Abstracts

Pancreatic beta cells secrete insulin, an endocrine hormone that regulates blood glucose levels and maintains normal physiological activity in humans and animals. Diabetes mellitus type II is a consequence of the gradual destruction of these important cells, likely by human islet amyloid polypeptide (hIAPP) that is co-secreted along with insulin. Increasing health care costs, coupled with the World Health Organization's prediction of a worldwide diabetic epidemic by year 2030, make experimental diabetes research a crucial prologue to future clinical trials in prevention, diagnosis, and treatment of Diabetes mellitus type II. Our experimental set-up simulates hIAPP and pancreatic beta cell membrane interactions in order to uncover factors that initiate and promote progression of beta cell death. Results from our study establish the potential role of various fragments of hIAPP in the disease process and explore the molecular mechanisms involved in pancreatic damage.

The inhibition of plasminogen activator-inhibitor-1 (PAI-1) is anticipated to increase our understanding of various human ailments including diabetes, stroke, and atherosclerosis, with which high levels of PAI-1 have been associated. Previous accounts have reported the synthesis of inhibitors that bind to PAI-1 with a low affinity and fail to inhibit PAI-1 when vitronectin, a cofactor of PAI-1, is present. Therefore, the synthesis of small-molecule inhibitors of PAI-1 that improve upon these properties has been the main goal of this research. The refinement of one of these synthesized moieties into a selective and highly active inhibitory species has been achieved. IC50 values of our synthetic inhibitors were determined in an ex vivo plasma inhibition assay.

Bringing new technologies into classrooms, lecture halls, laboratories, and online tutorials are ongoing projects in today's curricula. Although studies have questioned the efficacy of using technology to promote content learning, technology does pave the way in making some subject matter more interesting to students. The objective of our work was to design and produce different forms of media that could be made available to students during chemistry courses. Technologies that were investigated, used, and integrated pedagogically were flip videos, online calculator tutorials, podcasts, and animations. These tools were then made accessible to students outside the classroom to heighten their learning process and enjoy ability of science.

Plasminogen activator inhibitor-1 (PAI-1) is a mammalian protein active in the regulation of fibrinolysis. Data indicates that individuals in various disease states _ namely cancer, diabetes, and cardiovascular disease _ have elevated levels of PAI-1, resulting in disordered fibrinolysis, and an increased risk of thrombosis and embolism. Reduction of excessive levels of active PAI-1 may decrease the risk of thrombosis and embolism. Several inhibitors of PAI-1 have been synthesized, however, most either compete directly with naturally occurring inhibitors in vivo or possess inhibition activity in vitro exclusively, and are not feasible drug candidates. Here we present a novel class of inhibitors designed to have improved pharmacological potential. Based on previous research, the inhibitors take advantage of functional groups that have proven inhibitor-activity relationships while making use of a novel pyrrolidine ring core. Half maximal inhibitory concentration (IC50) data indicates that the pyrrolidine core improves inhibitor binding affinity and potency. The design and synthesis of the inhibitors is discussed, and the supporting IC50 data are presented.

Amphiphilic block copolymers are composed of distinct segments exhibiting different solubilities. In solution, block copolymers may self-assemble to form micelles when triggered by a change in solvent polarity. The effect of chain rigidity was investigated for its role in micellization. Monomers were chosen for their similar chemical properties but their difference in reported glass transition temperature (Tg), a proxy of chain rigidity. Four diblock acrylate copolymers were synthesized by a controlled free radical (RAFT) polymerization. The reversible self-assembly of the polymers was monitored as a function of temperature and solvent polarity by observing peak broadening and measurement of their longitudinal (T1) and transverse (T2) relaxation time constants by 1H NMR. It was found that the rigidity of the segments in the core of the micelle has an effect on the point of micelle formation. Better control of the length of the polymer blocks is necessary for further investigating this effect.

Metal and alloy nanoparticles have attracted much attention over the last decade resulting in the synthesis of new materials of varying size, shape and composition. These nanoparticles have gained much attention due to the diverse chemical and physical properties dependent on their size, shape and composition. The present study describes the effect of various sizes of gold (Au), silver (Ag) and Au/Ag alloy nanoparticles on the fluorescence properties of phosphorescent dye, tris (2,2 _ bipyridyl) dichloro ruthenium (II) hexahydrate (Ru(bpy)32+). There are several methods for the synthesis of metal and alloy nanoparticles but only some methods result in the formation of controlled and homogenous nanoparticles. For our preparation of Au/Ag alloys starch was been used as protective agent and glucose was been used as mild reducing agent. The phosphorescent quenching of Ru(bpy)32+ by gold, silver and alloy nanoparticles was studied by steady state measurements. Steady state measurements resulted in the presence of quenching of adsorption of Ru (II) complex on the nanoparticles surfaces. This quenching may be due to electron transfer between the nanoparticles and the Ru (II) complex. The fluorescence quenching of Ru (II) complex differs according to the type and size of nanoparticles.

