38 - Stereochemical synthesis of Lugdunin – An antimicrobial cyclic peptide

Stereochemical synthesis of Lugdunin – An antimicrobial cyclic peptide The consequence of overuse of antibiotics is that the bacteria have developed a various mechanism to overcome the effect of these molecules, which we now address as antibiotic resistance. In fact, antibiotic resistance has become a serious issue in hospitals where the local microbial flora has evolved under constant selection pressure from the various antibiotics in use. The Center for Disease Control has developed an extensive list of many multi-drug resistant bacteria. This includes many bacteria, which otherwise would be simple to treat, but because of acquired resistance have become a serious threat. e.g. Methicillin-resistant Staphylococcus aureus (MRSA). In efforts to combat antibiotic resistance, researchers are constantly trying to identify new antibiotics or design better antimicrobial agents. Recently, Zipperer et. al. have found that a bacteria (Staphylococcus lugdunensis) found in the nose of humans make a cyclic peptide (lugdunin) that shows promise against a variety of Gram-positive bacteria, including opportunistic pathogens such as MRSA and vancomycin-resistant Enterococcus. Lugdunin, when isolated from the bacteria, is a mixture of two cyclic peptides that only differ in the orientation of a single bond in space. This mixture of stereoisomers of lugdunin has never been resolved and their individual activities are unknown. It is common knowledge in medicinal chemistry that stereoisomers of the same molecule can have vastly different activity. In fact, in some cases, one stereoisomer can either partially or completely inhibit the activity of the other. In our study, we are working on a strategy to chemically synthesize lugdunin as pure stereoisomers. The chemical synthesis of individual isomers will allow us to better understand their specific activity. This poster highlights our efforts in achieving stereochemical control in the synthesis of lugdunin. Keywords: Multi-drug resistance, MRSA, Antimicrobials, Lugdunin, Stereochemical synthesi

Efficiency of Railroad Track Circuits in Relation to Safety and Energy Use

Abstract The goal of this research is to test the efficiency of railroad track circuit detection systems. Railcar collisions are some of the deadliest accidents in the United States and are very under reported publicly. The research from this project will determine whether or not money should be invested towards track detection systems if the safety aspect passes or fails efficiency testing. Using electrical measurement instruments on the rails, the potential(voltage) and current(amperage) will be measured. Using the measured data and comparing to the data provided by the transportation companies, a conclusion will be made about the efficiency of railroad track circuit detection systems. Hundreds of lives can be saved with the research done as money can better be allocated towards other safety methods if the track circuit detection systems are proven inefficient and energy can be saved or redirected for an environmentally friendlier use. Introduction Since the year 2004, about 205,714 railroad related accidents and incidents have occurred in the United States with 13,335 of those being fatal (Overview reports, 2020). Even a single death or injury is too much and indicates that there is something wrong with methods of railroad safety and a problem does exist. Some of these accidents may be inevitable from the position of the transportation company, but not all are. These flaws in track circuits can include power supply failure, failure of relay, nature related problems, loose cable from vibrations, and many more (Patra & Kumar). If this research is conducted, private transportation companies will have a better understanding of where their allocation of time and money will be most effective. The railroad safety measures are not efficient enough in the United States and this research will provide crucial data on whether or not track circuit detection systems are contributing to the decrease accidents or not contributing at all. With track circuits proven to be inefficient, energy related expenses can be determined. Using electricity on something that does not do its only purpose is a poor investment and a waste of environmental resources. Materials & Methods First rail car transportation companies will be contacted seeking approval to be onsite and to obtain data sheets of their installed track circuits. Once approval is achieved, proper attire is worn such as long pants and safety training will be conducted. Once on site, experimentation will begin using multimeters and extra-long test leads in order to measure the current and potential between two rails. Multiple sites will be chosen to obtain precise and accurate data. The study will be done during freezing and summer temperatures in order to account for the nature aspect. Five trials are conducted in total for each site and then the interpretation of the data will be key. Interpretation of the data will be compared to the data sheets provided by the rail car company in order to determine where track circuits are working properly which leads directly to the results. Results If potential and current averages are measured to be much lower than what the data sheets provided by the transportation company, then we can say that a material with much lower resistance would be able to set alarm the track circuit detection system. If potential and current averages measure much higher, then there is an error in the experiment. This step should be noticeable during experimentation and not after. If potential and current averages are near identical to the data sheet, we calculate for the resistivity needed to close the circuit. This resistivity will help us determine which materials can easily short circuit the rails. A short circuit test (not in methods section) using the copper bars will help confirm the measured data and analyze the minimum conditions necessary to alert the track circuit detection system. With amperage and voltage both calculated, joules per second or watts can be calculated thus giving us a magnitude of energy. Using this, energy costs will be calculated in relation to the local electricity companies rate by kilowatt hour giving a net price of how much electricity costs are. Electrical costs and energy will then be used to determine its significance in relation to track circuit efficiency. Conclusions The present understanding for the importance in research of railroad safety would be taken far more seriously if transportation companies knew that that the existing system is not efficient. Testing for the quality of railroad safety would increase as a result. Harnessing electricity is not cheap, nor does it have zero effects on the environment. Where coal is primarily the source of energy and track circuits are operated, an increased risk of polluting the air is present as harnessing energy from coal is not environmentally friendly. If inefficiency of track circuits is proven for this key region, electricity would be better used for other purposes. This project will help the applicant’s professional development as a scholar as the research will help improve the scientific process methods used. The applicant will gain much skill and lesson on how the process can be done in the quickest and easiest way then be able to convey the knowledge to other scholars in a subtle, easy to understand method

