Behavioral characterization of animal models for Alzheimer's Disease is critical for the development of potential therapeutics and treatments against the disease. While there are several known animal models of AD, three current models--APPsw, P301L, and APPsw+P301L--have not been well characterized, if at all. This study, therefore, aimed to perform a full behavioral characterization of these three models in order to better understand the impairments associated with each one. Between 5 and 8.5 months of age, animals were behaviorally tested in a variety of sensorimotor, anxiety, and cognitive tasks. The number of tau+ neurons in the forebrains of P301L mice was then compared to their behavioral performance. Results of this study indicate that retinal degeneration (rd) seriously impairs the performance of mice in behavioral tasks. Animals that carry the homozygous allele of this mutation must, therefore, be eliminated from any such study requiring visual acuity. After this elimination, my findings indicate that APP mice are impaired in several cognitive tasks (including platform recognition, Morris maze, Y-maze, and radial-arm water maze) at a young early age (5 to 8.5 months of age). These mice have fairly normal sensorimotor function, showing significant impairment only in balance beam performance starting at 5 months. Although P301L mutant Tau mice, as a group, did not have significant impairments in any sensorimotor or cognitive task, correlation analysis revealed that higher numbers of tau+ neurons in cortex and hippocampus were associated with poorer cognitive performance. Finally, discriminant function analysis (DFA) appears able to accurately discriminate between the three transgenic groups of mice using only an 8-measure data set. In conclusion, this study provides the first comprehensive, multiple task behavioral assessment of the APPsw and P301L animal models of AD, indicating that APPsw mice are cognitively impaired at an early age while P301L mice are largely unimpaired through 8.5 months. Nonetheless, correlational analysis implicates the formation of neurofibrillary tangles in the onset of cognitive impairments. Finally, my findings recommend the continued use of DFA to determine if groups of animals, based on different transgenicity or therapeutic treatment, could be discriminated between from their behavior alone.

The heavily developed Long Key is located in Pinellas County in west-central Florida. The structured Blind Pass at the north end of the barrier island interrupts the southward longshore sediment transport, resulting in severe and chronic beach erosion along the northern portion of the island. Frequent beach nourishments were conducted to mitigate the erosion. In this study, the performance of the most recent beach nourishment in 2010 is quantified through time-series beach profile surveys. Over the 34-month period, the nourished northern portion of the island, Upham Beach, lost up to 330 m3/m of sand, with a landward shoreline retreat of up to 100 m. The middle portion of the island gained up to 25 m3/m of sand, benefiting from the sand lost from Upham Beach. The southern portion of Long Key lost a modest amount of sediment, largely due to Tropical Storm Debby, which approached from the south in June 2012. The severe erosion along Upham Beach is induced by a large negative longshore transport gradient. The beach here has no sand bar and retreated landward persistently over the 34-month study period. In contrast the profiles in the central section of the island generally have a sand bar which moved landward and seaward in response to seasonal and storm-induced wave-energy changes. The sand volume across the entire profile in the central portion of the island is mostly conserved. Two typical example beach profiles, LK3A and R157, were selected to examine the ability of the commonly used principal component analysis (PCA), also commonly known as empirical orthogonal function analysis (EOF), to identify beach profile ix changes induced by longshore and cross-shore sediment transport gradients. For the longshore-transport driven changes at the non-barred profile LK3A, the principal eigenvector accounted for over 91% of the total variance, with a dominant broad peak in the cross-shore distribution. At the barred R157, the profile changes were caused mainly by cross-shore transport gradients with modest contribution from longshore transport gradient; eigenvalue one only accounted for less than 51% of the total variance, and eigenvalues two and three still contributed considerably to the overall variance. In order to verify the uniqueness of the PCA results from LK3A and R157, five numerical experiments were conducted, simulating changes at a barred and non-barred beach driven by longshore, cross-shore, and combined sediment transport gradients. Results from LK3A and R157 compare well with simulated beach erosion (or accretion) due to variable longshore sediment transport gradients and due to both cross-shore and longshore sediment transport gradients, respectively. Different PCA results were obtained from different profile change patterns.

