Structural analysis of Alba Patera, Mars : from deep-seated to shallow events

Today, the planet Mars is in a phase of volcanic and tectonic quiescence. However, the 11.000 m high and 8000 km wide volcanic dome of the Tharsis region, transected by giant tectonic features, bears witness to past intense activity on the red planet. At the northernmost boundary of the Tharsis dome, the volcanic edifice of Alba Patera forms a widespread shield of 2700 km diameter and 7.000 m maximum elevation. The tectonics on Alba Patera has been the particular object of attention. The volcano and its environment are intensely breached by lineaments, which are interpreted as being fault-type structures. The orientation of those faults is in general north-south, radial to the Tharsis dome. On the flanks of Alba Patera, however, the faults curve around and are arranged in concentric pattern, encircling the summit of the edifice. In this thesis, the structural information of Alba Patera was reviewed and newly analysed based on Viking Mosaic data. Due to the high resolution of 60 m pro pixel, details about the fault development on Alba Patera are observable. Based on cross-cutting relationships of the observed lineaments, it becomes obvious that concentric fracturing of Alba Patera formed progressively, after radial fracturing. The further focus of this thesis is to study the implications of observed structures for hidden subvolcanic processes and to infer coupled genetic mechanisms that generate tension within the crust and the volcanic edifice. It is demonstrated that the lineaments record the dynamic past of Alba Patera, enlightening that this region of the red planet suffered a multifaceted history of crustal and volcanic evolution. Modelling the observed structures is used as a crucial key to understand their formation. Two modelling methods were used. Most of the analysis was performed by numerical models using the Finite Element code TEKTON. Semi-automatic Fortran subroutines were programmed to accelerate Finite Element data input and allow modelling with a large variety of unknown mechanical parameters. The numerically predicted surface deformation and fault arrangements are compared to the Viking Mosaic lineaments, and finally reproduced qualitatively by analogue experiments in a sand-box. Variations of subsurface source characteristics have been investigated specifically their interplay with the volcanic loading, and their superposition with a regional extension representative of the Tharsis doming. This study shows that the observed radial structures, i.e. the Tantalus Fossae, that extend from the flanks of Alba Patera toward large northern distance, reflect the extensional surface effect of local uplift. This supports the idea that Alba Patera was an autonomous hotspot and structural dome. The following tectonic phase on Alba Patera is dominated by the formation of concentric grabens on the western and eastern mid and upper flanks of the volcano. The orientation and position of these grabens are found to be best reproduced by local crustal subsidence, superposed with a regional extensional stress field. Simulating these mechanisms in analogue sand-box models also produced surface-structures of arrangements that almost perfectly mimic the observed lineaments on Alba Patera. As seen from the mosaic image analysis, the formation of the circumferential grabens was incrementally and increasingly pronounced towards the final stages of volcanic shield construction. Since this spans a time period probably on the order of a billion years, this suggests long-term geodynamic processes to be responsible for subsidence of the central Alba Patera area. The progressive change toward higher concentricity likely resulted from an increase of density by cooling and accumulation of intrusive material during the construction of the volcano – and thus subsidence of the region above this volcanic root. The reader will find within various parts of the thesis implications for the potential mechanical properties of Alba Patera and the Martian crust. Also the absence of lineaments can be used, to infer new information about the mechanical properties of the planet’s upper lithosphere. For instance, the absence of bending signatures surrounding the Martian volcano provides information about the mechanical properties of the lithosphere. The methodical work presented in the second part of this thesis is devoted to the modelling of lithospheric flexure under the load of Alba Patera. It is shown that the lithospheric viscosity together with the load emplacement, the planet curvature and the crustal strength are primordial parameters to reduce the flexural stresses, and thus explaining the absence of flexural fractures surrounding the volcano. Summary and perspective: Due to the minor crustal plate movement and erosion, a very long-term creation history of Alba Patera is reconstructable. The formation of lineaments, as analysed by Viking photo-mosaics, was simulated by numerical and analogue methods to elucidate the dynamic history of this volcanic edifice. The proposed vertical tectonic processes may have been not only of importance on Alba Patera, probably on Earth similar mechanisms exist on similar dimensions that are however obscured by plate tectonics

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors

Modeling volcanic deformation in a regional stress field: Implications for the formation of graben structures on Alba Patera, Mars

Abundant grabens transect the volcano Alba Patera. Their complex geometry and formation mechanisms are still poorly understood. Tectonic processes and magmatic intrusions are responsible for these long surface features. Cross-cutting relationships of the grabens show radial fractures that were formed during early stages and were progressively overprinted by concentric fractures on the mid and upper flanks of the volcano. Two modeling methods are used to understand the formation of the observed structures and to evaluate their implications for hidden subvolcanic processes. Surface deformation and fault arrangements predicted in finite element models are compared to the graben systems observed in Viking images. The orientation and position of the concentric grabens are found to be best reproduced by local crustal subsidence, superimposed on a regional NW-SE oriented extension with decreasing magnitude from south to north. In analogue sandbox models we also simulate surface structures of arrangements that almost perfectly mimic the observed lineaments on Alba Patera. Formation of the grabens spans a period on the order of a billion years, suggesting long-term geodynamic processes to be responsible for the subsidence of the central Alba Patera area. The progressive change toward higher concentricity is likely resultant from an increase in density in the crust by accumulation of intrusive material and cooling, thus causing subsidence of the region above this volcanic root

Equol: a comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro

It has been postulated that the R- and S-equol enantiomers have different biological properties given their different binding affinities for the estrogen receptor. S-(-)equol is produced via the bacterial conversion of the soy isoflavone daidzein in the gut. We have compared the biological effects of purified S-equol to that of racemic (R and S) equol on breast and prostate cancer cells of varying receptor status in vitro. Both racemic and S-equol inhibited the growth of the breast cancer cell line MDA-MB-231 (> or = 10 microM) and the prostate cancer cell lines LNCaP (> or = 5 microM) and LAPC-4 (> or = 2.5 microM). The compounds also showed equipotent effects in inhibiting the invasion of MDA-MB-231 and PC-3 cancer cells through matrigel. S-equol (1, 10, 30 microM) was unable to prevent DNA damage in MCF-7 or MCF-10A breast cells following exposure to 2-hydroxy-4-nonenal, menadione, or benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. In contrast, racemic equol (10, 30 microM) prevented DNA damage in MCF-10A cells following exposure to 2-hydroxy-4-nonenal or menadione. These findings suggest that racemic equol has strong antigenotoxic activity in contrast to the purified S-equol enantiomer implicating the R-, rather than the S-enantiomer as being responsible for the antioxidant effects of equol, a finding that may have implications for the in vivo chemoprotective properties of equol