Diverted from its former course to the Pacific Ocean by basalt flows in Gem Valley, Idaho, the Bear River presently flows south into the Bonneville Basin. Constraining the timing of the river's diversion is pivotal to understanding the hydrologic budgets, and thus the climatological implications of the Bonneville Basin lakes. This study employs strontium (Sr) isotopes in mollusc fossils as a tracer of the Bear River water that entered Lake Thatcher, a small, closed-basin lake into which the redirected river flowed en route to the Bonneville Basin. The Sr ratios, combined with the temporal control afforded by amino acid geochronology and tephrochronology, were compared to mixing models constructed from the 87Sr/86Sr composition of the modern rivers draining into the basin to stimulate the Sr isotropic composition of Lake Thatcher. Strontium ratios of six fossil molluscs collected from the lower-most exposed section of the Main Canyon Formation (MCF) indicate that during the early Quaternary (>620 ka), Thatcher Basin was occupied by a locally fed, isotopically-enriched (87Sr/86Sr=0.71309) lake and did not receive input form the Bear River. Eleven fossils, collected from the uppermost exposed section of the MCF, indicate at least three course changes of the Bear River in the late Quaternary: diversion into the basin around 140 ka, diversion from the basin sometime between 140 and 100 ka, and finally diversion back into the basin around 50 ka. Hydrologic modeling of Thatcher Basin with and without the input of the Bear River suggests that water from both a Bear River-influenced or a locally fed lake is capable of filling the basin and causing it to spillover into the adjacent Bonneville Basin. Thus, the Bonneville Basin may have been receiving water from either the Bear River, or the Thatcher Basin rivers, significantly earlier than the ~30 ka previously proposed. Additional hydrologic modeling in Thatcher Basin suggests that a two-fold reduction in the effective precipitation as compared to modern conditions would be required to lower a locally fed Lake Thatcher the ~30 m necessary to account for the paleosol exposed in the uppermost MCF.

No description available.

No description available.

Depuis sa découverte, le gène TP63 a soulevé un intérêt considérable grâce à son rôle majeur dans la morphogenèse des épithélia. La quasi-totalité de nos connaissances dérive de l’observation des phénotypes des souris déficientes qui présentent une absence d’épithélia pluristratifiés, due à un défaut d'expression des complexes d'adhérence cellule-matrice extra cellulaire et cellules-cellules. De plus, TP63 est amplifié et surexprimé dans environ 25% des carcinomes épidermoïdes de l’œsophage et est quasi absent des adénocarcinomes du même organe. Dans ce travail nous avons étudié l’expression de p63 dans la muqueuse œsophagienne, et nous avons montré que p63 exerce un rôle de régulateur de l’expression des complexes d’adhérence intra-épithéliaux lors de la transition entre les cellules basales/suprabasales hautement prolifératives et les couches les plus différenciées incapables de proliférer. Puis, nous avons étudié le rôle possible de p63 dans la formation de la métaplasie intestinale, une lésion précurseur de l’adénocarcinome. Dans ce contexte, nous avons établi qu’un traitement reconstituant le stress acido-biliaire induit une perte d’expression de p63 secondaire à une dégradation par le protéasome dans des cellules primaires et des lignées dérivées de carcinomes œsophagiens. Enfin, à l’aide d’un modèle de peau reconstruite, nous avons montré l’implication de p63 dans la stratification épithéliale, dans la prolifération, la différenciation et les interactions épithélium-mésenchyme. Ces réstultats clarifient le rôle de TP63 comme un ongène potentiel dans le carcinome épidermoïde de l’œsophage et comme potentiel suppresseur dans l’adénocarcinome / Since its discovery in 1998, the TP63 gene has raised considerable interest due to its major role in epithelial morphogenesis. The vast majority of our current knowledge is based on the phenotypes of TP63 deficient mice, which show a lack of stratified epithelia associated with defects in the expression of cell-cell and cell-matrix adhesion complexes. In addition, TP63 systematically overexpressed in squamous cell carcinomas and amplified in about 25% of œsophageal squamous cell carcinomas, whereas it is barely detectable in adenocarcinomas that arise in the same organ. This work analyzes the expression of p63 in normal œsophageal mucosa and demonstrates its regulatory role in the expression of cell-cell adhesion complexes at the transition between highly proliferative basal/suprabasal layers and more differentiated, non-proliferative superficial layers. Next, the role of p63 in the formation of intestinal metaplasia, a precursor of adenocarcinoma, is addressed in experiments reconstituting in vtro the effects of acid-bile gastro-oesophageal reflux. We show that this form of stress induces a loss of p63 in cell lines derived from oesophageal cancers, due to its rapid proteasome-dependent degradation. Finally, we have used an in vitro skin reconstruction model to demonstrate the involvement of p63 in the process of epidermal stratification, proliferation, differentiation, and epithelium-mesenchyme interactions. These results clarify the role of TP63 as a potential oncogene in œsophageal squamous cell carcinoma, and as a potential suppressor in adenocarcinoma