This research better resolves the environmental mosaic that is typically reconstructed for the A. robustus-bearing faunal assemblages of South Africa and evaluates whether A. robustus were habitat specialists or habitat generalists by testing whether they are associated with numerous, different reconstructed habitats, or if they can be associated with a single, more homogeneous habitat type. Determining the habitat preferences of A. robustus holds important implications for understanding the behavior of these hominins and, potentially, for understanding whether their ultimate extinction might have been climatically influenced, as fluctuations in the environments associated with the robust australopiths provide direct evidence about the responses of hominins to environmental change. To achieve this, a 2-dimensionsal morphometric tool was developed for accurately identifying the abundant bovid teeth that are found in direct association with the hominins using Elliptical Fourier Function Analysis. More accurate taxonomic identifications facilitate more precise estimates of the relative abundance of ecologically sensitive bovids, allowing for finer resolution when segmenting the various components of the reconstructed habitat mosaics. The fossil bovids abundances were compared across the assemblages over time in order to define the environmental mosaic in each assemblage and to determine if environmental heterogeneity existed across the assemblages. The relative abundances of the bovid fossil assemblages and A. robustus were compared to assess the habitat preferences of these hominins. A. robustus were not consistently associated with a particular habitat type suggesting that perhaps they were habitat generalists, capable of surviving in multiple types of habitats.

Gold mine waste poses a significant challenge for rehabilitation practitioners and can negatively impact on soil, air, surface water and groundwater quality. This, in turn, can affect the environmental quality of humans and other biota in nearby settlements and surrounding ecosystems. All mines are required to have a plan in place to impede or mitigate these environmental impacts and to ensure that all legislation is complied with to apply for closure. Site closure is the eventual goal of all mine residue complexes, as it is the stage at which a company becomes released from all legal and financial liability. The South African legislation is comprehensive and essentially requires that all latent and residual environmental impacts are addressed and that an end land-use designation is put in place that conforms to the principles of sustainable development. The Chemwes Tailings Storage Facility complex near Stilfontein was monitored to provide a strategic assessment of the state of the rehabilitation, and to provide recommendations for the successful remediation of problem sites. A combination of vegetation sampling, landscape function assessments and substrate chemical analyses were conducted to gain a predictive understanding of rehabilitation progress. The monitoring was conducted over two years across a chronosequence of rehabilitating sites from tailings dam slopes and an adjacent spillage site. An undisturbed grassland and a starter-wall served as reference sites. The data were first analysed independently and then by making use of multivariate data ordinations. This allowed for holistic investigations of the relationships between sites, substrate chemistry, vegetation composition and landscape function. The results showed that the tailings dams had a distinctly different suite of vegetation from the reference sites, but had no statistically significant differences in composition across the rehabilitating chronosequence. There were positive correlations between rehabilitation site age and landscape function indices, suggesting that some aspects of ecosystem development were occurring over time. In some sites, deterioration in the substrate quality as a growth medium was observed with increases in acidity and salinity. This was most likely caused by pyrite oxidation in the tailings and the high concentrations of free salts. The increasing acidity and salinity resulted in vegetation senescence and declines in landscape function. However, those sites that possessed higher landscape function appeared to have the ecosystem processes in place that temporarily suppressed negative chemical changes. Whilst this was encouraging,the rehabilitation chronosequence had not yet proven the self-sustainability that it would require for closure purposes. Further monitoring would be required over time. The sustainability of the rehabilitating chronosequence was brought into question by the high acid-forming potential of the tailings growth medium. Concerns were also raised over the ability of the established vegetation cover to persist under conditions of increasing stress and disturbance. Furthermore, the land-use capabilities of the sites are limited by current rehabilitation procedures and various recommendations were made to rectify this. A more streamlined monitoring framework for the tailings complex was also proposed. The contribution of this work lies in its holistic integration of monitoring techniques and the meaningful analysis of ecosystem function, an aspect largely ignored in minesite rehabilitation. / Thesis (M.Sc. (Environmental Sciences and Management))--North-West University, Potchefstroom Campus, 2009.

