SYNTHESIS OF SMALL-MOLECULE, THIOSEMICARBAZONE-BASED INHIBITORS OF CATHEPSIN L FOR THE TREATMENT OF METASTATIC CANCER
Danielle S. Suh
Westlake High School
Austin, TexasFaculty Mentor: Dr. Kevin G. Pinney
Department of Chemistry and Biochemistry
Cancer is a broad group of diseases marked by the uncontrolled growth and spread of abnormal cells. A primary characteristic of malignant tumors is their migration and invasion into surrounding tissues. This spreading of cancer, known as metastasis, is a leading cause of death among cancer patients. Metastasis is facilitated by increased proteolytic activity, which helps digest the extracellular matrix, allowing the tumor to spread to other locations in the body. Cathepsin L, a cysteine protease, is overexpressed in cancer cells and in cells involved in angiogenesis. It is anticipated that inhibition of cathepsin L will limit or arrest cancer metastasis, thus establishing cathepsin L as a promising anti-cancer target. Previous work in the Pinney Laboratory (Baylor University) has created a small library of cathepsin L inhibitors bearing the thiosemicarbazone moiety. Their biological mechanism of action presumably involves nucleophilic attack by the cysteine-25 thiolate. Ideal analogs will hinder the ability of cathepsin L to cleave peptide bonds, while also remaining selective and reversible with a low cytotoxicity. Consequently, the objective of this research project is to synthesize new thiosemicarbazone analogs and ultimately evaluate their inhibitory activity against cathepsin L.
THERMOPHORETIC EFFECT ON THE CRYSTAL STRUCTURE OF BILAYER COMPLEX PLASMA
The Harker School
Faculty Mentor: Dr. Victor Land, Dr. Lorin Matthews
Department of Physics
The study of dusty plasmas is relevant for star and planet formation as well as in industries, such as semiconductor manufacturing. Complex plasmas, which are ionized gases containing micrometer-sized particles, were studied in a Gaseous Electronic Conference (GEC) cell. Argon plasma was first formed at low pressure; dust particles were added afterwards. The heating and cooling of the lower electrode established a temperature gradient and generated a thermophoretic force. The interactions of 8.89-micrometer and 6.50-micrometer diameter particles were observed for different temperatures. The objective of the study is to explore the ion wake field effect that organizes particles into crystal bilayers. Top view images were analyzed with Voronoi diagrams to study how the upper particle layer influences the lower layer. Experimental conditions were then modeled with the box_tree program.
Characterization and Optimization of the Rutland 504 Wind Turbine
Faculty Mentor: Dr. Van Treuren
The Rutland 504 Windcharger is a six-bladed, 510 millimeter diameter commercial wind turbine used primarily to charge batteries on small sailing vessels. Testing was carried out on this turbine to characterize its performance, as well as to explore the effects of roughness on the turbine’s blades to improve performance. The results of the characterization showed that the data provided by the manufacturer were overly optimistic. Manufacturer testing conditions were also not clearly explained. The current experimental testing was conducted at wind speeds of five, ten, and fifteen miles per hour, within a Reynolds number range, based on blade chord, of 9000 and 29000. A 1/8 inch strip of 330U grit sandpaper was used to create roughness in full span configurations 5/8 inch from the leading edge, 5/16 inch from the leading edge, and directly on the leading edge. Also tested were configurations with the strips on the leading edge of the outer 1/3 span, middle 1/3 span, and inner 1/3 span. The full span configuration placed on the leading edge showed a 17.73% power increase over the baseline Rutland at ten miles per hour, and the leading edge, inner 1/3 span arrangement created a 23.18% improvement in power at the same wind speed. This improvement is believed to be due to delay of flow separation over the blades.
POPULATION BIOLOGY AND ECOLOGICAL STOICHIOMETRY OF SIMYRA HENRICI IN A CENTRAL TEXAS WETLAND
Poudre High School
Fort Collins, Colorado
Faculty Mentor: Dr. Robert Doyle
Department of Biology
I investigated an outbreak of Simyra henrici (Henry’s Marsh Moth) in the Lake Waco Wetlands in Waco, Texas. This caterpillar was first observed in late May and by June 15 had consumed around fifty percent of the cattail (Typha sp.) population; cattails currently dominate the aquatic plant community. The caterpillar population appeared to move as a front and areas of high activity had densities ranging from twenty-eight to 224 caterpillars per m2 and an average of eighty-four and a median of sixty-two.
Laboratory and field experiments were conducted to determine grazing rate (ingestion) and rate of fecal production (egestion). The grazing rate varied little with size with an average around ten mg per caterpillar per hour. In contrast, egestion increased with size showing that smaller caterpillars had higher assimilation rates (ingestion – egestion).
We analyzed the phosphorous content of the caterpillars’ food source (cattails), the caterpillar tissue and feces. The food source was low in phosphorous with an average of 0.13% phosphorous. Phosphorous content of the caterpillar tissue ranged from .4 to 1.6 % dry mass. Smaller caterpillars had higher percentages. We show that phosphorous retention is linked to the phosphorous content of the caterpillars. Small, rapidly growing caterpillars with higher demand for phosphorous rich molecules for growth retain more phosphorous.