Chemical characterization of rock paintings is important for reliable dating using radiocarbon analysis. Identification of the sugar composition of these materials can tell about their sources, which would thus help in selecting the right candidates for dating. A GC-MS method, which involves the formation of diethyldithioacetal trimethylsilyl derivatives of monosaccharides, was employed to characterize carbohydrates in archaeological materials such as rock paintings and a stone tool residue. Carbohydrates were not detected in any of the three rock painting samples while the stone tool residue was found to contain carbohydrates. The GC-MS method of determining carbohydrates in artifacts involves complex chemical derivatization, even though it is successful. We are now developing a more rapid, efficient, and reliable method to determine sugar composition in these and other archaeological residues using thin layer chromatography coupled with DART-MS. Results from GC-MS and the ongoing TLC-DART-MS method will be discussed.

Bacteremia is the bacterial invasion of the blood. Bacterial proliferation in the blood requires that the organism adapts its metabolism to available nutrients. Nucleotide precursors that could be used are present at low levels in the blood and thus the invading bacteria must rely on de novo nucleotide biosynthesis for survival. The dihydroorotase domain is a key enzyme in pyrimidine biosynthesis and catalyzes the third step in the pathway. It was recently shown to be a promising drug target. The genes encoding the dihydroorotase and aspartate transcarbamoylase were cloned from the bacterium, Bacillus anthracis and expressed in Escherichia coli. The proteins were purified by affinity chromatography and visualized by SDS PAGE. The activity of these enzymes was determined by using enzyme assays. Interestingly, the activity of ATC was increased by about 2-fold when mixed with DHO in a 1:1 mole/mole ratio. In addition, their oligomeric structures were determined by S-300 gel filtration chromatography and cross-linking methods.

Amphiphilic block copolymers, materials that contain regions of differing chemical properties, show great promise as potential drug delivery devices. Controlled radical polymerizations by Reversible Addition-Fragmentation Chain Transfer polymerization (RAFT) and Atom Transfer Radical Polymerization (ATRP) were employed to synthesize diblock copolymers from different monomers. Hydrolysis of polymers from one block afforded the amphiphilic diblock copolymers, which were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy, to determine their ability to form micelles in solution. Rate determining experiments on the two polymerization techniques were performed to determine which would be the more useful for the synthesis of further materials. Further considerations of amphiphilic block copolymers rearranging in solution as a function of diblock chain length's ratios along with relative RAFT and ATRP rates of reaction will allow us to synthesize a promising amphiphilic macromolecule for medicinal applications.

Mammalian CAD, a multifunctional protein that catalyzes the first three steps of the pyrimidine bio synthetic pathway is known to be over expressed in several types of tumor cells. The analogues complex of CAD, found in Aquifex aeolicus, a hyperthermophilic organism, was used in this research to understand its structural organization. Gel filtration chromatography was used to study the interaction between the proteins along with chemical cross-linking with dimethyl suberimidate. Peptides designed to disrupt the interaction between specific proteins that form the DAC (dihydroorotate and aspartate transcarbamoylase) complex were used. It was found that these peptides inhibit the activities of the proteins by disrupting the complex at specific sites. Gel filtration chromatography is being used in order to unravel the interaction between carbamoyl phosphate synthetase (CPSase) and the other components of the pathway.

A variety of sulfur-based polyphenolic compounds have been synthesized to improve on previous generations of inhibitors found to have potent and selective inhibition to plasminogen activator inhibitor-1. This new class of compounds is designed with the intent of improving our understanding of relevant structure-activity relationship in plasma-based assay systems.

The main goal of this project is to synthesize pyrrolizidine, indolizidine, and quinolizidine alkaloids. These are bicyclic nitrogen-containing compounds, some of which have glycosidase, anti-cancer, and/or anti-HIV activity. The plan for synthesizing these compounds involves four efficient synthetic steps. A key step in the synthesis plan is an intramolecular pinacol coupling reaction of a nitrile and an aldehyde, which is a pioneering approach in synthesizing the bicyclic core of these compounds. This pinacol coupling reaction forms one of the two rings of the bicyclic core, installs a stereocenter, and provides a handle for forming another stereocenter. Efforts to optimize the key reaction conditions and to determine the relative stereochemistry of these products will be discussed.

