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Nanoparticle Toxicity And Molecular Mechanisms In Fish: A Case Study With Silver Nanoparticles, Jiejun Gao

Open Access Dissertations

Nanoparticles (NPs) are widely used in a myriad of commercial and industrial products making their entry to the environment a likely event. NPs have unique physical-chemical properties that result from their small size and high surface area to volume ratio, making them highly reactive and potentially toxic. In Chapter 1, we summarize the effects and mechanisms of metal-based NPs on the vascular system. In vitro studies have shown that NPs are anti-angiogenic because they cause inflammation, oxidative stress, and apoptosis of endothelial cells resulting in increased permeability and decreased proliferation and migration. Whole animal studies examining the effects of NPs …

The Development Of Preclinical Strategies For Facilitation Of Lead Candidate Selection, Christopher Dale Kulczar

Open Access Dissertations

Chapter 1 details a background of techniques used for modeling the blood-brain barrier (BBB). The BBB represents a diffusive barrier to both paracellular and transcellular movement of many compounds in and out of the brain. The main rate- limiting barriers of the BBB include exclusive tight junctions that prevent the movement of hydrophilic molecules through intercellular gaps, and efflux proteins in the membrane which pump many hydrophobic molecules back into the blood. In addition, the BBB contains metabolizing enzymes, including Cytochrome P450s. This barrier acts to protect the vulnerable tissues of the brain from harmful xenobiotics, but also can serve …

Ambient Ionization - Mass Spectrometry: Advances Toward Intrasurgical Cancer Detection, Alan Keith Jarmusch

Open Access Dissertations

My dissertation research has focused on the development of ambient ionization – mass spectrometry (MS) for clinical measurements, specifically intrasurgical cancer detection. The molecular differences between normal and cancerous tissue were detected via direct tissue analysis in vitro by touch spray ionization (TS) or by analyzing sectioned or smeared tissue using desorption electrospray ionization (DESI). The physical form of the tissue, e.g. in vitro sampling, sectioned, or smeared, was inconsequential in differentiating normal from cancerous tissue; however, the spectra acquired by TS and DESI differed due to differences in ionization processes. We envision that TS-MS and DESI-MS could impact diagnostic …

Quantifying Terrestrial Ecosystem Carbon Dynamics With Mechanistically-Based Biogeochemistry Models And In Situ And Remotely Sensed Data, Shaoqing Liu

Open Access Dissertations

Terrestrial ecosystem plays a critical role in the global carbon cycle and climate system. Therefore, it is important to accurately quantify the carbon dynamics of terrestrial ecosystem under future climatic change condition. This dissertation evaluates the regional carbon dynamics by using upscaling approach, mechanistically-based biogeochemistry models and in situ and remotely sensed data.

The upscaling studies based on FLUXNET network has provided us the spatial and temporal pattern of the carbon fluxes but it fails to consider the atmospheric CO2 effect given its important physiological role in carbon assimilation. In the second chapter, we consider the effect of atmospheric CO2 …

The Relationship Between Protein And Phosphorus Digestion And Retention In Growing Pigs And Broiler Chickens, Pengcheng Xue

Open Access Dissertations

Xue, Pengcheng. Ph.D., Purdue University, December 2016. The Relationship between Protein and Phosphorus Digestion and Retention in Growing Pigs and Broiler Chickens. Major Professor: Dr. Layi Adeola. The objective of this study was to investigate the relationship between protein and P digestion and retention in growing pigs and broiler chickens. The methodology of determining the digestibility of AA and P and the effect of dietary N and P on the digestion and retention of these two nutrients were investigated.

An experiment was conducted in growing pigs to investigate the additivity of AID or SID of CP and AA in mixed …

Examining The Impact Of The Affordable Care Act On Small Businesses And Industries In Northwest Indiana, Onias Muza Taruwinga

Open Access Dissertations

This research examined the lived experiences of small businesses in Northwest Indiana with the implementation of the Affordable Care Act. The interviews were conducted over a period of six months with an attempt to answer the question, “What was the impact of the Affordable Care Act on small businesses and industries in Northwest Indiana?” Additional research questions were, “Did the Affordable Care Act extend coverage to the uninsured, include other medical services that were not covered before, and reduce cost sharing and what lessons can be learned from the implementation of the Affordable Care Act for future policy implementation?” 15 …

