No description available.

No description available.

Viral vectors derived from mouse polyomavirus are a convenient tool for studying the targeted delivery of therapeutical agents into the cells and cellular organelles. Vectors derived from mouse polyomavirus face difficulties similar to other nanoparticles, as they often end up trapped inside an endosome where they are subsequently degraded. This diploma explored the potential of vector modifications, which have the potential to make the transport to the nucleus or cytosol more effective. This work had particularly focused on increasing the transduction efficiency by modifying particle's internally localized VP3 capsid protein with covalently bound membrane-penetrating peptides. Primary covalent genetic modification to the VP3 protein was the polyhistidine peptide KH27K. Its potential of improving the transduction effectivity was compared with two other peptide modifications - LAH4 and R8. The results of the transduction test showed that covalently bound R8 peptide had many-fold improved the transport to the nucleus when compared to the unmodified particles. The modification with LAH4 peptide had been regarded more effective only when was associated with the particles non-covalently. In such scenario the transduction efficiency rose 40-times when compared with unmodified particles. Polyhistidine...

The Bahamas Island archipelago grows by the precipitation and secretion of calcium carbonate. A majority of this growth is by lateral accretion of shoreline sedimentary deposits. Previous research is not clear on whether the growth is largely due to eustasy, sediment input from catastrophic events, or a combination of both. The Bahamas is an ideal location for studying Holocene carbonate generation and deposition, but there is limited research on the analysis of strandlines in relation to lateral accretion. Carbonate strandline deposits are commonly classified as low-energy beach ridge deposits. Previous researchers have primarily focused on ooid shoals and subtidal regions. Understanding the mechanisms of platform and shoreline growth in the Bahamas is important for creating petroleum reservoir analogs for exploration. We use ground penetrating radar (GPR) to image and interpret the internal fine-scale stratigraphy of Bahamian carbonate strand plains and thereby constrain our understanding of the processes by which the islands grow. Although GPR has been used extensively to analyze the interior of clastic strandline deposits across the world, tropical carbonate settings have received little attention. We are the first to utilize GPR to study strand plains in Crooked Islands, The Bahamas, our primary location for 2D GPR data acquisition. We integrate our interpretation of these data with a 3D GPR data volume collected on Pleistocene eolianites on San Salvador Island, The Bahamas. We used a GSSI (Geophysical Survey Systems, Inc.) bistatic 400-MHz antenna with a field frequency filter of 100"“800 MHz for all datasets. GPR allowed visualization of the interior of the strand plains down to a depth of about 2 m with high resolution. Data processing was performed using state-of-the-art petroleum industry techniques (e.g., gain control, deconvolution, migration, seismic attribute computation) to better visualize the reflectivity. Our data constrains a model that the lateral accretion of carbonate sediment preserved in strandline was deposited in a combination of storm processes and gradual sediment progradation, rather than one or the other. Our conclusions help determine that The Bahamas is ideal for GPR imaging of strandlines due to being assessable, high data quality, no clastic influence, and a dry environment during parts of the world

Concrete bridge decks in Utah are experiencing observable deterioration due primarily to freeze-thaw cycles and the routine application of deicing salts during winter maintenance activities. Given the need for increasingly cost-effective strategies for bridge deck maintenance, rehabilitation, and replacement (MR&R), the Utah Department of Transportation (UDOT) initiated this research to ultimately develop a protocol offering guidance as to whether deteriorated bridge decks should be rehabilitated or replaced. While threshold values for various non-destructive condition assessment methods were proposed in earlier UDOT research, this work focused on implementing the recommended test criteria. Twelve bridges were identified by UDOT engineers for inclusion in the study, and data were collected from each deck to determine whether the bridge decks warranted rehabilitation or replacement based on the proposed threshold values. Several evaluation techniques were employed to assess concrete bridge deck condition, including visual inspection, hammer sounding and chaining, dielectric measurements, ground-penetrating radar imaging, resistivity testing, half-cell potential testing, and chloride concentration testing. The condition assessment testing confirmed that chloride-induced corrosion of reinforcing steel is the primary mechanism of deck deterioration and that inadequate cover over the upper steel mat facilitated accelerated corrosion damage in many instances. The bridge deck condition analyses produced from the results of non-destructive testing were compared to the visual inspection ratings assigned to each deck by UDOT. Concrete bridge deck condition data should be collected regularly through inspection and monitoring programs to facilitate prioritization of MR&R strategies for individual bridges and to evaluate the impact of such strategies on the overall condition of the network. Performance indices based on selected condition assessment parameters should be developed for use in bridge management activities, and mathematical deterioration models should be calibrated in order to forecast both network-level and project-level conditions and predict funding requirements for various possible MR&R strategies. Further research, including statistical analyses of the data presented in this report, should be completed to develop relevant mathematical deterioration models for predicting the service lives of concrete bridge decks in Utah.

