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Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley 2010 Wright State University

Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley

Browse all Theses and Dissertations

A comprehensive understanding of the molecular signaling pathways that regulate cell growth and proliferation is essential in the realization of new therapeutic options to facilitate early detection and eradication of malignancy. Understanding the transcriptional regulation of the YPEL3 and FHIT genes forms the basis of this dissertation. YPEL3, or Yippee-like 3, is a newly identified p53 target gene that inhibits tumor cell growth and is thus itself, a novel tumor suppressor gene. FHIT, or Fragile histidine triad, is a well known tumor suppressor gene and is regulated at the transcriptional level by another growth inhibitory protein, FOXO3a, a Forkhead box ...


Characterization And Improvement Of A Cone-Beam Ct Scanner For Quantitative Imaging, Jimish Dilip Joshi 2010 Wright State University

Characterization And Improvement Of A Cone-Beam Ct Scanner For Quantitative Imaging, Jimish Dilip Joshi

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Computed tomography (CT) has various applications in different fields. In our case, the cone-beam CT scanner is used in the industrial field for qualitative and quantitative assessment of Procter and Gamble products. The Flash CT scanner, on which we do our research, has a microfocus x-ray tube, a detector size of 30 cm x 40 cm and a rotating stage for the object to be imaged. The x-ray tube can be operated up to 225 kV. Non-linearities in the response of the detector, scatter and beam hardening may cause false interpretations of the image values. To allow appropriate assessment of ...


Cellular Effects Of Replicating A Polypurine-Polypyrimidine Sequence And The Interactions Of Due-B With Replication Proteins, Shere Lynne Myers 2010 Wright State University

Cellular Effects Of Replicating A Polypurine-Polypyrimidine Sequence And The Interactions Of Due-B With Replication Proteins, Shere Lynne Myers

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This work investigates two questions regarding DNA replication. The first aim examines the interactions of DUE-B with replication proteins and the second explores the cellular effects of replicating a polypurine polypyrimidine sequence in human cells.

DUE-B siRNA decreases the chromatin binding of essential replication proteins Cdc45, PCNA and RPA. DUE-B also co-immunoprecipitates with Cdc45 and TopBP1. In vitro kinase assays suggest that the checkpoint protein ATR may phosphorylate DUE-B. These experiments lend further evidence that DUE-B plays an important role in the initiation of eukaryotic DNA replication.

To investigate the effects of replicating a polypurine-polypyrimidine sequence prone to secondary structure ...


Cytochrome C Oxidase From Rhodobacter Sphaeroides: Oligomeric Structure In The Phospholipid Bilayer And The Structural And Functional Effects Of A C-Terminal Truncation In Subunit Iii, Teresa L. Cvetkov 2010 Wright State University

Cytochrome C Oxidase From Rhodobacter Sphaeroides: Oligomeric Structure In The Phospholipid Bilayer And The Structural And Functional Effects Of A C-Terminal Truncation In Subunit Iii, Teresa L. Cvetkov

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Cytochrome c oxidase (COX) of the mitochondrial electron transport chain catalyzes the reduction of oxygen to water while concomitantly translocating protons across the inner mitochondrial membrane. This two part dissertation is a structural and functional investigation of COX using the bacterial model system from Rhodobacter sphaeroides (R.sph.).

First, the oligomeric structure of R.sph. COX within the lipid bilayer was investigated using discontinuous sucrose gradient ultracentrifugation. Utilizing this technique, liposomes containing R.sph. COX (pCOV) were separated from liposomes lacking enzyme (COV). The net buffering capacity and degree of light scattering per COX molecule were reduced in pCOVs, making ...


Finding Cadaveric Human Head Masses And Center Of Gravity: A Comparison Of Direct Measurement To 3d Ing, Grant Corwin Roush 2010 Wright State University

Finding Cadaveric Human Head Masses And Center Of Gravity: A Comparison Of Direct Measurement To 3d Ing, Grant Corwin Roush

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Mass properties of the human head are critical elements in developing neck injury threshold criteria in acceleration and impact environments. In order to accurately simulate the dynamics of the head in impact and acceleration environments, valid mass properties data for the human head must exist.