The Effects Of Dietary Probiotic Inclusion On Skeletal Health Of Poultry And Its Possible Mechanisms, Feifei Yan

Open Access Dissertations

Probiotics are live microorganisms which may confer health benefits on the host when administered in appropriate amounts. Numerous studies have shown that probiotics improve bone health in humans and rodents with less information available on the skeletal health of avians given probiotics. The objective of this study was to determine the effects of probiotic supplementation on bone health of egg-laying and meat-type chickens. Dietary supplementation of a multi-species based probiotic reduced the percentage of shell-less eggs beginning at 4 wk following treatment and increased tibial and femoral bone mineral density in egg-laying hens at 7 wk post-treatment. Similarly, bone mineralization …

Lower Food Web Dynamics In Lakes Michigan And Huron: Spatial And Temporal Responses To Recent Oligotrophication, Margaret Hutton Stadig

Open Access Theses

Nutrient abatement programs, originally enacted to counter eutrophication have successfully suppressed nutrient loads and relative primary production in marine and freshwater systems. Recently, the additive impacts of invasive filter feeders have further reduced offshore primary production in several aquatic systems throughout the world. It has been hypothesized that the biological activity of these invasive species may sequester nutrients within the nearshore benthic environment, creating steep gradients in primary production between nearshore and offshore habitats. In the Laurentian Great Lakes, past studies of oligotrophication have primarily focused on food web responses in offshore habitats. Organisms at higher trophic levels have been …

Mathematical Analysis Of Feedback Targets Of Bmp Signaling In Drosophila Embryonic Development, Yan Luo

Open Access Theses

Bone morphogenetic proteins (BMPs) drive a range of cellular processes especially in the early stages of embryonic development. This family of proteins acts as one of the most important extracellular signals in development pattern formation across the animal kingdom. Cells in embryos differentiate into different cell types in response to the concentration level of BMP. This complex process is regulated by multiple regulators that serve to tune the signal response.

Extensive experimental and computational research has been performed to analyze BMP regulation in Drosophila, a widely studied model organism, and has advanced our understanding of animal development. Because of …

Innovative Novel Immunotherapies For The Treatment Of Glioblastoma Multiforme, Salma Salem

Open Access Theses

Glioblastoma Multiforme GBM is a very aggressive type of malignant brain tumors that affects peoples’ lives. The diffusive, infiltrative, and metastatic behaviour of GBM is the major reason for the disease recurrence. The morphological and immunohistological characteristics of Central Nervous System (CNS) tumors including GBM are heterogeneous. GBM is either primary (de novo) or secondary to low-grade astrocytomas.

Current treatment options include surgery, radiotherapy, and temozolomide chemotherapy have not achieved any improvement in success rates over the past decades. The survival time reached by GBM patients was approximately 12 months only after being treated with radiotherapy alone without temozolomide. However, …

Exploring The Cause Of Injury Or Death In Grain Entrapment, Engulfment And Extrication, Salah F. Issa

Open Access Dissertations

Grain entrapments and engulfments are one of most common hazards associated with grain storage facilities. Since the 1970’s over 1,880 incidents have been documented in agricultural confined spaces of which 65% of all recorded incidents were grain entrapments and engulfments. There have been several studies conducted on the contributing factors behind these incidents; however, there have been very few attempts to understand the environmental, physiological or psychological factors the victims experience while entrapped, engulfed, or extricated. This includes understanding how secondary injuries are caused by grain or during extrication by first responders. The research effort was divided into three segments. …

Gonadal Intersex In Teleosts: Mechanisms, Molecular Biomarkers And Diagnostic Assays, Ahmed M.E. Abdel-Moneim Mohamed

Open Access Dissertations

Natural and synthetic estrogenic and androgenic compounds are continuously released into aquatic ecosystems. Exposure of teleost fishes to these contaminants can negatively impact sex differentiation and reproductive output. Specifically, development of gonadal intersex in gonochoristic (fixed sex) fish species has been studied extensively in relation to exposure to this class of compounds. The main objectives of this dissertation were to: 1) conduct field and laboratory studies to investigate the molecular signaling pathways behind the development of gonadal intersex; and 2) establish molecular biomarkers and assays for testing the ability of environmental pollutants to develop this condition using a battery of …