Gold mine waste poses a significant challenge for rehabilitation practitioners and can negatively impact on soil, air, surface water and groundwater quality. This, in turn, can affect the environmental quality of humans and other biota in nearby settlements and surrounding ecosystems. All mines are required to have a plan in place to impede or mitigate these environmental impacts and to ensure that all legislation is complied with to apply for closure. Site closure is the eventual goal of all mine residue complexes, as it is the stage at which a company becomes released from all legal and financial liability. The South African legislation is comprehensive and essentially requires that all latent and residual environmental impacts are addressed and that an end land-use designation is put in place that conforms to the principles of sustainable development. The Chemwes Tailings Storage Facility complex near Stilfontein was monitored to provide a strategic assessment of the state of the rehabilitation, and to provide recommendations for the successful remediation of problem sites. A combination of vegetation sampling, landscape function assessments and substrate chemical analyses were conducted to gain a predictive understanding of rehabilitation progress. The monitoring was conducted over two years across a chronosequence of rehabilitating sites from tailings dam slopes and an adjacent spillage site. An undisturbed grassland and a starter-wall served as reference sites. The data were first analysed independently and then by making use of multivariate data ordinations. This allowed for holistic investigations of the relationships between sites, substrate chemistry, vegetation composition and landscape function. The results showed that the tailings dams had a distinctly different suite of vegetation from the reference sites, but had no statistically significant differences in composition across the rehabilitating chronosequence. There were positive correlations between rehabilitation site age and landscape function indices, suggesting that some aspects of ecosystem development were occurring over time. In some sites, deterioration in the substrate quality as a growth medium was observed with increases in acidity and salinity. This was most likely caused by pyrite oxidation in the tailings and the high concentrations of free salts. The increasing acidity and salinity resulted in vegetation senescence and declines in landscape function. However, those sites that possessed higher landscape function appeared to have the ecosystem processes in place that temporarily suppressed negative chemical changes. Whilst this was encouraging,the rehabilitation chronosequence had not yet proven the self-sustainability that it would require for closure purposes. Further monitoring would be required over time. The sustainability of the rehabilitating chronosequence was brought into question by the high acid-forming potential of the tailings growth medium. Concerns were also raised over the ability of the established vegetation cover to persist under conditions of increasing stress and disturbance. Furthermore, the land-use capabilities of the sites are limited by current rehabilitation procedures and various recommendations were made to rectify this. A more streamlined monitoring framework for the tailings complex was also proposed. The contribution of this work lies in its holistic integration of monitoring techniques and the meaningful analysis of ecosystem function, an aspect largely ignored in minesite rehabilitation. / Thesis (M.Sc. (Environmental Sciences and Management))--North-West University, Potchefstroom Campus, 2009.

Sex estimation in bioarchaeological research is paramount for comparative analyses of skeletal remains and developing estimates of other demographic variables. Frequently, sex is estimated utilizing the morphology of pelvic and cranial bones in archaeological skeletal samples. Regrettably, these bones are often damaged, destroyed, or lost and cannot be employed for the estimation of sex. Fortunately, a variety of metric and visual sex estimation methods have been developed on modern skeletal samples with known demography. Disappointingly, due to the population specific nature of many of these metric methods, they cannot be accurately applied directly to alternate skeletal samples. However, these methods can be redeveloped and retested for archaeological skeletal samples if the proper protocol is utilized. This research utilizes the protocol for developing methods of sex estimation on samples with unknown sex developed by Murail et al. (1999). Utilizing select hand and foot bones from four prehistoric Native American skeletal samples from Alabama and Illinois, multiple discriminant functions were developed and tested on both Archaic and Mississippian Period skeletal samples. Furthermore, the four individual site samples were combined into two geographical and two temporal samples, as well as an all pooled sample in order to test the broader applicability of these methods. The results indicate that sex estimation methods can be developed on samples where sex is not known. Additionally, the discriminant functions developed produce high levels of classification for the sites, individually, as well as for the geographic, temporal, and all pooled samples. The latter suggests these functions have broader applicability for these regions and temporal periods. Moreover, the concordance rates for these functions are similar to the accuracy rates when these bones were applied to samples with known sex.

