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Theses/Dissertations

2018

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Full-Text Articles in Biological Engineering

Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz Dec 2018

Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz

Graduate Theses and Dissertations

Biofiltration without pre-ozonation has the capability to remove natural organic matter (NOM) fractions that serve as precursors of disinfection byproducts (DBPs), which include the four regulated trihalomethanes (THMs) and dichloroacetonitrile (DCAN). Rapid small-scale column tests (RSSCTs) and Pilot Plant filters operated at empty-bed contact times (EBCTs) of 4, 8, and 16 minutes were used to evaluate the performance of nutrient-amended (free ammonia and phosphorus) biofiltration for THM and DCAN precursor removal, as measured using formation potential (FP) tests. NOM surrogates – which include dissolved organic carbon (DOC), specific ultraviolet absorbance (SUVA254) and fluorescence-PARAFAC components – were measured weekly throughout the …


Production And Biocompatibility Of Spider Silk Proteins In Goat Milk, Richard E. Decker Jr Dec 2018

Production And Biocompatibility Of Spider Silk Proteins In Goat Milk, Richard E. Decker Jr

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Due to its strength, flexibility, and biocompatibility, spider silk is a highly appealing material for applications in the medical field. Unfortunately, natural spider silk is difficult to obtain in large quantities because spiders are territorial and cannibalistic, making them impractical to farm. Synthetic spider silk proteins produced by transgenic hosts such as bacteria and goats have made it possible to obtain the quantities of spider silk needed to study it more fully and to investigate its potential uses. The spider silk proteins produced in our laboratory do not have an optimal purification method to remove all of the non-biocompatible contaminants …


Identification And Engineering Of Nonribosomal Peptide Biosynthetic Systems, Fuchao Xu Dec 2018

Identification And Engineering Of Nonribosomal Peptide Biosynthetic Systems, Fuchao Xu

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focuses on the understanding and engineering of nonribosomal peptide biosynthetic pathways in Streptomyces coelicolor CH999, Escherichia coli BAP1 and Saccharomyces cerevisiae BJ5464-NpgA. The biosynthetic systems of indigoidine from bacteria and beauvericin/bassianolide from fungi were studied in this research. The production of these valuble products was significantly increased by enhancing their synthetic pathway with metabolic engineering approaches.

Indigoidine is a bacterial natural product with antioxidant and antimicrobial activities. Its bright blue color resembles the industrial dye indigo, thus representing a new natural blue dye that may find uses in industry. Indigo is a dark blue crystalline powder and has …


Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz Nov 2018

Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz

Doctoral Dissertations

Breast cancer is plagued by two key clinical challenges; drug resistance and metastasis. Most work to date probes these events on an extremely rigid plastic surface, which recapitulates few aspects of these processes in humans. A malignant cell first resides in breast tissue, then likely travels to the bone, brain, liver, or lung, each of which has a distinct mechanical and biochemical profile. Cells transmit mechanical forces into intracellular tension and biochemical signaling events, and here we hypothesize that this mechanotransduction influences drug response, growth, and migration. To probe the impact of extracellular matrix on drug resistance, we defined a …


Microfluidic Electrical Impedance Spectroscopy, John J. Foley Sep 2018

Microfluidic Electrical Impedance Spectroscopy, John J. Foley

Master's Theses

The goal of this study is to design and manufacture a microfluidic device capable of measuring changes in impedance valuesof microfluidic cell cultures. Tocharacterize this, an interdigitated array of electrodes was patterned over glass, where it was then bonded to a series of fluidic networks created in PDMS via soft lithography. The device measured ethanol impedance initially to show that values remain consistent over time. Impedance values of water and 1% wt. saltwater were compared to show that the device is able to detect changes in impedance, with up to a 60% reduction in electrical impedance in saltwater. Cells were …


Studying The Applicability Of Biostimulated Calcite Precipitation In Stabilizing Expansive Soils, Md Touhidul Islam Aug 2018

Studying The Applicability Of Biostimulated Calcite Precipitation In Stabilizing Expansive Soils, Md Touhidul Islam

