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One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS.

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a

Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a way of quantifying the concentration of the drug and the distribution of the drug during a period of time. This study aims to do that by utilizing Materialise Mimics to analyze the MRI images of local drug delivery in glioblastoma in canines and antimicrobial gel in rabbit femurs. The focus of the technique is to register the anatomy in T1-weighted spin echo images to the drug delivery in T2 flow attenuated inversion recovery (FLAIR) images in order to see where the drug went and did not go relative to the anatomical part. Both studies focus on addressing effective volumes of drug to a designated anatomical area, in which the delivery can be difficult as it involves bypassing the blood brain barrier in the first study and achieving effective volumes while preventing toxicity to the kidneys in the second study. The goal of this project lies in determining the drug volumes and location for the specified duration and anatomical part.
ContributorsJehng, Hope (Author) / Caplan, Michael (Thesis director) / Sirianni, Rachael (Committee member) / Chemical Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a

The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a Blank IUD (without Levo), or a Levo-releasing IUD (Levo IUD), enabling us to evaluate the effects of Ovx and the effects of IUD administration on cognition. Two weeks after surgery, all treatment groups were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. At sacrifice, upon investigation of the uteri, it was determined that some of the IUDs were no longer present in animals from these groups: Sham\u2014Blank IUD, Ovx\u2014Blank IUD, and Sham\u2014Levo IUD. Results from the remaining three groups showed that compared to Sham animals with no IUDs, Ovx animals with no IUDs had marginally impaired working memory performance, and that Ovx animals with Levo IUDs as compared to Ovx animals with no IUDs had marginally enhanced memory performance, not specific to a particular memory type. Results also showed that Ovx animals with Levo IUDs had qualitatively more cells in their vaginal smears and increased uterine horn weight compared to Ovx animals with no IUDs, suggesting local stimulation of the Levo IUDs to the uterine horns. Overall, these results provide alternative evidence to the hypothesis that the Levo IUD administers Levo in solely a localized manner, and suggests that the possibility for the Levo IUD to affect reproductive cyclicity in ovary-intact animals is not rejected. The potential for the Levo IUD to exert effects on cognition suggests that either the hormone does in fact systemically circulate, or that the Levo IUD administration affects cognition by altering an as yet undetermined hormonal or other feedback between the uterus and the brain.
ContributorsStrouse, Isabel Martha (Author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Sirianni, Rachael (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by

Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.
ContributorsCeton, Ricki Ronea (Author) / Stabenfeldt, Sarah (Thesis director) / Sirianni, Rachael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
There is growing interest in intranasal delivery of therapeutics because of direct nose-to-brain pathways which are able to bypass biological barriers, such as the blood-brain barrier (BBB), that have historically limited our ability to effectively deliver drugs to the central nervous system (CNS). Since these pathways were first discovered, there

There is growing interest in intranasal delivery of therapeutics because of direct nose-to-brain pathways which are able to bypass biological barriers, such as the blood-brain barrier (BBB), that have historically limited our ability to effectively deliver drugs to the central nervous system (CNS). Since these pathways were first discovered, there has been significant preclinical success in delivering a wide range of therapeutics to the CNS with additional growing efforts to further improve delivery through nanoparticle drug delivery systems. Here we sought to improve intranasal delivery of DiR, a lipophilic small molecule cyanine dye, to the CNS by surface modifying a poly (lactic-co-glycolic acid) (PLGA) nanoparticle with a short peptide derived from the rabies virus glycoprotein (RVG). The specific aims of this thesis were to evaluate administration route-dependent delivery of RVG nanoparticles to the CNS, and to identify anatomical transport pathways by which nanoparticles facilitate transport of small lipophilic molecules. Route-dependent delivery kinetics and distribution were studied by administering DiR loaded nanoparticles to healthy Balb/C mice. Specific tissues were homogenized and the fluorescent intensity of DiR was measured and compared to control tissue spiked with known amounts of dye. While bioavailability of DiR after intranasal administration was near 0% with minimal exposure to peripheral organs, quick and efficient delivery to the CNS was still observed. CNS delivery after intranasal administration was rapid with peak concentrations at 30 minutes post-administration followed by broad clearance by 2 hours. Regional differences of delivery of DiR to the CNS demonstrated engagement of direct nose-to-brain transport pathways with high delivery being observed to the olfactory bulb, brain stem, and trigeminal nerve. RVG modification however presented only modest targeting benefits. In conclusion, the biodistribution of DiR after intranasal administration of DiR loaded nanoparticles showed high potential for the direct nose-to-brain delivery while limiting peripheral exposure of lipophilic small molecule drugs.
ContributorsChung, Eugene Paul (Author) / Kodibagkar, Vikram (Thesis director) / Sirianni, Rachael (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description

This paper will cover topics regarding remote work. More specifically, remote work for the field of logistics. It will also dive into remote work platforms themselves e.g., Slack, Zoom, etc. Microsoft Teams, the specific software we used while I was at my internship, will be analyzed as well. I will,

This paper will cover topics regarding remote work. More specifically, remote work for the field of logistics. It will also dive into remote work platforms themselves e.g., Slack, Zoom, etc. Microsoft Teams, the specific software we used while I was at my internship, will be analyzed as well. I will, specifically, be analyzing the fundamental issues that occurred during my internship, developing a feasible solution with a laid-out process for each one. After the proper execution of these processes, I will discuss my results. I found that time is the most critical component of an optimal transition to remote work. Finally, I will conclude with reflections on my findings, insights from current working supply chain professionals, and prompt further research that could be done.

