The desmoplastic response : mechanisms of tumour-induced fibrogenesis

The main concern of this thesis is with desmoplasia - a process in which excessive connective tissue is deposited in a neoplasm. This is a common phenomenon in neoplasia but one whose mechanisms are poorly understood. To study the process, I used a human malignant melanoma cell line (UCT-Mel 7) that was established in this laboratory and that, when injected into athymic mice, gave rise to tumours that showed a number of interesting features. Firstly, the tumour induced a marked desmoplastic response as evidenced by a high content of hydroxyproline in tumour lysates, intense staining for reticulin in sections of the tumour and infiltration of the tumour by host mesenchymal cells. Secondly, the desmoplasia was associated in UCT-Mel 7-derived tumours with an unusual phasic pattern of growth that was related to the in vitro passage number of the melanoma cells. On occasions, murine tumours developed at the site of inoculation of human tumour cells. I have identified 2 possible mechanisms by which UCT-Mel 7 cells could have induced the desmoplastic response: either the tumour cells could have exerted their effect indirectly, i.e. via macrophages, or they could have stimulated the host's stromal cells directly. UCT-Mel 7 cells were shown to be chemotactic for mouse macrophages and human foreskin fibroblasts were stimulated, in a dose-dependent manner, to synthesize increased amounts of collagen when co-cultured with mouse peritoneal exudate cells. Stimulation could only be effected by direct cell:cell contact; medium conditioned by macrophages was not effective. The amount of stimulation was not dependent on the state of activation of the peritoneal cells nor on the strain of mouse used. Tumour cells were also found to act directly. Co-culture of UCT-Mel 7 cells and fibroblasts resulted in increased collagen synthesis by the fibroblasts. Increased synthesis of the protein was reflected in an increase in the amount of collagen mRNA. UCT-Mel 7 cell stimulated in a dose-dependent manner with an absolute requirement for intimate cell:cell contact with the fibroblasts. DNA synthesis was not required. Dexamethasone, retinoic acid and the tumour promoter, phorbol myristate acetate, had significant primary effects on fibroblast collagen synthesis but did not modify the response to melanoma cells. Indomethacin, however, had a minimal primary effect upon the fibroblasts but significantly augmented the melanoma cell effect. The nature of the stimulatory cell:cell contact is still uncertain. The gap junction inhibitor, α-glycyrrhetinic acid, did not diminish the melanoma cell effect. Preliminary findings suggested that cell-surface proteoglycans may be important. Removal of the proteoglycans with the inhibitor of proteoglycan assembly, 4-methylumbelliferyl-β-D-xyloside, abrogated the melanoma cell:fibroblast interaction. Recombinant basic fibroblast growth factor did. not seem to be involved in the desmoplastic response. It was of incidental interest to note that this compound inhibited fibroblast collagen synthesis in a manner that was augmented by the concomitant addition of heparin. A surprising finding was the production of a potent inhibitor of collagen synthesis by superinduced cells of the mouse macrophage cell line, P388D₁. This inhibitor has not been fully characterised

Analysing Threshold Value in Fire Detection Algorithm Using MODIS Data

Abstract - MODIS instruments have been designed to include special channels for fire monitoring by adding more spectral thermal band detector on them. The basic understanding of remote sensing fire detection should be kept in mind to be able to improve the algorithm for regional scale detection purposes. It still gives many chances for more exploration. This paper describe the principle of fire investigation applied on MODIS data. The main used algorithm in this research is contextual algorithm which has been developed by NASA scientist team. By varying applied threshold of T4 value in the range of 320-360K it shows that detected fire is significantly changed. While significant difference of detected FHS by changing ΔT threshold value is occurred in the range of 15-35K. Improve and adjustment of fire detection algorithm is needed to get the best accuracy result proper to local or regional conditions. MOD14 algorithm is applied threshold values of 325K for T4 and 20K for ΔT. Validation has been done from the algorithm result of MODIS dataset over Indonesia and South Africa. The accuracy of MODIS fire detection by MOD14 algorithm is 73.2% and 91.7% on MODIS data over Sumatra-Borneo and South Africa respectively

Detecting trend and seasonal changes in bathymetry derived from HICO imagery: A case study of Shark Bay, Western Australia

The Hyperspectral Imager for the Coastal Ocean (HICO) aboard the International Space Station has offered for the first time a dedicated space-borne hyperspectral sensor specifically designed for remote sensing of the coastal environment. However, several processing steps are required to convert calibrated top-of-atmosphere radiances to the desired geophysical parameter(s). These steps add various amounts of uncertainty that can cumulatively render the geophysical parameter imprecise and potentially unusable if the objective is to analyze trends and/or seasonal variability. This research presented here has focused on: (1) atmospheric correction of HICO imagery; (2) retrieval of bathymetry using an improved implementation of a shallow water inversion algorithm; (3) propagation of uncertainty due to environmental noise through the bathymetry retrieval process; (4) issues relating to consistent geo-location of HICO imagery necessary for time series analysis, and; (5) tide height corrections of the retrieved bathymetric dataset. The underlying question of whether a temporal change in depth is detectable above uncertainty is also addressed. To this end, nine HICO images spanning November 2011 to August 2012, over the Shark Bay World Heritage Area, Western Australia, were examined. The results presented indicate that precision of the bathymetric retrievals is dependent on the shallow water inversion algorithm used. Within this study, an average of 70% of pixels for the entire HICO-derived bathymetry dataset achieved a relative uncertainty of less than ± 20%. A per-pixel t-test analysis between derived bathymetry images at successive timestamps revealed observable changes in depth to as low as 0.4 m. However, the present geolocation accuracy of HICO is relatively poor and needs further improvements before extensive time series analysis can be performed