This project analyzes the sexual dimorphism of the femur and tibia using geometric morphometrics. The study sample includes 250 individuals of known sex and age at death with complete, non-damaged, non-pathological skeletal remains from the William M. Bass Donated Skeletal Collection at the University of Tennessee, Knoxville. Ages range from 19-96 for males (mean=56.92 years) and 29-97 for females (mean=59.48 years). A combination of landmarks and semi-landmarks were collected on the proximal and distal epiphyses of each bone using a Microscribe, which helps capture the overall size and shape variation present in the sample. Only individuals from one population, White, where analyzed in order to eliminate population variation bias. Classification rates for males and females for the proximal femur were 80.8% and 78.4% respectively, for the distal femur 92.6% and 89.6% respectively, for the proximal tibia 80.8% and 83.2% respectively, and the distal tibia 81.6% and 80.8% respectively, all with a p<0.0001. These rates created a classification model for which epiphysis gave the most accurate assessment of sex: the distal femur, followed by the proximal tibia, then the distal tibia, and lastly the proximal femur. This study indicates the knee joint is the most dimorphic, followed by the ankle and then the hip. The results fall in line with another study indicating the knee is more sexually dimorphic in a modern White population (Spradley and Jantz 2011), though in contrast to their results this study found the distal femur was more dimorphic than the proximal tibia. This method indicates that in comparison to standard measurements, geometric morphometrics may provide a more reliable method for sex estimation when used, specifically on the knee. Certain landmarks were then selected based on the standard taphonomic process of coffin wear and postmortem damage (Pokines and Baker 2014) for exclusion to determine the usability of the method on fragmented or damaged skeletal remains. When combinations of landmarks were removed, the distal femur still possessed the highest classification rates with over 80% accuracy.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2017-07-03T11:47:36Z No. of bitstreams: 2 Dissertação - Marcelo Machado de Lima - 2017.pdf: 1874559 bytes, checksum: f24752927f810c9e49c1d1e7b537fa3d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-07-10T11:30:35Z (GMT) No. of bitstreams: 2 Dissertação - Marcelo Machado de Lima - 2017.pdf: 1874559 bytes, checksum: f24752927f810c9e49c1d1e7b537fa3d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-07-10T11:30:35Z (GMT). No. of bitstreams: 2 Dissertação - Marcelo Machado de Lima - 2017.pdf: 1874559 bytes, checksum: f24752927f810c9e49c1d1e7b537fa3d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-05-30 / This work aims, with the help of GeoGebra Software, make an analysis of the Function f(x)=a + b sin(cx + d) (and also the Functions f(x)=a + b cos(cx + d) and f(x)=a + b tan(cx + d)) where we show the student what happens to the graph of the Function (And through of the graph analyze the changes in the domain, image and period, and also analyze the parity of these Functions) When we vary, separately, the values of a, b, c and d. In the end we hope that the student can do the analysis of a complete Function f(x) = a + b sin(cx + d) (and also the Functions f(x) = a + b cos(cx + d) and f(x) = a + b tan(cx + d)). / Este trabalho visa, com a ajuda do Software GeoGebra, fazer uma análise da Função f(x)=a + b sen(cx + d) (e também das Funções f(x)=a + b cos(cx + d) e f(x)=a + b tg(cx + d) ) onde mostramos ao aluno o que acontece com o gráfico da Função (e através do gráfico analisar as mudanças no domínio, imagem e período, e também analisar a paridade destas Funções) quando variamos, separadamente, os valores de a, b, c e d. No final esperamos que o aluno consiga fazer a análise de uma Função completa f(x)=a + b sen(cx + d) (e também das Funções f(x)=a + b cos(cx + d) e f(x)=a + b tg(cx + d)).

Human p-glycoprotein (P-gp) is an ATP-binding cassette transporter that actively transports a diverse set of substrates at the plasma membrane. Specifically, P-gp is expressed most highly at important blood tissue barriers on the lumenal side of endothelial cells and secretory tissues asymmetrically where it provides generalized protection against xenobiotics due to its promiscuous substrate binding pocket. Substrates typically interact with P-gp within the inner leaflet of the plasma membrane before being effluxed through large conformation changes driven by ATP binding and hydrolysis. Since many small molecule drugs are substrates of P-gp and P-gp has the ability to transport chemically and structurally diverse molecules, delivery of bioavailable small molecule therapies and treatment of diseases beyond blood-tissue barriers may be difficult. In cancer, expression of P-gp may confer a multidrug resistance phenotype due to upregulation of the MDR1 gene, which encodes P-gp, in response to treatment with chemotherapies. Treatments of diseases beyond blood-tissue barriers and some cancers may be more complex given the protective role of P-gp coupled with it promiscuous substrate binding site.