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The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth LeBegue 2019 University of South Carolina

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to ...


Interfacial Stress In The Development Of Biologics: Fundamental Understanding, Current Practice, And Future Perspective, Jinjiang Li, Mary E. Krause, Xiaodong Cheng, Yuan Cheng, Weiguo Dai, John J. Hill, Min Huang, Susan Jordan, Daniel LaCasse, Linda Narhi, Evgenyi Shalaev, Ian C. Shieh, Justin C. Thomas, Raymond Tu, Songyan Zheng, Lily Zhu 2019 Wolfe Labs

Interfacial Stress In The Development Of Biologics: Fundamental Understanding, Current Practice, And Future Perspective, Jinjiang Li, Mary E. Krause, Xiaodong Cheng, Yuan Cheng, Weiguo Dai, John J. Hill, Min Huang, Susan Jordan, Daniel Lacasse, Linda Narhi, Evgenyi Shalaev, Ian C. Shieh, Justin C. Thomas, Raymond Tu, Songyan Zheng, Lily Zhu

Publications and Research

Biologic products encounter various types of interfacial stress during development, manufacturing, and clinical administration. When proteins come in contact with vapor–liquid, solid–liquid, and liquid–liquid surfaces, these interfaces can significantly impact the protein drug product quality attributes, including formation of visible particles, subvisible particles, or soluble aggregates, or changes in target protein concentration due to adsorption of the molecule to various interfaces. Protein aggregation at interfaces is often accompanied by changes in conformation, as proteins modify their higher order structure in response to interfacial stresses such as hydrophobicity, charge, and mechanical stress. Formation of aggregates may elicit immunogenicity ...


Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan 2019 Temple University

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional ...


Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan 2019 Temple University

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential ...


Visual Contributions To Balance Control During Gait, Kyle Brozek 2019 University of Nebraska at Omaha

Visual Contributions To Balance Control During Gait, Kyle Brozek

Student Research and Creative Activity Fair

We propose to isolate the contributions of continuous OF to the orthogonal relationship between balance and gait control during treadmill walking using a series of conditions. Manipulating the direction of OF using a CAREN (Motek Medical, Amsterdam, Netherlands) virtual reality treadmill environment will isolate these visual contributions in human subjects as they walk. We plan to tease out the effect of OF direction on the relationship between gait and balance control by having healthy young adults perform a series of treadmill walking trials while immersed in a VR environment. This will be done by manipulating the direction of walking and ...


Day To Day And Leg To Leg Variation In Gene Expression, Zohal Alizai 2019 University of Nebraska at Omaha

Day To Day And Leg To Leg Variation In Gene Expression, Zohal Alizai

Student Research and Creative Activity Fair

BACKGROUND: Skeletal muscle biopsies are extensively used in research to determine the effects of exercise. Usually, sequential biopsies are taken before and after exercise in order to determine the influence of exercise on gene expression. Often it is not clear if the results are due to exercise or as a result of damage cause by the biopsy to the muscle. Previous studies have proven that multiple biopsies in the same leg cause stress to the muscle and such stress leads to inflammation and other response pathways that alter the gene expression. PURPOSE: The purpose of this study is to determine ...


Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao 2019 Southern Methodist University

Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an ...


Heterodera Glycines Utilizes Promiscuous Spliced Leaders And Demonstrates A Unique Preference For A Species-Specifc Spliced Leader Over C. Elegans Sl1, Stacey N. Barnes, Rick E. Masonbrink, Tom R. Maier, Arun S. Seetharam, Anoop S. Sindhu, Andrew J. Severin, Thomas J. Baum 2019 Iowa State University

Heterodera Glycines Utilizes Promiscuous Spliced Leaders And Demonstrates A Unique Preference For A Species-Specifc Spliced Leader Over C. Elegans Sl1, Stacey N. Barnes, Rick E. Masonbrink, Tom R. Maier, Arun S. Seetharam, Anoop S. Sindhu, Andrew J. Severin, Thomas J. Baum