<p>  </p> <p>The access of ring junction functionalized 5,6-hydrindanone systems has been elusive in the realm of synthetic methodology, and the functionalization of a pre-built ring system rarely explored. These 5,6-hydridanone systems are prevalent in a variety of terpenoid ring systems, especially that of steroidal molecules. Previous synthetic methods to reach these systems using a Diels-Alder cycloaddition proved to be difficult and lacked labile functional groups that would be useful for substitution after the cycloaddition. The design of the α-nitrile cyclopentenone dienophile allows for both post-cyclization adduct functionalization, as well as lowering the energy barrier of the cycloaddition itself. In this work, it is shown that the Lewis acid promoted Diels-Alder reaction with α-nitrile β-methyl cyclopentenone dienophile can be performed under standard temperatures and pressures unlike previously established methods.1 This reaction can generate four chiral centers in a single synthetic step when the starting materials are prochiral. After the generation of 5,6-hydrindanone systems, radical cleavage of the nitrile functionality also allowed for electrophile trapping at the ring junction. This radical cleavage and electrophile trapping pathway allows for functionalization of a quaternary carbon at the ring junction, a method that should be fruitful in the generation of difficult to synthesize steroidal and other terpenoid molecules.</p> <p>In the work on synthetic cell penetrating peptides, camptothecin whilst a notably effective topoisomerase I inhibitor, has never quite reached it’s potential as a therapeutic due to its poor solubility in living systems. Previously, cationic amphiphilic polyproline helices (CAPH) molecules from the Chmielewski lab have been hydrophobically functionalized through O-alkylation of hydroxyprolines at specific regions within the peptide to generate a hydrophobic face. The combination of the cationic faces and the hydrophobic face have made the CAPH molecules notably cell penetrant and tunable. With camptothecin’s notable insolubility in water, it may serve as valuable surrogate to the hydrophobic groups on CAPH molecules and allowing it to be delivered intracellularly. Using an endogenously cleavable linker, we have worked towards a CPP that acts as a drug delivery vehicle. Acting as a replacement of the hydrophobic residue of a CAPH molecule, camptothecin will be chaperoned into the cell and should be released through the action of intracellular esterases.</p>

No description available.

No description available.

Ultra-high-resolution subsurface stratigraphy mapped from 3D ground-penetrating radar (GPR) can provide insights into the fine-scale heterogeneity of reservoirs and other geologic features. Analog models derived from 3D GPR aid in understanding reservoir compartmentalization that may be sub-seismic but still affect fluid flow. We integrate 2D profiles and 3D GPR volumes with measured stratigraphic sections from outcrop exposure to characterize the fine-scale stratigraphy of an ancient Lake Bonneville shoreline deposit (locally, circa 20 ka based on carbon-14 dating) in the Great Basin (northwestern Utah). The heterogeneity of the deposit is expressed as multiple discordant patterns, separated by unconformities that likely were influenced by fluctuating lake levels on the lake margin. Although the study site is only ~8,000 square meters in area, the detailed stratigraphic relationships can be scaled up to inform the characterization of larger sedimentary deposits with economic reservoir potential. The sands, gravels, and marls composing the stratigraphy were deposited during the transgressive phase of the pluvial lake, which preserved shoreline features such as spits and barrier bars. We interpret our site as a spit that extended out into the Pleistocene lake, at times connecting to a nearby persistently subaerially exposed island to form a tombolo. The deposited strata are well-exposed in a fortuitously located gravel quarry. The site provides an excellent natural laboratory for detailed 3D imaging due to the mostly flat ground surface (the quarry floor), low-clay, low-salinity, and low-moisture content of the site. The GPR data were acquired with a 200-MHz antenna (for 2D profiles) and a 400-MHz antenna (for 3D volumes). For the latter, the line spacing was about 0.3 meters with a trace spacing of 2.5 cm. The GPR dataset offers high-resolution images of clinoform sequence stratigraphy down to about 3 meters below the surface of the quarry. The vertical resolution (Rayleigh criterion) of the data is about 6 cm (for 3D volumes) and 13 cm (for 2D profiles). Migration collapsed diffractions and re-positioned dipping reflectors correctly. Deconvolution suppressed multiple reflections and tightened the waveforms. Using petroleum industry mapping software, amplitudes were binned into voxels to create precise 3D volumes, which facilitated more accurate geometrical interpretation (e.g., true dip direction of reflectors). Facies associations from stratigraphic sections measured just above the GPR acquisition level (quarry floor) help to describe and reconstruct the depositional history of the spit. The lithologic interpretation of the GPR reflectors is constrained by the correlation (or extrapolation) of the measured sections to the subsurface data volumes. Reflectivity is controlled by variations in porosity and matrix content (e.g., quartz vs. clays vs. calcite). Our study furnishes a model of transgressive deposits in a lacustrine environment and an analog for clastic sediments deposited on a larger scale in such environments.

