in dermal fibroblast cultures of individuals of different ages yielded a tentative "centenarian signature". A subset of genes that were up- or downregulated in centenarians showed the same response to ectopic expression of p21, yielding a putative "p21-centenarian" signature. Trough RQ-PCR (as well Microarrays studies whose analysis is in progress) we tested the DNA damage response of the p21-centenarian signature genes showing a correlation stress/aging in additional sets of young and old samples treated with p21-inducing drug doxorubicin thus finding for a subset of of them , a response to stress age-related.

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This doctoral work gains deeper insight into the dynamics of knowledge flows within and across clusters, unfolding their features, directions and strategic implications. Alliances, networks and personnel mobility are acknowledged as the three main channels of inter-firm knowledge flows, thus offering three heterogeneous measures to analyze the phenomenon. The interplay between the three channels and the richness of available research methods, has allowed for the elaboration of three different papers and perspectives. The common empirical setting is the IT cluster in Bangalore, for its distinguished features as a high-tech cluster and for its steady yearly two-digit growth around the service-based business model. The first paper deploys both a firm-level and a tie-level analysis, exploring the cases of 4 domestic companies and of 2 MNCs active the cluster, according to a cluster-based perspective. The distinction between business-domain knowledge and technical knowledge emerges from the qualitative evidence, further confirmed by quantitative analyses at tie-level. At firm-level, the specialization degree seems to be influencing the kind of knowledge shared, while at tie-level both the frequency of interaction and the governance mode prove to determine differences in the distribution of knowledge flows. The second paper zooms out and considers the inter-firm networks; particularly focusing on the role of cluster boundary, internal and external networks are analyzed, in their size, long-term orientation and exploration degree. The research method is purely qualitative and allows for the observation of the evolving strategic role of internal network: from exploitation-based to exploration-based. Moreover, a causal pattern is emphasized, linking the evolution and features of the external network to the evolution and features of internal network. The final paper addresses the softer and more micro-level side of knowledge flows: personnel mobility. A social capital perspective is here developed, which considers both employees’ acquisition and employees’ loss as building inter-firm ties, thus enhancing company’s overall social capital. Negative binomial regression analyses at dyad-level test the significant impact of cluster affiliation (cluster firms vs non-cluster firms), industry affiliation (IT firms vs non-IT fims) and foreign affiliation (MNCs vs domestic firms) in shaping the uneven distribution of personnel mobility, and thus of knowledge flows, among companies.

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The intensity of regional specialization in specific activities, and conversely, the level of industrial concentration in specific locations, has been used as a complementary evidence for the existence and significance of externalities. Additionally, economists have mainly focused the debate on disentangling the sources of specialization and concentration processes according to three vectors: natural advantages, internal, and external scale economies. The arbitrariness of partitions plays a key role in capturing these effects, while the selection of the partition would have to reflect the actual characteristics of the economy. Thus, the identification of spatial boundaries to measure specialization becomes critical, since most likely the model will be adapted to different scales of distance, and be influenced by different types of externalities or economies of agglomeration, which are based on the mechanisms of interaction with particular requirements of spatial proximity. This work is based on the analysis of the spatial aspect of economic specialization supported by the manufacturing industry case. The main objective is to propose, for discrete and continuous space: i) a measure of global specialization; ii) a local disaggregation of the global measure; and iii) a spatial clustering method for the identification of specialized agglomerations.

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Monitoring foetal health is a very important task in clinical practice to appropriately plan pregnancy management and delivery. In the third trimester of pregnancy, ultrasound cardiotocography is the most employed diagnostic technique: foetal heart rate and uterine contractions signals are simultaneously recorded and analysed in order to ascertain foetal health. Because ultrasound cardiotocography interpretation still lacks of complete reliability, new parameters and methods of interpretation, or alternative methodologies, are necessary to further support physicians’ decisions. To this aim, in this thesis, foetal phonocardiography and electrocardiography are considered as different techniques. Further, variability of foetal heart rate is thoroughly studied. Frequency components and their modifications can be analysed by applying a time-frequency approach, for a distinct understanding of the spectral components and their change over time related to foetal reactions to internal and external stimuli (such as uterine contractions). Such modifications of the power spectrum can be a sign of autonomic nervous system reactions and therefore represent additional, objective information about foetal reactivity and health. However, some limits of ultrasonic cardiotocography still remain, such as in long-term foetal surveillance, which is often recommendable mainly in risky pregnancies. In these cases, the fully non-invasive acoustic recording, foetal phonocardiography, through maternal abdomen, represents a valuable alternative to the ultrasonic cardiotocography. Unfortunately, the so recorded foetal heart sound signal is heavily loaded by noise, thus the determination of the foetal heart rate raises serious signal processing issues. A new algorithm for foetal heart rate estimation from foetal phonocardiographic recordings is presented in this thesis. Different filtering and enhancement techniques, to enhance the first foetal heart sounds, were applied, so that different signal processing techniques were implemented, evaluated and compared, by identifying the strategy characterized on average by the best results. In particular, phonocardiographic signals were recorded simultaneously to ultrasonic cardiotocographic signals in order to compare the two foetal heart rate series (the one estimated by the developed algorithm and the other provided by cardiotocographic device). The algorithm performances were tested on phonocardiographic signals recorded on pregnant women, showing reliable foetal heart rate signals, very close to the ultrasound cardiotocographic recordings, considered as reference. The algorithm was also tested by using a foetal phonocardiographic recording simulator developed and presented in this research thesis. The target was to provide a software for simulating recordings relative to different foetal conditions and recordings situations and to use it as a test tool for comparing and assessing different foetal heart rate extraction algorithms. Since there are few studies about foetal heart sounds time characteristics and frequency content and the available literature is poor and not rigorous in this area, a data collection pilot study was also conducted with the purpose of specifically characterising both foetal and maternal heart sounds. Finally, in this thesis, the use of foetal phonocardiographic and electrocardiographic methodology and their combination, are presented in order to detect foetal heart rate and other functioning anomalies. The developed methodologies, suitable for longer-term assessment, were able to detect heart beat events correctly, such as first and second heart sounds and QRS waves. The detection of such events provides reliable measures of foetal heart rate, potentially information about measurement of the systolic time intervals and foetus circulatory impedance.