Plasminogen Activator Inhibitor-1 (PAI-1) plays a key role in the inhibition of fibronolysis, the process by which blood clots are broken down. In many cases it becomes necessary to increase the rate of fibrinolysis, which can be accomplished by inhibiting PAI-1. Many symmetric polyphenolic compounds have been shown to be effective inhibitors of PAI-1. In this work, a series of asymmetric, ring based sulfonamide compounds are examined. The structures of these compounds vary in terms of the amount of strain introduced by the ring systems and the orientation of the rings. Density Functional Theory is used to explore the relationship between the activities of several inhibitors and their structural traits. Specifically, relaxed scan calculations at the B3LYP/6-31G and B3LYP/3-21G levels of theory are used to sample low energy conformations. These are then examined for possible correlations between inhibitor activity and the relative position of key atoms in the molecule.

This research, conducted over four trimesters, explores the role of computer animations in a secondary science classroom setting. The purpose of this study is to promote understanding of chemical concepts to secondary science students and focuses on the nature of matter, atomic structure and types of chemical reactions. The goals of this research include having students make clear connections between the nature of matter, atomic structure and types of chemical reactions and the microscopic world of chemistry. Students benefited greatly through the usage of animations, both coupled with lecture-based learning and creating their own animations, through retention of the material as well as a deeper comprehension of chemical concepts. Results and conclusions indicate that students had an over-all positive impression of the animations while coupled with lecture-based learning used in the classroom and had a positive impression of their own animations created in laboratories.

Amylin (human Islet Amyloid Polypeptide, hIAPP) is a 37 amino acid polypeptide, co-secreted with insulin from pancreatic beta cells, which plays a role in cell membrane damage by forming amyloid fibrils in Type 2 diabetes. Recent studies suggest that the N-terminal region of hIAPP (hIAPP 1-19) is responsible for initial interactions with the membrane, rather than the central amyloidogenic region (hIAPP 20-29), likely by attractive forces between the positively charged residues and the negatively charged membrane phospholipids. This research involves the synthesis of an uncharged peptide analogue of hIAPP (1-19) by replacing positively charged residues lysine and arginine with isosteric aminoheptanoic acid (Ahept) and acetylation of the N-terminus. Expected to have minimal activity and test the charge attraction theory, the peptide was synthesized, cleaved from resin, purified, and analyzed. A dye leakage assay was then employed to assess the membrane disruptive potential of the synthesized peptide.

A series of polyphenolic sulfonamide and sulfonimide inhibitors of plasminogen activator inhibitor-1 (PAI-1) have been synthesized and screened for biological activity. These compounds were designed to improve on previous generations of sulfonamide and sulfonimide polyphenolic inhibitors of PAI-1, which has been implicated in a variety of conditions, such as myocardial infarction and stroke. The design rationale, synthesis, and structure-activity relationships of this series of compounds will be addressed.

The focus of this project is the comparison between standard impedance and resonance impedance spectroscopic techniques using interdigitated electrodes (IDE). Standard impedance spectroscopy graphically shows phase angles and impedance as a function of frequency, plotting the log of impedance verses the log of frequency. A new modification of the standard impedance technique involves inclusion of a magnetic inductance element as a part of the standard IDE connection. The impedance/induction interaction produces a different impedance phase angle data set where graphical presentation produces a sharp resonance peak. This study focuses on comparison of a new impedance resonance technique with the standard impedance spectrum to determine if the new technique offers any significant advantages in sensitivity and/or selectivity

This presentation and interactive demonstration will share the work done in fall 2011 in partnership with Ypsilanti's Michigan Works! office. The presenter devised and facilitated a workshop that sought to provide participants with an opportunity to reflect on experiences relating to job loss and joblessness, while building their confidence and soft skills. Using a blend of interactive theatre and creative drama exercises, the workshop focused on the questions of 'who am I?' 'where have I been?' and 'what do I have to offer?' The presenter will discuss both the experience of creating and leading the workshop and the evaluation methods developed to measure the difficult to quantify impact and results of this endeavor.

We define our existence by telling stories. Storytelling can help us not only make sense of our own lives but also discover connections to the larger narratives of human history. How then do we approach the stories from other times, other cultures? How can these stories help us imagine a world where all of our narratives are connected in some way? In this presentation, I will discuss the process of interpreting, staging and performing a Native American Folktale: the creation story of Sky Woman and Grandmother Turtle. I will discuss how framing this story in the personal stories of the females in my own family helped me to make meaning of both the original tale and the narrative of my family her-story.

While medical school training arms students with a wide array of technical skills, a physician also needs the ability to communicate clearly with and understand the viewpoint of the patient. Previous research has demonstrated that role-playing techniques can serve as effective tools for teaching these skills, but the methods have varying degrees of success. I have designed a series of lessons based on improvisational theater exercises, tailored to meet the specific needs of aspiring physicians. This paper focuses on three key areas: nonverbal communication, an understanding of status, and the impact of risk and trust on the patient/physician relationship. Implementing this program will help to develop physicians with stronger communication skills, leading to better patient compliance and ultimately improving health outcomes.