The purpose of this study was two-fold: First, to directly measure and generate a useful data set of human head mass properties and anthropometry, and second, compare the results from the direct measurement to measurements obtained using computed tomographic (CT) analyses of the human head. Four cadaveric human heads, all male, were measured.

For the ...


Charaterization Of Chlorpyrifos Toxicity On The Pancreatic Beta Cell Line Rinm5f, Zhongyu Yan 2010 Wright State University

Charaterization Of Chlorpyrifos Toxicity On The Pancreatic Beta Cell Line Rinm5f, Zhongyu Yan

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Chlorpyrifos (CPF) is a well-known organophosphate (OP) insecticide that inhibits acetylcholinesterase (AChE). Organophosphates have been shown to induce hyperglycemia in both humans and animals that cannot be explained by AChE inhibition alone. Pancreatic β-cells are responsible for secreting insulin and playing a fundamental role in glucose homeostasis. The aim of this research was to investigate CPF toxicity on the insulin secreting β-cell line RINm5f (RIN). In the first part of this dissertation, we determined that cytotoxic concentrations of CPF between 50 µM and 200 µM induced a dose-dependent increase in RIN cell apoptotic and necrotic death (p<0.05). Lower doses, i.e., 5-25 µM did not induce apoptosis or necrosis. In further mechanistic studies, inhibitors of c-Jun N-terminal kinase (JNK) and P38 pathways, i.e., SP600125 and SB202190, successfully attenuated CPF-induced apoptosis (p<0.05), suggesting cell death is mediated by JNK and/or p38. In addition, N-Acetyl-L-cysteine (NAC), an antioxidant, inhibited apoptosis suggesting that oxidative stress is also involved in RIN cell death. In the second part of this dissertation, low dose CPF's effects on insulin synthesis and secretion was studied. Our results showed that RIN cells treated with CPF for 4 hr exhibited a dose-dependent decrease in insulin secretion in response to stimulation by 50 mM potassium (p<0.05). Insulin secretion stimulated by 25 mM glucose also showed significant decreases upon incubation with various doses of CPF (p<0.05). Insulin synthesis involves proteolytic cleavage of proinsulin at two specific sites. The enzymes responsible for promoting proinsulin cleavage, i.e, prohormone convertase (PC) 1/3 and 2 (PC2), contain a serine hydrolase catalytic triad, His-Asp-Ser, similar to AChE. CPF modification of PC enzymes similar to AChE, could potentially interrupt the conversion of proinsulin to insulin and disrupt insulin secretion. PC2 enzyme activity was significantly inhibited by CPF at concentrations as low as 10 µM (p<0.01). RIN cells, for the first time, were found to secrete proinsulin was through a constitutive instead of a regulated pathway. In summary, our results show that CPF not only exerts a direct cytotoxic effect at concentrations above 50 µM, but also significantly impairs insulin secretion at lower doses. Low dose CPF could potentially affect endocrine function in vivo by inhibiting the proinsulin processing enzyme PC2.


Dna Linking Number Change Induced By Sequence-Specific Dna-Binding Proteins, Bo Chen, Yazhong Xiao, Chang Liu, Chen-zhong Li, Fenfei Leng 2010 Department of Chemistry and Biochemistry, Florida International University

Dna Linking Number Change Induced By Sequence-Specific Dna-Binding Proteins, Bo Chen, Yazhong Xiao, Chang Liu, Chen-Zhong Li, Fenfei Leng

Department of Chemistry and Biochemistry

Sequence-specific DNA-binding proteins play a key role in many fundamental biological processes, such as transcription, DNA replication and recombination. Very often, these DNA-binding proteins introduce structural changes to the target DNA-binding sites including DNA bending, twisting or untwisting and wrapping, which in many cases induce a linking number change (ΔLk) to the DNA-binding site. Due to the lack of a feasible approach, ΔLk induced by sequence-specific DNA-binding proteins has not been fully explored. In this paper we successfully constructed a series of DNA plasmids that carry many tandem copies of a DNA-binding site for one sequence-specific DNA-binding protein ...