Boise State University Theses and Dissertations

Of the four types of soils, clays are often associated with issues related to low bearing capacity, high compressibility, swelling and shrinking nature. For example, expansive soils swell and shrink with moisture ingress and digress and are prevalent in several parts of the world causing billions of dollars in damages annually to various civil infrastructures. Several ground improvement techniques such as chemical stabilization, deep soil mixing, moisture barriers, and others were employed to counteract these soils. However, these methods are impractical in certain situations and unsustainable in others due to their economic and environmental impacts. Microbiological treatment of soils could …


Development And Characterization Of Aqueous-Based Recombinant Spider Silk Protein Biomaterials With Investigations Into Potential Applications, Thomas I. Harris Aug 2018

Development And Characterization Of Aqueous-Based Recombinant Spider Silk Protein Biomaterials With Investigations Into Potential Applications, Thomas I. Harris

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Spider silks are incredible natural materials that possess desirable combinations of strength, elasticity, weight, and robustness. Other properties such as biocompatibility and biodegradability further increase the worth of these materials. The possibility of farming spiders is impractical due to spiders’ natural behaviors. Modern biotechnologies have allowed for recombinant spider silk proteins (rSSps) to be produced without the use of spiders. However, the features responsible for spider silks impressive properties can cause difficulties with producing silk materials. A recently developed water-based and biomimetic solvation method has provided a solution to such difficulties and has also led to novel silk biomaterials. Most …


Biomass And Phycocyanin From Oil And Natural Gas Extraction Produced Water Utilizing A Cyanobacteria Dominated Rotating Algal Biofilm Reactor (Rabr), Jonathan L. Wood Aug 2018

Biomass And Phycocyanin From Oil And Natural Gas Extraction Produced Water Utilizing A Cyanobacteria Dominated Rotating Algal Biofilm Reactor (Rabr), Jonathan L. Wood

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The production of cyanobacterial biofilm biomass and phycocyanin from Rotating Algal Biofilm Reactors utilizing undiluted produced water from oil and natural gas extraction as a culture medium was investigated in this study. Produced water is the largest waste stream generated by the oil and natural gas industries and represents a large volume of non-potable water that may be available for algae culture with minimal impact on freshwater resources. Combining the use of produced wastewater as culture medium with the production of high value algal pigments, such as phycocyanin, may increase the economic viability of algae culture and wastewater purification. High …


Development And Optimization Of A Produced Water, Biofilm Based Microalgae Cultivation System For Biocrude Conversion With Hydrothermal Liquefaction, Benjamin L. Peterson Aug 2018

Development And Optimization Of A Produced Water, Biofilm Based Microalgae Cultivation System For Biocrude Conversion With Hydrothermal Liquefaction, Benjamin L. Peterson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Extraction of oil and gas in Utah’s Uintah Basin results in large quantities of wastewater, or produced water, with nutrients and residual organic chemical that represent a significant resource for producing energy-related and value-added products. Produced water was obtained as a biomass producing nutrient source from industries operating in Utah’s Uintah Basin. Within the Uintah Basin (defined as Uintah and Duchesne Counties within Utah) approximately 93 million barrels of water were produced in 2013 while only 11% of the water was disposed of through evaporation, with the national average at 2%. The rest is reinjected into the subsurface.

The goal …


Novel Methods To Produce Large Recombinant Spider Silk Proteins Via Polymerization, Nathan L. Hebert Aug 2018

Novel Methods To Produce Large Recombinant Spider Silk Proteins Via Polymerization, Nathan L. Hebert

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Spider silk has long been a subject of scientific research due to its remarkable mechanical properties. Until recently, there has been no way to effectively obtain spider silk except by harvesting it from individual spiders. With advances in technology, the genes that code for the individual spider silk proteins have been isolated and genetically engineered into other hosts to produce recombinant spider silk proteins (rSSp) of varying sizes, Larger rSSp have correspondingly greater mechanical properties in any resulting materials. Using current production methods, larger rSSp cannot be produced in commercially viable quantities while simultaneously being economically viable. The current production …


Evaluation Of A Solar Powered Variable Flow Tail Water Recovery System For Furrow Irrigation, Vaishali Kandpal Aug 2018

Evaluation Of A Solar Powered Variable Flow Tail Water Recovery System For Furrow Irrigation, Vaishali Kandpal