Synthetic Routes of Toll-Like Receptor-7 Agonists
Wood River Rural High School
Wood River, Nebraska
Faculty Mentor: Dr. Robert Kane
Department of Chemistry/Biochemistry
Toll-like receptors (TLRs) are transmembrane proteins that are a part of the first line of defense in the innate immune system. Several organic molecules have been shown to induce an immune response by activating these Toll-like receptors. Such molecules are referred to as Toll-like receptor-7 agonists. Through previous research, it has been found that the yields of TLR-7 agonists have been lower than desired. We have attempted to find alternative synthetic routes that will increase the yields of these compounds. We attached a directing group to the 6 position on a purine ring, which could increase agonist production in previously found synthetic routes. The directing group will prevent the formation of unwanted isomers in our reaction scheme. Succinic anhydride was the directing group, and we attempted to attach it to aniline. Aniline has similar properties to 2-chloro 6-amino purine, our starting material. Following the procedure from the synthesis of N-phenylsuccinimide and carrying out a two solvent recrystallization, we determined that the succinic anhydride and aniline reaction yielded our desired product. Therefore, the succinic anhydride was reacted with 2-chloro 6-amino purine to produce our desired molecule, and further research is being done to synthesize this molecule. Further work with these synthetic routes may ultimately produce compounds that enhance immune responses in the human body.
Obtaining Aptamers to Bind to Escherichia Coli Using the Cell-SELEX Process
Lutheran South Academy
Faculty Mentor: Dr. Sung-Kun Kim
Department of Chemistry/Biochemistry
With thousands of reported cases each year, Escherichia coli contaminates water and food throughout the world. To detect outbreaks of E. coli, we acquired double strained DNA (dsDNA) and attempted to obtain single strained DNA oligonucleotides. These oligonucleotides can bind with E. coli DH5α with high affinity and specificity using Systematic Evolution of Ligands via Exponential Enrichment (SELEX). DNA oligonucleotides that target specific cells are known as aptamers. The cell-SELEX process consists of repetitive rounds of incubation, partition, elution, counter-selection, polymerase chain reaction, cloning, and sequencing. We determined the dissociation constant (Kd) of the dsDNA aptamers using a flourometer to obtain the binding affinity of the aptamer to the cell. The dsDNA aptamer produced through the cell-SELEX rounds has a Kd value of 6.719 pM, which indicates that the aptamer has high binding affinity for E. coli cells. To ensure the validity of these results, we are attempting to use flow cytometry to determine the binding affinity of the aptamers produced through cell-SELEX. With a laser, photomultipliers, and photodiodes, the flow cytometer evaluates the binding affinity of the aptamer by measuring its reflection, diffraction, refraction, and fluorescence. If the low Kd value is confirmed by flow cytometry, the final aptamers can be used as a detection system to identify E. coli in water or food, or as a diagnostic tool to identify E. coli in patients.
The effect of Thermophoresis on Vertical Alignment of Dust Particles in Bilayer Complex Plasma
Manatee High School
Faculty Mentors: Dr. Victor Land and Dr. Lorin Matthews
Department of Physics
This research examines the vertical alignment of dust particles in a complex plasma into “chains” due to the ion wake field effect and how these chains change with the upward force of thermophoresis. We studied the effects of thermophoresis on a monodisperse layer of 8.9μm melamine formaldehyde dust as well as its effects on a bilayer complex plasma with both 8.9μm and 6.5μm particles sizes. Numerical models using similar cell settings and particle numbers were run to compare experimental data to results expected from theory and literature. Using thermophoresis, the levitation height of the particles was increased in both cases and there was an evident change in the length and stability of chains as the temperature increased on the lower electrode.
A Comprehensive Review of the Consumption of Commercially Isolated Stevioside and Rebaudioside A Glycosidic Compounds
DeBakey High School for Health Professions
Faculty Mentor: Dr. Janelle Walter
Department of Family and Consumer Sciences
Due to the rapid exponential growth of the rates of diabetes and obesity, the search for a low-calorie sugar substitute that mimics the taste and quality of white sugar and other traditional sweeteners remains essential for many groups of people. In December 2008, the Food and Drug Administration (FDA) approved a natural sweetener known and marketed as a stevia extract. Comprised of heat-stable steviol glycosides, extracts from the leaves of the Stevia rebaudiana plant contains compounds that are 250 to 300 times sweeter than sucrose and have a low calorific value. Unsurprisingly, stevioside and rebaudioside A compounds, the two main constituents of stevia extracts, have undergone extensive genetic, mutagenic, and toxicity testing. Toxicity studies generally reveal a very low toxicity associated with stevioside consumption, including reproductive toxicity. Recent medical research with stevia shows promise in treating obesity, hypertension, and heart disease and, because of its low glycemic index, is appropriate for diabetics and patients with phenylketonuria. Additionally, stevia is also being investigated for its virustatic and virucidal properties against retroviruses, antihyperglycemic and insulinotropic induction, in vitro antioxidant properties, and free radical suppression. General literature about stevia, the properties of its extracts, toxicological and biochemical aspects, and the physiological effects of human consumption, as well as consumer interest, is discussed.