Failure of slopes

The dynamic mechanism of slope failure is studied both experimentally and analytically to establish the spatial and temporal process of failure initiation and propagation during collapse of a natural or man-made slope. Model slopes, constructed of a brittle cemented sand material, are tested to collapse in a geotechnical centrifuge and the dynamics of failure recorded by motion picture film and mechanical detectors within the slope specimen. Shear failure is observed to initiate at the toe and propagate rapidly to the crest in the presence of crest tension cracking. A finite difference approach is taken to numerically solve the plane strain slope stability problem under gravity, based on unstable material behavior. Using a Lagrangian differencing scheme in space and explicit integration in time with dynamic relaxation, the numerical method finds the equilibrium state of the slope as the large-time limit of a dynamic problem with artificial parameters. The solution predicts localized shear failure zones which initiate at the slope toe and propagate to the slope crest in the manner and geometry observed in the centrifuge tests. In so doing, the finite difference algorithm also demonstrates an apparent ability to predict shear failure mechanisms in solid continua in general

Constant angular velocity of the wrist during the lifting of a sphere.

The primary objective of the experiments was to investigate the wrist motion of a person while they were carrying out a prehensile task from a clinical hand function test. A sixcamera movement system was used to observe the wrist motion of 10 participants. A very light sphere and a heavy sphere were used in the experiments to study any mass effects. While seated at a table, a participant moved a sphere over a small obstacle using their dominant hand. The participants were observed to move their wrist at a constant angular velocity. This phenomenon has not been reported previously. Theoretically, the muscles of the wrist provide an impulse of force at the start of the rotation while the forearm maintains a constant vertical force on a sphere. Light–heavy mean differences for the velocities, absolute velocities, angles and times taken showed no significant differences (p¼0.05)

Phase-slip avalanches in the superflow of 4^4He through arrays of nanopores

Recent experiments by Sato et al. [1] have explored the dynamics of $^4$He superflow through an array of nanopores. These experiments have found that, as the temperature is lowered, phase-slippage in the pores changes its character, from synchronous to asynchronous. Inspired by these experiments, we construct a model to address the characteristics of phase-slippage in superflow through nanopore arrays. We focus on the low-temperature regime, in which the current-phase relation for a single pore is linear, and thermal fluctuations may be neglected. Our model incorporates two basic ingredients: (1) each pore has its own random value of critical velocity (due, e.g., to atomic-scale imperfections), and (2) an effective inter-pore coupling, mediated through the bulk superfluid. The inter-pore coupling tends to cause neighbours of a pore that has already phase-slipped also to phase-slip; this process may cascade, creating an avalanche of synchronously slipping phases. As the temperature is lowered, the distribution of critical velocities is expected to effectively broaden, owing to the reduction in the superfluid healing length, leading to a loss of synchronicity in phase-slippage. Furthermore, we find that competition between the strength of the disorder in the critical velocities and the strength of the inter-pore interaction leads to a phase transition between non-avalanching and avalanching regimes of phase-slippage. [1] Sato, Y., Hoskinson, E. Packard, R. E. cond-mat/0605660.Comment: 8 pages, 5 figure