Office of Biotechnology Publications

Spliced leader trans-splicing (SLTS) plays a part in the maturation of pre-mRNAs in select species across multiple phyla but is particularly prevalent in Nematoda. The role of spliced leaders (SL) within the cell is unclear and an accurate assessment of SL occurrence within an organism is possible only after extensive sequencing data are available, which is not currently the case for many nematode species. SL discovery is further complicated by an absence of SL sequences from high-throughput sequencing results due to incomplete sequencing of the 5'-ends of transcripts during RNA-seq library preparation, known as 5'-bias. Existing datasets and ...


Identification And Characterization Of Barrier Insulator Activity In The T-Cell Receptor Alpha Locus Control Region, Gayathri Devi Raghupathy 2019 The Graduate Center, City University of New York

Identification And Characterization Of Barrier Insulator Activity In The T-Cell Receptor Alpha Locus Control Region, Gayathri Devi Raghupathy

All Dissertations, Theses, and Capstone Projects

Genes of different spatiotemporal expression profiles are often juxtaposed in the genome. This organization raises risks of cross-regulatory influences from neighboring genes; for instance heterochromatin can spread over euchromatin or long-range acting enhancers can inappropriately activate genes. Gene regulatory elements such as Locus Control Regions (LCR) and Insulators prevent such cross-communications and allow for normal gene expression patterns. In transgenic systems, LCRs limit influences from surrounding chromatin by providing site-of-integration independent and specific spatiotemporal expression upon a linked transgene. The field’s understanding of the ability of an LCR to overcome chromatin influences and allow site-of-integration independent expression is minimal ...


Industry Spotlight: Medical Devices, Evan D. Poff 2019 Brigham Young University

Industry Spotlight: Medical Devices, Evan D. Poff

Marriott Student Review

Medical devices restore and even redefine health. This Industry Spotlight examines pre-market barriers, medtech business model quirks, current and future developments in the field, and the present-day move to value-based care in the medical device industry.


Characterization And Optimization Of Parylene-C Deposition Process Using Scs Parylene Coater, Hannah Hastings, Eric D. Johnston, Gyuseok Kim 2019 Singh Center for Nanotechnology

Characterization And Optimization Of Parylene-C Deposition Process Using Scs Parylene Coater, Hannah Hastings, Eric D. Johnston, Gyuseok Kim

Tool Data

Parylene-C has been deposited on bare Si wafers by physical vapor deposition using the SCS Coating Systems. Results show a 12 µm thick Parylene-C film with 10 g of dimer and negligible thickness variation across a wafer. We find a positive linear relationship between film thickness and mass of dimer at a range of 1 g to 18 g. However, the Al boat for dimer was burnt with 18 g of dimer, suggesting multiple depositions with 1 g to 10 g of dimer are recommended to achieve the Parylene-C film thicker than 12 µm.


Biotechnological Application In Aquaculture And Its Sustainability Constraints, Olaganathan Rajee, Tang Kar Mun Alicia 2019 Embry-Riddle Aeronautical University

Biotechnological Application In Aquaculture And Its Sustainability Constraints, Olaganathan Rajee, Tang Kar Mun Alicia

Publications

The valuable nutritional and biochemical properties have made fisheries products one of the most vital high-quality protein sources for human consumption. Aquaculture has become the great alternative to substitute wild catches when the yield from fishing are no longer sufficient to sustain the massive food demand of the human population which is constantly burgeoning. However, aquaculture requires multidisciplinary approaches with holistic and environmental-friendly management measures to ensure its long term success and sustainability. Biotechnological applications have enhanced the effectiveness and cost-efficiencies of aquaculture by augmenting the productivity of aquaculture to meet global needs. Despite the benefits, the biotechnological application in ...


