971 resultados para Within-generation variance
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A total of 20,065 weights recorded on 3016 Nelore animals were used to estimate covariance functions for growth from birth to 630 days of age, assuming a parametric correlation structure to model within-animal correlations. The model of analysis included fixed effects of contemporary groups and age of dam as quadratic covariable. Mean trends were taken into account by a cubic regression on orthogonal polynomials of animal age. Genetic effects of the animal and its dam and maternal permanent environmental effects were modelled by random regressions on Legendre polynomials of age at recording. Changes in direct permanent environmental effect variances were modelled by a polynomial variance function, together with a parametric correlation function to account for correlations between ages. Stationary and nonstationary models were used to model within-animal correlations between different ages. Residual variances were considered homogeneous or heterogeneous, with changes modelled by a step or polynomial function of age at recording. Based on Bayesian information criterion, a model with a cubic variance function combined with a nonstationary correlation function for permanent environmental effects, with 49 parameters to be estimated, fitted best. Modelling within-animal correlations through a parametric correlation structure can describe the variation pattern adequately. Moreover, the number of parameters to be estimated can be decreased substantially compared to a model fitting random regression on Legendre polynomial of age. © 2004 Elsevier B.V. All rights reserved.
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A bilevel programming approach for the optimal contract pricing of distributed generation (DG) in distribution networks is presented. The outer optimization problem corresponds to the owner of the DG who must decide the contract price that would maximize his profits. The inner optimization problem corresponds to the distribution company (DisCo), which procures the minimization of the payments incurred in attending the expected demand while satisfying network constraints. The meet the expected demand the DisCo can purchase energy either form the transmission network through the substations or form the DG units within its network. The inner optimization problem is substituted by its Karush- Kuhn-Tucker optimality conditions, turning the bilevel programming problem into an equivalent single-level nonlinear programming problem which is solved using commercially available software. © 2010 IEEE.
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In this study, a novel approach for the optimal location and contract pricing of distributed generation (DG) is presented. Such an approach is designed for a market environment in which the distribution company (DisCo) can buy energy either from the wholesale energy market or from the DG units within its network. The location and contract pricing of DG is determined by the interaction between the DisCo and the owner of the distributed generators. The DisCo intends to minimise the payments incurred in meeting the expected demand, whereas the owner of the DG intends to maximise the profits obtained from the energy sold to the DisCo. This two-agent relationship is modelled in a bilevel scheme. The upper-level optimisation is for determining the allocation and contract prices of the DG units, whereas the lower-level optimisation is for modelling the reaction of the DisCo. The bilevel programming problem is turned into an equivalent single-level mixed-integer linear optimisation problem using duality properties, which is then solved using commercially available software. Results show the robustness and efficiency of the proposed model compared with other existing models. As regards to contract pricing, the proposed approach allowed to find better solutions than those reported in previous works. © The Institution of Engineering and Technology 2013.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Pós-graduação em Agronomia (Genética e Melhoramento de Plantas) - FCAV
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Background: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.Results: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient. The distance between any two variants calculated over the component correlated strongly with nucleotide distances (r = 0.9499; p = 0.0001), a better correlation than the one obtained with Neighbour-Joining trees (r = 0.7624; p = 0.0001). In each patient, components were well separated, with the average distance between (6.53%) being 10 times greater than within each component (0.68%). The ratio of nonsynonymous to synonymous changes was calculated and some patients (6.9%) showed a mixture of networks under strong negative and positive selection. All components were robust to in silico stochastic sampling; even after randomly removing 85% of all reads, the largest connected component in the new subsample still involved 82.4% of remaining nodes. In vitro sampling showed that 93.02% of components present in the original sample were also found in experimental replicas, with 81.6% of reads found in both. When syringe-sharing transmission events were simulated, 91.2% of all simulated transmission events seeded all components present in the source.Conclusions: Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The early phase of post-collisional granitic magmatism in the Camboriu region, south Brazil, is represented by the porphyritic biotite +/- hornblende Rio Pequeno Granite (RPG; 630-620 Ma) and the younger (similar to 610 Ma), equigranular, biotite +/- muscovite Serra dos Macacos Granite (SMG). The two granite types share some geochemical characteristics, but the more felsic SMG constitutes a distinctive group not related to RPG by simple fractionation processes, as indicated by its lower FeOt, TiO2, K2O/Na2O and higher Zr Al2O3, Na2O, Ba and Sr when compared to RPG of similar SiO2 range. Sr-Nd-Pb isotopes require different sources. The SMG derives from old crustal sources, possibly related to the Paleoproterozoic protoliths of the Camboriu Complex, as indicated by strongly negative epsilon Nd-t (-23 to -24) and unradiogenic Pb (e.g., Pb-206/Pb-204 = 16.0-16.3; Pb-207/Pb-204 = 15.3-15.4) and confirmed by previous LA-MC-ICPMS data showing dominant zircon inheritance of Archean to Paleoproterozoic age. In contrast, the RPG shows less negative epsilon Nd-t (-12 to -15) and a distinctive zircon inheritance pattern with no traces of post-1.6 Ga sources. This is indicative of younger sources whose significance in the regional context is still unclear; some contribution of mantle-derived magmas is indicated by coeval mafic dykes and may account for some of the geochemical and isotopic characteristics of the least differentiated varieties of the RPG. The transcurrent tectonics seems to have played an essential role in the generation of mantle-derived magmas despite their emplacement within a low-strain zone. It may have facilitated their interaction with crustal melts which seem to be to a large extent the products of reworking of Paleoproterozoic orthogneisses from the Camboriu Complex. (C) 2012 Elsevier Ltd. All rights reserved.
