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Aggregation Challenges In The Formulation Development Of Multi-Dose Peptide Products, Jingtao Zhang, Katelyn Smith, Wei Xu, Yongchao Su, Suzanne D’Addio, Yogita Krishnamachari, Jameson Bothe, Daniel Yin, Xinpei Mao 2019 Merck, USA

Aggregation Challenges In The Formulation Development Of Multi-Dose Peptide Products, Jingtao Zhang, Katelyn Smith, Wei Xu, Yongchao Su, Suzanne D’Addio, Yogita Krishnamachari, Jameson Bothe, Daniel Yin, Xinpei Mao

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

The formulation development of parenteral peptide therapeutics frequently encounters aggregation challenges. In-depth biophysical understanding of the molecule and formulation are required to achieve formulation robustness. Further, unique considerations need to be given for peptide products that require multi-dose as the use of preservatives can promote aggregation while preservative effectiveness can also be impacted by its interaction with the peptide. This presentation will focus on the reversible and irreversible fibril aggregates in peptide formulations. Biophysical characterization of aggregation and formulation will be discussed in detail. Formation of reversible aggregates and the impact of excipients especially preservatives will be discussed. For the ...


Conference Program, Samiul Amin, Paolo Arosio, Miguel Rodrigues 2019 Manhattan College, USA

Conference Program, Samiul Amin, Paolo Arosio, Miguel Rodrigues

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

No abstract provided.


Resolving Intravoxel White Matter Structures In The Human Brain Using Regularized Regression And Clustering, Andrea Hart, Brianna Smith, Sean Smith, Elijah Sales, Jacqueline Hernandez-Camargo, Yarlin Mayor Garcia, Felix Zhan, Lori Griswold, Brian Dunkelberger, Michael R. Schwob, Sharang Chaudhry, Justin Zhan, Laxmi Gewali, Paul Oh 2019 Army Education Outreach Program UNITE

Resolving Intravoxel White Matter Structures In The Human Brain Using Regularized Regression And Clustering, Andrea Hart, Brianna Smith, Sean Smith, Elijah Sales, Jacqueline Hernandez-Camargo, Yarlin Mayor Garcia, Felix Zhan, Lori Griswold, Brian Dunkelberger, Michael R. Schwob, Sharang Chaudhry, Justin Zhan, Laxmi Gewali, Paul Oh

Computer Science Faculty Publications

The human brain is a complex system of neural tissue that varies significantly between individuals. Although the technology that delineates these neural pathways does not currently exist, medical imaging modalities, such as diffusion magnetic resonance imaging (dMRI), can be leveraged for mathematical identification. The purpose of this work is to develop a novel method employing machine learning techniques to determine intravoxel nerve number and direction from dMRI data. The method was tested on multiple synthetic datasets and showed promising estimation accuracy and robustness for multi-nerve systems under a variety of conditions, including highly noisy data and imprecision in parameter assumptions.


Microwave Assisted Sol-Gel Synthesis Of Silica-Spider Silk Composites, Abul Bashar Mohammad Giasuddin, David W. Britt 2019 Utah State University

Microwave Assisted Sol-Gel Synthesis Of Silica-Spider Silk Composites, Abul Bashar Mohammad Giasuddin, David W. Britt

Biological Engineering Faculty Publications

This study introduces a simple and environmentally friendly method to synthesize silica-protein nanocomposite materials using microwave energy to solubilize hydrophobic protein in an aqueous solution of pre-hydrolyzed organo- or fluoro-silane. Sol-gel functionality can be enhanced through biomacromolecule incorporation to tune mechanical properties, surface energy, and biocompatibility. Here, synthetic spider silk protein and organo- and fluoro-silane precursors were dissolved and mixed in weakly acidic aqueous solution using microwave technology. Scanning electron microscopy (SEM) and Atomic force microscopy (AFM) images revealed the formation of spherical nanoparticles with sizes ranging from 100 to 500 nm depending, in part, on silane fluoro- or organo-side ...


A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Protein, Yi Zhu, Yizhi Xiao, Elizabeth Gillies, Walter L. Siqueira 2019 School of Dentistry and Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario

A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Protein, Yi Zhu, Yizhi Xiao, Elizabeth Gillies, Walter L. Siqueira

Western Research Forum

Dental caries remains one of the most common chronic diseases worldwide. In previous studies, salivary proteins (e.g. histatin 3, statherin) have demonstrated biological functions including the inhibition of crystal growth, antibacterial activities, which are directly related to tooth homeostasis and prevention of dental caries. However, proteins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to protect proteins against enzymatic degradation at physiological salivary pH, in addition to swell selectively at lower pH conditions to facilitate the release of the encapsulated proteins, as major oral complications ...


