Hierarchical Heterogeneity Research Articles

Deformation Behavior of an Austempered Ductile Cast Iron Studied by Neutron Diffraction

Tensile and compressive deformation behaviors of an austempered ductile cast iron (ADI) were studied using neutron diffraction. The stress partitioning among the bainitic ferrite matrix, the retained austenite and graphite is shown during elastic and plastic deformation. The austenite is found to be plastically stronger than the ferrite matrix, resulting in increasing of work hardening. The graphite particle bears little stress, so that it plays like cavity. The stress-induced martensitic transformation occurs in the retained austenite, where crystal orientation dependence is observed. Hence, it is revealed that hierarchical heterogeneity in plastic deformation of the ADI includes intergranular stresses, phase stresses and stress-induced martensite transformation, which can be monitored in situ by the time of flight method of neutron diffraction.

Quantitative Monitoring of BCR-ABL mRNA Harboring the T315I Mutation in Chronic Myeloid Leukemia (CML).

Imatinib mesylate (IM) is currently the first line treatment for patients with Chronic Myeloid Leukemia (CML) allowing induction of major molecular responses in the majority of patients. Nevertheless, resistance develops in a small proportion of patients principally due to missense mutations in the ABL-kinase domain of the BCR-ABL fusion gene. New drugs, such as Dasatinib or Nilotinib, which have recently been designed to overcome IM-resistant mutants, remain inefficient against the mutation at the gatekeeper position (T315I). Thus, this mutation is likely to become the most critical hurdle in patients who fail to benefit from ABL competitive inhibitors. Consequently, when a T315I mutation is detected, a quantitative monitoring of 315 mutants seems to be crucial to evaluate the response to new therapies. For that purpose, we developed a sensitive quantitative-RT-PCR method using allele specific primers to quantify mRNA harboring the T315I mutation. Each cDNA from blood samples were tested in duplicates for ABL, BCR-ABL and BCR-ABL-315I mRNA expression. Serial dilutions of a p210BCR-ABL-315I plasmid were used to construct standard curves allowing the determination of numbers of ABL, BCR-ABL and BCR-ABL-315I mRNA copies. Results were expressed as the BCR-ABL/ABL ratio and BCR-ABL-315I/ABL. To ensure the quality of the results, several controls were analyzed together with patient samples: distilled water, cDNA from healthy blood donors, cDNA from CML patients at diagnosis and cDNA from IM-resistant CML patients exhibiting a T315I mutation. Using this protocol, we retrospectively studied cDNA samples from 5 patients with an acquired resistance to IM therapy due to the presence of the T315I mutation. The periods of follow-up went from 6 months to 2 years. The BCR-ABL/ABL and BCR-ABL-315I/ABL ratios were determined for all cDNA samples and the kinetics for the two transcripts were carried out for each patient. The Q-RT-PCR method, with the standard curves and the different controls, appears to be efficient enough to allow a reliable investigation. Figure shows the results obtained for patient D and C. In patient D, showing a total resistance to IM, a slow and constant increase in the expression of the BCR-ABL-315I mRNA was observed. Conversely, in patient C, BCR-ABL-315I mRNA increased more rapidly after an initial IM-responsive phase. The differential kinetics observed between the two patients suggest that target stem cells for T315I mutation could have some hierarchical heterogeneity with regard to their emergence. Similar results were obtained for the 3 other patients. In conclusion, the quantitative RT-PCR assay that we developed to estimate the relative amount of BCR-ABL mRNA exhibiting the T315I mutation could be of major interest not only for the evaluation of the mechanism of resistance but also for the follow-up of T315I-bearing CML stem cells in patients undergoing targeted therapy using new non-ATP competitive BCR-ABL inhibitors. [Display omitted]

A multiscale study of silty soil structure

SummaryDependency of soil properties on scale is a crucial issue in soil physics. In this paper, fractal approaches are used in two case studies in France and Australia, respectively, to study how measured physical soil properties change with the sample spacing and the scale of observation. At a scale of 10–1000 m (104 to 106 mm), fractals were applied to sample data from a linear transect, while at the 10−6 to 102 mm scale, fractals were applied in two dimensions to analyse both soil micro‐ and macrostructure, based on thin section samples. Porosity was characterized by short‐range spatial variations using sample spacings of 0.5 and 5 m (from the transect data), and a sample spacing of 1 cm (from the thin section analysis). The size of the representative elementary volume (REV) or representative elementary area (REA), required to represent statistically the elementary soil structure, was identified in three ways: (i) by the correlation length of a representative interconnected pore network, (ii) by the upper limit of the non‐linear increase with observation scale of mean porosity (upper limit of the solid mass fractal domain), and (iii) by the non‐linear decrease with observation scale of the coefficient of variation, CV, of mean porosity. Two embedded REAs were identified: the first (0.1–0.4 mm) related to the soil microstructure whereas a second (11–44 mm) related to the soil macrostructure. The solid mass fractal dimensions of the two embedded structural domains showed that hierarchical heterogeneity of soil structure was more pronounced for microstructures than for macrostructures. The mean area ratio of microstructural matrix/total surface and the CV of mean microporosity both scale similarly at observation scales smaller than the REA size. Their scaling exponents were both related to the fractal dimension of microstructural matrix. This preliminary study shows that the theory of fractals applied to soil structures at a specific scale range cannot be directly applied to predict soil physical properties at another scale range. This is because there are different interdependent structuring processes operating at different scales resulting in fractal dimensions being consistent only over particular domain limits.

Taming heterogeneity - the Ptolemy approach

Modern embedded computing systems tend to be heterogeneous in the sense of being composed of subsystems with very different characteristics, which communicate and interact in a variety of ways-synchronous or asynchronous, buffered or unbuffered, etc. Obviously, when designing such systems, a modeling language needs to reflect this heterogeneity. Today's modeling environments usually offer a variant of what we call amorphous heterogeneity to address this problem. This paper argues that modeling systems in this manner leads to unexpected and hard-to-analyze interactions between the communication mechanisms and proposes a more structured approach to heterogeneity, called hierarchical heterogeneity, to solve this problem. It proposes a model structure and semantic framework that support this form of heterogeneity, and discusses the issues arising from heterogeneous component interaction and the desire for component reuse. It introduces the notion of domain polymorphism as a way to address these issues.