Catalytic Strategies Of Glycoside Hydrolases, Luis Petersen 2010 Iowa State University

Catalytic Strategies Of Glycoside Hydrolases, Luis Petersen

Graduate Theses and Dissertations

Glycoside hydrolases (GHs) are enzymes that catalyze the hydrolysis of the glycosidic bond between two carbohydrate residues or a carbohydrate unit linked to a non-carbohydrate aglycon unit. Despite years of research dedicated to GHs, there are still several mechanistic details, relevant for individual GH enzymes, that remain to be investigated. In this work, a computational analysis of the detailed mechanism of several GHs is presented. QM/MM metadynamics simulations of two glycoside hydrolases, GH8 endoglucanase and GH43 β-xylosidase, give insight into the enzymatic deconstruction of the plant cell wall, and the detailed reaction mechanism of both enzymes. In addition, an ...


The Development Of A Mesenchymal Stem Cell Based Biphasic Osteochondral Tissue Engineered Construct, Scott Maxson 2010 Clemson University

The Development Of A Mesenchymal Stem Cell Based Biphasic Osteochondral Tissue Engineered Construct, Scott Maxson

All Dissertations

The ability of human articular cartilage to respond to injury is poor. Once cartilage damage has occurred, an irreversible degenerative process can occur and will often lead to osteoarthritis (OA). An estimated 26.9 million of U.S. adults are affected by OA. Osteochondral grafting is currently used to treat OA and osteochondral defects; however, complications can develop at the donor site and defect area. Osteochondral tissue engineering provides a potential treatment option and alternative to osteochondral grafting. The long term goal of this work is to develop a tissue engineered mesenchymal stem cell (MSC) based osteochondral construct to repair ...


Cytocompatible Cross-Linking Of Electrospun Zein Fibers For The Development Of Water-Stable Tissue Engineering Scaffolds, Quiran Jiang, Narendra Reddy, Yiqi Yang 2010 University of Nebraska–Lincoln

Cytocompatible Cross-Linking Of Electrospun Zein Fibers For The Development Of Water-Stable Tissue Engineering Scaffolds, Quiran Jiang, Narendra Reddy, Yiqi Yang

Biological Systems Engineering: Papers and Publications

This paper reports a new method of cross-linking electrospun zein fibers using citric acid as a non-toxic cross-linker to enhance the water stability and cytocompatibility of zein fibers for tissue engineering and other medical applications. The electrospun structure has many advantages over other types of structures and protein-based biomaterials possess unique properties preferred for tissue engineering and other medical applications. However, ultrafine fiber matrices developed from proteins have poor mechanical properties and morphological stability in the aqueous environments required for medical applications. Efforts have been made to improve the water stability of electrospun protein scaffolds using cross-linking and other approaches ...


Net Radiation Dynamics: Performance Of 20 Daily Net Radiation Models As Related To Model Structure And Intricacy In Two Climates, Suat Irmak, Denis Mutiibwa, José O. Payero 2010 University of Nebraska-Lincoln

Net Radiation Dynamics: Performance Of 20 Daily Net Radiation Models As Related To Model Structure And Intricacy In Two Climates, Suat Irmak, Denis Mutiibwa, José O. Payero

Biological Systems Engineering: Papers and Publications

We compared daily net radiation (Rn) estimates from 19 methods with the ASCE‐EWRI Rn estimates in two climates: Clay Center, Nebraska (sub‐humid) and Davis, California (semi‐arid) for the calendar year. The performances of all 20 methods, including the ASCE‐EWRI Rn method, were then evaluated against Rn data measured over a non‐stressed maize canopy during two growing seasons in 2005 and 2006 at Clay Center. Methods differ in terms of inputs, structure, and equation intricacy. Most methods differ in estimating the cloudiness factor, emissivity (α), and calculating net longwave radiation (Rnl ...


