Physical Sciences and Mathematics Commons^™

Development Of Cell-Active Inhibitors And Activity-Based Probe Of Cysteine Cathepsins, Dibyendu Dana

Dissertations, Theses, and Capstone Projects

Cysteine cathepsins are an important class of enzymes that coordinate a variety of important cellular processes, and are implicated in various types of human diseases. Still however, many of their cellular function remain poorly understood. Chemical biology approaches employing small molecules can be utilized for this purpose. Unfortunately small molecule probes that are cell-permeable and non-peptidyl in nature are scarcely available.

In this work, first a library of sulfonyloxiranes is synthesized. From this library, 2-(2-ethylphenylsulfonyl)oxirane is identified as a selective inhibitor of cysteine cathepsins. Cell-based study reveals that 2-(2-ethylphenylsulfonyl)oxirane is a cell-permeable, covalent, and irreversible inhibitor of cathepsin B with …

Paleoecology Of Late Cretaceous Methane Cold-Seeps Of The Pierre Shale, South Dakota, Kimberly Cynthia Handle

Dissertations, Theses, and Capstone Projects

Most investigations of ancient methane seeps focus on either the geologic or paleontological aspects of these extreme environments. In contrast, this thesis encompasses both disciplines to evaluate the paleoecology of these systems with greater detail than previously published either within the Western Interior Basin or elsewhere. This thesis addresses the following questions: 1) Are the changes in mineralogy of a seep discernable and predictable as a seep shifts from a clay-based environment to a carbonate-based environment? 2) What are the foundation organism(s) of Late Cretaceous methane cold-seeps? 3) Is there a correlation to the mineralogic changes and shifts in community …

Component Trees For The Exploration Of Macromolecular Structures In Biology, Lucas Oliveira

Dissertations, Theses, and Capstone Projects

Understanding the three-dimensional structure of a macromolecular complex is essential for understanding its function. A component tree is a topological and geometric image descriptor that captures information regarding the structure of an image based on the connected components determined by different grayness thresholds. This dissertation presents a novel interactive framework for visual exploration of component trees of the density maps of macromolecular complexes, with the purpose of improved understanding of their structure. The interactive exploration of component trees together with a robust simplification methodology provide new insights in the study of macromolecular structures. An underlying mathematical theory is introduced and …

Interactions Of Eukaryotic Translation Initiation Factors And 3' Untranslated Region Of Barley Yellow Dwarf Virus Mrna During Protein Synthesis: A Study Of Equilibrium Binding, Kinetics And Thermodynamics, Bidisha Banerjee

Dissertations, Theses, and Capstone Projects

Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley Yellow Dwarf Virus (BYDV) employs a cap-independent mechanism of translation initiation which is mediated by a structural element BTE (BYDV translation element) located in the 3’ UTR of its mRNA. eIF4F bound the BTE and a translational inactive mutant with high affinity; thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5-164% compared to WT were studied. Using fluorescence anisotropy …

Variation In Habitat Thresholds: An Analysis Of Minimum Habitat Requirements Of North American Breeding Birds, Yntze Van Der Hoek

Dissertations, Theses, and Capstone Projects

Many species show dramatic changes in population extinction or persistence probability at particular habitat amounts. These `extinction thresholds' could be translated to conservation targets, under the condition that we can derive generalities. I investigated the level of variation in landscape-level habitat thresholds for a suite of North American, forest-associated, breeding birds. Records from Breeding Bird Atlases and the availability of remotely-sensed land cover data allowed me to compare habitat thresholds for 25 species across the states of Massachusetts, Michigan, New York, Ohio, Pennsylvania, and Vermont. I show that variation in thresholds is considerable (Chapter II, III), as thresholds range from …

Conformational Features Of The Human U2-U6 Snrna Complex, Ravichandra Bachu

Dissertations, Theses, and Capstone Projects

The splicing of precursor messenger (pre-m) RNA, during which noncoding intervening sequences are excised and flanking coding regions ligated, is an integral reaction of gene expression. In eukaryotes, it is carried out by a dynamic RNA-protein complex called the spliceosome, in which five small nuclear (sn) RNA components are actively involved in recognition and chemical aspects of the process. A complex formed between U2 and U6 snRNAs is implicated in the chemistry of pre-mRNA splicing. The catalytic activity of the U2-U6 snRNA complex is dependent on the presence of Mg2+ ions, and the complex has been shown to have several …

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …

An Experimental Investigation Into The Mechanisms Of Bacterial Evolution, Zhenmao Wan

Dissertations, Theses, and Capstone Projects

This thesis studies the two fundamental mechanisms of bacterial evolution — horizontal gene transfer and spontaneous mutation, in the bacterium Escherichia coli through novel experimental assays and mathematical simulations. First, I will develop a growth assay utilizing the quantitative polymerase chain reaction (qPCR) to provide real-time enumeration of genetic marker abundance within bacterial populations. Second, I will focus on horizontal gene transfer in E. coli occurring through a process called conjugation. By fitting the qPCR data to a resource limited, logistic growth model, I will obtain estimated values of several key parameters governing the dynamics of DNA transfer through conjugation …

Long-Term Warming And The Size And Phenology Of Long Island Sound Plankton, Edward Rice

Dissertations, Theses, and Capstone Projects

In coastal ecosystems with decades of eutrophication and other anthropogenic stressors, the impact of climate change on planktonic communities can be difficult to detect. A time-series of monthly surface water temperatures in the Central Basin of Long Island Sound (LIS) from the late 1940s until 2012 indicates a warming rate of 0.03°C per year, with recent summer temperatures increasing most consistently. During this warming trend, the proportion of chlorophyll produced by smaller phytoplankton and flagellates appears to be higher during warmer summer and fall months, enabling an increase in annual chlorophyll despite static nutrient levels. The phenology of phytoplankton and …

Analysis Of Dna Motifs In The Human Genome, Yupu Liang

Dissertations, Theses, and Capstone Projects

DNA motifs include repeat elements, promoter elements and gene regulator elements, and play a critical role in the human genome. This thesis describes a genome-wide computational study on two groups of motifs: tandem repeats and core promoter elements.

Tandem repeats in DNA sequences are extremely relevant in biological phenomena and diagnostic tools. Computational programs that discover tandem repeats generate a huge volume of data, which can be difficult to decipher without further organization. A new method is presented here to organize and rank detected tandem repeats through clustering and classification. Our work presents multiple ways of expressing tandem repeats using …

Phylogeny And Population Genetics Of The Endangered Dwarf Bear-Poppy, Arctomecon Humilis Coville (Papaveraceae) Using Microsatellite Markers, Joshua Simpson

Dissertations, Theses, and Capstone Projects

The genus Arctomecon (Papaveraceae) is comprised of three narrowly endemic rare species that are largely restricted to gypsum soils of the eastern Mojave Desert. The small, remaining populations of these species have become increasingly isolated by urban development and habitat fragmentation. Arctomecon humilis is federally listed as endangered due to its limited distribution within a ~15 km radius of an actively expanding city. Organizations involved with land management and conservation have called for greater insight into the genetic variation and population structure of the remaining subpopulations as they make important decisions regarding where to focus their efforts and resources.

The …