Os melanomas são o tipo mais mortal de câncer de pele, apesar da baixa incidência, 80% das mortes de câncer de pele são devem-se ao melanoma metastático. Novas abordagens farmacológicas e a busca por novos compostos para a terapêutica do melanoma, em aplicações isolados ou em combinação com outros fármacos é imprescindível. Esta busca ocorre principalmente no campo das terapias de alvos específicos, devido à aquisição de resistência tumoral e recidiva. O resveratrol (RES) é um polifenol com atividade anti-oxidante, e seu efeito anti-tumoral foi mostrado pela indução de morte celular, porém o seu estudo não foi aprofundado pela inviabilidade do uso de altas doses in vitro para observação de efeitos celulares. Outro composto, o 2-methoxiestradiol (2ME) é um metabólito do estrógeno cujo efeitos anti-câncer já foi demonstrado em melanoma, porém sem elucidação das vias de sinalização envolvidas. O efeito em células com resistência adquirida também nunca foram testados. Neste estudo ampliamos o painel de linhagens celulares de melanoma humano, e demonstramos que o 2ME induz morte celular, inibe a proliferação destas células sendo que esta inibição está associada a indução de senescência. Pela primeira vez foi observada a inibição de proliferação pelo 2ME em células com a mutação BRAF V600E resistentes ao vemurafenibe (inibidor de BRAF) e duplo resistentes ao vemurafenibe e trametinibe (inibidor de MEK). A inibição de proliferação foi acompanhada pela modulação de p21Cip1, Ciclina B1, pRb, proteínas envolvidas na regulação do ciclo celular. A exposição prolongada ao 2ME inibiu a formação de colônias em todas as linhagens de melanoma (não resistentes e resistentes), mas não teve o mesmo efeito em fibroblastos primários, mostrando efeito seletivo. Em modelo tridimensional de esferóides, foi observado que as linhagens resistentes (Sk-Mel-28R) e duplo resistentes (Sk- Mel-28RT) são mais invasivas que a parental (Sk-Mel-28). Neste modelo, o 2ME foi capaz de inibir a invasão e viabilidade destas células. No modelo de pele reconstituída, na ausência de tratamento, observa-se invasão das células de melanoma pela derme, porém este fenômeno é diminuído quando as peles são tratadas com 2ME. Estes resultados demonstram que o 2ME é um efetivo agente anti-melanoma, independente de sua resistência. / Melanomas are the deadliest type of skin cancer, and in spite of the low incidence, 80% of the skin cancer associated death cases are due to metastatic melanoma. New pharmacological approaches and the search of new compounds for melanoma therapeutics, for monotherapy or combination therapy, are essential. This search occurs mainly in the targeted therapy field because of the melanoma acquisition of resistance to the current treatments. Resveratrol (RES) is a polyphenol with anti-oxidant activity, and its anti-tumor effect has been shown through the induction of cell death. However, the study of this compound has been discontinued in this work due to the impossibility of using high doses in vitro for the observation of cellular effects. Another compound, 2-methoxyestradiol (2ME) is a metabolite from estrogen, and its anti-cancer effects has already been shown in melanoma, but with no elucidation of the signaling pathways involved. Furthermore, the effects in cells with acquired resistance have never been shown. In this study we used a broader panel of human melanoma cell lines and demonstrated that 2ME induces cell death, inhibits proliferation of these cells, and this inhibition is associated with the induction of cell senescence. The inhibition of proliferation caused by 2ME was observed for the first time in BRAF V600E cells that are resistant to Vemurafenib (BRAF inhibitor) and double resistant to Vemurafenib and Trametinib (MEK inhibitor). The proliferation inhibition was related to the modulation of p21Cip1,Cyclin B1 and pRb, which are proteins involved in cell cycle regulation. Long exposure to 2ME in colony formation assay showed the inhibition of colony in all melanoma cell lines (regardless of resistance and mutational status), but not in primary fibroblasts, showing selective effect. In three-dimensional spheroid model, it was observed that the resistant (Sk-Mel- 28R) and double-resistant (Sk-Mel-28RT) cell lines were more invasive than the parental cell line (Sk-Mel-28). In this model, 2ME was able to inhibit cell invasion and cell viability. In the skin reconstruct model, in the absence of treatment, melanoma cell invasion can be observed in the dermis layer. However, after the treatment with 2ME these cell invasion foci are inhibited. Altogether, these effects demonstrate that 2ME is an effective anti-melanoma agent, regardless of resistance.