Testing Fuel Efficiency Of A Tractor With A Continuously Variable Transmission, Bart A. Coffman, Michael F. Kocher, Viacheslav I. Adamchuk, Roger M. Hoy, Erin E. Blankenship 2010 University of Nebraska-Lincoln

Testing Fuel Efficiency Of A Tractor With A Continuously Variable Transmission, Bart A. Coffman, Michael F. Kocher, Viacheslav I. Adamchuk, Roger M. Hoy, Erin E. Blankenship

Biological Systems Engineering: Papers and Publications

A John Deere 8530 IVT tractor (Waterloo, Iowa) with a continuously variable transmission (CVT) that could be operated in automatic (CVT) or manual (fixed gear ratio) mode was tested for fuel consumption at a setpoint travel speed of 9 km·h‐1 with 17 different drawbar loads. Linear regression analysis results showed that with the throttle set to maximum in both transmission modes, operating the tractor with the transmission in the automatic mode was more fuel efficient than operating with the transmission in the manual mode when the drawbar power was approximately 78%, or less, of maximum power. When load ...


Testing Fuel Efficiency Of Tractors With Both Continuously Variable And Standard Geared Transmissions, Christopher N. Howard 2010 University of Nebraska at Lincoln

Testing Fuel Efficiency Of Tractors With Both Continuously Variable And Standard Geared Transmissions, Christopher N. Howard

Biological Systems Engineering--Dissertations, Theses, and Student Research

A John Deere 8295R IVT tractor with a continuously variable transmission (CVT) and a John Deere 8295R PowerShift (PST) tractor (Waterloo, Iowa) with a standard geared transmission (GT) were tested for fuel consumption at three different travel speeds with six different load levels applied per speed. The JD 8295R PST tractor was tested both at full throttle (FT) and shifted up two gears and throttled back (SUTB) to achieve the same travel speed as at full throttle conditions. The three speeds tested corresponded to the maximum speeds achieved in 6th, 8th and 10th gear for the JD 8295R PST tractor ...


Merlin.Net Automation Of External Reports Verification Process, Gabriel John Wettlaufer 2010 California Polytechnic State University, San Luis Obispo

Merlin.Net Automation Of External Reports Verification Process, Gabriel John Wettlaufer

Master's Theses and Project Reports

Merlin.net Patient Care Network is a St. Jude Medical product that is used for remote patient management. The basic concept of Merlin.net is to allow the physician to view patient device follow-up information as well as general patient and device information on a web application. The Merlin.net system also interfaces with the patient and will send them notification if they miss a follow-up. All device information will be collected automatically while the patient is sleeping. This information is sent through a telephone line to a Merlin.net server to process a report package and display the collected ...


Use Of A 3d Perfusion Bioreactor With Osteoblasts And Osteoblast/Endothelial Cell Co-Cultures To Improve Tissue-Engineered Bone, Matthew J. Barron 2010 Michigan Technological University

Use Of A 3d Perfusion Bioreactor With Osteoblasts And Osteoblast/Endothelial Cell Co-Cultures To Improve Tissue-Engineered Bone, Matthew J. Barron

Dissertations, Master's Theses and Master's Reports - Open

The delivery of oxygen, nutrients, and the removal of waste are essential for cellular survival. Culture systems for 3D bone tissue engineering have addressed this issue by utilizing perfusion flow bioreactors that stimulate osteogenic activity through the delivery of oxygen and nutrients by low-shear fluid flow. It is also well established that bone responds to mechanical stimulation, but may desensitize under continuous loading. While perfusion flow and mechanical stimulation are used to increase cellular survival in vitro, 3D tissue-engineered constructs face additional limitations upon in vivo implantation. As it requires significant amounts of time for vascular infiltration by the host ...


