Biomedical Engineering and Bioengineering Commons^™

Predicting Propofol-Induced Burst Suppression Using An Individualized Model-Based Approach Over Repeated Treatments, Jason C. Huang

Utah Space Grant Consortium

Our group is investigating the antidepressant effects of high-dose propofol, but dosing propofol to induce standardized changes in EEG activity (“burst suppression”) is challenging due to limited knowledge of each subject’s pharmacokinetics (PK) and pharmacodynamics (PD). In this paper, we approximated PK-PD models for propofol-induced burst suppression (PIBS), based on multiple subjects over repeated treatments. We then applied these models to predict BSR in each subject’s repeated treatment, then evaluate their predictive performances. We hypothesized that predicting BSR from a greater number of previous treatments would improve performance, but our current results are not conclusive enough to validate the hypothesis. …

Identification And Heterologous Reconstitution Of A 5-Alk(En)Ylresorcinol Synthase From Endophytic Fungus Shiraia Sp. Slf14, Huiwen Yan, Lei Sun, Jinge Huang, Yixing Qiu, Fuchao Xu, Riming Yan, Du Zhu, Wei Wang, Jixun Zhan

Biological Engineering Faculty Publications

A new type III polyketide synthase gene (Ssars) was discovered from the genome of Shiraia sp. Slf14, an endophytic fungal strain from Huperzia serrata. The intron-free gene was cloned from the cDNA and ligated to two expression vectors pET28a and YEpADH2p-URA3 for expression in Escherichia coli BL21(DE3) and Saccharomyces cerevisiae BJ5464, respectively. SsARS was efficiently expressed in E. coli BL21(DE3), leading to the synthesis of a series of polyketide products. Six major products were isolated from the engineered E. coli and characterized as 1,3-dihydroxyphenyl-5-undecane, 1,3-dihydroxyphenyl-5-cis-6'-tridecene,1,3-dihydroxyphenyl-5-tridecane, 1,3-dihydroxyphenyl-5-cis-8'-pentadecene, 1,3-dihydroxyphenyl-5-pentadecane and 1,3-dihydroxyphenyl-5-cis-10'-heptadecene, respectively, …

An Efficient Process For Co-Production Of Γ-Aminobutyric Acid And Probiotic Bacillus Subtilis Cells, Hongbo Wang, Jinge Huang, Lei Sun, Fuchao Xu, Wei Zhang, Jixun Zhan

Biological Engineering Faculty Publications

This study was to establish an integrated process for the co-production of γ-aminobutyric acid (GABA) and live probiotics. Six probiotic bacteria were screened and Bacillus subtilis ATCC 6051 showed the highest GABA-producing capacity. The optimal temperature and initial pH value for GABA production in B. subtilis were found to be 30 °C and 8.0, respectively. A variety of carbon and nitrogen sources were tested, and potato starch and peptone were the preferred carbon and nitrogen sources for GABA production, respectively. The concentrations of carbon source, nitrogen source and substrate (sodium L-glutamate) were then optimized using the response surface methodology. The …

Method For The Destruction Of Endotoxin In Synthetic Spider Silk Proteins, Richard E. Decker, Thomas I. Harris, Dylan R. Memmott, Christopher J. Peterson, Randolph V. Lewis, Justin A. Jones

Biological Engineering Faculty Publications

Although synthetic spider silk has impressive potential as a biomaterial, endotoxin contamination of the spider silk proteins is a concern, regardless of the production method. The purpose of this research was to establish a standardized method to either remove or destroy the endotoxins present in synthetic spider silk proteins, such that the endotoxin level was consistently equal to or less than 0.25 EU/mL, the FDA limit for similar implant materials. Although dry heat is generally the preferred method for endotoxin destruction, heating the silk proteins to the necessary temperatures led to compromised mechanical properties in the resultant materials. In light …

Whole Cell Cross-Linking To Discover Host-Microbe Protein Cognate Receptor/Ligand Pairs, Bart C. Weimer, Poyin Chen, Prerak T. Desai, Dong Chen, Jigna Shah

Biological Engineering Faculty Publications

Bacterial surface ligands mediate interactions with the host cell during association that determines the specific outcome for the host–microbe association. The association begins with receptors on the host cell binding ligands on the microbial cell to form a partnership that initiates responses in both cells. Methods to determine the specific cognate partnerships are lacking. Determining these molecular interactions between the host and microbial surfaces are difficult, yet crucial in defining biologically important events that are triggered during association of the microbiome, and critical in defining the initiating signal from the host membrane that results in pathology or commensal association. In …

Production Of Genetically Engineered Golden Syrian Hamsters By Pronuclear Injection Of The Crispr/Cas9 Complex, Rong Li, Jinxin Miao, Seokhwan Song, Il-Keun Kong, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The pronuclear (PN) injection technique was first established in mice to introduce foreign genetic materials into the pronuclei of one-cell stage embryos. The introduced genetic material may integrate into the embryonic genome and generate transgenic animals with foreign genetic information following transfer of the injected embryos to foster mothers. Following the success in mice, PN injection has been applied successfully in many other animal species. Recently, PN injection has been successfully employed to introduce reagents with gene-modifying activities, such as the CRISPR/Cas9 system, to achieve site-specific genetic modifications in several laboratory and farm animal species. In addition to mastering the …