An example of watershed disturbance activity undertaken to gain access to the oil sands is large scale mining in the Athabasca basin, Alberta, Canada. One of the remedial activities of this disturbance is the reclamation of the disturbed lands. In the process of reclamation, the overburden soil is placed back into the mined pits and reformed with soil covers (alternatively called reconstructed watersheds). In the design process of reclamation, a major concern is hydrological sustainability, which includes the soils ability to store enough moisture for the water requirements of vegetation growth and land-atmospheric moisture fluxes. Typically, the goal of the reclamation is to restore the disturbed watersheds, so that they mimic the natural watersheds in terms of the ecological sustainability. Therefore, a comparative evaluation of the hydrological sustainability of the reconstructed watersheds with natural watersheds is required.<p>The considered reconstructed watershed in this study (the flat top of the South Bison Hill, Fort McMurray, Alberta, which is about 6 years old) constitutes a thin layer of a peat-mineral mix (20 cm thick) overlying an 80 cm thick secondary (glacial till) layer on the shale formation, mimicking the natural soil horizons of undisturbed watersheds. As the reconstructed watershed is located in the boreal forest region, a mature boreal forest (Old Aspen site, about 88 years old) located in the Southern Study Area (SSA), BOREAS, Saskatchewan, Canada, is considered as a representative of natural watershed. The A-horizon with 25 cm of sandy loam texture, the B-horizon with 45 cm-thick sandy clay loam, and the C-horizon with 40 cm of a mixture of sandy clay loam and loam are considered in this study.<p>An existing System Dynamics Watershed (SDW) model (lumped and site-specific) is modified and adapted to model the hydrological processes of the reconstructed and natural watersheds, such as soil moisture, evapotranspiration, and runoff. The models are calibrated and validated on daily time scale using two years data (growing season) in each case. The hydrological processes are simulated reasonably well despite the high complexity involved in the processes of soil moisture dynamics and the evapotranspiration, for both study areas. Using the modified and calibrated models, long term simulations (48 years) are carried out on both the reconstructed and natural watersheds. Vegetation properties are switched between the reconstructed and natural watersheds and two scenarios are generated. Consequently, long term simulations are performed. With the help of a probabilistic approach, the daily soil moisture results are used to address the comparative soil moisture storage capability of the watersheds.<p>The results indicate that the selected reconstructed watershed is able to provide its designed store-and-release moisture of 160 mm (a requirement of the land capability classification for forest ecosystems in the oil sands) for the vegetation and meteorological moisture demands at a non-exceedance probability of 93%. The comparative study shows that the reconstructed watershed provides less moisture for evapotranspiration requirements than the natural watershed. The reconstructed watershed is able to provide less moisture than the natural watershed for both small and also mature vegetation scenarios. A possible reason for this may be that the reconstructed site is still in the process of restoration and that it may take a few more years to get closer to natural watersheds in terms of the hydrological sustainability. The study also demonstrates the utility of the system dynamics approach of modeling the case study under consideration. The future addition of a vegetation growth model to the hydrological model, and the development of a generic watershed modeling technique would be helpful in decision making and management practices of watershed reclamation.