Repurposing Non-Antimicrobial Drugs To Treat Multi-Drug Resistant Bacterial And Fungal Infections, Shankar Thangamani

Open Access Dissertations

Bacterial and fungal resistance to conventional antimicrobials is a burgeoning global health epidemic that necessitates urgent action. Even more alarming, the development of new antimicrobials to treat these multidrug-resistant pathogens has not kept pace with the rapid emergence of resistance to current antimicrobials. Antimicrobial drug development through the traditional de novo process is a risky venture given the significant financial and time investment required by researchers and limited success rate of translating these compounds to the clinical setting. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). …

Understanding The Formation Of American Mental Health Policy Preferences, 1952-1981, Andrew D. Tuholski

Open Access Dissertations

In the United States, the emergence of an outpatient-centered, drug-based model of mental health care was physically feasible from the 1950s onward, with the introduction of thorazine and other first-generation antipsychotics. However, it was not until 1981, with President Reagan’s veto of the Mental Health Systems Act, that American mental health policy tipped over definitively into the outpatient-centered, drug-based model. In this quantitative study of the formation of policy preference, the delay between the feasibility of the outpatient-centered, drug-based model and its adoption was explored through five research questions answered through corpus analysis and time series statistics: How do shifts …

Unraveling The Fingerprints Of Nox Using Stable Isotopes: Implications For Nox Source Partitioning And Oxidation Chemistry, Wendell William Walters

Open Access Dissertations

The nitrogen (N) and oxygen (O) stable isotope composition (δ15N & δ18O) of nitrogen oxides (NOx )may be a useful tool for constraining NOx emission sources as well as for understanding the atmospheric oxidation pathways responsible for its removal if various NOx sources and sink processes exhibit characteristic isotopic compositions (“fingerprints”). However, this requires (1) an accurate and complete inventory of δ15N(NOx) values from major emission sources, (2) an assessment of the kinetic and equilibrium isotope effects that can impact δ15N and δ18O values of NOx, (3) and test these assumptions by conducting accurate in situ δ15N and δ18O measurements …

Structure-Function Analysis Of The Dopamine Transporter In The Presence Of Synthetic Cathinones And Amphetamines, Shari Melissa Radford

Open Access Theses

The dopamine transporter (DAT) is a monoamine transporter that regulates dopamine (DA) neurotransmission by clearing DA from the synapse. DAT is acted on by a number of psychostimulant drugs, which block reuptake and potentiate DA signaling. Several inhibitors of DAT, both amphetamines and cathinones, also cause reversal of transport. Previous research has shown the importance of a conserved salt bridge in another monoamine transporter, the serotonin transporter, in amphetamine-induced efflux. In our studies here, we engineered a mutant Drosophila melanogaster DAT (dDAT D475N) designed to interrupt this salt bridge and examine the effects on amphetamine- and cathinone-induced efflux in vitro. …

Intestinal Cytoplasmic Lipid Droplets, Associated Proteins, And The Regulation Of Dietary Fat Absorption, Theresa M. D'Aquila

Open Access Dissertations

Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, and cardiovascular disease. The small intestine absorbs dietary fat through an efficient multi step process of digestion, uptake, metabolism, and secretion or storage. When dietary fat is taken up by the absorptive cells of the small intestine, enterocytes, it can be secreted into circulation where it contributes to blood lipid levels or temporarily stored in cytoplasmic lipid droplets (CLDs). The objective of this dissertation is to investigate …

The Effects Of Including Almonds In An Energy-Restricted Diet On Weight, Body Composition, Visceral Adipose Tissue, Blood Pressure And Cognitive Function, Jaapna Dhillon

Open Access Dissertations

Inclusion of almonds in an energy restricted diet has been reported to enhance or have no effect on weight loss. Their effects specifically on visceral fat stores during energy restriction have not been widely examined. Additionally, almond consumption has been associated with reduced blood pressure, but whether this is linked to or is independent of changes of body composition has not been examined. Moreover, almond consumption during energy restriction may be an effective strategy for reversing the negative effects of dieting on cognitive performance. The unique nutrient profile of almonds also has the potential to influence cognitive function post-prandially. The …

Biochemical Changes In Animal Models Of Fetal Alcohol Spectrum Disorder, Christine E. M. Keller