A Computational Study Of Vegf Production By Patterned Retinal Epithelial Cell Colonies As A Model For Neovascular Macular Degeneration, Qanita Bani Baker, Gregory J. Podgorski, Elizabeth Vargis, Nicholas Flann

Biology Faculty Publications

Background: The configuration of necrotic areas within the retinal pigmented epithelium is an important element in the progression of age-related macular degeneration (AMD). In the exudative (wet) and non-exudative (dry) forms of the disease, retinal pigment epithelial (RPE) cells respond to adjacent atrophied regions by secreting vascular endothelial growth factor (VEGF) that in turn recruits new blood vessels which lead to a further reduction in retinal function and vision. In vitro models exist for studying VEGF expression in wet AMD (Vargis et al., Biomaterials 35(13):3999–4004, 2014), but are limited in the patterns of necrotic and intact RPE epithelium they can …

Importance Of Heat And Pressure For Solubilization Of Recombinant Spider Silk Proteins In Aqueous Solution, Justin A. Jones, Thomas I. Harris, Paula F. Oliveira, Brianne E. Bell, Abdulrahman Alhabib, Randolph V. Lewis

Biology Faculty Publications

The production of recombinant spider silk proteins continues to be a key area of interest for a number of research groups. Several key obstacles exist in their production as well as in their formulation into useable products. The original reported method to solubilize recombinant spider silk proteins (rSSp) in an aqueous solution involved using microwaves to quickly generate heat and pressure inside of a sealed vial containing rSSp and water. Fibers produced from this system are remarkable in their mechanical ability and demonstrate the ability to be stretched and recover 100 times. The microwave method dissolves the rSSPs with dissolution …

Investigation Of The Tailoring Steps In Pradimicin Biosynthesis, Kandy L. Napan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focused on the investigation of the late steps in the biosynthetic pathway of the novel antifungal and antiviral pradimicins A-C. Pradimicins were first isolated from the soil bacterium Actinomadura hibisca. These bioactive molecules are assembled by a type II polyketide biosynthetic pathway. Although the biosynthetic gene cluster of pradimicin has been identified, the functions of the biosynthetic genes and how they work collaboratively to form the final structures of pradimicins remain unknown. This research aims to functionally characterize the enzymes involved in the late steps of the biosynthetic route.

The early biosynthetic steps of pradimicins have been …

Beyond The Fiber: Novel Spider Silk Coatings And Adhesives, Danielle A. Gaztambide, Breton A. Day

Research on Capitol Hill

Natural spider silks have long been recognized for their combination of incredible strength and elasticity. Spider silk is more elastic than nylon, tougher than Kevlar, and stronger than steel by weight. Due to an inability to farm spiders, much work has been done to produce spider silks in transgenic hosts for large -scale production. Our work was done using recombinant spider silk proteins produced in transgenic goats and the bacteria E. coli.

More recently spider silks have also been recognized for their biocompatibility and lack of immunogenicity. Spider silks' incredible strength and ability to be implanted safely within the body …

Fluorescent Nanocomposite Of Embedded Ceria Nanoparticles In Crosslinked Pva Electrospun Nanofibers, Nader Shehata, Soha Gaballah, Effat Samir, Aya Hamed, Marwa Saad

Biology Faculty Publications

This paper introduces a new fluorescent nanocomposite of electrospun biodegradable nanofibers embedded with optical nanoparticles. In detail, this work introduces the fluorescence properties of PVA nanofibers generated by the electrospinning technique with embedded cerium oxide (ceria) nanoparticles. Under near-ultra violet excitation, the synthesized nanocomposite generates a visible fluorescent emission at 520 nm, varying its intensity peak according to the concentration of in situ embedded ceria nanoparticles. This is due to the fact that the embedded ceria nanoparticles have optical tri-valiant cerium ions, associated with formed oxygen vacancies, with a direct allowed bandgap around 3.5 eV. In addition, the impact of …

Characterization And Application Of Dynamic In Vitro Models Of Human Airway, Hemangkumar J. Patel

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

In recent years, respiratory diseases have emerged as a leading cause of mortality across the globe. In the United States alone respiratory diseases are the fourth leading cause of deaths annually. Moreover, with the rapid increase of industrialization and urbanization, the occurrences of respiratory diseases are expected to remain high with strong chances of increasing in the future. To ameliorate the epidemic of respiratory disease, it is first important to understand its underlying mechanisms.

Respiratory research studies in animals have elucidated the chronological order of the pathological events and systemic responses inside the lung, but understanding the response of individual …

A Study On The Applications And Toxicity Assessments Of Carbon Nanotubes In Tissue Engineering, Rena Baktur

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Carbon nanotubes (CNTs) are one of the most popular nanomaterials. There has been increasing interest in the development and applications of carbon nanotubes due to their huge potential in industrial and medical applications. Recent applications of carbon nanotubes include development of scaffolds and drug delivery systems. Despite rapidly emerging applications of CNTs, little is known about the impact of CNTs on cellular processes, especially mesenchymal stem cell (MSC)'s differentiation. Also, the effects of nanoparticle exposure under different conditions on cellular responses have not been well characterized yet.