Graduate Theses and Dissertations

Furrow irrigation is a very common irrigation method for growing crops like soybean, cotton and corn in Arkansas. A major portion of this irrigation water is lost as runoff from the field significantly reducing the irrigation application efficiency. There are various methods of improving irrigation efficiency and one of the methods is using tail-water recovery. A tail-water recovery system utilizes tail-water recovery ditches or pits to collect tail-water which can be re-used for irrigation. However, this method is very labor intensive and has been found to be economically non-feasible for some farms in the past research studies. In order to …


Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund Jul 2018

Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund

Doctoral Dissertations

The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …


Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora Jul 2018

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …


Comparative Analysis Of Physiological Measurements And Environmental Metrics On Predicting Heat Stress Related Events, Mckenzie Lee Barlow Jun 2018

Comparative Analysis Of Physiological Measurements And Environmental Metrics On Predicting Heat Stress Related Events, Mckenzie Lee Barlow

Master's Theses

Exposure to high heat and humidity can lead to serious health risks, including heat exhaustion and heat stroke. Wet Bulb Globe Temperature (WBGT) and heat index have historically been used to predict heat stress events, but individualized factors are not included in the measurement. It has been shown that there is a relationship between cardiovascular measurements and heat stress, which could be used to measure heat stress risk on an individual level. Research has been done to find relationships between cardiovascular metrics in a workplace environment, however the study did not include the use of a controlled environment as a …


Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender May 2018

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …


Nutrient Limitation Of Algal Growth In Fishery Lakes, Madeline Ludwig May 2018

Nutrient Limitation Of Algal Growth In Fishery Lakes, Madeline Ludwig

Biological and Agricultural Engineering Undergraduate Honors Theses

This study investigated the effect of nutrient addition on algal growth in three United States Forest Service lakes for fishery management in Arkansas. In fishery managed lakes, fertilization works by manipulating algae growth, a basal food resource in lakes, to promote the growth of the fish population. For the nutrient addition experiments, water was collected from each lake in cubitainers and spiked with nutrients; the treatments included the control, nitrogen (+N), phosphorus (+P), and nitrogen and phosphorus (+N +P). When algal growth was visually observed, a water sample was collected from each cubitainer and analyzed for chlorophyll-α. The results showed …


In-Cage Surface Wetting System For Cooling Poultry In Transport, Ryan Clark May 2018

In-Cage Surface Wetting System For Cooling Poultry In Transport, Ryan Clark

Biological and Agricultural Engineering Undergraduate Honors Theses

Abstract

Poultry health and mortality rates are important considerations in poultry production, as companies can minimize product loss and appeal to a consumer base whose concern for animal welfare continues to grow. Although animal welfare is a consideration for the entire poultry production process, this project focuses on the live-haul phase of the process, specifically during transport from grow houses to processing facilities. During the summer months, broiler chickens being transported can suffer from heat stress that can lead to death. This project consists of the designing and testing of an in-cage surface wetting system to minimize heat stress incidents …


Silane Modulation Of Protein Conformation And Self-Assembly, Abul Bashar Mohammad Giasuddin May 2018

Silane Modulation Of Protein Conformation And Self-Assembly, Abul Bashar Mohammad Giasuddin

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focused on development of nanoparticle- based therapeutics against amyloid fibrils. Amyloid fibrils are associated with various diseases such as Parkinson’s, Huntington’s, mad cow disease, Alzheimer’s, and cataracts. Amyloid fibrils develop when proteins change their shape from a native form to a pathogenic “misfolded” form. The misfolded proteins have the ability to recruit more native proteins into the pathogenic forms, which self-assemble into amyloid fibrils that are hallmarks of the various protein-misfolding diseases listed above. Amyloid fibrils are highly resistant to degradation, which may contribute to the symptoms of amyloid diseases. Synthetic drugs, natural compounds, and antibodies are widely …


The Use Of Microfluidics And Dielectrophoresis For Separation, Concentration, And Identification Of Bacteria, Cynthia Hanson May 2018

The Use Of Microfluidics And Dielectrophoresis For Separation, Concentration, And Identification Of Bacteria, Cynthia Hanson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Typical bacterial analysis involves culturing and visualizing colonies on an array of agar plates. The growth patterns and colors among the array are used to identify the bacteria. For fast growing bacteria such as Escherichia coli, analysis will take one to two days. However, slow growing bacteria such as mycobacteria can take weeks to identify. In addition, there are some species of bacteria that are viable but nonculturable. This lengthy analysis time is unacceptable for life-threatening infections and emergency situations. It is clear that to decrease the analysis of the bacteria, the culturing and growth steps must be avoided. …


