992 resultados para Immune Parameters


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In the present investigation, experiments were conducted on a tribological couple-copper pin against steel plate-using an inclined pin-on-plate sliding tester to understand the role of surface texture and roughness parameters of the plate on the coefficient friction and transfer layer formation. Two surface characteristics of the steel plates-roughness and texture-were varied in the tests. It was observed that the transfer layer formation and the coefficient of friction along with its two components, namely, the adhesion and plowing, are controlled by the surface texture of the plate. The plowing component of friction was highest for the surface texture that promotes plane strain conditions while it was lowest for the texture that favors plane stress conditions at the interface. Dimensionless quantifiable roughness parameters were formulated to describe the degree of plowing and hence the plane strain/stress type deformations taking place at the asperity level.

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Acidity in terms of pH and titratable acids influences the texture and flavour of fermented dairy products, such as Kefir. However, the methods for determining pH and titratable acidity (TA) are time consuming. Near infrared (NIR) spectroscopy is a non-destructive method, which simultaneously predicts multiple traits from a single scan and can be used to predict pH and TA. The best pH NIR calibration model was obtained with no spectral pre-treatment applied, whereas smoothing was found to be the best pre-treatment to develop the TA calibration model. Using cross-validation, the prediction results were found acceptable for both pH and TA. With external validation, similar results were found for pH and TA, and both models were found to be acceptable for screening purposes.

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Background: The Ewing sarcoma family of tumors (ESFT) are rare but highly malignant neoplasms that occur mainly in bone or but also in soft tissue. ESFT affects patients typically in their second decade of life, whereby children and adolescents bear the heaviest incidence burden. Despite recent advances in the clinical management of ESFT patients, their prognosis and survival are still disappointingly poor, especially in cases with metastasis. No targeted therapy for ESFT patients is currently available. Moreover, based merely on current clinical and biological characteristics, accurate classification of ESFT patients often fails at the time of diagnosis. Therefore, there is a constant need for novel molecular biomarkers to be applied in tandem with conventional parameters to further intensify ESFT risk-stratification and treatment selection, and ultimately to develop novel targeted therapies. In this context, a greater understanding of the genetics and immune characteristics of ESFT is needed. Aims: This study sought to open novel insights into gene copy number changes and gene expression in ESFT and, further, to enlighten the role of inflammation in ESFT. For this purpose, microarrays were used to provide gene-level information on a genomewide scale. In addition, this study focused on screening of 9p21.3 deletion sizes and frequencies in ESFT and, in another pediatric cancer, acute lymphocytic leukemia (ALL), in order to define more exact criteria for highrisk patient selection and to provide data for developing a more reliable diagnostic method to detect CDKN2A deletions. Results: In study I, 20 novel ESFT-associated suppressor genes and oncogenes were pinpointed using combined array CGH and expression analysis. In addition, interesting chromosomal rearrangements were identified: (1) Duplication of derivative chromosome der(22)(11;22) was detected in three ESFT patients. This duplication included the EWSR1-FLI1 fusion gene leading to increase in its copy number; (2) Cryptic amplifications on chromosomes 20 and 22 were detected, suggesting a novel translocation between chromosomes 20 and 22, which most probably produces a fusion between EWSR1 and NFATC2. In study II, bioinformatic analysis of ESFT expression profiles showed that inflammatory gene activation is detectable in ESFT patient samples and that the activation is characterized by macrophage gene expression. Most interestingly, ESFT patient samples were shown to express certain inflammatory genes that were prognostically significant. High local expression of C5 and JAK1 at the tumor site was shown to associate with favorable clinical outcome, whereas high local expression of IL8 was shown to be detrimental. Studies III and IV showed that the smallest overlapping region of deletion in 9p21.3 includes CDKN2A in all cases and that the length of this region is 12.2 kb in both Ewing sarcoma and ALL. Furthermore, our results showed that the most widely used commercial CDKN2A FISH probe creates false negative results in the narrowest microdeletion cases (<190 kb). Therefore, more accurate methods should be developed for the detection of deletions in the CDKN2A locus. Conclusions: This study provides novel insights into the genetic changes involved in the biology of ESFT, in the interaction between ESFT cells and immune system, and in the inactivation of CDKN2A. Novel ESFT biomarker genes identified in this study serve as a useful resource for future studies and in developing novel therapeutic strategies to improve the survival of patients with ESFT.

