Biomedical Engineering and Bioengineering Commons^™

Phospholipase D: Key Player In Macrophage-Mediated Inflammation And Resolution, Ramya Ganesan

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Phospholipase D (PLD) is a cell membrane remodeling and signaling protein implicated in the pathology of chronic inflammation. As PLD is also central to macrophage cell migration, we investigated the molecular basis of PLD's involvement and regulation in macrophage-initiated inflammation (atherosclerosis) and resolution. We have found that PLD is associated with signaling proteins and positively affects cell movement, phagocytosis and NADPH-initiated release of Reactive Oxygen Species (ROS). We found that PLD2 but not PLD1 is important for foam cell formation that causes atherogenesis. We have also found a novel way of inducing macrophage class-switch (polarization) by PLD overexpression. PLD induces …

Proteomic Analysis Of Ischemic Stroke Blood Biomarkers, April Arnold Daubenspeck

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Stroke is a global burden that claims 6 million lives and permanently disables another 5 million each year. The risk of morbidity and mortality following stroke decreases when early diagnosis and treatment are achieved. However there is no blood test to diagnose ischemic stroke because biomarkers to date have not shown adequate sensitivity and specificity to be adopted into hospital protocols. The overall objective of this dissertation was to identify novel blood protein biomarkers of ischemic stroke. We achieved this by using a number of proteomic and statistical techniques to investigate the differential abundance of proteins in the blood of …

Making Meaning: Shifts In Meaningfulness Across Three Modeling Units, Jeannette Manger

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Recent reform calls for a more comprehensive approach to science education that positions learners as constructors of knowledge via scientific practices (NRC, 2012; Osborne, 2014). This 'practice turn' shifts from passive science learning to incorporating science actions with epistemic thinking (Duschl & Grandy, 2013; Ford & Forman, 2006; Osborne, 2014; Shouse, Schweingruber, & Duschl, 2007). Teachers are often underprepared in understanding the nuances of scientific practices, and frequently struggle with supporting students in meaningful practice engagement (Abd-El-Khalick & Akerson, 2004; Crawford, 1999; Davis, Petish, & Smithey, 2006; Duschl & Gitomer, 1997). Here, I draw upon the Berland et al. Epistemologies …

Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri

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Advancements in the nanotechnology have taken a huge leap in 21st century resulting in 1814 consumer products containing nanomaterials. About 47% of these products belong to the health and fitness sector and ~24% utilize silver nanoparticles (AgNPs). Despite the promising biomedical applications of AgNPs (e.g. bone cements, contrasting agents, and drug-carriers), lack of standardized methods for examining their nanokinetics (i.e., Absorption, Distribution, Metabolism, and Elimination (ADMEs)) limit their clinical implementation. The current work addresses this knowledge gap by developing analytical-based approaches for studying in vitro ADMEs of AgNPs. To demonstrate the versatility of these methodologies, two in vitro kidney study …

Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite

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Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor under various stressors will promote phenotypic cellular changes, known as epithelial-to-mesenchymal transition (EMT), which allows cells to begin to invade surrounding tissue, enter the circulatory system, and eventually seed a distant metastatic site. The phospholipase D (PLD) enzymes are critical regulators of cell signaling pathways necessary for cell migration. While the importance of PLD enzymes in cancer cell invasion is well known, clinically applicable methods of PLD inhibition are not yet available. The best-studied isoforms …

Identification Of Novel Ligands And Structural Requirements For Heterodimerization Of The Liver X Receptor Alpha, Shimpi Bedi

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LXRs, LXRa (NR1H3) and LXRß (NR1H2), are ligand-activated transcription factors that are members of the nuclear receptor superfamily. Oxysterols and nonsteroidal synthetic compounds bind directly to LXRs and influence the expression of LXR dependent genes. The use of murine models and LXR-selective agonists have established the important role of LXRs as sterol sensors that govern the absorption, transport, and catabolism of cholesterol. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver to aid in the removal of excess cholesterol. Not surprisingly, LXR dysregulation is a feature of several human diseases, …