Investigations Of Polyhydroxyalkanoate Secretion And Production Using Sustainable Carbon Sources, Chad L. Nielsen May 2018

Investigations Of Polyhydroxyalkanoate Secretion And Production Using Sustainable Carbon Sources, Chad L. Nielsen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Polyhydroxyalkanoates (PHAs) are a type of biologically-produced plastic known for their biocompatibility and biodegradability. They have the potential to replace petroleum-based plastics as an environmentally-friendly alternative. This is beneficial because the release of plastics into environments such as the ocean and the buildup of plastics in landfills are major concerns facing society today. Currently, however, PHAs are significantly more expensive than their petroleum-based counterparts. This is largely due to the cost of carbon sources and of extracting the bioplastics from bacteria. The goal of these studies was to examine replacing traditional carbon sources used in PHA production like sugar and …


Designing A Synthetic Spider Silk-Based Coating For Urinary Catheters To Reduce The Risk Of Cautis, Alexander Cook May 2018

Designing A Synthetic Spider Silk-Based Coating For Urinary Catheters To Reduce The Risk Of Cautis, Alexander Cook

Undergraduate Honors Capstone Projects

Urinary and Intravenous (IV) catheters are two of the most commonly used medical devices for administering vital drugs and obtaining diagnostic samples from patients. Unfortunately, hospital acquired infections (HAIs) occur at alarming rates due to catheter usage. The aim of this project was to design a urinary catheter that would decrease the occurrence of these infections with a catheter coating that utilizes the antimicrobial properties of synthetic spider silk in combination with the antiseptic chlorhexidine. This synthetic spider silk catheter will introduce a novel approach to catheterization in the medical industry.


Optimizing Genetic Manipulation Of Methanogens Through Faster Cloning Techniques, Merrisa Jennings May 2018

Optimizing Genetic Manipulation Of Methanogens Through Faster Cloning Techniques, Merrisa Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

Methanogenesis is the biological production of methane. Only anaerobic archaea known as methanogens are capable of such a metabolic feat. They have strict living conditions and substrate sources which determine their rate of metabolism. This is of particular importance from a greenhouse gas reduction perspective or biogas capturing perspective. One of the best ways to optimize methanogen methane production is via genetic manipulation. The current procedures are timely though, therefore a faster cloning processes should be developed. The objective of this study was to optimize a premade genetic transformation kit known as the Gibson Kit. The Gibson Kit was supposed …


Designing A Synthetic Spider Silk Based Coating For Urinary Catheters To Reduce The Risk Of Cautis, Tess Marie Armbrust May 2018

Designing A Synthetic Spider Silk Based Coating For Urinary Catheters To Reduce The Risk Of Cautis, Tess Marie Armbrust

Undergraduate Honors Capstone Projects

Catheter associated urinary tract infections (CAUTis) are a leading cause of morbidity and mortality in patients with life-threatening conditions. Foley catheters are the most common catheter used when a patient requires hospitalization but can become burdened with microbes which lead to CAUTis, the most common source of hospital acquired infection (HAI). The attached bacteria can form biofilms on the catheter which are difficult to treat using oral antibiotics and can lead to chronic infections. Synthetic spider silk as a catheter coating shows great promise because of demonstrated strength, biocompatibility, and antimicrobial properties. In addition, the antiseptic chlorhexidine can enhance the …


Computational Fluid Dynamics Model For Air Velocity Through A Poultry Transport Trailer In A Holding Shed, Christian Heymsfield May 2018

Computational Fluid Dynamics Model For Air Velocity Through A Poultry Transport Trailer In A Holding Shed, Christian Heymsfield

Graduate Theses and Dissertations

Broiler production in Arkansas was valued at over $3.6 billion in 2013 (University of Arkansas Division of Agriculture Cooperative Extension Service). Consequently, improvement in any phase of the production process can have significant economic impact and animal welfare implications. One area of concern for the poultry industry is thermal stress experienced by the birds after arrival at the processing plant and before they are taken in to be processed, during which time they are left to wait in holding sheds. Various cooling strategies exist to mitigate heat stress in holding sheds, but in most cases it is unlikely that they …


