Digital Commons Network^™

Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang

Journal Articles

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and …

Laboratory Management Models In Core Facilities, Karmen Michael Owen

Theses and Dissertations

Core biotechnology facilities are often defined as laboratories that house shared resources for research. These laboratories are of great importance to research communities because a large portion of scientific research data is generated at these facilities. Different investigators can use core facilities to help further their research. In a university setting, there are several management strategies from small cores that house a specific type of instrument, to large cores that house many different technologies. Funding strategies also differ significantly, from those that are funded by a small group of well-funded investigators, to cores managed by a specific department or school, …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Journal Articles

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Algorithmic Bias: Causes And Effects On Marginalized Communities, Katrina M. Baha

Undergraduate Honors Theses

Individuals from marginalized backgrounds face different healthcare outcomes due to algorithmic bias in the technological healthcare industry. Algorithmic biases, which are the biases that arise from the set of steps used to solve or analyze a problem, are evident when people from marginalized communities use healthcare technology. For example, many pulse oximeters, which are the medical devices used to measure oxygen saturation in the blood, are not able to accurately read people who have darker skin tones. Thus, people with darker skin tones are not able to receive proper health care due to their pulse oximetry data being inaccurate. This …

The Contribution Of Ethical Governance Of Artificial Intelligence & Machine Learning In Healthcare, Tina Nguyen

Electronic Theses and Dissertations

With the Internet Age and technology progressively advancing every year, the usage of Artificial Intelligence (AI) along with Machine Learning (ML) algorithms has only increased since its introduction to society. Specifically, in the healthcare field, AI/ML has proven to its end-users how beneficial its assistance has been. However, despite its effectiveness and efficiencies, AI/ML has also been under scrutiny due to its unethical outcomes. As a result of this, two polarizing views are typically debated when discussing AI/ML. One side believes that AI/ML usage should continue regardless of its unsureness, while the other side argues that this technology is too …

Bioactive Peptides From Algae: Traditional And Novel Generation Strategies, Structure-Function Relationships, And Bioinformatics As Predictive Tools For Bioactivity, Jack O'Connor, Marco Garcia-Vaquero, Steve Meaney, Brijesh Kumar Tiwari

Articles

Over the last decade, algae have been explored as alternative and sustainable protein sources for a balanced diet and more recently, as a potential source of algal-derived bioactive peptides with potential health benefits. This review will focus on the emerging processes for the generation and isolation of bioactive peptides or cryptides from algae, including: (1) pre-treatments of algae for the extraction of protein by physical and biochemical methods; and (2) methods for the generation of bioactive including enzymatic hydrolysis and other emerging methods. To date, the main biological properties of the peptides identified from algae, including anti-hypertensive, antioxidant and antiproliferative/ …

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

The Mrna-Lnp Platform's Lipid Nanoparticle Component Used In Preclinical Vaccine Studies Is Highly Inflammatory, Sonia Ndeupen, Zhen Qin, Sonya Jacobsen, Aurélie Bouteau, Henri Estanbouli, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of …

China’S Strategies For Governance Of Biotechnological Changes And New Ethical Challenges, Yaojin Peng, Zhou Qi

Bulletin of Chinese Academy of Sciences (Chinese Version)

Biotechnology is changing greatly over recent years, providing huge benefits to human society. However, the ethics, safety, and negative externalities of biotechnology have become increasingly prominent. Currently, biotechnology is still in the early stage of development, and full of high uncertainty. Technological changes in this field have the characteristics of stronger subversiveness, complexity, and social relevance. The world is facing a process of great development of biotechnology, new outbreaks of ethical challenges, and ethical governance reforms. China should take this opportunity to promote the high-quality development of biotechnology on the one hand, and on the other hand, adopt a multi-pronged …

Transcatheter Mitral Valve Replacement And Repair Technology, Joel Thomas

Senior Honors Theses

The mitral valve is a two-cusp valve that is located between the left atrium and left ventricle of the heart. As blood flows from the lungs and enters the atrium, it must pass through this valve in one direction to enter the ventricle and be pumped out to the systemic circuit.

Mitral valve disease occurs when normal mitral valve function is impaired. Many different repair and replacement options exist. These options are contingent upon age and risk factors for patients. This paper focuses on the four main transcatheter mitral valve replacement devices that have limited human trials. It concludes that …

Characterization Of Dental Pulp Stem Cell Responses To Functional Biomaterials Including Mineralized Trioxide Aggregates, Sejin Bae, Bueonguk Kang, Hyungbin Lee, Harrison Luu, Eric Mullins, Karl Kingsley

Dental Medicine Faculty Publications

Introduction: Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo growth, viability, and proliferation, as well as differentiation of DPSC-although much remains to be discovered. Based upon this information, the primary objective of this study was to understand the functional biomaterials needed to more effectively direct DPSC viability, growth, and proliferation. Methods: Using an approved protocol, previously collected and isolated samples of DPSC from an …

