The availability of several methods to unambiguously mark individual cells has strongly fostered the understanding of clonal developments in hematopoiesis and other stem cell driven regenerative tissues. While cellular barcoding is the method of choice for experimental studies, patients that underwent gene therapy carry a unique insertional mark within the transplanted cells originating from the integration of the retroviral vector. Close monitoring of such patients allows accessing their clonal dynamics, however, the early detection of events that predict monoclonal conversion and potentially the onset of leukemia are beneficial for treatment. We developed a simple mathematical model of a self-stabilizing hematopoietic stem cell population to generate a wide range of possible clonal developments, reproducing typical, experimentally and clinically observed scenarios. We use the resulting model scenarios to suggest and test a set of statistical measures that should allow for an interpretation and classification of relevant clonal dynamics. Apart from the assessment of several established diversity indices we suggest a measure that quantifies the extension to which the increase in the size of one clone is attributed to the total loss in the size of all other clones. By evaluating the change in relative clone sizes between consecutive measurements, the suggested measure, referred to as maximum relative clonal expansion (mRCE), proves to be highly sensitive in the detection of rapidly expanding cell clones prior to their dominant manifestation. This predictive potential places the mRCE as a suitable means for the early recognition of leukemogenesis especially in gene therapy patients that are closely monitored. Our model based approach illustrates how simulation studies can actively support the design and evaluation of preclinical strategies for the analysis and risk evaluation of clonal developments.

Dynamics of species, families and plant functional types (PFTs), and diversity of a natural grassland submitted or not to burning and grazing, in different relief positions (concave a convex slope) were evaluated. Treatments consisted of the associations of those three factors, in a completely randomized design, with variable number of replicates, from two to five. Rotational grazing were used, with an average occupation period of six days. Grazing animals were from Nelore, Charolais and its crosses. Stocking rate was calculated to obtain between 20 to 35 % of disappearing of forage mass. Diversity was evaluated using Shannon and Simpson index and frequency of species. The analysis of dry matter availability, on the relative participation of main species and the relative frequency of the other species were performed by double sampling. Data were submitted to cluster and ordination analysis and an analysis of variance via randomization tests. With respect to diversity, burned and grazed areas had lower index than those only grazed. Considering relief and grazing interaction, higher diversity occurred in convex slope. Including burning interaction, diversity was higher in concave slope. In grazing excluded areas, higher index were observed under burning effect, and considering this factor, higher diversity were registered in convex slope. Analyzing frequency of families, Poaceae, Cyperaceae and Asteraceae were present in all plots. The most versatile species were A. lateralis, Frimbristylis diphylla and Dichanthelium sabulorum, occurring in all treatments. Burning and grazing had a positive influence in vegetation diversity, however when interacting or in its absence, they turned dynamics to a dominance of a few species. The evaluation of dynamics showed that interpretation of the results through PFTs were more efficient to explore the differences between treatments, when compared to analysis by families or by species. The seasonal dynamics of the vegetation was affected both by grazing, burning and relief position, independently if evaluated through species or functional types of plants. / Foi avaliada a dinâmica por meio de espécies, famílias e tipos funcionais de plantas (TFs), e a diversidade de uma pastagem natural submetida aos fatores queima (presença ou ausência) e pastejo (ausência ou presença), em diferentes posições topográficas (encosta ou baixada). Os tratamentos foram constituídos pela associação dos três fatores, em um delineamento completamente casualizado com número variável de repetições, entre duas e cinco. O pastejo foi rotacionado, com um período de ocupação médio de seis dias, sendo utilizados animais das raças Nelore, Charolês e suas cruzas. A carga foi calculada adotando-se uma taxa de desaparecimento entre 20-35% da massa de forragem existente. A diversidade foi avaliada através dos índices de Shannon, Simpson e da freqüência de ocorrência de espécies. As avaliações da disponibilidade total de matéria seca, da participação relativa das principais espécies e da freqüência relativa das demais espécies foram realizadas por meio de dupla amostragem. Os dados obtidos foram submetidos às análises de agrupamento, ordenação e de variância via teste de aleatorização. Com relação à diversidade, as áreas queimadas com pastejo possuíram índices menores do que apenas com pastejo. Considerando a interação relevo e pastejo, a maior diversidade se deu na encosta. Incluindo-se a interação com o efeito de queima, essa foi superior nas áreas de baixada. Na exclusão de pastejo, os índices mais elevados foram encontrados com queima, e dentro desse distúrbio, maiores índices na posição de relevo de encosta. Já na ausência da queima, o maior índice foi observado na baixada. Na análise da freqüência de ocorrência por família, destacaram-se Poaceae, Cyperaceae e Asteraceae, com presença em todos os ambientes estudados. Já as espécies com maior versatilidade foram A. lateralis, Frimbristylis diphylla e Dichanthelium sabulorum, encontrados em todos os tratamentos avaliados. O emprego da queima ou pastejo tiveram uma influência positiva na diversidade da vegetação, porém quando em conjunto ou totalmente ausentes direcionaram a dinâmica a uma dominância de poucas espécies. O estudo da dinâmica mostrou que a interpretação dos resultados através dos TFs foi mais eficiente para explorar as diferenças entre os tratamentos, quando comparado às análises por famílias botânicas ou por espécies. A dinâmica estacional da vegetação foi afetada pelos fatores pastejo, queima e posição de relevo, independentemente se avaliados através de espécies ou tipos funcionais de plantas.