A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis

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Imperative to genomic stability is the ability of the cell to repair damaged DNA which can occur from numerous endogenous byproducts of metabolism or exogenous components from the environment. The Fanconi anemia pathway is a DNA repair mechanism used by human cells to resolve multiple forms of DNA damage including interstrand crosslinks (ICL). Fanconi anemia (FA) is an autosomal recessive inherited disorder characterized by genome instability, developmental abnormalities, cancer predisposition and bone marrow failure. FA is attributed to a mutations in at least 18 genes (FANCA-FANCT) that play a concerted role in DNA repair. FANCT is the latest discovery in …

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …

Identifying The Impact Of Noise On Anomaly Detection Through Functional Near-Infrared Spectroscopy (Fnirs) And Eye-Tracking, Ryan Dwight Gabbard

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Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance (ISR) operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts' decision making process. In this study the effects of different noise stimuli on analysts' performance and workload in anomaly detection were investigated by simulating a noisy work environment. Functional near infrared spectroscopy (fNIRS) was utilized to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbD) concentration changes in the prefrontal cortex (PFC), as well as behavioral measures which include eye-tracking, reaction time, and accuracy rate. It was found that HbO for some of …

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs is controversial. Determining the direction of NKCC1- mediated fluxes is …

Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent

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Neurotoxicity is one of the most significant side effects diminishing clinical efficacy and patient quality of life during and following chemotherapy. Oxaliplatin (OX) is a platinum based chemotherapy agent used in the treatment of colorectal cancer. Colorectal cancer currently ranks as the 4th most common cancer, and the majority of patients receive OX as a part of their adjuvant therapy. OX based adjuvant therapies significantly improve 5 year survival rates, however in many cases patients must stop treatment early because of the neurotoxic side effects. OX causes two clinically distinct forms of neurotoxicity. Acutely, within hours and for days following …

Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak

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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to …

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na⁺/ K⁺ ATPase and the Na⁺/ K⁺/ 2Cl^- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na⁺ and Cl^- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs …

Somatic Stimulation Causes Frontoparietal Cortical Changes In Neonates: A Functional Near-Infrared Spectroscopy Study, Nasser H. Kashou, Irfaan Akram Dar, Kathryn Hasenstab, Ramzi W. Nahhas, Sudarshan R. Jadcherla

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Palmar and plantar grasp are the foremost primitive neonatal reflexes and functions. Persistence of these reflexes in infancy is a sign of evolving cerebral palsy. Our aims were to establish measurement feasibility in a clinical setting and to characterize changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD) concentration in the bilateral frontoparietal cortex in unsedated neonates at the crib-side using functional near-infrared spectroscopy (fNIRS). We hypothesized that bilateral concentration changes will occur upon somatic central and peripheral somatic stimulation. Thirteen preterm neonates (five males) underwent time 1, and six (two males) returned for time 2 (mean PMA ¼ 41.6 and 47.0 …

Quantitative Analysis Of Retrieved Glenoid Liners, Katelyn Childs, Lynn Crosby, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Revision of orthopedic surgeries is often expensive and involves higher risk from complications. Since most total joint replacement devices use a polyethylene bearing, which serves as a weak link, the assessment of damage to the liner due to in vivo exposure is very important. The failures often are due to excessive polyethylene wear. The glenoid liners are complex and hemispherical in shape and present challenges while assessing the damage. Therefore, the study on the analysis of glenoid liners retrieved from revision surgery may lend insight into common wear patterns and improve future product designs. The purpose of this pilot study …

Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase, Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas N. Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Background

Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).

Methods

Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30–60 U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.

Results

The study included 24 …

Novel Cell Killing Mechanism Of Hydroxyurea In The Fission Yeast Schizosaccharomyces Pombe And Its Implications In Improving Antifungal Therapy, Amanpreet Singh

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Hydroxyurea (HU, also known as hydroxycarbamide) is a well known ribonucleotide reductase (RNR) inhibitor that depletes cellular deoxyribonucleoside triphosphates (dNTPs, the building blocks of DNA). Depleted dNTP pools inside the proliferating cells stalls ongoing DNA replication forks, leading to the activation of the well-conserved DNA replication checkpoint (also known as intra-S phase checkpoint) pathway. One of the major functions of the checkpoint pathway is to protect ongoing forks from collapsing. Stalled forks, if not protected by the checkpoint pathway, lead to DNA damage and ultimately cell death. Thus it is believed that DNA damage resulting from collapsed forks is the …