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The relationship between emotion and cognition is a topic that raises great interest in research. Recently, a view of these two processes as interactive and mutually influencing each other has become predominant. This dissertation investigates the reciprocal influences of emotion and cognition, both at behavioral and neural level, in two specific fields, such as attention and decision-making. Experimental evidence on how emotional responses may affect perceptual and attentional processes has been reported. In addition, the impact of three factors, such as personality traits, motivational needs and social context, in modulating the influence that emotion exerts on perception and attention has been investigated. Moreover, the influence of cognition on emotional responses in decision-making has been demonstrated. The current experimental evidence showed that cognitive brain regions such as the dorsolateral prefrontal cortex are causally implicated in regulation of emotional responses and that this has an effect at both pre and post decisional stages. There are two main conclusions of this dissertation: firstly, emotion exerts a strong influence on perceptual and attentional processes but, at the same time, this influence may also be modulated by other factors internal and external to the individuals. Secondly, cognitive processes may modulate emotional prepotent responses, by serving a regulative function critical to driving and shaping human behavior in line with current goals.

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The latter part of the 20th century was a period characterized by a fundamental demographic transition of western society. This substantial and structural demographic change proposes several challenges to contemporary society and fosters the emergence of new issues and challenges. Among these, none is more crucial than the comprehension of the mechanisms and the processes that lead people to positive aging. Rowe and Kahn’s model of successful aging highlights the interplay between social engagement with life, health, and functioning for a positive aging experience. Other systemic models of successful aging (Kahana et al., 1996; 2003; Stevernik et al., 2006) emphasize the role of internal and external resources for attaining positive aging. Among these, the proactive coping strategies are indicated as important active strategies for avoiding the depletion of resources, counterbalancing the declines and maintaining social and civic involvement. The study has analyzed the role of proactive coping strategies for two facets of positive aging, the experience of a high social well-being and the presence of personal projects in fundamental life domains. As expected, the proactive coping strategies, referred to as the active management of the environment, the accumulation of resources and the actualization of human potentials are confirmed as positive predictors of high level of social well-being and of many personal projects focused on family, culture, leisure time, civic and social participation. Perceived health status give a significant contribution only to the possession of many personal projects. Gender and level of school education give also a significant contribution to these two dimensions of positive aging, highlighting how positive aging is rooted not only in the possession of personal resources, but also in historical models of education and in positive longitudinal chains related to early development.

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It is well known that ageing and cancer have common origins due to internal and environmental stress and share some common hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury. Moreover, ageing is involved in a number of events responsible for carcinogenesis and cancer development at the molecular, cellular, and tissue levels. Ageing could represent a “blockbuster” market because the target patient group includes potentially every person; at the same time, oncology has become the largest therapeutic area in the pharmaceutical industry in terms of the number of projects, clinical trials and research and development (R&D) spending, but cancer remains one of the leading causes of mortality worldwide. The overall aim of the work presented in this thesis was the rational design of new compounds able to modulate activity of relevant targets involved in cancer and aging-related pathologies, namely proteasome and immunoproteasome, sirtuins and interleukin 6. These three targets play different roles in human cells, but the modulation of its activity using small molecules could have beneficial effects on one or more aging-related diseases and cancer. We identified new moderately active and selective non-peptidic compounds able to inhibit the activity of both standard and immunoproteasome, as well as novel and selective scaffolds that would bind and inhibit SIRT6 selectively and can be used to sensitize tumor cells to commonly used anticancer agents such gemcitabine and olaparib. Moreover, our virtual screening approach led us also to the discovery of new putative modulators of SIRT3 with interesting in-vitro and cellular activity. Although the selectivity and potency of the identified chemical scaffolds are susceptible to be further improved, these compounds can be considered as highly promising leads for the development of future therapeutics.