The Effect Of Radial Head Hemiarthroplasty Stem Fit On Radiocapitellar Contact Mechanics: Is Loose Fit Better Than Rigidly Fixed?, Jakub Szmit, Graham J.W. King, James A. Johnson, G. Daniel G. Langohr 2019 Western University

The Effect Of Radial Head Hemiarthroplasty Stem Fit On Radiocapitellar Contact Mechanics: Is Loose Fit Better Than Rigidly Fixed?, Jakub Szmit, Graham J.W. King, James A. Johnson, G. Daniel G. Langohr

Western Research Forum

Background/Methods: Radial head hemiarthroplasty is commonly employed to manage comminuted displaced fractures. With regards to implant fixation, current designs vary with some prostheses aiming to achieve a tight 'fixed' fit, and others utilizing a smooth stem with an over reamed 'loose' fit. The purpose of the present study was to evaluate the effect of radial head hemiarthroplasty stem fit on radiocapitellar contact using a finite element model which simulated both fixed (size-for-size) and loose (1, 2 & 3mm over reamed) stem fits.

Hypothesis: It was hypothesized that a loose stem fit would improve radiocapitellar contact mechanics, with increased contact area ...


Multifunctional Hybrid Sol-Gel Implant Coatings On Anodized Titanium Substrates To Improve Osseointegration And Antimicrobial Effectiveness, Zach Gouveia 2019 Western University

Multifunctional Hybrid Sol-Gel Implant Coatings On Anodized Titanium Substrates To Improve Osseointegration And Antimicrobial Effectiveness, Zach Gouveia

Western Research Forum

To improve patient outcomes in orthopedic and dental implantation procedures, the development of multifunctional implant coatings that can inhibit microbial cell proliferation while promoting osseointegration have been sought out by clinicians. While recent developments in material science and cell biology have seen the development of such coatings, many proposed systems lack clinical translatability. For example, to reach the clinic, modern coating systems must be highly adherent to their substrate (to avoid delamination upon implantation), have sufficient wettability (to promote the fixation of cells), and facilitate the controlled and sustained release of antimicrobial factors (falling within the therapeutic window to prevent ...


Fibrinogen, Factor Xiii And Fibronectin: A Biophysical And Kinetic Characterization Of Their Interactions, Frank Fabian 2019 University of Nebraska - Lincoln

Fibrinogen, Factor Xiii And Fibronectin: A Biophysical And Kinetic Characterization Of Their Interactions, Frank Fabian

Chemical & Biomolecular Engineering Theses, Dissertations, & Student Research

The development of recombinant-based liquid fibrin tissue sealants having enhanced hemostatic and wound healing properties will involve understanding as yet not well characterized interactions between fibrinogen, fibrin (Fbn) factor XIII, thrombin and fibronectin. We study these phenomena in the context of comparing plasma derived fibrinogen to recombinant fibrinogen (rFI) produced in the milk of transgenic cows. An abundance of purified γγ and γγ’ FI subspecies enables detailed study of γγ or γγ’ biomonomer and their respective Fbn biopolymer formation as having different substrate behaviors of activated plasma derived factor XIII (pFXIIIa2b2). High pressure size exclusion (HPSEC) and ...


Remote Navigation And Contact-Force Control Of Radiofrequency Ablation Catheters, Daniel Gelman 2019 The University of Western Ontario

Remote Navigation And Contact-Force Control Of Radiofrequency Ablation Catheters, Daniel Gelman

Electronic Thesis and Dissertation Repository

Atrial fibrillation (AF), the most common and clinically significant heart rhythm disorder, is characterized by rapid and irregular electrical activity in the upper chambers resulting in abnormal contractions. Radiofrequency (RF) cardiac catheter ablation is a minimally invasive curative treatment that aims to electrically correct signal pathways inside the atria to restore normal sinus rhythm. Successful catheter ablation requires the complete and permanent elimination of arrhythmogenic signals by delivering transmural RF ablation lesions contiguously near and around key cardiac structures. These procedures are complex and technically challenging and, even when performed by the most skilled physician, nearly half of patients undergo ...