Improving the mesodermal differentiation potential of human embryonic stem cells

Human embryonic stem cells (hESCs) are thought to have enormous potential for use in regenerative medicine, whilst simultaneously allowing us insights into human embryonic development, disease modelling and drug discovery. Differentiation to mesodermal lineages, such as cardiomyocytes and blood, may allow for improved treatment of cardiac and haematopoietic diseases. hESC-derived immune cell types may also allow the circumnavigation of the immune barrier. This thesis aims to test the hypothesis that formation of hESC derivatives is regulated by the same mechanisms and ontology as in vivo embryo development. Therefore, by identifying and facilitating the mechanisms of mesoderm induction, hESC differentiation can be optimised to maximise the production of mesoderm, and, ultimately, mesoderm derivatives. Using a Xenopus laevis animal cap model with simultaneous treatment with activin B or fgf4, together with tall, Im02 and gatal mRNA, resulted in substantial increases in mesodermal, haemangioblast and erythropoietic cell markers. One of the most successful methods for hESC differentiation is by the formation of human embryoid bodies (hEBs). To reduce first the number of variables in current mass culture protocols for hEB formation, such as hEB size, a forced aggregation system was established that produced homogeneous hEBs from defined numbers of cells. This system was then optimised to enhance production beating cardiomyocytes by varying the number of hESCs used for hEB formation and also the number of days in culture. This system was assessed in four hESC lines and demonstrated substantial inter-line variability in cardiomyocyte production (1.6± 1.0% to 9.5±0.9°0). Differentiation was also performed using chemically defined media (CDM) with the addition of actiyin A and FGF2 and resulted in 23.6±3.6% of hESs producing beating cardiomyocytcs. In addition immunohistochemistry was performed to assess the relationship of cells expressing markers for mesoderm, pluripotency, ectoderm, and endoderm to establish a standard spatial and temporal map of hEB differentiation

Improving the mesodermal differentiation potential of human embryonic stem cells

Human embryonic stem cells (hESCs) are thought to have enormous potential for use in regenerative medicine, whilst simultaneously allowing us insights into human embryonic development, disease modelling and drug discovery. Differentiation to mesodermal lineages, such as cardiomyocytes and blood, may allow for improved treatment of cardiac and haematopoietic diseases. hESC-derived immune cell types may also allow the circumnavigation of the immune barrier. This thesis aims to test the hypothesis that formation of hESC derivatives is regulated by the same mechanisms and ontology as in vivo embryo development. Therefore, by identifying and facilitating the mechanisms of mesoderm induction, hESC differentiation can be optimised to maximise the production of mesoderm, and, ultimately, mesoderm derivatives. Using a Xenopus laevis animal cap model with simultaneous treatment with activin B or fgf4, together with tall, Im02 and gatal mRNA, resulted in substantial increases in mesodermal, haemangioblast and erythropoietic cell markers. One of the most successful methods for hESC differentiation is by the formation of human embryoid bodies (hEBs). To reduce first the number of variables in current mass culture protocols for hEB formation, such as hEB size, a forced aggregation system was established that produced homogeneous hEBs from defined numbers of cells. This system was then optimised to enhance production beating cardiomyocytes by varying the number of hESCs used for hEB formation and also the number of days in culture. This system was assessed in four hESC lines and demonstrated substantial inter-line variability in cardiomyocyte production (1.6± 1.0% to 9.5±0.9°0). Differentiation was also performed using chemically defined media (CDM) with the addition of actiyin A and FGF2 and resulted in 23.6±3.6% of hESs producing beating cardiomyocytcs. In addition immunohistochemistry was performed to assess the relationship of cells expressing markers for mesoderm, pluripotency, ectoderm, and endoderm to establish a standard spatial and temporal map of hEB differentiation

Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity

Nonerythrocyte spectrins: actin-membrane attachment proteins occurring in many cell types

The properties of brain fodrin have been analyzed and compared with those of erythrocyte spectrin. Both proteins consist of high molecular weight polypeptide doublets on SDS polyacrylamide gels and in solution behave as very large asymmetric molecules. Both proteins show a characteristic increase in sedimentation coefficient in the presence of 20 mM KCl. Antibodies against the brain protein cross-react with erythrocyte spectrin and cross-react with similar high molecular weight doublet polypeptides in SDS polyacrylamide gels of other cell types and plasma membrane preparations. Both proteins bind actin. The brain protein and erythrocyte spectrin show specific and competitive binding to erythrocyte membranes and this binding is inhibited by antibodies against erythrocyte ankyrin. Several of these properties distinguish these proteins from the class of high molecular weight actin-binding proteins that includes filamin and macrophage actin-binding protein. We conclude that together with erythrocyte spectrin, the brain protein and equivalent, immunologically related proteins in other cell types belong to a single class of proteins with the common function of attachment of actin to plasma membranes. Based on the structural and functional similarities, the name spectrin would seem appropriate for this whole class of proteins