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Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin-angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective ATI receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P) H oxidase-mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT(1)-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. (c) 2012 Elsevier Inc. All rights reserved.
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A model for computing the generation-recombination noise due to traps within the semiconductor film of fully depleted silicon-on-insulator MOSFET transistors is presented. Dependence of the corner frequency of the Lorentzian spectra on the gate voltage is addressed in this paper, which is different to the constant behavior expected for bulk transistors. The shift in the corner frequency makes the characterization process easier. It helps to identify the energy position, capture cross sections, and densities of the traps. This characterization task is carried out considering noise measurements of two different candidate structures for single-transistor dynamic random access memory devices.
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Abstract Background Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis. Results Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis. Conclusion Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.
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This study addresses a vehicle routing problem with time windows, accessibility restrictions on customers, and a fleet that is heterogeneous with regard to capacity and average speed. A vehicle can performmultiple routes per day, all starting and ending at a single depot, and it is assigned to a single driverwhose totalwork hours are limited.Acolumn generation algorithmis proposed.The column generation pricing subproblem requires a specific elementary shortest path problem with resource constraints algorithm to address the possibility for each vehicle performingmultiple routes per day and to address the need to set the workday’s start time within the planning horizon. A constructive heuristic and a metaheuristic based on tabu search are also developed to find good solutions.
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This thesis deal with the design of advanced OFDM systems. Both waveform and receiver design have been treated. The main scope of the Thesis is to study, create, and propose, ideas and novel design solutions able to cope with the weaknesses and crucial aspects of modern OFDM systems. Starting from the the transmitter side, the problem represented by low resilience to non-linear distortion has been assessed. A novel technique that considerably reduces the Peak-to-Average Power Ratio (PAPR) yielding a quasi constant signal envelope in the time domain (PAPR close to 1 dB) has been proposed.The proposed technique, named Rotation Invariant Subcarrier Mapping (RISM),is a novel scheme for subcarriers data mapping,where the symbols belonging to the modulation alphabet are not anchored, but maintain some degrees of freedom. In other words, a bit tuple is not mapped on a single point, rather it is mapped onto a geometrical locus, which is totally or partially rotation invariant. The final positions of the transmitted complex symbols are chosen by an iterative optimization process in order to minimize the PAPR of the resulting OFDM symbol. Numerical results confirm that RISM makes OFDM usable even in severe non-linear channels. Another well known problem which has been tackled is the vulnerability to synchronization errors. Indeed in OFDM system an accurate recovery of carrier frequency and symbol timing is crucial for the proper demodulation of the received packets. In general, timing and frequency synchronization is performed in two separate phases called PRE-FFT and POST-FFT synchronization. Regarding the PRE-FFT phase, a novel joint symbol timing and carrier frequency synchronization algorithm has been presented. The proposed algorithm is characterized by a very low hardware complexity, and, at the same time, it guarantees very good performance in in both AWGN and multipath channels. Regarding the POST-FFT phase, a novel approach for both pilot structure and receiver design has been presented. In particular, a novel pilot pattern has been introduced in order to minimize the occurrence of overlaps between two pattern shifted replicas. This allows to replace conventional pilots with nulls in the frequency domain, introducing the so called Silent Pilots. As a result, the optimal receiver turns out to be very robust against severe Rayleigh fading multipath and characterized by low complexity. Performance of this approach has been analytically and numerically evaluated. Comparing the proposed approach with state of the art alternatives, in both AWGN and multipath fading channels, considerable performance improvements have been obtained. The crucial problem of channel estimation has been thoroughly investigated, with particular emphasis on the decimation of the Channel Impulse Response (CIR) through the selection of the Most Significant Samples (MSSs). In this contest our contribution is twofold, from the theoretical side, we derived lower bounds on the estimation mean-square error (MSE) performance for any MSS selection strategy,from the receiver design we proposed novel MSS selection strategies which have been shown to approach these MSE lower bounds, and outperformed the state-of-the-art alternatives. Finally, the possibility of using of Single Carrier Frequency Division Multiple Access (SC-FDMA) in the Broadband Satellite Return Channel has been assessed. Notably, SC-FDMA is able to improve the physical layer spectral efficiency with respect to single carrier systems, which have been used so far in the Return Channel Satellite (RCS) standards. However, it requires a strict synchronization and it is also sensitive to phase noise of local radio frequency oscillators. For this reason, an effective pilot tone arrangement within the SC-FDMA frame, and a novel Joint Multi-User (JMU) estimation method for the SC-FDMA, has been proposed. As shown by numerical results, the proposed scheme manages to satisfy strict synchronization requirements and to guarantee a proper demodulation of the received signal.