Novel Method of Supplementing Current Depression Treatments: Using Autonomous Sensory Meridian Response-Centered Therapy to Improve Constipation-Associated Comorbidity of Depression

One-third of individuals struggling with constipation also suffer chronically from comorbid depression, but the evidently shared etiology has remained relatively ambiguous. This proposed study aims to analyze the role of Autonomous Sensory Meridian Response (ASMR), a newly recorded neural phenomenon that causes relaxing “tingles” from unique “triggers” in a subset of individuals, in altering serotonin (5-HT) levels within the ENS to aid with both depression and constipation. In depressed individuals, reduced 5-HT has been clinically accepted as a key symptom and is frequently treated with ineffective SSRIs. Prospective alternative methods of non-invasive treatment, such as ASMR, would not only aid in cost-reduction, but also explain the role of external influences on gut 5-HT levels. 5-HT additionally plays a key role in promoting gut motility, and a posited connection between the gastrointestinal microbiome and the brain may exist along a “gut-brain axis.” Further research could improve our understanding of depression-related physiology

A Pilot Research Project to Enhance Inquiry-Based Learning by Mapping the Microbiome of the Southern Appalachian Region

As humans continue to advance healthcare resources, we face a growing threat of nosocomial multidrug-resistant bacteria. The rise of these antibiotic-resistant microorganisms has been placed on the World Health Organization’s watchlist as one of the biggest threats to global health. We continue to have a shortage of effective antibiotics with the rise of these “superbugs”. With the growing number of deadly pathogens, the future of medicine relies on scientific findings to combat multidrug-resistant bacteria. Appalachia could be the answer to combat this new health threat. As the most biodiverse temperate forest region in North America, our beautiful backyard in the Smoky Mountains contains a plethora of microorganisms that have become genetically diversified over billions of years. Many of these soil bacteria naturally produce their own antibiotics. With the wide variation of natural bacteria, Appalachia serves as a testing ground to harness the power of natural antibiotics. A gram of soil contains more than 10,000 different species of bacteria. The biodiversity of these microbes is still largely unknown, as almost 99% of these species cannot be cultured in a normal lab setting. This pilot project will lay the foundations of discovering Appalachia’s microbiota which has, thus far, never been cataloged