Open Access Dissertations

Fetal alcohol spectrum disorder (FASD) is a completely preventable disease, that has profound effects on life-long health and function of the affected individual. Prevalence estimates of FASD in the United States indicate 33.5 per 1,000 live births are affected with this disorder (Roozen, 2016). FASD is caused by maternal ethanol intake during pregnancy. However, recommendations of the amounts of alcohol safe to drink during pregnancy are not established. Further, we lack a comprehensive understanding of the biochemical pathways modified in prenatal ethanol exposure. Biomarkers are also lacking. Our results demonstrate the vast array of biochemical pathways modified in the chronic …

Influence Of Dietary Polyphenols On Carbohydrate Intestinal Digestion And Absorption, Sydney E. Moser

Open Access Dissertations

Both epidemiological and clinical evidence support the notion that polyphenol rich foods and beverages may modify glycemic response, glucose homeostasis and subsequent risk of Type-2 diabetes. In vitro evidence typically derived from experiments with pure phenolics and phenolic rich extracts have pointed to this benefit being associated with two potential mechanisms: (1) the ability of specific polyphenolics to inhibit carbohydrate digestion (amylase and glucosidase) and (2) polyphenolic inhibition of intestinal glucose transport. While the high potential of these activities is evident, little is actually known regarding the extent to which these benefits are extendable to the actual food matrix these …

Intestinal Adaptation To Repeated Exposure Of Flavonoid-Rich Foods: In Vitro And Clinical Data, Bejamin W. Redan

Open Access Dissertations

Interest in application of flavonoids for chronic disease prevention has grown significantly, but the low oral bioavailability of these compounds from acute doses is commonly highlighted as a limitation when considering their biological significance. Still, the impact of broad dietary patterns such as repeated exposure on flavonoid’s absorption, metabolism, and eventual efficacy is critical to consider since evidence suggests that their bioavailability may be enhanced with repeated exposure. To fill this gap in knowledge, this dissertation will focus on three major areas including characterization of flavonoid metabolites, in addition to use of in vitro models and clinical work to test …

Optical Dosimetry Tools And Monte Carlo Based Methods For Applications In Image Guided Optical Therapy In The Brain, Akshay N Prabhu Verleker

Open Access Dissertations

Purpose: The long-term goal of this research is to determine the feasibility of using near infra-red light to stimulate drug release in metastatic lesions within the brain. In this work, we focused on developing the tools needed to quantify and verify photon fluence distribution in biological tissue. To accomplish this task, an optical dosimetry probe and Monte Carlo based simulation code were fabricated, calibrated and developed to predict light transport in heterogeneous tissue phantoms of the skull and brain. Empirical model (EM) of photon transport using CT images as input were devised to provide real-time calculations capable of being translated …

X-Ray Fluorescence For Quantification Of Lead And Strontium In Vivo, Aaron James Specht

Open Access Dissertations

Lead (Pb) is a toxicant well known for its effects on almost every organ system in the body. Pb use in industry has declined since removal of Pb from gasoline, but many developing countries still have significant use of Pb. Exposure to Pb has been linked with diseases causing neurodegeneration and thus have lasting effects long after the initial exposure. Another metal, strontium (Sr), has been linked with bone disease in particular situations and shown to have uses in treating osteoporosis as a supplement. However, there are no studies of the effects of Sr using a meaningful biomarker. The most …

The Graphic Side Of Fear: The Effects Of Anti-Tobacco Graphic Threat Appeals, Latasha R. Swanson

Open Access Dissertations

Many public health organizations have proposed and implemented campaigns and policies involving graphic ads or warnings to deter individuals from smoking. The current study evaluated how high-cigarette dependent smokers evaluate these messages compared to low-cigarette dependent smokers using a mixed, 3 x 2 factorial design. A pilot study involving focus groups, interviews, and evaluation questionnaires (N=10) was conducted to classify graphic threat appeals and develop stimulus materials for the primary study. For the primary study, three graphic threat appeal conditions were evaluated by Amazon Mechanical Turk (MTurk) users (N=200). Findings suggested that the graphicness of the …

A Dose Distribution Study Of Uranyl Nitrate In Zebrafish Using Liquid Scintillation And Passivated Implanted Planar Silicon Detectors, Lee A. Alleman