Exploration Of The Role Of Serum Factors In Maintaining Bone Mass During Hibernation In Black Bears, Rachel Marie Bradford 2010 Michigan Technological University

Exploration Of The Role Of Serum Factors In Maintaining Bone Mass During Hibernation In Black Bears, Rachel Marie Bradford

Dissertations, Master's Theses and Master's Reports - Open

Disuse osteoporosis is a condition in which reduced mechanical loading (e.g. bed-rest, immobilization, or paralysis) results in unbalanced bone turnover. The American black bear is a unique, naturally occurring model for the prevention of disuse osteoporosis. Bears remain mostly inactive for up to half a year of hibernation annually, yet they do not lose bone mechanical strength or structural properties throughout hibernation. The long-term goal of this study is to determine the biological mechanism through which bears maintain bone during hibernation. This mechanism could pinpoint new signaling pathway targets for the development of drugs for osteoporosis prevention. In this ...


Influence Of Traumatic Impaction And Pathological Loading On Knee Menisci, Megan Leigh Killian 2010 Michigan Technological University

Influence Of Traumatic Impaction And Pathological Loading On Knee Menisci, Megan Leigh Killian

Dissertations, Master's Theses and Master's Reports - Open

Nearly half of the US population faces the risk of developing knee osteoarthritis (OA). Both in vitro and in vivo studies can aid in a better understanding of the etiology, progression, and advancement of this debilitating disorder. The knee menisci are fibrocartilagenous structures that aid in the distribution of load, attenuation of shock, alignment and lubrication of the knee. Little is known about the biochemical and morphological changes associated with knee menisci following altered loading and traumatic impaction, and investigations are needed to further elucidate how degradation of this soft tissue advances over time. The biochemical response of porcine meniscal ...


Frustrated Drift Of An Anchored Scroll-Wave Filament And The Geodesic Principle, Marcel Wellner, Christian W. Zemlin, Arkady M. Pertsov 2010 Old Dominion University

Frustrated Drift Of An Anchored Scroll-Wave Filament And The Geodesic Principle, Marcel Wellner, Christian W. Zemlin, Arkady M. Pertsov

Bioelectrics Publications

We investigate anchored scroll-wave filaments in an excitable medium whose diffusivity matrix, including its determinant, is spatially nonuniform. The study is motivated by cardiological applications where scroll-wave behavior in the presence of diffusivity gradients is believed to play an important role in the development of severe arrhythmias. A diffusivity gradient is expected to make the filament drift, unless drift is prevented ("frustrated") by anchoring to localized defects in the propagation medium. The resulting stationary filament is a geodesic curve, as demonstrated here in the case of a nonzero but constant gradient. That is, the diffusivity matrix has a determinant that ...


Virtual Pre-Operative Reconstruction Planning For Comminuted Articular Fractures, Thaddeus Paul Thomas 2010 University of Iowa

Virtual Pre-Operative Reconstruction Planning For Comminuted Articular Fractures, Thaddeus Paul Thomas

Theses and Dissertations

Highly comminuted intra-articular fractures are complex and difficult injuries to treat. Once emergent care is rendered, the definitive treatment objective is to restore the original anatomy while minimizing surgically induced trauma. Operations that use limited or percutaneous approaches help preserve tissue vitality, but reduced visibility makes reconstruction more difficult. A pre-operative plan of how comminuted fragments would best be re-positioned to restore anatomy helps in executing a successful reduction. The objective of this work was to create new virtual fracture reconstruction technologies that would deliver that information for a clinical series of severe intra-articular fractures. As a step toward clinical ...


Metabolic Engineering For Production Of Biorenewable Fuels And Chemicals: Contributions Of Synthetic Biology, Laura R. Jarboe, Xueli Zhang, Xuan Wang, Jonathan C. Moore, K. T. Shanmugam, Lonnie O. Ingram 2010 Iowa State University

Metabolic Engineering For Production Of Biorenewable Fuels And Chemicals: Contributions Of Synthetic Biology, Laura R. Jarboe, Xueli Zhang, Xuan Wang, Jonathan C. Moore, K. T. Shanmugam, Lonnie O. Ingram

Chemical and Biological Engineering Publications

Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemicalbased production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use ...


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