As one of the most powerful error-correcting codes, Low-density parity check codes are widely used in digital communications. Because of the performance of LDPC codes are capable to close the shannon limited extraordinarily, LDPC codes are to be used in the new Digital Video Broadcast-Satellite-Second Generation(DVB-S2) and it is the first time that LDPC codes are included in the broadcast standard in 2003. In this thesis, a restructured parity-check matrices which can be divided into sub-matrices for LDPC code in DVB-S2 is provided. Corresponded to this restructured parity-check matrix, a reconstructed decoding table is invented. The encoding table of DVB-S2 standard only could obtain the unknown check nodes from known variable nodes, while the decoding table this thesis provided could obtain the unknown variable nodes from known check nodes what is exactly the Layered-massage passing algorithm needed. Layered-message passing algorithm which also known as "Turbo-decoding message passing" is used to reduce the decoding iterations and memory storage for messages. The thesis also investigate Bp algorithm, lambda-min algorithm, Min-sum algorithm and SISO-s algorithm, meanwhile, simulation results of these algorithms and schedules are also presented.

An example of watershed disturbance activity undertaken to gain access to the oil sands is large scale mining in the Athabasca basin, Alberta, Canada. One of the remedial activities of this disturbance is the reclamation of the disturbed lands. In the process of reclamation, the overburden soil is placed back into the mined pits and reformed with soil covers (alternatively called reconstructed watersheds). In the design process of reclamation, a major concern is hydrological sustainability, which includes the soils ability to store enough moisture for the water requirements of vegetation growth and land-atmospheric moisture fluxes. Typically, the goal of the reclamation is to restore the disturbed watersheds, so that they mimic the natural watersheds in terms of the ecological sustainability. Therefore, a comparative evaluation of the hydrological sustainability of the reconstructed watersheds with natural watersheds is required.<p>The considered reconstructed watershed in this study (the flat top of the South Bison Hill, Fort McMurray, Alberta, which is about 6 years old) constitutes a thin layer of a peat-mineral mix (20 cm thick) overlying an 80 cm thick secondary (glacial till) layer on the shale formation, mimicking the natural soil horizons of undisturbed watersheds. As the reconstructed watershed is located in the boreal forest region, a mature boreal forest (Old Aspen site, about 88 years old) located in the Southern Study Area (SSA), BOREAS, Saskatchewan, Canada, is considered as a representative of natural watershed. The A-horizon with 25 cm of sandy loam texture, the B-horizon with 45 cm-thick sandy clay loam, and the C-horizon with 40 cm of a mixture of sandy clay loam and loam are considered in this study.<p>An existing System Dynamics Watershed (SDW) model (lumped and site-specific) is modified and adapted to model the hydrological processes of the reconstructed and natural watersheds, such as soil moisture, evapotranspiration, and runoff. The models are calibrated and validated on daily time scale using two years data (growing season) in each case. The hydrological processes are simulated reasonably well despite the high complexity involved in the processes of soil moisture dynamics and the evapotranspiration, for both study areas. Using the modified and calibrated models, long term simulations (48 years) are carried out on both the reconstructed and natural watersheds. Vegetation properties are switched between the reconstructed and natural watersheds and two scenarios are generated. Consequently, long term simulations are performed. With the help of a probabilistic approach, the daily soil moisture results are used to address the comparative soil moisture storage capability of the watersheds.<p>The results indicate that the selected reconstructed watershed is able to provide its designed store-and-release moisture of 160 mm (a requirement of the land capability classification for forest ecosystems in the oil sands) for the vegetation and meteorological moisture demands at a non-exceedance probability of 93%. The comparative study shows that the reconstructed watershed provides less moisture for evapotranspiration requirements than the natural watershed. The reconstructed watershed is able to provide less moisture than the natural watershed for both small and also mature vegetation scenarios. A possible reason for this may be that the reconstructed site is still in the process of restoration and that it may take a few more years to get closer to natural watersheds in terms of the hydrological sustainability. The study also demonstrates the utility of the system dynamics approach of modeling the case study under consideration. The future addition of a vegetation growth model to the hydrological model, and the development of a generic watershed modeling technique would be helpful in decision making and management practices of watershed reclamation.