Stimulus And Optode Placement Effects On Functional Near-Infrared Spectroscopy Of Visual Cortex, Nasser H. Kashou, Brenna M. Giacherio

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Functional near-infrared spectroscopy has yet to be implemented as a stand-alone technique within an ophthalmology clinical setting, despite its promising advantages. The present study aims to further investigate reliability of visual cortical signals. This was achieved by: (1) assessing the effects of optode placements using the 10–20 International System of Electrode Placement consisting of 28 channels, (2) determining effects of stimulus size on response, and (3) evaluating response variability as a result of cap placement across three sessions. Ten participants with mean age 23.8 4.8 years (five male) and varying types of hair color and thickness were recruited. Visual stimuli …

Hand-Grasping And Finger Tapping Induced Similar Functional Near-Infrared Spectroscopy Cortical Responses, Nasser H. Kashou, Brenna M. Giacherio, Ramzi W. Nahhas, Sudarshan R. Jadcherla

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Despite promising advantages such as low cost and portability of functional near-infrared spectroscopy (fNIRS), it has yet to be widely implemented outside of basic research. Specifically, fNIRS has yet to be proven as a standalone tool within a clinical setting. The objective of this study was to assess hemodynamic concentration changes at the primary and premotor motor cortices as a result of simple whole-hand grasping and sequential finger-opposition (tapping) tasks. These tasks were repeated over 3 days in a randomized manner. Ten healthy young adults (23.8 4.8 years) participated in the study. Quantitatively, no statistically significant differences were discovered between …

Finite Element Analysis Of Superior C3 Cervical Vertebra Endplate And Cancellous Core Under Static Loads, Isaac Mabe, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Subsidence is a type of failure associated with implanted cervical cages or artificial intervertebral discs. It is defined as a loss of postoperative disc height. Actuarial rates show a risk of subsidence at 16 weeks at 70.7 percent. This study examines the changes in the vertebral endplate morphology and the resulting effect on the stresses developed in the endplate and in the vertebral core. A three-dimensional linear elastic model was created from computed tomographic (CT) scans and material properties were assigned according to various studies. Particular care was taken in the superior endplate that was modeled according to experimental measurements. …

Analysis Of A Clinically Failed, Mechanically Intact, Hemi-Toe Implant, Swetha Varadharajan, Richard T. Laughlin, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

In this case study a clinically failed, mechanically intact, hemi-toe device was investigated. The clinical indication of the failure constitutes radiolucent line indicating loosening of the implant and possible interactions among the bone-implant initiated by osteolysis may become a factor, producing pain, inflammatory reactions, deformity and discomfort. The patient file was not available to determine these parameters. The device was titanium coated, Cobalt Chromium alloy used for making hemi-toe. Degeneration of hemi implant was due to spalling of the coating from the surface, causing loosening of stem from bone. However, pre-removal X-ray films were not available to confirm. Mechanism by …

Low-Cost, Wireless Optical Oximeter For Monitoring Of Brain Function In High-Risk Pediatric Population, Zahra Meghjani

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Nearly 4 million neonates die every year due to brain injuries, most caused by hypoxia. Neonatal ICU requires newborns with critical health conditions to be monitored continuously calling for the need of a non-invasive, compact and portable device. However, commercial devices are mostly bulky and/or expensive. The neonatal mortality is higher in under-developed countries, where such expensive and large devices are not affordable. Hence, my thesis focuses on building first generation compact, inexpensive, and wireless device that can monitor and provide feedback to clinicians during intervention. This approach is based on light absorption by oxy- and deoxy-hemoglobin chromophores. The total …

Modification Reactivity Analysis Of Human Replication Protein A In Biologically Important States, Ryan James Yoakum

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Human Replication Protein A (RPA) is a heterotrimeric protein consisting of 70, 32, and 14 kDa subunits. RPA is the predominant single stranded DNA binding protein within the cell. It is involved in all forms of the DNA metabolic pathways, including but not limited to, replication, recombination, damage repair, as well as cell cycle and DNA check point signaling. RPA is phosphorylated (pRPA) during G1-S phase and is dephosphorylated during M phase. Further, RPA is hyperphosphorylated during DNA damage. Through the use of x-ray crystallography and nuclear magnetic resonance, researchers have proposed models and structures based on truncated portions of …