Building New Organs With Tissue Engineering Bps 208g, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Genomic Variations In Patients With Myelodysplastic Syndrome And Karyotypes Without Numerical Or Structural Changes, Cristiano Luiz Ribeiro, Irene P. Pinto, Samara S. S. Pereira, Lysa B. Minasi, Fernanda De S. M. Kluthcouski, Adriano De M. Arantes, Aparecido D. Cruz, Marcio Almeida, Tom E. Howard

School of Medicine Publications and Presentations

Myelodysplastic syndrome (MDS) is an onco-hematologic disease with distinct levels of peripheral blood cytopenias, dysplasias in cell differentiation and various forms of chromosomal and cytogenomic alterations. In this study, the Chromosomal Microarray Analysis (CMA) was performed in patients with primary MDS without numerical and/or structural chromosomal alterations in karyotypes. A total of 17 patients was evaluated by GTG banding and eight patients showed no numerical and/or structural alterations. Then, the CMA was carried out and identified gains and losses CNVs and long continuous stretches of homozygosity (LCSHs). They were mapped on chromosomes 1, 2, 3, 4, 5, 6, 7, 9, …

Comparing Long-Term Value Creation After Biotech And Non-Biotech Ipos, 1997–2016, Ekaterina Galkina Cleary, Laura M. Mcnamee, Skyler De Boer, Jeremy Holden, Liam Fitzgerald, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

We compared the financial performance of 319 BIOTECH companies focused on developing therapeutics with IPOs from 1997–2016, to that of paired, non-biotech CONTROL companies with concurrent IPO dates. BIOTECH companies had a distinctly different financial structure with high R&D expense, little revenue, and negative profits (losses), but a similar duration of listing on public markets and frequency of acquisitions. Through 2016, BIOTECH and CONTROL companies had equivalent growth in market cap and shareholder value (> $100 billion), but BIOTECH companies had lower net value creation ($93 billion vs $411 billion). Both cohorts exhibited a high-risk/high reward pattern of return, with …

Late-Stage Product Development And Approvals By Biotechnology Companies After Initial Public Offering, 1997-2016, Laura M. M. Mcnamee, Ekaterina Galkina Cleary, Sunyi Zhang, Usama Salim, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Purpose: This work describes the late-stage product portfolios of the biotechnology companies that completed initial public offerings (IPOs) from 1997 to 2016. We asked whether these emerging companies continue to develop innovative, biologic products and produce the innovation promised by the early biotechnology industry.

Methods: We identified therapeutic products that reached Phase III development from 1997 to 2016, the characteristics of the products, the dates of the initiation of Phase III and product approval, proxy indicators of the innovativeness of each product, and the contribution of each biotechnology company. Companies were characterized by IPO window and clinical status of the …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Constitutionalizing Nature's Law: Dignity And The Regulation Of Biotechnology In Switzerland, James Toomey

Elisabeth Haub School of Law Faculty Publications

The Swiss Constitution was amended by referendum in 1992 to include two unique provisions: Article 119, which imposes strict limits on genetic and reproductive technologies in humans in order to protect ‘human dignity’, and Article 120, which commits the Swiss federal government to limiting genetic technologies in non-human species on the basis of the ‘dignity of the creature’. This article analyzes the role of ‘dignity’ as a limit on biotechnologies in the Swiss constitutional order. It concludes that the understanding of dignity the constitution embraces codifies a contestable metaphysical theory of value at the constitutional level. Specifically, the Swiss constitutional …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Faculty Publications

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise …

Cost-Effective Paper-Based Diagnostic Using Split Proteins To Detect Yeast Infections, Zachary R. Berglund, Kevin V. Solomon, Mohit S. Verma, Moiz Rasheed, Zachary Hartley, Kevin Fitzgerald, Kok Zhi Lee, Janice Chan, Julianne Dejoie, Makayla Schacht, Alex Zavala

The Summer Undergraduate Research Fellowship (SURF) Symposium

The common yeast infection, vulvovaginal candidiasis, affects three out of four women throughout their lifetime and can be spread to their child in the form of oral candidiasis (thrush). This disease is caused by the fungal pathogen Candida albicans, which is also a major cause of systemic candidiasis, a rarer but deadly disease with up to a 49% lethality rate. Current widely-used diagnostic methods include cell cultures, pH tests, and antibody detection, to assist effective treatment. Despite availability of various diagnostic methods, there is no inexpensive, rapid, and accurate way to detect C. albicans infection. This project aims to …

Where Trying To Conceive Becomes A Community Effort: A Digital Ethnography Of Online Infertility Forums, Megan Burns

Sociology Honors Papers

Online forums for women using in vitro fertilization (IVF), or similar assisted reproductive technologies (ARTs), provide a useful setting to further evaluate and understand women’s expectations of motherhood, the relationship infertile women have with physicians and biomedicine, and their interactions on the forums. Some critics of ARTs consider them a tool of oppression in a pronatalist state. The pressure and desire to become a biological mother leads the women with access to these technologies to use them regardless. Through digital ethnographic research on four online ART forums, this research examines the intersection of altruism and self-interest in the ways forum-users …

Coevolving Residues And The Expansion Of Substrate Permissibility In Laglidadg Homing Endonucleases, Thomas A. Mcmurrough