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis, progressive joint destruction, and disability. Reactive arthritis (ReA) is a sterile joint inflammation following a distant mucosal infection. The clinical course of these diseases is variable and cannot be predicted with reasonable accuracy by clinical and laboratory markers. The predictive value of circulating soluble interleukin-2 receptor (sIL-2R), a marker of lymphocyte activation, measured by Immulite® automated immunoassay analyzer, was evaluated in two cohorts of RA patients. In 175 patients with active early RA randomized to treatment with either on disease-modifying antirheumatic drug (DMARD) or a combination of 3 DMARDs and prednisolone, low baseline sIL-2R level predicted remission after 6 months in patients treated with a single DMARD. In 24 patients with active RA refractory to DMARDs, low baseline sIL-2R level predicted rapid clinical response to treatment with infliximab, an anti-tumour necrosis factor antibody. Furthermore, in a cohort of 26 patients with acute ReA, high baseline sIL-2R level predicted remission after 6 months. Levels of circulating soluble E-selectin (sE-selectin), a marker of endothelial activation, were measured annually by enzyme-linked immunosorbent assay (ELISA) in a cohort of 85 patients with early RA. During a five-year follow-up, sE-selectin levels were associated with activity and outcome of RA. The levels of neutrophil and monocyte CD11b/CD18 expression measured by flow cytometry, and circulating levels of sE-selectin measured by ELISA, and procalcitonin by immunoluminometric assay, were compared in 28 patients with acute ReA and 16 patients with early RA. The levels of the markers were comparable in ReA, RA, and healthy control subjects. In conlusion, sIL-2R may provide a new predictive marker in early RA treated with a single DMARD and refractory RA treated with infliximab. In addition, sIL-2R level predicts remission in acute ReA.

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Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

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A total of 4063 young bulls of two tropical genotypes (1639 Brahman and 2424 Tropical Composite) raised in northern Australia were evaluated for a comprehensive range of production and reproduction traits up to 24 months of age. Prior to weaning, peripheral blood concentrations of luteinising hormone (LH) and inhibin were measured at 4 months of age. At weaning (6 months) blood insulin-like growth factor-1 (IGF-I) and flight time were recorded. Body composition traits of fat depth and eye-muscle area were determined by ultrasonography at 15 months of age when additional measurements of liveweight, hip height and body condition score were recorded. Bull breeding soundness was evaluated at similar to 12, 18 and 24 months of age when measurements of scrotal circumference, sheath score, semen mass activity, progressive motility of individual sperm and percent morphologically normal sperm were recorded. Magnitude of heritability and genetic correlations changed across time for some traits. Heritability of LH, inhibin, IGF-I and of 18-month scrotal circumference, mass activity, progressive motility and percent normal sperm was 0.31, 0.74, 0.44, 0.75, 0.24, 0.15 and 0.25, respectively, for Brahmans and 0.48, 0.72, 0.36, 0.43, 0.13, 0.15 and 0.20, respectively, for Tropical Composites. Inhibin and IGF-I had moderate genetic association with percent normal sperm at 24 months in Brahmans but low to negligible associations in Tropical Composites. Body condition score in Brahmans and sperm motility (mass and individual) traits in both genotypes had moderate to strong genetic correlation with percent normal sperm and may prove useful candidates for indirect selection. There is scope to increase scrotal circumference by selection and this will be associated with favourable correlated responses of improved semen quality in both genotypes. The lack of genetic antagonism among bull traits indicates that selection for improved semen quality will not adversely affect other production traits.