Use Of Eeg To Understand Brain Intensity In Engineering Students Using A Stem Educational Mobile Application, Kevin Hatcher

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In the first two years of undergraduate work in engineering, students are taught concepts such as physics, electronics, and most importantly calculus. It is especially important for students to get a better grasp on foundational math concepts, such as calculus in the beginning or they will be overwhelmed by the workload to come. The focus of this research was to understand how students learning calculus, could benefit from an augmented-educational mobile application. In the study students were measured with electroencephalography (EEG) measurements utilized by the Emotive EPOC® as they attempted to solve different limit themed problems in order to determine …

Extension Of Multivariate Analyses To The Field Of Microbial Ecology, Vijay Shankar

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Ground-breaking advancements in molecular and analytical techniques in the past decade have enabled researchers to accumulate data at an extraordinary rate. Especially in the field of microbial ecology, the introduction of technologies such as high-throughput sequencing, quantitative microarrays, nuclear magnetic resonance and mass spectrometry has led to the interrogation of diverse and previously unexplored microbial communities at unparalleled depth. Analysis and interpretation of patterns within datasets acquired with such high-throughput methods require powerful statistical approaches. A class of such techniques called multivariate statistical analyses is an excellent choice for analysis of complex microbiota-related datasets. This field of statistics is constantly …

Characterization Of Peripheral Lung Lesions By Statistical Image Processing Of Endobronchial Ultrasound Images, Aaron T. Madaris

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This thesis introduces the concept of implementing greyscale analysis, also known as intensity analysis, on endobronchial ultrasound (EBUS) images for the purposes of diagnosing peripheral lung tumors. The statistical methodology of using greyscale and histogram analysis allows the characterization of lung tissue in EBUS images. Regions of interest (ROI) will be analyzed in MATLAB and a feature vector will be created. A feature vector of first-order, second-order and histogram greyscale analysis will be created and used for the classification of malignant vs benign peripheral lung tumors. The tools that were implemented were MedCalc for the initial statistical analysis of receiver …

Improving Anomaly Detection Through Identification Of Physiological Signatures Of Unconscious Awareness, Alyssa Marie Piasecki

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Missed anomalies have the potential to cause detrimental effects in the Intelligence, Surveillance, and Reconnaissance (ISR) domain. One possible cause of these missed anomalies is that cognitive processing may not reach conscious awareness and may only be perceived by the unconscious mind. Identification of correlates of these unconscious processes could provide an insight into potential missed targets. The present study explored missed anomalies in a visual search task and the possibility of unconscious awareness. Eye metrics were recorded and a "Detection Threshold Model" was created and validated with a nominal logistic regression model, in order to characterize the search patterns …

Novel Therapeutic Approach For Regulating The Susceptibility Of Epitheliato Adenovirus Infection, Mahmoud Soliman Salem Alghamri

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Human Adenoviruses (AdVs) are etiologic agents for respiratory tract, digestive tract, heart, and eye infections. Although most AdV infections are self-resolving, some infections progress to acute respiratory disease with up to 50% mortality, particularly in immunosuppressed people. Except for vaccines for serotypes, 4 and 7, serotypes that are prevalent in the military, no vaccines or therapeutics that specifically prevent or treat AdV infection exist. On the other hand, AdV remains the most common vector system used in gene therapy clinical trials worldwide and several AdV vectors show promise in phase III clinical trials. The majority of AdVs use the coxsackievirus …

Modeling Effects Of Diet On Human Gut Microbiota, Richard Thomas Agans

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The human gut microbiota is integrally involved in the metabolism of nutrients contained within the human diet. Studies into human nutrition have primarily been carried out using human and animal models. These studies are extremely important in our understanding of human nutrition, however, suffer from inherent limitations including unique microbial compositions between individuals, compliance in human studies, inability to carry out mechanistic studies, and inability to interrogate proximal regions of the gut without applying invasive techniques. In vitro gut simulator systems circumvent many of these limitations in animal and human models by allowing control of gut environmental conditions, decreasing variability …