<br>Many studies of P-gp have been centered around understanding the structure function relationship of how P-gp effluxes small molecules across the plasma membrane. Here we have used a transient Vaccinia virus expression system to rapidly express many mutants of P-gp in human cells for analysis. Transient expression using the Vaccinia system was optimized to produce a large amount of protein while avoiding significant cell death. Optimization of the Vaccinia expression system has also helped to show that changes in P-gp surface expression are not correlated to changes in substrate accumulation within cells expressing P-gp, a topic that has yet to be addressed within the field of P-gp study. Reduced surface expression of P-gp to 68% maintained the same level of reduced cellular accumulation of two substrates, calcein-AM and rhodamine 123, relative to a WT P-gp control. Further study of P-gp mutations revealed a Y998A mutation had a 90% reduction of surface expression but the same reduction of cellular accumulation of rhodamine 123 further supporting that changes in surface expression do not correlate to changes in substrate transport.<br>We then sought to demonstrate how flexibility in transmembrane helix (TMH) 12 of P-gp affected overall stability and transport ability in vitro. TMH 12 in inward facing conformations shows a region of decreased hydrogen bonding in the backbone of the helix leading to a “kink” present in many crystal structures of C. elegans and mouse P-gp as well as in an occluded structure of human P-gp. Outward facing crystal structures of C. elegans, mouse, and human P-gp show TMH 12 where the backbone of the helix is fully hydrogen bonded and ordered. The change in hydrogen bonding pattern and the presence of the kink in TMH 12 suggest the importance of flexibility in the function of TMH 12. Clustal Omega was used to align the primary structure of P-gp between 8 species and a conserved sequence of 996-PDYAKA-1001 was identified aligning with the kink observed in crystallographic data. The kinked nature of this region led to our development of a rigid poly-alanine mutation and a flexible poly-glycine mutation based on the propensity of these amnio acids to form helices. The more flexible poly-glycine mutation obtained no significant transport while the poly-alanine mutation maintained some ability to transport fluorescent substrate relative to a WT control. Crosslinking of the nucleotide binding domains (NBDs) revealed a decrease of NBD dimerization likely correlating to decreased transport. Thus, some degree of flexibility within the kink region is critical for substrate transport as rigid and flexible mutations of this region abrogate transport of fluorescent substrates.<br>While the substrate binding pocket it located towards the interior of P-gp within the lipid bilayer, it has been theorized that substrates may interact with P-gp at the lipid-protein interface of the inner leaflet near portals for substrate entry formed by pairs of helices either side of the protein. To test this hypothesis, aromatic residues on TMH 12 and adjacent elbow helix 2 near the interface region of the inner leaflet, that have also been observed to interact with a cyclic peptide in a crystal structure of P-gp, were mutated to alanine. Y998, on TMH 12, was shown to interact with the cyclic peptide and is ideally located at the protein-lipid interface near a surface formed by elbow helix 2 and TMH 9 and was observed to have the largest effect on substrate accumulation. Accumulation of fluorescent substrates, relative to WT P-gp, was increased though not all substrates were affected similarly. No increase of accumulation was observed with rhodamine 123 while accumulation of BD-prazosin increased 65% relative to WT P-gp. It is to be expected that the large diversity of substrates recognized by P-gp would interact preferentially with carrying residues at the protein-lipid interface similar to observations of substrate binding at the substrate binding pocket. Variability in accumulation signifies that substrates do interact with P-gp at the lipid-protein interface and substrates interact differently at this interface similarly to substrate interaction at the substrate biding pocket.<br>

The sexing of human skeletal remains is important for identification and demographic purposes. It is made more difficult when elements such as the skull and pelvis are not recovered or are in too poor of a condition to assess. Previous studies have used carpal (wrist) bones of contemporary populations to assess the viability of these skeletal elements exhibiting sexual dimorphism, as these bones are small, compact elements that are usually recovered in good condition. This study evaluates the use of carpal bones recovered from an ancient Maya population from Belize to determine the biological sex of individuals. The study sample is part of the Maya Archaeological Skeletal Collection (MASC), which contains individuals from the sites of Lamanai, San Pedro, Altun Ha, and Marco Gonzalez and dates from the Late Maya Pre-Classic (400 BC-AD 250) to the Spanish Colonial period (AD 1521-1821). Multiple measurements were taken on 36 capitate, 34 lunate, 34 scaphoid, 27 trapezium, 24 hamate, 22 triquetral, 22 trapezoid, and 16 pisiform bones from several individuals. Discriminant function analysis was used to determine if sexual dimorphism is measurable in this population using these elements. Previous studies used populations with known identities, assessing individuals from crypts, graveyards, or medical collections from the last few centuries. This study varies from previous studies as it utilizes archaeological remains, making this study one of the first to evaluate non-contemporary remains with unknown sex. Results of this study demonstrate that this population exhibits sexual dimorphism and discriminant function analysis can be used to distinguish between two groups. This demonstrates that carpals could be used to help determine biological sex of archaeological populations as well as a tool to help with identification in forensic cases.