Pharmacokinetic Modeling Of 99mtc-Hmpao Images Of Isolated Perfused Rat Lungs, Katherine C. Barry Apr 2018

Pharmacokinetic Modeling Of 99mtc-Hmpao Images Of Isolated Perfused Rat Lungs, Katherine C. Barry

Master's Theses (2009 -)

The single-photon emission tomography (SPECT) imaging biomarker technetium-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) exists in two forms, the oxidized, cell-permeable form and the reduced, cell-impermeable form. Recent studies revealed that the lung uptake of 99mTc-HMPAO increases early in rat models of human acute lung injury. Lung uptake of 99mTc-HMPAO is the net result of multiple cellular and vascular processes, many of which can vary with acute illness. Thus, when a change in the lung uptake of 99mTc-HMPAO is detected, it is unclear how much of this change is due to alteration in the activity of the targeted cellular process versus alteration of …


Tumor-Targeted Double Emulsions For Ultrasound-Triggered Delivery Of Molecular Therapeutics., Connor S Centner Apr 2018

Tumor-Targeted Double Emulsions For Ultrasound-Triggered Delivery Of Molecular Therapeutics., Connor S Centner

Electronic Theses and Dissertations

Cancer is the second leading cause of death in the United States, with 1.74 million new cancer cases diagnosed and 610,000 cancer deaths expected in 2018 alone. Current treatments often result in negative systemic effects and ineffective treatment of the tumor. Drug delivery vehicles have been developed for more effective local delivery methods, but many drug delivery vehicles lack spatial and temporal control. Targeted double emulsions are a new class of drug delivery vehicles which present a promising option for a high payload and controlled delivery. The purpose of our project was to develop and characterize an aptamer-chelated double emulsion …


Probing The Effects Of Substrate Stiffness On Astrocytes Mechanics, Ariege Bizanti Jan 2018

Probing The Effects Of Substrate Stiffness On Astrocytes Mechanics, Ariege Bizanti

Electronic Theses and Dissertations

Astrocytes are among the most functionally diverse population of cells in the central nervous system (CNS) as they are essential to many important neurological functions including maintaining brain homeostasis, regulating the blood brain barrier, and preventing build-up of toxic substances within the brain, for example. Astrocyte importance to brain physiology and pathology has inspired a host of studies focused on understanding astrocyte behavior primarily from a biological and chemical perspective. However, a clear understanding of astrocyte dysfunction and their link to disease has been hampered by a lack of knowledge of astrocyte behavior from a biomechanical perspective. Furthermore, astrocytes (and …


Regulation Of Pituitary Progenitor Differentiation By Β-Catenin, Julie Leann Youngblood Jan 2018

Regulation Of Pituitary Progenitor Differentiation By Β-Catenin, Julie Leann Youngblood

Theses and Dissertations

The pituitary gland is a critical organ that is necessary for many physiological processes, including growth, reproduction, and stress response. These vital processes are regulated through the secretion of pituitary hormones from specialized cell types. Pituitary hormone-producing cells arise from a common pool of pituitary progenitors in the developing Rathke’s pouch, and mutations that disrupt the formation and differentiation of pituitary progenitors often result in hypopituitarism, pituitary adenomas, or craniopharyngiomas. Thus, it is necessary to determine the mechanisms of pituitary development in order to understand the ways in which these congenital defects and tumors develop and disrupt pituitary function. Canonical …


The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter Jan 2018

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …


Characterization And Engineering Of Human Proteins As Therapeutic Candidates, Kyungbo Kim Jan 2018

Characterization And Engineering Of Human Proteins As Therapeutic Candidates, Kyungbo Kim

Theses and Dissertations--Pharmacy

Protein engineering has been a useful tool in the fight against human diseases. Human insulin was the first recombinant DNA-derived therapeutic protein (Humulin®) approved by the US FDA in 1982. However, many of the early protein drugs were only recombinant versions of natural proteins with no modification of their primary amino acid sequence and most of them did not make optimal drug products mainly due to their short half-life or suboptimal affinity, leading to poor therapeutic efficacy. The difficulty in the large-scale production of some therapeutic proteins was another important issue. In the past three decades, different protein …