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The simultaneous state and parameter estimation problem for a linear discrete-time system with unknown noise statistics is treated as a large-scale optimization problem. The a posterioriprobability density function is maximized directly with respect to the states and parameters subject to the constraint of the system dynamics. The resulting optimization problem is too large for any of the standard non-linear programming techniques and hence an hierarchical optimization approach is proposed. It turns out that the states can be computed at the first levelfor given noise and system parameters. These, in turn, are to be modified at the second level.The states are to be computed from a large system of linear equations and two solution methods are considered for solving these equations, limiting the horizon to a suitable length. The resulting algorithm is a filter-smoother, suitable for off-line as well as on-line state estimation for given noise and system parameters. The second level problem is split up into two, one for modifying the noise statistics and the other for modifying the system parameters. An adaptive relaxation technique is proposed for modifying the noise statistics and a modified Gauss-Newton technique is used to adjust the system parameters.

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A very general and numerically quite robust algorithm has been proposed by Sastry and Gauvrit (1980) for system identification. The present paper takes it up and examines its performance on a real test example. The example considered is the lateral dynamics of an aircraft. This is used as a vehicle for demonstrating the performance of various aspects of the algorithm in several possible modes.

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Abstract is not available.

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We present a Bayesian sampling algorithm called adaptive importance sampling or population Monte Carlo (PMC), whose computational workload is easily parallelizable and thus has the potential to considerably reduce the wall-clock time required for sampling, along with providing other benefits. To assess the performance of the approach for cosmological problems, we use simulated and actual data consisting of CMB anisotropies, supernovae of type Ia, and weak cosmological lensing, and provide a comparison of results to those obtained using state-of-the-art Markov chain Monte Carlo (MCMC). For both types of data sets, we find comparable parameter estimates for PMC and MCMC, with the advantage of a significantly lower wall-clock time for PMC. In the case of WMAP5 data, for example, the wall-clock time scale reduces from days for MCMC to hours using PMC on a cluster of processors. Other benefits of the PMC approach, along with potential difficulties in using the approach, are analyzed and discussed.

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Key message Eucalyptus pellita demonstrated good growth and wood quality traits in this study, with young plantation grown timber being suitable for both solid and pulp wood products. All traits examined were under moderate levels of genetic control with little genotype by environment interaction when grown on two contrasting sites in Vietnam. Context Eucalyptus pellita currently has a significant role in reforestation in the tropics. Research to support expanded of use of this species is needed: particularly, research to better understand the genetic control of key traits will facilitate the development of genetically improved planting stock. Aims This study aimed to provide estimates of the heritability of diameter at breast height over bark, wood basic density, Kraft pulp yield, modulus of elasticity and microfibril angle, and the genetic correlations among these traits, and understand the importance of genotype by environment interactions in Vietnam. Methods Data for diameter and wood properties were collected from two 10-year-old, open-pollinated progeny trials of E. pellita in Vietnam that evaluated 104 families from six native range and three orchard sources. Wood properties were estimated from wood samples using near-infrared (NIR) spectroscopy. Data were analysed using mixed linear models to estimate genetic parameters (heritability, proportion of variance between seed sources and genetic correlations). Results Variation among the nine sources was small compared to additive variance. Narrow-sense heritability and genetic correlation estimates indicated that simultaneous improvements in most traits could be achieved from selection among and within families as the genetic correlations among traits were either favourable or close to zero. Type B genetic correlations approached one for all traits suggesting that genotype by environment interactions were of little importance. These results support a breeding strategy utilizing a single breeding population advanced by selecting the best individuals across all seed sources. Conclusion Both growth and wood properties have been evaluated. Multi-trait selection for growth and wood property traits will lead to more productive populations of E. pellita both with improved productivity and improved timber and pulp properties.

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Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (similar to 6 nm), large cavity (similar to 40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (similar to 250 mu g/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 mu g of oE2 plus 10 mu g of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 mu g of oE2 adsorbed to 250 mu g of SV-140) or oE2/SV-140 together with 10 mu g of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10(4), the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512-1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery. (C) 2014 Elsevier Ltd. All rights reserved.

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Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.