Analysing Threshold Value in Fire Detection Algorithm Using MODIS Data

MODIS instruments have been designed to include special channels for fire monitoring by adding more spectral thermal band detector on them. The basic understanding of remote sensing fire detection should be kept in mind to be able to improve the algorithm for regional scale detection purposes. It still gives many chances for more exploration. This paper describes the principle of fire investigation applied on MODIS data. The main used algorithm in this research is contextual algorithm which has been developed by NASA scientist team. By varying applied threshold of T4 value in the range of 320-360K it shows that detected fire is significantly changed. While significant difference of detected FHS by changing ΔT threshold value is occurred in the range of 15-35K. Improve and adjustment of fire detection algorithm is needed to get the best accuracy result proper to local or regional conditions. MOD14 algorithm is applied threshold values of 325K for T4 and 20K for ΔT. Validation has been done from the algorithm result of MODIS dataset over Indonesia and South Africa. The accuracy of MODIS fire detection by MOD14 algorithm is 73.2% and 91.7% on MODIS data over Sumatra-Borneo and South Africa respectively

Paramyxovirus persistence

In this study, SV5 infection of Balb/c mouse fibroblast cells has been used as a model system to investigate the possible mechanisms underlying the establishment and maintenance of Paramyxovirus persistence. It was found that following entry to these cells, the virus initiated a wave of transcription and replication, similar to that of a permissive infection, in which normal levels of each of the virus proteins were synthesized. However, by 48-72 hours post infection (p.i.) there was an almost complete cessation of virus mRNA and protein synthesis. Despite the decrease in virus activity, full length viral genome RNA and P and NP, the proteins involved in transcription and replication, could be detected at consistently high levels up to 5 days p.i., although the levels of HN, M, F and V declined. Immunofluorescence analysis supported these data showing that at later times p.i. although there were some cells positive for all the viral proteins, a high proportion of cells were strongly positive for NP, L and P, but negative for M, F and HN. In these cells, NP, L and P were often located in discrete cytoplasmic foci. These results suggested that the persistently infected cell population consisted of some cells in which the virus was active and other in which it was quiescent within cytoplasmic inclusions. A series of cell lines was established from a monolayer of Balb/c cells that had been infected at a high multiplicity. Immunofluorescence studies showed only a minority of cells in these clones to be infected with virus, indicating that during division, not all daughter cells became infected. Of the infected cells, some were positive for all the viral proteins, while others were positive for only NP and P. Co-cultivation of the cloned cells with Vero cells, which are permissive for SV5 replication, rapidly yielded non-defective virus, suggesting that the virus was active in some cells. These results suggested that the persisting virus was in a state of flux, able to reside as inclusions of inactive nucleocapids from which it could reactivate to initiate a new round of infection. Experiments aiming to determine if the persistently infected cells were resistant to immune attack demonstrated that cells at 5 days p.i., in which the majority of cells were quiescently infected, were less susceptible to immune lysis than cells at 1 day p.i. in which there was ongoing protein synthesis. Further experiments were carried out both to try to determine what had induced the persistent state in mouse cells and also to examine factors which might induce a similar state in different cell lines

Improving the optimization solution for a semi-analytical shallow water inversion model in the presence of spectrally correlated noise

In coastal regions, shallow water semi-analytical inversion algorithms may be used to derive geophysical parameters such as inherent optical properties (IOPs), water column depth, and bottom albedo coefficients by inverting sensor-derived sub-surface remote sensing reflectance, rrs. The uncertainties of these derived geophysical parameters due to instrumental and environmental noise can be estimated numerically via the addition of spectral noise to the sensor-derived rrs before inversion. Repeating this process multiple times allows the calculation of the standard error and average for each derived parameter. Apart from spectral non-uniqueness, the optimization algorithm employed in the inversion must converge onto a single minimum to obtain a true representation of the uncertainty for a given set of noise-perturbed rrs. Failure to do so inflates the uncertainty and affects the average retrieved value (accuracy). We show that the standard approach of seeding the optimization with an arbitrary, fixed initial guess, can lead to the convergence to multiple minima, each having substantially different centroids in multi-parameter solution space. We present the Update-Repeat Levenberg-Marquardt (UR-LM) and Latin Hypercube Sampling (LHS) routines that dynamically search the solution space for an optimal initial guess, that when applied to the optimization allows convergence to the best local minimum. We apply the UR-LM and LHS methods on HICO-derived and simulated rrs and demonstrate the improved computational efficiency, precision, and accuracy afforded from these methods compared with the standard approach. Conceptually, these methods are applicable to remote sensing based, shallow water or oceanic semi-analytical inversion algorithms requiring nonlinear least squares optimization