Os melanomas são o tipo mais mortal de câncer de pele, apesar da baixa incidência, 80% das mortes de câncer de pele são devem-se ao melanoma metastático. Novas abordagens farmacológicas e a busca por novos compostos para a terapêutica do melanoma, em aplicações isolados ou em combinação com outros fármacos é imprescindível. Esta busca ocorre principalmente no campo das terapias de alvos específicos, devido à aquisição de resistência tumoral e recidiva. O resveratrol (RES) é um polifenol com atividade anti-oxidante, e seu efeito anti-tumoral foi mostrado pela indução de morte celular, porém o seu estudo não foi aprofundado pela inviabilidade do uso de altas doses in vitro para observação de efeitos celulares. Outro composto, o 2-methoxiestradiol (2ME) é um metabólito do estrógeno cujo efeitos anti-câncer já foi demonstrado em melanoma, porém sem elucidação das vias de sinalização envolvidas. O efeito em células com resistência adquirida também nunca foram testados. Neste estudo ampliamos o painel de linhagens celulares de melanoma humano, e demonstramos que o 2ME induz morte celular, inibe a proliferação destas células sendo que esta inibição está associada a indução de senescência. Pela primeira vez foi observada a inibição de proliferação pelo 2ME em células com a mutação BRAF V600E resistentes ao vemurafenibe (inibidor de BRAF) e duplo resistentes ao vemurafenibe e trametinibe (inibidor de MEK). A inibição de proliferação foi acompanhada pela modulação de p21Cip1, Ciclina B1, pRb, proteínas envolvidas na regulação do ciclo celular. A exposição prolongada ao 2ME inibiu a formação de colônias em todas as linhagens de melanoma (não resistentes e resistentes), mas não teve o mesmo efeito em fibroblastos primários, mostrando efeito seletivo. Em modelo tridimensional de esferóides, foi observado que as linhagens resistentes (Sk-Mel-28R) e duplo resistentes (Sk- Mel-28RT) são mais invasivas que a parental (Sk-Mel-28). Neste modelo, o 2ME foi capaz de inibir a invasão e viabilidade destas células. No modelo de pele reconstituída, na ausência de tratamento, observa-se invasão das células de melanoma pela derme, porém este fenômeno é diminuído quando as peles são tratadas com 2ME. Estes resultados demonstram que o 2ME é um efetivo agente anti-melanoma, independente de sua resistência. / Melanomas are the deadliest type of skin cancer, and in spite of the low incidence, 80% of the skin cancer associated death cases are due to metastatic melanoma. New pharmacological approaches and the search of new compounds for melanoma therapeutics, for monotherapy or combination therapy, are essential. This search occurs mainly in the targeted therapy field because of the melanoma acquisition of resistance to the current treatments. Resveratrol (RES) is a polyphenol with anti-oxidant activity, and its anti-tumor effect has been shown through the induction of cell death. However, the study of this compound has been discontinued in this work due to the impossibility of using high doses in vitro for the observation of cellular effects. Another compound, 2-methoxyestradiol (2ME) is a metabolite from estrogen, and its anti-cancer effects has already been shown in melanoma, but with no elucidation of the signaling pathways involved. Furthermore, the effects in cells with acquired resistance have never been shown. In this study we used a broader panel of human melanoma cell lines and demonstrated that 2ME induces cell death, inhibits proliferation of these cells, and this inhibition is associated with the induction of cell senescence. The inhibition of proliferation caused by 2ME was observed for the first time in BRAF V600E cells that are resistant to Vemurafenib (BRAF inhibitor) and double resistant to Vemurafenib and Trametinib (MEK inhibitor). The proliferation inhibition was related to the modulation of p21Cip1,Cyclin B1 and pRb, which are proteins involved in cell cycle regulation. Long exposure to 2ME in colony formation assay showed the inhibition of colony in all melanoma cell lines (regardless of resistance and mutational status), but not in primary fibroblasts, showing selective effect. In three-dimensional spheroid model, it was observed that the resistant (Sk-Mel- 28R) and double-resistant (Sk-Mel-28RT) cell lines were more invasive than the parental cell line (Sk-Mel-28). In this model, 2ME was able to inhibit cell invasion and cell viability. In the skin reconstruct model, in the absence of treatment, melanoma cell invasion can be observed in the dermis layer. However, after the treatment with 2ME these cell invasion foci are inhibited. Altogether, these effects demonstrate that 2ME is an effective anti-melanoma agent, regardless of resistance.

No description available.