Strain-Specific Protein Interaction And Localization Of Two Strains Of Potato Yellow Dwarf Virus And Functional Domains Of Their Matrix Protein, Chanyong Jang 2019 University of Kentucky

Strain-Specific Protein Interaction And Localization Of Two Strains Of Potato Yellow Dwarf Virus And Functional Domains Of Their Matrix Protein, Chanyong Jang

Theses and Dissertations--Plant Pathology

Potato yellow dwarf virus (PYDV) is the type species of the genus nucleorhabdovirus which is typified by its nucleotropic characters of the members. The virus accomplishes its replication and morphogenesis in the nuclei of infected cells. Two strains, Constricta strain (CYDV) and Sanguinolenta strain (SYDV) have been described at the level of vector-specificity. CYDV is vectored by Agallia constricta and SYDV is transmitted by Aceratagllia sanguinolenta. The full-length genome of CYDV was sequenced. The 12,792 nt antisense genome encodes seven open reading frames in the order of, nucleocapsid protein (N), unknown protein (X), phosphoprotein (P), movement protein (Y), matrix ...


The Small Rna Teg41 Regulates Expression Of The Alpha Phenol-Soluble Modulins And Is Required For Virulence In Staphylococcus Aureus, Rachel L. Zapf, Richard E. Wiemels, Rebecca A. Keogh, Donald L. Holzschu, Kayla M. Howell, Emily Trzeciak, Andrew R. Caillet, Kellie A. King, Samantha A. Selhorst, Michael J. Naldrett, Jeffrey L. Bose, Ronan K. Carroll 2019 Ohio University

The Small Rna Teg41 Regulates Expression Of The Alpha Phenol-Soluble Modulins And Is Required For Virulence In Staphylococcus Aureus, Rachel L. Zapf, Richard E. Wiemels, Rebecca A. Keogh, Donald L. Holzschu, Kayla M. Howell, Emily Trzeciak, Andrew R. Caillet, Kellie A. King, Samantha A. Selhorst, Michael J. Naldrett, Jeffrey L. Bose, Ronan K. Carroll

Papers from the Nebraska Center for Biotechnology

Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general and in Gram-positive bacteria in particular. In the major human pathogen Staphylococcus aureus, hundreds of sRNAs have been identified; however, only a few have been characterized in detail. In this study, we investigate the role of the sRNA Teg41 in S. aureus virulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenolsoluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic ...


The Ethics Of Big Data In Genomics: The Instructive Icelandic Saga Of The Incidentalome, Donna M. Gitter 2019 Baruch College, Zicklin School of Business, City University of New York

The Ethics Of Big Data In Genomics: The Instructive Icelandic Saga Of The Incidentalome, Donna M. Gitter

Washington University Global Studies Law Review

DeCODE Genetics, Inc., a pioneering Icelandic biotech firm, recently introduced a free website that permits Icelanders to learn whether they carry mutations in the BRCA2 gene that are known to increase cancer risk, even if these citizens have never participated in genetic testing. Approximately five thousand Icelanders have elected thus far to receive their status. This site is made possible by the consanguinity of Icelandic citizens, who number fewer than 350,000, and their detailed genealogical records dating back centuries, a set of circumstances that presents a unique opportunity to study genetic mutations and the medical disorders associated with them ...


Looking For Maize Genes Involved In Cold Response: Producing Knockouts For Arabidopsis Homologs Of Maize Candidate Genes Using A Crispr/Cas9 Approach, Katie Hillmann 2019 Hamline University

Looking For Maize Genes Involved In Cold Response: Producing Knockouts For Arabidopsis Homologs Of Maize Candidate Genes Using A Crispr/Cas9 Approach, Katie Hillmann

Departmental Honors Projects

Most of today’s maize is cultivated outside its original climate zone, where yields are constrained by the changes in climate. Maize is especially vulnerable to high temperatures and drought stress, both of which negatively affect corn yields. An important strategy to combat this is early sowing, which avoids the effects of summer droughts and high temperatures in many places around the globe. However, maize is a cold sensitive species (Sanghera et al., 2011), making improvement to cold stress crucial for its adaption. The relatively new system CRISPR (Clustered regularly-interspaced short palindromic repeats)/Cas9 offers the potential to study cold-stress ...


Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr. 2019 Liberty University

Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr.

Senior Honors Theses

Therapeutic delivery technology is a current area of high interest in both university and industrial settings. These technologies are being developed in order to deliver therapeutic agents, such as genes, proteins, and drugs, to patients more efficiently. Nanoscale delivery vehicles have proven to be useful for these applications; these vehicles may either be naturally produced or chemically synthesized. The physical properties of these nanomaterials must be characterized correctly using instrumentation that evaluates their size, morphology, and potential for agglomeration. These technologies represent a high-growth economic area that fosters entrepreneurship and innovation. Because of this innovative spirit, research and economic interest ...


Field Evaluation Of Tobacco Engineered For High Leaf-Oil Accumulation, James Perry 2019 University of Kentucky

Field Evaluation Of Tobacco Engineered For High Leaf-Oil Accumulation, James Perry

Theses and Dissertations--Plant and Soil Sciences

The biofuel market is dominated by ethanol and biodiesel derived from cellulosic and lipid-based biomass crops. This is largely due to the relatively low costs and reliability of production. At present, production of non-food plant-derived oils for biofuel production in the U.S. is minimal. A research team from the Commonwealth Scientific and Industrial Research Organization (CSIRO), an independent Australian federal government research institution, has developed an efficient transgenic system to engineer oil production in tobacco leaves. This novel system is comprised of multiple transgenes that direct the endogenous metabolic flux of oil precursors towards triacylglycerol (TAG) production. Additional genes ...


Terpene Synthase Genes Originated From Bacteria Through Horizontal Gene Transfer Contribute To Terpenoid Diversity In Fungi, Qidong Jia, Xinlu Chen, Tobias G. Kollner, Jan Rinkel, Jianyu Fu, Jessy Labbe, Wangdan Xiong, Jeroen S. Dickschat, Jonathan Gershenzon, Feng Chen 2019 University of Nebraska - Lincoln

Terpene Synthase Genes Originated From Bacteria Through Horizontal Gene Transfer Contribute To Terpenoid Diversity In Fungi, Qidong Jia, Xinlu Chen, Tobias G. Kollner, Jan Rinkel, Jianyu Fu, Jessy Labbe, Wangdan Xiong, Jeroen S. Dickschat, Jonathan Gershenzon, Feng Chen

Papers from the Nebraska Center for Biotechnology

Fungi are successful eukaryotes of wide distribution. They are known as rich producers of secondary metabolites, especially terpenoids, which are important for fungi-environment interactions. Horizontal gene transfer (HGT) is an important mechanism contributing to genetic innovation of fungi. However, it remains unclear whether HGT has played a role in creating the enormous chemical diversity of fungal terpenoids. Here we report that fungi have acquired terpene synthase genes (TPSs), which encode pivotal enzymes for terpenoid biosynthesis, from bacteria through HGT. Phylogenetic analysis placed the majority of fungal and bacterial TPS genes from diverse taxa into two clades, indicating ancient divergence. Nested ...


Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori 2019 Old Dominion University

Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori

Bioelectrics Publications

Accumulating data indicates that some cancer treatments can restore anticancer immunosurveillance through the induction of tumor immunogenic cell death (ICD). Nanosecond pulsed electric fields (nsPEF) have been shown to efficiently ablate melanoma tumors. In this study we investigated the mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Our data show that in vitro nsPEF (20-200, 200-ns pulses, 7 kV/cm, 2 Hz) caused a rapid dose-dependent cell death which was not accompanied by caspase activation or PARP cleavage. The lack of nsPEF-induced apoptosis was confirmed in vivo in B16F10 tumors. NsPEF also failed to trigger ICD-linked responses ...


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