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2015
Friday, April 17th
9:00 AM

Retinoic Acid Hydroxylase Inhibitors as a Novel Therapy for Alzheimer’s Disease

Isabel Makman, University of Montana - Missoula

UC 330

9:00 AM - 9:20 AM

Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative diseases afflicting the modern world. As no cure for AD has yet been discovered we sought to explore a potential treatment option based on the inhibition of retinoic acid (RA) metabolism, the active metabolite of vitamin A. Beta-amyloid plaques form in the brain and decrease cognitive function in AD patients. In a recent preclinical study RA was shown to decrease these plaques and rescue memory deficits in an Alzheimer’s mouse model (Ding et al. 2008). However, in the human body RA is quickly cleared away by an enzyme, resulting in a loss of activity during long-term treatment. We hypothesize that the inhibition of the enzyme that clears RA would cause an increase in the amount of RA present in the brain. This increased amount of RA would decrease plaques, thereby improving AD patient outcomes. Using two behavioral maze tests, the Morris Water Maze (MWM) and Y maze, we assessed cognitive function based on how quickly the mice maneuvered the mazes. We have begun preclinical testing of the prototypical enzyme inhibitor in Alzheimer’s mice relative to wild type (WT) litter-mates. A MWM measure of latency to the end of the maze showed a discrepancy between the performances of AD and WT mice, with the AD mice exhibiting a considerable cognitive deficit. The mice then received 8 weeks of treatment with the enzyme inhibitor (3 times per week at 10 mg/kg i.p.). A follow-up MWM was performed and no significant reversal of cognitive deficits in AD mice was detected. A more recent MWM study of 31 treated AD mice is currently being analyzed and shows promising similarities between AD and WT latencies. These results provide a strong foundation from which to further explore the use of these inhibitors in treating AD.

9:20 AM

Analysis of Recent DDoS Attacks: an Application of Mirkovic and Peng Taxonomies

Jose Rodriguez, University of Montana - Missoula

UC 330

9:20 AM - 9:40 AM

Distributed Denial of Service (DDoS) is a threat for all companies. Every second that the company is offline, a tremendous amount of money is lost. Since the introduction of the Internet, DDoS attacks have been a common occurrence, yet solutions to counter them have been limited. This research project analyzes the recent DDoS attacks based upon the financial, societal and technical impact. Besides that, the taxonomies of Mirkovic and Peng will be used to classify details of recent DDoS attacks with the goal of identifying common characteristics. Mirkovic's taxonomy analyzes in a very technical depth the DDoS attacks meanwhile Peng's taxonomy is more generic. Both these taxonomies are quoted by several authors although nobody has used them to create a classification of attacks. This research project is useful to individuals interested in developing solutions for computer network and information security since there is no classification made or any method for classifying them.

10:00 AM

Advantages of Halogen Bonding for Halide Recognition in Wet Solvents

George F. Neuhaus Mr., University of Montana - Missoula

UC 330

10:00 AM - 10:20 AM

The goal of anion recognition is to develop molecules capable of binding to specific anions, such as chloride, in solutions that mimic biological and environmental systems. Anion detection in biological solutions has implications for medical technologies, such as diagnostics. For example, cystic fibrosis is often diagnosed by measuring chloride levels in sweat. However, challenges arise while designing receptors because anions and their receptors are affected by anything with a charge. Because water, the solvent of biology, is polarized, it is an especially challenging solvent for anion recognition. To overcome recognition challenges, we can make small structural changes to the anion receptor, such as switching an atom, and drastically change how the receptor interacts with the anion and solvent. Understanding non-covalent interactions (e.g. hydrogen bonding, and hydrophobic interactions) is the driving force in the evolution of anion recognition because it allows chemists to predict the properties of a molecule in a given environment and how changing these properties can alter activity in different solvents. An underexplored non-covalent interaction is the halogen bond—an attractive force between an electropositive halogen and an electronegative Lewis base (e.g. anion). Our research develops two anion receptors, only differing through exchange of hydrogen for iodine, which allows comparison of halogen and hydrogen bonding. X-ray diffraction, NMR titrations, and computational methods were used to explore the significance of this exchange. Interestingly, the halogen bond was found to maintain strong selective halide recognition in competitive polar environments (1% D2O:CD3CN), while the hydrogen bond showed poor recognition capability in the same conditions. This provides evidence that halogen bond donors can be used to overcome anion recognition challenges of competitive biological environments (e.g. water) and have a positive impact on the development of medical technologies.