Electronic Thesis and Dissertation Repository

Genome-editing (GE) is a form of genetic engineering that permits the deliberate manipulation of genetic material for the study of biological processes, agricultural and industrial biotechnologies, and developing targeted therapies to cure human disease. While the potential application of GE is wide-ranging, the efficacy of most strategies is dependent upon the ability to accurately introduce a double-stranded break at the genomic location where alterations are desired. LAGLIDADG homing endonucleases (LHEs) are a class of mobile genetic element that recognize and cleave 22-bp sequences of DNA. Given this high degree of specificity, LHEs are powerful GE reagents, …

Improving The Thermal Stability Of Cellobiohydrolase Cel7a From Hypocrea Jecorina By Directed Evolution, Frits Goedegebuur, Lydia Dankmeyer, Peter Gualfetti, Saeid Karkehabadi, Henrik Hansson, Suvamay Jana, Vicky Huynh, Bradley R. Kelemen, Paulien Kruithof, Edmund A. Larenas, Pauline J. M. Teunissen, Jerry Ståhlberg, Christina M. Payne, Colin Mitchinson, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

Secreted mixtures of Hypocrea jecorina cellulases are able to efficiently degrade cellulosic biomass to fermentable sugars at large, commercially relevant scales. H. jecorina Cel7A, cellobiohydrolase I, from glycoside hydrolase family 7, is the workhorse enzyme of the process. However, the thermal stability of Cel7A limits its use to processes where temperatures are no higher than 50 °C. Enhanced thermal stability is desirable to enable the use of higher processing temperatures and to improve the economic feasibility of industrial biomass conversion. Here, we enhanced the thermal stability of Cel7A through directed evolution. Sites with increased thermal stability properties were combined, and …

Consumer Knowledge, Perception And Attitudes Of Unlabeled Genetically Modified Foods Of An Educated Population In The State Of Kentucky, Aldious A. Waite

Masters Theses & Specialist Projects

Genetically modified (GM) foods technology is a novel idea for improving food and crop production, but the supposed health risk of GM foods, such as possible negative long-term health effects to humans, animals and the environment, have provoked the European Union to create assessment protocols to monitor and regulate the safety of GM foods and crops. This research investigates the perception and attitudes of unlabeled GM foods of the WKU faculty and staff. A survey was administered via WKU Qualtrics, and chi-square tests were performed to see how the benefits and disadvantages of GM foods may affect the purchasing decisions …

Crispr: The Last Piece Of The Genetic Puzzle, Brad Broyles

BU Well

CRISPR/Cas9 is an emerging gene editing tool. This technology, which evolved naturally as a defense mechanism for bacteria and other prokaryotes, has been repurposed to edit genes in a wide array of cells, including human cells. This paper outlines the discovery, mechanism, and potential applications of CRISPR/Cas9.

A Bioethics Tool For The Implementation Of Global Principles By The Pharmaceutical Industry, Daniel J. Hurst

Electronic Theses and Dissertations

Due to scandals of scientific misconduct, a climate of mistrust of science exists amongst the general public. This becomes of concern when we acknowledge that it is difficult for science and technology to flourish without broad societal trust. The pharmaceutical industry has often felt the brunt of such mistrust and has suffered many reputational setbacks over the past several years. Such reputational decline has a strong moral dimension, as it stems from issues such as the questionable conduct of clinical trials, pricing schemas, and access to medicines for low- or middle-income countries. The end product of such issues is the …

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, …

A Multi-Channel 3d-Printed Bioreactor For Evaluation Of Growth And Production In The Microalga Dunaliella Sp, Cristian A. Cox

Electronic Theses and Dissertations

We explored the capabilities of additive manufacturing using a photo-cured jetted material 3D printer to manufacture a milli-microfluidic device with direct application in microalgae Dunaliella sp growth and intracellular compounds biosynthesis tests. A continuous microbioreactor for microalgae culture was CAD designed and successfully built in 1 hour and 49 minutes using black photopolymer cured by UV and a support material. The microreactor was made up of 2 parts including the bioreactor itself and a microchannel network for culture media fluids and microalgae. Both parts were assembled to form a single unit. Additional optical and auxiliar components were added. An external …

Ethics, Drugs And Rock And Roll: On The Integration Of Bioethics Into The Entrepreneurial Life, Angela Rossetti

NYMC Faculty Publications

No abstract provided.

Decline In Ethical Concerns About Reproductive Technologies Among A Representative Sample Of Us Women, Arthur L. Greil, Kathleen S. Slauson-Blevins, Karina M. Shreffler, Katherine M. Johnson, Michele Lowry, Andrea R. Burch, Julia Mcquillan

Department of Sociology: Faculty Publications

Public awareness and utilization of assisted reproductive technology has been increasing, but little is known about changes in ethical concerns over time. The National Survey of Fertility Barriers, a national, probability-based sample of US women, asked 2031 women the same set of questions about ethical concerns regarding six reproductive technologies on two separate occasions approximately 3 years apart. At Wave 1 (2004–2007), women had more concerns about treatments entailing the involvement of a third party than about treatments that did not. Ethical concerns declined between Wave 1 and Wave 2, but they declined faster for treatments entailing the involvement of …