To characterize the effects of CNTs on creating nanoscale scaffolds for tissue engineering, …

Selective Biochlorination Of Hydroxyquinolines By A Flavin-Dependent Halogenase, Fuchao Xu, Amanda Merkley, Dayu Yu, Jixun Zhan

Biological Engineering Faculty Publications

Rdc2 is a flavin-dependent halogenase from Pochonia chlamydosporia. Through the introduction of a His₆-tag to both the N- and C-termini, the isolation yield of Rdc2 from Escherichia coli using Ni-NTA affinity chromatography was increased by three-fold. In vitro reaction of Rdc2 and a flavin reductase (Fre) with seven different hydroxyquinolines revealed that 3-hydroxyquinoline (3), 5-hydroxyquinoline (5), 6-hydroxyquinoline (6), and 7-hydroxyquinoline (7) can be specifically halogenated. These products were prepared by incubating the corresponding substrates with IPTG-induced E. coli BL21(DE3)/Rdc2. They were respectively characterized as 3-hydroxy-4-chloroquinoline (3a), 5-hydroxy-6-chloroquinoline (5a), 5-chloro-6-hydroxyquinoline (6a), and 7-hydroxy-8-chloroquinoline (7a) by NMR and MS …

The Hypericum Perforatum Herb As An Antimycobacterial Agent And Its Implications As An Additional Tuberculosis Medication, Trent W. Mortensen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

An immediate demand exists for new tuberculosis (TB) antibiotics due to the ever-increasing spread of drug-resistant strains. The drug-development process goes through four phases, the first (Phase 0) of which is to demonstrate and investigate drug effectiveness and toxicity. This research investigated the effectiveness of the Hypericum perforatum herb (commonly St. John's wort (SJW)) in its growth inhibition of mycobacteria and its viability effect on human lung cells.

Organic-solvent SJW extracts were effective at inhibiting every nonpathogenic genetically sequenced Mycobacterium isolate currently available (six isolates) in preliminary studies. Quantitative studies of five Mycobacterium isolates showed an order of concentration sensitivity …

A Synthetic Biological Engineering Approach To Secretion- Based Recovery Of Polyhydroxyalkanoates And Other Cellular Products, Elisabeth Linton

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The costs associated with cellular product recovery commonly account for as much as 80% of the total production expense. As a specific example, significant recovery costs limit commercial use of polyhydroxyalkanoates (PHA), which comprise a class of microbially-accumulated polyesters. PHAs are biodegradable compounds that are of interest as a sustainable alternative to petrochemically-derived plastics. Secretion-based recovery of PHAs was studied to decrease PHA production costs. Type I and II secretory pathways are commonly used for the translocation of recombinant proteins out of the cytoplasm of E. coli. Proteins were targeted for translocation using four signal peptides (HlyA, TorA, GeneIII, …

Designing An Instrument Based On Native Fluorescence To Determine Soil Microbial Content At A Mars Analog Site, Heather D. Smith

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

For this research project we designed an instrument to detect bacteria via biomolecular fluorescence. We introduce the current understanding of astrobiology, our knowledge of life beyond Earth, and the commonality of Earth life as it pertains to the search for life on Mars. We proposed a novel technique for searching for direct evidence of life on the surface of Mars using fluorescence. We use the arid region of the Mojave Desert as an analog of Mars. Results indicate the fluorescence of the biotic component of desert soils is approximately as strong as the fluorescence of the mineral component. Fluorescence laboratory …

Inducing A Normal Phenotype In Breast Epithelial Cells Using A Three-Dimensional Basement Membrane Extract Culture System: A Study On The Reversion Of Cancer, Ross H. Booth

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Experimentally, traditional developmental models and transgenic animals consistently underscore the importance of studying cell behavior in the correct tissue context. However, live animal experimentation is inherently complex, and systematic assessment of the effects of individual variables, such as cell shape and matrix compliance on cell behavior, is extremely difficult at best. Two-dimensional monolayer culture of key individual cell types has provided abundant, fundamental information on cell response, but cannot be used to show the normal phenotype of breast epithelial cells. Furthermore, their results often fail to translate into in vivo and clinical studies. It has been previously established that normal …

Evapotranspiration Using A Satellite-Based Surface Energy Balance With Standardized Ground Control, Ricardo Trezza

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This study evaluated the potential of using the Surface Energy Balance Algorithm for Land (SEBAL) as a means for estimating evapotranspiration (ET) for local and regional scales in Southern Idaho. The original SEBAL model was refined during this study to provide better estimation of ET in agricultural areas and to make more reliable estimates of ET from other surfaces as well, including mountainous terrain. The modified version of SEBAL used in this study, termed as SEBAL_ID (lD stands for Idaho) includes standardization of the two SEBAL "anchor" pixels, the use of a water balance …