Relationship between residual stresses and mechanical behavior in ceramic composites

En este trabajo, materiales de tipo alúmina/Y-TZP (ZrO2 tetragonal, estabilizada con 3 mol. % Y2O3), como sistema cerámico popular por sus mejoradas propiedades mecánicas en comparación con las cerámicas de alúmina puras, han sido estudiados en términos de propiedades mecánicas y tensiones residuales. El novedoso método de colado en cinta, consistente en el apilamiento de cintas de cerámica verde a temperatura ambiente y el uso de bajas presiones, se ha escogido para la presente investigación con el fin de poder aprovechar al máximo el futuro desarrollo de materiales laminados de alúmina-óxido de circonio. Se han determinado las propiedades de los materiales obtenidos por este nuevo método de procesamiento comparándolas con las de los materiales obtenidos por “slip casting”, con el fin de analizar si el método propuesto afecta a la microestructura y, por tanto, a las propiedades mecánicas y tensiones residuales propias de estos materiales. Para analizar la idoneidad del proceso de fabricación, utilizado para evitar la presencia de discontinuidades en las intercaras entre las láminas así como otros fenómenos que puedan interferir con las propiedades mecánicas, se estudiaron materiales cerámicos con la misma composición en cintas. Por otra parte también se analizó el efecto de la adición de óxido de circonio sobre la aparición de tensiónes residuales en cerámicas Al2O3/Y-TZP, teniendo en cuenta su notable influencia sobre las propiedades microestructurales y mecánicas de los materiales, así como el requisito de co-sinterización de capas con diferentes materiales compuestos en materiales laminados. La caracterización del material incluye la determinación de la densidad, el análisis de la microestructura, la obtención de las propiedades mecánicas (módulo de elasticidad, dureza, resistencia a la flexión y tenacidad de fractura) así como de las tensiones residuales. En combinación con otros métodos de medida tradicionales, la nanoindentación también se empleó como una técnica adicional para la medida del módulo de elasticidad y de la dureza. Por otro lado, diferentes técnicas de difracción con neutrones, tanto las basadas en longitud de onda constante (CW) como en tiempo de vuelo (TOF), han sido empleadas para la medición fiable de la deformación residual a través del grosor en muestras a granel. Las tensiones residuales fueron determinadas con elevada precisión, aplicando además métodos de análisis apropiados, como por ejemplo el refinamiento de Rietveld. Las diferentes fases en cerámicas sinterizadas, especialmente las de zirconia, se examinaron con detalle mediante el análisis de Rietveld, teniendo en cuenta el complicado polimorfismo del Óxido de Zirconio (ZrO2) así como las posibles transformaciones de fase durante el proceso de fabricación. Los efectos del contenido de Y-TZP en combinación con el nuevo método de procesamiento sobre la microestructura, el rendimiento mecánico y las tensiones residuales de los materiales estudiados (Al2O3/Y-TZP) se resumen en el presente trabajo. Finalmente, los mecanismos de endurecimiento, especialmente los relacionados con las tensiones residuales, son igualmente discutidos. In present work, Alumina/Y-TZP (tetragonal ZrO2 stabilized with 3 mol% Y2O3) materials, as an popular ceramic system with improved mechanical properties compared with the pure alumina ceramics, have been studied in terms of mechanical properties and residual stresses. The novel tape casting method, which involved the stacking of green ceramics tapes at room temperature and using low pressures, is selected for manufacturing and investigation, in order to take full advantage of the future development of alumina-zirconia laminated materials. Features of materials obtained by the new processing method are determined and compared with those of materials obtained by conventional slip casting in a plaster mold, in order to study whether the proposed method of processing affects microstructure and thereby the mechanical properties and residual stresses characteristics of materials. To analyse the adequacy of the manufacturing process used to avoid the presence of discontinuities at the interfaces between the sheets and other phenomena that interfere with the mechanical properties, ceramic materials with the same composition in tapes were investigated. Moreover, the effect of addition of zirconia on residual stress development of Al2O3/Y-TZP ceramics were taken into investigations, considering its significantly influence on the microstructure and mechanical properties of materials as well as the requirement of co-sintering of layers with different composites in laminated materials. The characterization includes density, microstructure, mechanical properties (elastic modulus, hardness, flexure strength and fracture toughness) and residual stresses. Except of the traditional measurement methods, nanoindentation technique was also used as an additional measurement of the elastic modulus and hardness. Neutron diffraction, both the constant-wavelength (CW) and time-of-flight (TOF) neutron diffraction techniques, has been used for reliable through-thickness residual strain measurement in bulk samples. Residual stresses were precisely determined combined with appropriate analysis methods, e.g. the Rietveld refinement. The phase compositions in sintered ceramics especially the ones of zirconia were accurately examined by Rietveld analysis, considering the complex polymorph of ZrO2 and the possible phase transformation during manufacturing process. Effects of Y-TZP content and the new processing method on the microstructure, mechanical performance and residual stresses were finally summarized in present studied Al2O3/Y-TZP materials. The toughening mechanisms, especially the residual stresses related toughening, were theoretically discussed.

Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase

Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 μM in 2 days and effectively eliminates the parasite in 2–4 days at 10–100 μM. Clodinafop is not toxic to the host cell even at much higher concentrations. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, and Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form.

Residual delay maps unveil global patterns of atmospheric nonlinearity and produce improved local forecasts

We use residual-delay maps of observational field data for barometric pressure to demonstrate the structure of latitudinal gradients in nonlinearity in the atmosphere. Nonlinearity is weak and largely lacking in tropical and subtropical sites and increases rapidly into the temperate regions where the time series also appear to be much noisier. The degree of nonlinearity closely follows the meridional variation of midlatitude storm track frequency. We extract the specific functional form of this nonlinearity, a V shape in the lagged residuals that appears to be a basic feature of midlatitude synoptic weather systems associated with frontal passages. We present evidence that this form arises from the relative time scales of high-pressure versus low-pressure events. Finally, we show that this nonlinear feature is weaker in a well regarded numerical forecast model (European Centre for Medium-Range Forecasts) because small-scale temporal and spatial variation is smoothed out in the grided inputs. This is significant, in that it allows us to demonstrate how application of statistical corrections based on the residual-delay map may provide marked increases in local forecast accuracy, especially for severe weather systems.

Acylation stabilizes a protease-resistant conformation of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides

Protein acylation is an important way in which a number of proteins with a variety of functions are modified. The physiological role of the acylation of cellular proteins is still poorly understood. Covalent binding of fatty acids to nonintegral membrane proteins is thought to produce transient or permanent enhancement of the association of the polypeptide chains with biological membranes. In this paper, we investigate the functional role for the palmitoylation of an atypical membrane-bound protein, yeast protoporphyrinogen oxidase, which is the molecular target of diphenyl ether-type herbicides. Palmitoylation stabilizes an active heat- and protease-resistant conformation of the protein. Palmitoylation of protoporphyrinogen oxidase has been demonstrated to occur in vivo both in yeast cells and in a heterologous bacterial expression system, where it may be inhibited by cerulenin leading to the accumulation of degradation products of the protein. The thiol ester linking palmitoleic acid to the polypeptide chain was shown to be sensitive to hydrolysis by hydroxylamine and also by the widely used serine-protease inhibitor phenylmethylsulfonyl fluoride.

Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy

Cancer relapse after surgery is a common occurrence, most frequently resulting from the outgrowth of minimal residual disease in the form of metastases. We examined the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade as an adjunctive immunotherapy to reduce metastatic relapse after primary prostate tumor resection. For these studies, we developed a murine model in which overt metastatic outgrowth of TRAMP-C2 (C2) prostate cancer ensues after complete primary tumor resection. Metastatic relapse in this model occurs reliably and principally within the draining lymph nodes in close proximity to the primary tumor, arising from established metastases present at the time of surgery. Using this model, we demonstrate that adjunctive CTLA-4 blockade administered immediately after primary tumor resection reduces metastatic relapse from 97.4 to 44%. Consistent with this, lymph nodes obtained 2 weeks after treatment reveal marked destruction or complete elimination of C2 metastases in 60% of mice receiving adjunctive anti-CTLA-4 whereas 100% of control antibody-treated mice demonstrate progressive C2 lymph node replacement. Our study demonstrates the potential of adjunctive CTLA-4 blockade immunotherapy to reduce cancer relapse emanating from minimal residual metastatic disease and may have broader implications for improving the capability of immunotherapy by combining such forms of therapy with other cytoreductive measures including surgery.

Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are consistent with a mathematical model in which host cell redistribution between lymph nodes and peripheral blood is a function of viral burden. Model fits to patient data suggest that, although therapy reduces HIV replication below replacement levels, substantial residual replication continues. This residual replication has important consequences for long-term therapy and the evolution of drug resistance and represents a challenge for future treatment strategies.

Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge

Diffusion of molecules in brain extracellular space is constrained by two macroscopic parameters, tortuosity factor λ and volume fraction α. Recent studies in brain slices show that when osmolarity is reduced, λ increases while α decreases. In contrast, with increased osmolarity, α increases, but λ attains a plateau. Using homogenization theory and a variety of lattice models, we found that the plateau behavior of λ can be explained if the shape of brain cells changes nonuniformly during the shrinking or swelling induced by osmotic challenge. The nonuniform cellular shrinkage creates residual extracellular space that temporarily traps diffusing molecules, thus impeding the macroscopic diffusion. The paper also discusses the definition of tortuosity and its independence of the measurement frame of reference.

NMR investigation of ferricytochrome c unfolding: Detection of an equilibrium unfolding intermediate and residual structure in the denatured state

Horse ferricytochrome c (cyt c) undergoes exchange of one of its axial heme ligands (Met-80) for one or more non-native ligands under denaturing conditions. We have used 1H NMR spectroscopy to detect two conformations of paramagnetic cyt c with non-native heme ligation through a range of urea concentrations. One non-native form is an equilibrium unfolding intermediate observed under partially denaturing conditions and is attributed to replacement of Met-80 with one or more Lys side chains. The second non-native form, in which the native Met ligand is replaced by a His, is observed under strongly denaturing conditions. Thermodynamic analysis of these data indicates a relatively small ΔG (17 kJ/mol) for the transition from native to the Lys-ligated intermediate and a significantly larger ΔG (47 kJ/mol) for the transition from native to the His-ligated species. Although CD and fluorescence data indicate that the equilibrium unfolding of cyt c is a two-state process, these NMR results implicate an intermediate with His-Lys ligation.

The domain structure of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides

Protoporphyrinogen oxidase (EC 1–3-3–4), the 60-kDa membrane-bound flavoenzyme that catalyzes the final reaction of the common branch of the heme and chlorophyll biosynthesis pathways in plants, is the molecular target of diphenyl ether-type herbicides. It is highly resistant to proteases (trypsin, endoproteinase Glu-C, or carboxypeptidases A, B, and Y), because the protein is folded into an extremely compact form. Trypsin maps of the native purified and membrane-bound yeast protoporphyrinogen oxidase show that this basic enzyme (pI > 8.5) was cleaved at a single site under nondenaturing conditions, generating two peptides with relative molecular masses of 30,000 and 35,000. The endoproteinase Glu-C also cleaved the protein into two peptides with similar masses, and there was no additional cleavage site under mild denaturing conditions. N-terminal peptide sequence analysis of the proteolytic (trypsin and endoproteinase Glu-C) peptides showed that both cleavage sites were located in putative connecting loop between the N-terminal domain (25 kDa) with the βαβ ADP-binding fold and the C-terminal domain (35 kDa), which possibly is involved in the binding of the isoalloxazine moiety of the FAD cofactor. The peptides remained strongly associated and fully active with the Km for protoporphyrinogen and the Ki for various inhibitors, diphenyl-ethers, or diphenyleneiodonium derivatives, identical to those measured for the native enzyme. However, the enzyme activity of the peptides was much more susceptible to thermal denaturation than that of the native protein. Only the C-terminal domain of protoporphyrinogen oxidase was labeled specifically in active site-directed photoaffinity-labeling experiments. Trypsin may have caused intramolecular transfer of the labeled group to reactive components of the N-terminal domain, resulting in nonspecific labeling. We suggest that the active site of protoporphyrinogen oxidase is in the C-terminal domain of the protein, at the interface between the C- and N-terminal domains.