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Donor-derived CD8+ cytotoxic T lymphocytes (CTLs) eliminating host leukemic cells mediate curative graft-versus-leukemia (GVL) reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The leukemia-reactive CTLs recognize hematopoiesis-restricted or broadly expressed minor histocompatibility and leukemia-associated peptide antigens that are presented by human leukocyte antigen (HLA) class I molecules on recipient cells. The development of allogeneic CTL therapy in acute myeloid leukemia (AML) is hampered by the poor efficiency of current techniques for generating leukemia-reactive CTLs from unprimed healthy donors in vitro. In this work, a novel allogeneic mini-mixed lymphocyte/leukemia culture (mini-MLLC) approach was established by stimulating CD8+ T cells isolated from peripheral blood of healthy donors at comparably low numbers (i.e. 10e4/well) with HLA class I-matched primary AML blasts in 96-well microtiter plates. Before culture, CD8+ T cells were immunomagnetically separated into CD62L(high)+ and CD62L(low)+/neg subsets enriched for naive/central memory and effector memory cells, respectively. The application of 96-well microtiter plates aimed at creating multiple different responder-stimulator cell compositions in order to provide for the growth of leukemia-reactive CTLs optimized culture conditions by chance. The culture medium was supplemented with interleukin (IL)-7, IL-12, and IL-15. On day 14, IL-12 was replaced by IL-2. In eight different related and unrelated donor/AML pairs with complete HLA class I match, numerous CTL populations were isolated that specifically lysed myeloid leukemias in association with various HLA-A, -B, or -C alleles. These CTLs recognized neither lymphoblastoid B cell lines of donor and patient origin nor primary B cell leukemias expressing the corresponding HLA restriction element. CTLs expressed T cell receptors of single V-beta chain families, indicating their clonality. The vast majority of CTL clones were obtained from mini-MLLCs initiated with CD8+ CD62L(high)+ cells. Using antigen-specific stimulation, multiple CTL populations were amplified to 10e8-10e10 cells within six to eight weeks. The capability of mini-MLLC derived AML-reactive CTL clones to inhibit the engraftment of human primary AML blasts was investigated in the immunodeficient nonobese diabetic/severe combined immune deficient IL-2 receptor common γ-chain deficient (NOD/SCID IL2Rγnull) mouse model. The leukemic engraftment in NOD/SCID IL2Rγnull was specifically prevented if inoculated AML blasts had been pre-incubated in vitro with AML-reactive CTLs, but not with anti-melanoma control CTLs. These results demonstrate that myeloid leukemia-specific CTL clones capable of preventing AML engraftment in mice can be rapidly isolated from CD8+ CD62L(high)+ T cells of healthy donors in vitro. The efficient generation and expansion of these CTLs by the newly established mini-MLLC approach opens the door for several potential applications. First, CTLs can be used within T cell-driven antigen identification strategies to extend the panel of molecularly defined AML antigens that are recognizable by T cells of healthy donors. Second, because these CTLs can be isolated from the stem cell donor by mini-MLLC prior to transplantation, they could be infused into AML patients as a part of the stem cell allograft, or early after transplantation when the leukemia burden is low. The capability of these T cells to expand and function in vivo might require the simultaneous administration of AML-reactive CD4+ T cells generated by a similar in vitro strategy or, less complex, the co-transfer of CD8-depleted donor lymphocytes. To prepare clinical testing, the mini-MLLC approach should now be translated into a protocol that is compatible with good manufacturing practice guidelines.