Structural Analysis of alpha-Fetoprotein (AFP)-like Peptides with Anti-Breast-Cancer Properties

The abundance of alpha-fetoprotein (AFP), a natural protein produced by the fetal yolk sac during pregnancy, correlates with lower incidence of estrogen receptor positive (ER+) breast cancer. The pharmacophore region of AFP has been narrowed down to a four amino acid (AA) region in the third domain of the 591 AA peptide. Our computational study focuses on a 4-mer segment consisting of the amino acids threonine-proline-valine-asparagine (TPVN). We have run replica exchange molecular dynamics (REMD) simulations and used 120 configurational snapshots from the total trajectory as starting configurations for quantum chemical calculations. We optimized structures using semiempirical (PM3, PM6, PM6-D2, PM6-H2, PM6-DH+, PM6-DH2) and density functional methods (TPSS, PBE0, M06-2X). By comparing the accuracy of these methods against RI-MP2 benchmarks, we devised a protocol for calculating the lowest energy conformers of these peptides accurately and efficiently. This protocol screens out high-energy conformers using lower levels of theory and outlines a general method for predicting small peptide structures.

Microbial community analysis of Lake Chillisquaque, a small water system in Central Pennsylvania

Cyanobacteria are photosynthetic organisms that require the absorption of light for the completion of photosynthesis. Cyanobacteria can use a variety of wavelengths of light within thevisible light spectrum in order to harvest energy for this process. Many species of cyanobacteria have light-harvesting proteins that specialize in the absorption of a small range of wavelengths oflight along the visual light spectrum; others can undergo complementary chromatic adaptation and alter these light-harvesting proteins in order to absorb the wavelengths of light that are mostavailable in a given environment. This variation in light-harvesting phenotype across cyanobacteria leads to the utilization of environmental niches based on light wavelength availability. Furthermore, light attenuation along the water column in an aquatic system also leads to the formation of environmental niches throughout the vertical water column. In order to better understand these niches based on light wavelength availability, we studied the compositionof cyanobacterial genera at the surface and depth of Lake Chillisquaque at three time points throughout the year: September 2009, May 2010, and July 2010. We found that cyanobacterialgenera composition changes throughout the year as well as with physical location in the water column. Additionally, given the light attenuation noted throughout the Lake Chillisquaque, we are able to conclude that light is a major selective factor in the community composition of Lake Chillisquaque.

The Modified Direct Analysis Method: an Extension of the Direct Analysis Method

The purpose of this research project is to study an innovative method for the stability assessment of structural steel systems, namely the Modified Direct Analysis Method (MDM). This method is intended to simplify an existing design method, the Direct Analysis Method (DM), by assuming a sophisticated second-order elastic structural analysis will be employed that can account for member and system instability, and thereby allow the design process to be reduced to confirming the capacity of member cross-sections. This last check can be easily completed by substituting an effective length of KL = 0 into existing member design equations. This simplification will be particularly useful for structural systems in which it is not clear how to define the member slenderness L/r when the laterally unbraced length L is not apparent, such as arches and the compression chord of an unbraced truss. To study the feasibility and accuracy of this new method, a set of 12 benchmark steel structural systems previously designed and analyzed by former Bucknell graduate student Jose Martinez-Garcia and a single column were modeled and analyzed using the nonlinear structural analysis software MASTAN2. A series of Matlab-based programs were prepared by the author to provide the code checking requirements for investigating the MDM. By comparing MDM and DM results against the more advanced distributed plasticity analysis results, it is concluded that the stability of structural systems can be adequately assessed in most cases using MDM, and that MDM often appears to be a more accurate but less conservative method in assessing stability.

Significance of the Deformation History within the Hinge Zone of the Pennsylvania Salient, Appalachian Mountains

Two competing models exist for the formation of the Pennsylvania salient, a widely studied area of pronounced curvature in the Appalachian mountain belt. The viability of these models can be tested by compiling and analyzing the patterns of structures within the general hinge zone of the Pennsylvania salient. One end-member model suggests a NW-directed maximum shortening direction and no rotation through time in the culmination. An alternative model requires a two-phase development of the culmination involving NNW-directed maximum shortening overprinted by WNW-directed maximum shortening. Structural analysis at 22 locations throughout the Valley and Ridge and southern Appalachian Plateau Provinces of Pennsylvania are used to constrain orientations of the maximum shortening direction and establish whether these orientations have rotated during progressive deformation in the Pennsylvania salient's hinge. Outcrops of Paleozoic sedimentary rocks contain several orders of folds, conjugate faults, steeply dipping strike-slip faults, joints, conjugate en echelon gash vein arrays, spaced cleavage, and grain-scale finite strain indicators. This suite of structures records a complex deformation history similar to the Bear Valley sequence of progressive deformation. The available structural data from the Juniata culmination do not show a consistent temporal rotation of shortening directions and generally indicate uniform,