ContributorsSchneider, Sam (Author) / Byrne, Jared (Thesis director) / Aguilar, Jared (Committee member) / Department of Supply Chain Management (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The purpose of this study is to create and establish an efficient and cost-effective solution to decrease the effects of sedentarism in pregnant women. Our team was given a propelling question, from which we had to narrow down our scope and conduct primary and secondary research to determine our ideal

The purpose of this study is to create and establish an efficient and cost-effective solution to decrease the effects of sedentarism in pregnant women. Our team was given a propelling question, from which we had to narrow down our scope and conduct primary and secondary research to determine our ideal customers. The design of our study intends to imitate the development of a startup where ideas are created from scratch and the final deliverable is a business model plan that shows some sort of traction. Our first major finding is that a sedentary lifestyle can be treated without major challenges in low-risk pregnancies. We determined that uncertainty and lack of concise and clear information is one of the main causes of an increased level of sedentary behavior in low-risk pregnancies. A significant driver for women to do some sort of activity or exercise stems from feeling supported, which doesn’t necessarily come from their partner or couple, but instead from other women that are going to a similar process as them. There are apps in the market that intend to serve pregnant women; however, there is not one that incorporates a social aspect to achieve their goal. In conclusion, there is opportunity in the market for a socially integrated pregnancy fitness app. The Gleam concept has been consciously developed to decrease sedentary behavior through concise, clear, and reliable information and by encouraging women through a socialization platform.

ContributorsFlores, Valeria Nicole (Co-author) / Mosier, Jacob (Co-author) / McCreary, Liam (Co-author) / Byrne, Jared (Thesis director) / Hall, Rick (Committee member) / Silverstein, Taylor (Committee member) / Industrial, Systems & Operations Engineering Prgm (Contributor) / Industrial, Systems & Operations Engineering Prgm (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This project examines methods of evaluating the quality of digital UI/UX design including the McKinsey Design Index, heuristics, and design principles.

ContributorsLewis, Janae Ann (Author) / Byrne, Jared (Thesis director) / Roumina, Kavous (Committee member) / Department of Information Systems (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The contemporary world is motivated by data-driven decision-making. Small 501(c)3 nonprofit organizations are often limited in their reach due to their size, lack of funding, and a lack of data analysis expertise. In an effort to increase accessibility to data analysis for such organizations, a Founders Lab team designed a

The contemporary world is motivated by data-driven decision-making. Small 501(c)3 nonprofit organizations are often limited in their reach due to their size, lack of funding, and a lack of data analysis expertise. In an effort to increase accessibility to data analysis for such organizations, a Founders Lab team designed a product to help them understand and utilize geographic information systems (GIS) software. This product – You Got GIS – strikes the balance between highly technical documentation and general overviews, benefiting 501(c)3 nonprofits in their pursuit of data-driven decision-making. Through the product’s use of case studies and methodologies, You Got GIS serves as a thought experiment platform to start answering questions regarding GIS. The product aims to continuously build partnerships in an effort to improve curriculum and user engagement.

ContributorsFletcher, Griffin (Co-author) / Heekin, Noah (Co-author) / Ferrara, John (Co-author) / Byrne, Jared (Thesis director) / Givens, Jessica (Committee member) / Satpathy, Asish (Committee member) / Historical, Philosophical & Religious Studies (Contributor) / Department of Supply Chain Management (Contributor) / Department of Economics (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

As part of the Founders’ lab program, this thesis explores a social venture idea whose concept is to connect the philanthropic community with individuals and organizations in need of funding a project relating to (Sustainable Development Goals) SDG indicators through a peer-to-peer donation-based crowdfunding platform. Through this platform, the philanthropic

As part of the Founders’ lab program, this thesis explores a social venture idea whose concept is to connect the philanthropic community with individuals and organizations in need of funding a project relating to (Sustainable Development Goals) SDG indicators through a peer-to-peer donation-based crowdfunding platform. Through this platform, the philanthropic community will have the possibility to easily access a wide range of projects to support as well as underserved individuals and communities seeking help, track their impact, donate in a complete transparent donation process, and automate donations through bank card round-ups. This social venture idea has been named PhilanthroGo.

ContributorsBoeh, Morgan Alexandra (Co-author) / Frank, Gregory (Co-author) / Veal, Hayley (Co-author) / Byrne, Jared (Thesis director) / Satpathy, Asish (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Management and Entrepreneurship (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05