Search results for: ethnic density

Authors: Nanine Fouche

Abstract:

The Cape Flats is a low-lying sand-covered expanse of approximately 460 square kilometres, situated to the southeast of the central business district of Cape Town in the Western Cape of South Africa. The aeolian sands masking this area are often loose and compressible in the upper 1m to 1.5m of the surface, and there is a general exceedance of the maximum allowable settlement in these sands. The settlement of shallow foundations on Cape Flats sands is commonly predicted using the results of in-situ tests such as the SPT or DPSH due to the difficulty of retrieving undisturbed samples for laboratory testing. Varying degrees of accuracy and reliability are associated with these methods. More recently, shear wave velocity (Vs) profiles obtained from seismic testing, such as continuous surface wave tests (CSW), are being used for settlement prediction. Such predictions have the advantage of considering non-linear stress-strain behaviour of soil and the degradation of stiffness with increasing strain. CSW tests are rarely executed in the Cape Flats, whereas SPT’s are commonly performed. For this reason, and to facilitate better settlement predictions in Cape Flats sand, equations representing shear wave velocity (Vs) as a function of SPT blow count (N60) and vertical effective stress (v’) were generated by statistical regression of site investigation data. To reveal the most appropriate method of overburden correction, analyses were performed with a separate overburden term (Pa/σ’v) as well as using stress corrected shear wave velocity and SPT blow counts (correcting Vs. and N60 to Vs1and (N1)60respectively). Shear wave velocity profiles and SPT blow count data from three sites masked by Cape Flats sands were utilised to generate 80 Vs-SPT N data pairs for analysis. Investigated terrains included sites in the suburbs of Athlone, Muizenburg, and Atlantis, all underlain by windblown deposits comprising fine and medium sand with varying fines contents. Elastic settlement analysis was also undertaken for the Cape Flats sands, using a non-linear stepwise method based on small-strain stiffness estimates, which was obtained from the best Vs-N60 model and compared to settlement estimates using the general elastic solution with stiffness profiles determined using Stroud’s (1989) and Webb’s (1969) SPT N60-E transformation models. Stroud’s method considers strain level indirectly whereasWebb’smethod does not take account of the variation in elastic modulus with strain. The expression of Vs. in terms of N60 and Pa/σv’ derived from the Atlantis data set revealed the best fit with R2 = 0.83 and a standard error of 83.5m/s. Less accurate Vs-SPT N relations associated with the combined data set is presumably the result of inversion routines used in the analysis of the CSW results showcasing significant variation in relative density and stiffness with depth. The regression analyses revealed that the inclusion of a separate overburden term in the regression of Vs and N60, produces improved fits, as opposed to the stress corrected equations in which the R2 of the regression is notably lower. It is the correction of Vs and N60 to Vs1 and (N1)60 with empirical constants ‘n’ and ‘m’ prior to regression, that introduces bias with respect to overburden pressure. When comparing settlement prediction methods, both Stroud’s method (considering strain level indirectly) and the small strain stiffness method predict higher stiffnesses for medium dense and dense profiles than Webb’s method, which takes no account of strain level in the determination of soil stiffness. Webb’s method appears to be suitable for loose sands only. The Versak software appears to underestimate differences in settlement between square and strip footings of similar width. In conclusion, settlement analysis using small-strain stiffness data from the proposed Vs-N60 model for Cape Flats sands provides a way to take account of the non-linear stress-strain behaviour of the sands when calculating settlement.

Keywords: sands, settlement prediction, continuous surface wave test, small-strain stiffness, shear wave velocity, penetration resistance

Procedia PDF Downloads 152

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

Abstract:

Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 140