The Southern Appalachian hardwood forests contain a wide diversity of flora and fauna. Understanding processes that affect nutrient availability in these forests is essential for sound forest management. Three interconnected research projects regarding soil resource heterogeneity were designed to increase our understanding of this ecosystem. The objective of these projects were as follows: 1) to examine and quantify the role of decaying stumps in regards to total carbon (C) and nitrogen (N) pools and fine-root dynamics, 2) compare and contrast the use of ground-penetrating radar (GPR) vs. a soil auger for estimating soil depth and site quality and 3) to evaluate how eastern red-backed salamanders (Plethodon cinereus) affect N-availability. For the stump study, results show that decomposing stumps occupy approximately 1.2% of the total soil volume and constitute 4% and 10% of total soil N and C pools. Significant differences in N (p = 0.0114), C (p = 0.0172), microbial biomass C (p = 0.0004), potentially mineralizable N (p = 0.0042), and extractable NH4+ (p = 0.0312) concentrations were observed when compared to mineral soil horizons. In particular, potentially mineralizable N was 2.5 times greater in stump soil than the A-horizon (103 vs. 39 mg kg-1), 2.7 times greater for extractable NH4+ (16 vs. 6 mg kg-1) and almost 4 times greater for MBC (1528 vs. 397 mg kg-1). These measured properties suggest higher N-availability, organic matter turnover and N uptake in stump soil versus the bulk soil. 19% of the total fine root length and 14% of fine root surface area also occurred in the stump soil. The increased fine root length suggests higher concentrations of labile nutrient in the stumps since roots often proliferate in areas with higher nutrient availability. Significant differences occurred in N and C concentrations between all four decay classes and the A-horizon, which validated the use of this system and the need to calculate weighted averages based on the frequency and soil volume influenced by each decay class. In the GPR Study, depth estimations were shallower using a soil auger compared to estimates obtained using GPR across all plots (p = 0.0002; Figure 3.4). On a soil volume basis, this was equivalent to about 3500 m3 of soil per hectare unaccounted for using traditional methods. In regards to using soil depth as a predictor for site quality, no significant relationships were observed with soil depth estimations obtained from the auger (Table 3.3). On the other hand, depth measurements from GPR explained significant amounts of variation across all sites and by physiographic region. Across all sites, soil depth estimates from GPR explained 45.5% of the residual variation (p = 0.001; Table 3.3). When the data were stratified by physiographic region, a higher amount of variation was explained by the regression equations; 85% for the Cumberland Plateau (p = 0.009), 86.7% for the Allegheny Plateau (0.007) and 66.7% for the Ridge and Valley (p = 0.013), respectively (Table 4.2). Results from this study demonstrate how inaccurate current methods can be for estimating soil depth rocky forests soils. Furthermore, depth estimations from GPR can be used to increase the accuracy of site quality in the southern Appalachians. In the salamander study, no significant salamander density treatment or treatment by time effects were observed over the entire study period (p < 0.05). However, when the data were separated by individual sampling periods a few significant treatment by time interactions occurred: 1) during August 2006 for available NH4+ under the forest floor (i.e. horizontal cation membranes; p = 0.001), 2) August and 3) September 2006 for available NH4+ in the A-horizon (p = 0.026), and 4) May 2007 for available NO3- under the forest floor (p = 0.011). As a result of these trends, an index of cumulative N-availability (i.e. NH4+ and NO3-) under the forest floor and in the A-horizon was examined through the entire study period. Cumulative N-availability under the forest floor was consistently higher in the low- and medium-density salamander treatments compared to the high-density treatment. For cumulative N-availability in the A-horizon, a gradient of high to low N-availability existed as salamander density increased. Factors such as a prolonged drought in 2007 may have affected our ability to accurately assess the effects of salamanders on N-availability. We concluded that higher salamander densities do not increase N-availability. Implementing methodologies that accurately account for soil nutrient pools such as stump soil, physical properties such as depth and fauna such as salamanders, increase our understanding of factors that regulate site productivity in these ecosystems. As a result, landscape-level and stand-level management decisions can be conducted more effectively. / Ph. D.