Open Access Theses

Standard curves for a Perkin Elmer TriCarb 2800 liquid scintillation detector (LSC) and a Ludlum 3030p Passivated Implanted Planar Silicon detector have been developed and utilized for studying the dose distribution of depleted uranium (DU) within zebrafish. The DU source was crystallized uranyl nitrate (N2O8U•6H2O) solution, normally used for staining in electron microscopy with a manufactured average specific activity of 0.3 uCi/g. Zebrafish, both larvae and adults, were exposed to three different mass concentrations, dissected, dissolved and counted using an LSC. The counts were compared to the standard curve correlating the measured activity to that of the mass absorbed. It …

Experimental Evaluation Of An Ipad-Based Augmentative And Alternative Communication Program For Early Elementary Children With Severe, Non-Verbal Autism, Ariana Azzato

Open Access Theses

The purpose of this study was to evaluate the efficacy of a treatment package including a modified protocol of the Picture Exchange Communication System (PECS) implemented via an autism-specific iPad application. A multiple probe design (Horner & Baer, 1978) was replicated across four individuals with severe, non-verbal autism to investigate effects on requesting skills, natural speech production, and social-communicative behaviors. Results suggest beneficial effects, if implemented with high fidelity. The largest effects were on the participants’ requesting skills. All four participants were able to consistently request for desired items by activating the tablet device, and this skill was maintained after …

Design, Optimization, And Characterization Of Novel Polymer-Based Formulations For Controlled Release Of Drugs, Mario Alberto Cano Vega

Open Access Theses

Pharmaceutical products are a key aspect of treatment and prevention of disease. For example, dibenzazepine (DBZ) is a drug that has proved to be useful for the treatment of obesity while progesterone is a common drug for hormonal replacement therapy in women. However, administration of these drugs by conventional dosage forms offers little control over the drug distribution and concentration in the body and often result in unintended adverse consequences on other cells/tissues.

Recent advances in nanotechnology and polymer science have enabled the design and development of controlled release systems that would allow spatiotemporal delivery of drugs with improved efficacy. …

Pilot Study Of The Effect Of High-Protein, Renal-Appropriate Meals During Hemodialysis On Intradialytic Hypotension In Maintenance Hemodialysis Patients, Mun Sun Choi

Open Access Theses

Background: In the United Sates (US), more than 400,000 people have end stage renal disease (ESRD) or chronic kidney disease (CKD) stage 5D requiring in-center hemodialysis (HD), and approximately $35 billion is spent annually in healthcare costs. Maintenance HD patients with ESRD have increased protein (1.2 g/kg/d) and energy (30-35 kcal/kg/d) requirements, but the average protein and energy intake in these patients is only 0.8-1.0 g/kg/d and 20-25 kcal/kg/d, respectively. Subsequently, protein-energy wasting (PEW) is common, affecting up to an estimated 75% of maintenance HD patients, and low protein and energy intake are one of the main contributors of …

Neural Processes Mediating Rhyme Processing In Young Children Who Stutter, Katelyn Lippitt

Open Access Theses

The current study investigated the development of phonological awareness and the functional brain activity underlying phonological processing in children who stutter (CWS) and their fluent peers (CWNS) ages 3;9-6;6.

In the first part of the current study, we investigated the percent accuracy of 63 children (40 CWS, 23 CWNS) completing a real-word rhyme judgment task. In the second part of the study, we investigated the functional brain activity mediating rhyme judgments, as indexed by event-related potentials (ERPs), in 21 children (12 CWS, 9 CWNS).

Part one findings indicated that CWS and CWNS develop rhyme at similar and typical rates. Part …

Manufacturer Perspectives On Content Transparency And Material Health In The Us Building Products Industry, Alexandra A. Muller

Open Access Theses

Flawed U.S. federal regulation of chemicals has resulted in a materials market that undervalues human and environmental health in favor of the more traditional attributes of price, performance and aesthetics. In the building products industry, global, dynamic supply chains and proprietary information concerns further complicate the task of assessing the material health of products.

Voluntary material health programs in the green building industry are intended to incentivize the manufacture and selection of safer products by getting companies to gather and assess ingredient, hazard and risk information from their supply chain. Building product manufacturers considered early adopters of the main material …