The availability of several methods to unambiguously mark individual cells has strongly fostered the understanding of clonal developments in hematopoiesis and other stem cell driven regenerative tissues. While cellular barcoding is the method of choice for experimental studies, patients that underwent gene therapy carry a unique insertional mark within the transplanted cells originating from the integration of the retroviral vector. Close monitoring of such patients allows accessing their clonal dynamics, however, the early detection of events that predict monoclonal conversion and potentially the onset of leukemia are beneficial for treatment. We developed a simple mathematical model of a self-stabilizing hematopoietic stem cell population to generate a wide range of possible clonal developments, reproducing typical, experimentally and clinically observed scenarios. We use the resulting model scenarios to suggest and test a set of statistical measures that should allow for an interpretation and classification of relevant clonal dynamics. Apart from the assessment of several established diversity indices we suggest a measure that quantifies the extension to which the increase in the size of one clone is attributed to the total loss in the size of all other clones. By evaluating the change in relative clone sizes between consecutive measurements, the suggested measure, referred to as maximum relative clonal expansion (mRCE), proves to be highly sensitive in the detection of rapidly expanding cell clones prior to their dominant manifestation. This predictive potential places the mRCE as a suitable means for the early recognition of leukemogenesis especially in gene therapy patients that are closely monitored. Our model based approach illustrates how simulation studies can actively support the design and evaluation of preclinical strategies for the analysis and risk evaluation of clonal developments.

Vegetative species diversity is under threat from environmental pressures, particularly climate change. As the impacts of climate change vary from place to place, response of vegetative species diversity to a changing climate also vary depending on geographical location. The response of vegetative species diversity under dry conditions in Zimbabwe is not well known. This study assessed the impact of climate change on vegetative species diversity under semiarid conditions of Masvingo province in Zimbabwe. This was achieved by determining climate change trends over a period of forty years (1974-2014), and examining the relationship between vegetative species diversity and spatially interpolated climate data. The absence of historical diversity data prompted the use of remote sensing to enable the assessment of spatial and temporal changes. Thus, the Normalised difference vegetation index (NDVI) was used to assess vegetative species diversity changes after establishing a positive relationship between species diversity and NDVI. The mixed methods research design was used as the strategy of inquiry. The non-aligned block sampling design was used as the sampling framework from which 198 sampling points were identified. Meteorological data obtained from Zimbabwe Meteorological Services Department (ZMSD) and the National Climate Data Centre (NCDC) were used for climate change analysis. Data collected through image analysis, direct observations, questionnaire surveys and interviews were used to assess the impact of climate change on vegetative species diversity. Results indicate that all temperature and precipitation variables have significant (p<0.05) trends over the period under study. However, the trend for seasonal total precipitation was not significant but declining. The significant trends indicate that climate change occurred over the period under study. 93% of the respondents confirmed having experienced the climate change phenomenon. Results also show a significant relationship between climate elements (precipitation and temperature) and vegetative species diversity represented by Shannon Weaver Index (H). More so, there is a positive relationship between NDVI and H. Vegetative species diversity represented by NDVI decreased over the period under review. The results indicate that climate change has contributed to the decrease of vegetative species diversity in Masvingo province, thus it is a force behind many other factors contributing to biodiversity loss. / College of Agriculture and Environmental Sciences / Ph. D. (Environmental Sciences)