Characterization of residual structure in the thermally denatured state of barnase by simulation and experiment: Description of the folding pathway

Residual structure in the denatured state of a protein may contain clues about the early events in folding. We have simulated by molecular dynamics the denatured state of barnase, which has been studied by NMR spectroscopy. An ensemble of 104 structures was generated after 2 ns of unfolding and following for a further 2 ns. The ensemble was heterogeneous, but there was nonrandom, residual structure with persistent interactions. Helical structure in the C-terminal portion of helix α1 (residues 13–17) and in helix α2 as well as a turn and nonnative hydrophobic clustering between β3 and β4 were observed, consistent with NMR data. In addition, there were tertiary contacts between residues in α1 and the C-terminal portion of the β-sheet. The simulated structures allow the rudimentary NMR data to be fleshed out. The consistency between simulation and experiment inspires confidence in the methods. A description of the folding pathway of barnase from the denatured to the native state can be constructed by combining the simulation with experimental data from φ value analysis and NMR.

A execução residual na tutela dos interesses individuais homogêneos

O presente trabalho tem como objetivo o estudo da execução residual na tutela dos interesses individuais homogêneos e as questões procedimentais que envolvem o instituto no direito processual brasileiro. Foram abordados aspectos relativos aos fundamentos do instituto no direito brasileiro, os requisitos para sua aplicação e o procedimento para a restituição da indenização devida aos indivíduos nos casos em que esta se faz necessária.

Ocular residual astigmatism and topographic disparity vector indexes in normal healthy eyes

Purpose: To define a range of normality for the vectorial parameters Ocular Residual Astigmatism (ORA) and topography disparity (TD) and to evaluate their relationship with visual, refractive, anterior and posterior corneal curvature, pachymetric and corneal volume data in normal healthy eyes. Methods: This study comprised a total of 101 consecutive normal healthy eyes of 101 patients ranging in age from 15 to 64 years old. In all cases, a complete corneal analysis was performed using a Scheimpflug photography-based topography system (Pentacam system Oculus Optikgeräte GmbH). Anterior corneal topographic data were imported from the Pentacam system to the iASSORT software (ASSORT Pty. Ltd.), which allowed the calculation of the ocular residual astigmatism (ORA) and topography disparity (TD). Linear regression analysis was used for obtaining a linear expression relating ORA and posterior corneal astigmatism (PCA). Results: Mean magnitude of ORA was 0.79 D (SD: 0.43), with a normality range from 0 to 1.63 D. 90 eyes (89.1%) showed against-the-rule ORA. A weak although statistically significant correlation was found between the magnitudes of posterior corneal astigmatism and ORA (r = 0.34, p < 0.01). Regression analysis showed the presence of a linear relationship between these two variables, although with a very limited predictability (R2: 0.08). Mean magnitude of TD was 0.89 D (SD: 0.50), with a normality range from 0 to 1.87 D. Conclusion: The magnitude of the vector parameters ORA and TD is lower than 1.9 D in the healthy human eye.