Inner Speech: Philosophical and Psychological Investigations

This project investigates philosophical and psychological aspects of “that little voice in our head”, or inner speech. Research on inner speech has been guided by the assumption that it is essentially a speech phenomenon. This dissertation argues against this assumption from three independent angles. In Chapter 2, I consider the idea that the content of inner speech is speech-specific. After arguing against this position, I go on to claim that the content of inner speech is vocalic. In Chapter 3, I examine models that treat inner speech as a prediction. I show that these models are problematic on both empirical and theoretical grounds. In their place, I argue for a model on which inner speech is treated as a goal state. In Chapter 4, I consider the popular idea that breakdowns in inner speech processing explain auditory verbal hallucination. I argue that inner speech-based explanations of AVH belong to a problematic class of psychological explanations, which confuse phenomenological and scientific understanding. My discussion of inner speech has implications for a wide range of topics, including metacognition, imagery, and the explanation of pathological mental states

The Innocence of the Innocent

My personal point of view of how my father\u27s alcoholism affected our family and my views of life growing up

Charting the Microbiome Biodiversity of the Appalachian Highlands Region: A Novel Study

The rapid expansion of medical discoveries has been met with growing number of deaths from nosocomial multidrug-resistant bacteria. The dramatic rise of these antibiotic-resistant microorganisms has been placed on the World Health Organization’s watchlist as one of the biggest threats to the future of healthcare. There continues to be a shortage of effective antibiotics with the rise of these “superbugs”. With the growing number of deadly pathogens, the future of medicine relies on scientific findings of novel compounds to combat multidrug-resistant bacteria. The Appalachian Highlands Region holds the potential for discovering these new compounds. As the most biodiverse temperate forest region in North America, the Smoky Mountains contains a plethora of microorganisms that have become genetically diversified over millions of years. In order to compete with one another, many of these soil bacteria naturally produce their own antibiotics. With the wide variation of natural bacteria, Appalachia serves as a testing ground to harness the power of natural antibiotics and understand how these compounds can aide in clinic use. A gram of soil contains more than 10,000 different species of bacteria. The biodiversity of these microbes is still largely unknown, as almost 99% of these species cannot be cultured in a normal lab setting. Utilizing the 16S genomic region of microbes, this pilot project will lay the foundations of discovering Appalachia’s microbiome, which has, thus far, never been cataloged

Thought Insertion without Thought

There are a number of conflicting accounts of thought insertion, the delusion that the thoughts of another are inserted into one’s own mind. These accounts share the common assumption of realism: that the subject of thought insertion has a thought corresponding to the description of her thought insertion episode. I challenge the assumption by arguing for an anti-realist treatment of first-person reports of thought insertion. I then offer an alternative account, simulationism, according to which sufferers merely simulate having a thought inserted into their heads. By rejecting realism, the paper undermines a widespread explanatory framework that unites otherwise competing cognitive models of thought insertion

From Speech to Voice: On the Content of Inner Speech

Abstract: Theorists have found it difficult to reconcile the unity of inner speech as a mental state kind with the diversity of its manifestations. I argue that existing views concerning the content of inner speech fail to accommodate both of these features because they mistakenly assume that its content is to be found in the ‘speech processing hierarchy’, which includes semantic, syntactic, phonemic, phonetic, and articulatory levels. Upon rejecting this assumption, I offer a position on which the content of inner speech is determined by voice processing, of which speech processing is but one component. The resulting view does justice to the idea that inner speech is a motley assortment of episodes that nevertheless form a kind

Random Sampling of Mellin Band-limited Signals

In this paper, we address the random sampling problem for the class of Mellin band-limited functions BT which is concentrated on a bounded cube. It is established that any function in BT can be approximated by an element in a finite-dimensional subspace of BT. Utilizing the notion of covering number and Bernstein's inequality to the sum of independent random variables, we prove that the random sampling inequality holds with an overwhelming probability provided the sampling size is large enough