Inverted Cone Convolutional Neural Network For Deboning Mris, Oliver John Palumbo 2019 Rowan University

Inverted Cone Convolutional Neural Network For Deboning Mris, Oliver John Palumbo

Theses and Dissertations

Data plenitude is the power but also the bottleneck for data-driven approaches, including neural networks. In particular, Convolutional Neural Networks (CNNs) require an abundant database of training images to achieve a desired high accuracy. Current techniques employed for boosting small datasets are data augmentation and synthetic data generation, which suffer from computational complexity and imprecision compared to original datasets. In this thesis, we intercalate prior knowledge based on the temporal relation between the images in the third dimension. Specifically, we compute the gradient of subsequent images in the dataset to remove extraneous information and highlight subtle variations between the images ...


A Systems Biology Approach Toward Understanding Seed Composition In Soybean, Ling Li, Manhoi Hur, Joon-Yong Lee, Wenxu Zhou, Zhihong Song, Nick Ransom, Cumhur Yusuf Demirkale, Daniel S. Nettleton, Mark E. Westgate, Zebulun Wayne Arendsee, Vidya Vaancheeswaran Iyer, Jacqueline V. Shanks, Basil Nikolau, Eve Wurtele 2019 Iowa State University

A Systems Biology Approach Toward Understanding Seed Composition In Soybean, Ling Li, Manhoi Hur, Joon-Yong Lee, Wenxu Zhou, Zhihong Song, Nick Ransom, Cumhur Yusuf Demirkale, Daniel S. Nettleton, Mark E. Westgate, Zebulun Wayne Arendsee, Vidya Vaancheeswaran Iyer, Jacqueline V. Shanks, Basil Nikolau, Eve Wurtele

Dan Nettleton

Background

The molecular, biochemical, and genetic mechanisms that regulate the complex metabolic network of soybean seed development determine the ultimate balance of protein, lipid, and carbohydrate stored in the mature seed. Many of the genes and metabolites that participate in seed metabolism are unknown or poorly defined; even more remains to be understood about the regulation of their metabolic networks. A global omics analysis can provide insights into the regulation of seed metabolism, even without a priori assumptions about the structure of these networks.

Results

With the future goal of predictive biology in mind, we have combined metabolomics, transcriptomics, and ...


Accounting For Host Cell Protein Behavior In Anion-Exchange Chromatography, Ryan K. Swanson, Ruo Xu, Daniel S. Nettleton, Charles Glatz 2019 Iowa State University

Accounting For Host Cell Protein Behavior In Anion-Exchange Chromatography, Ryan K. Swanson, Ruo Xu, Daniel S. Nettleton, Charles Glatz

Dan Nettleton

Host cell proteins (HCP) are a problematic set of impurities in downstream processing (DSP) as they behave most similarly to the target protein during separation. Approaching DSP with the knowledge of HCP separation behavior would be beneficial for the production of high purity recombinant biologics. Therefore, this work was aimed at characterizing the separation behavior of complex mixtures of HCP during a commonly used method: anion-exchange chromatography (AEX). An additional goal was to evaluate the performance of a statistical methodology, based on the characterization data, as a tool for predicting protein separation behavior. Aqueous two-phase partitioning followed by two-dimensional electrophoresis ...


Scale Optimization Of Milkguard Biosensor For Detecting E. Coli In Human Breast Milk, Jerard Roniel Del Rosario Madamba 2019 Santa Clara University

Scale Optimization Of Milkguard Biosensor For Detecting E. Coli In Human Breast Milk, Jerard Roniel Del Rosario Madamba

Bioengineering Master's Theses

Milkguard is an alginate-based biosensor developed to detect E. coli in human breast milk via the metabolism of X-gal (5-Bromo-4-Chloro-3-Indolyl β-D-Galactopyranoside) by β-galactosidase. In order to deconvolute metabolic reproducibility from scaling laws, the commercial enzyme β-galactosidase was used to mimic the biological function of the bacterial lac operon. Downscaling was explored as an optimization of the biosensor design based on numerical solutions to Fickian-based diffusion models. The characterization of large capsules (d ≅ 3 mm) and atomized microcapsules (d ≅ 300 ± 60 μm) yielded size-specific Michaelis-Menten constants. Small capsules (Km = 3.6 x 10-4 M; Vmax ’’ = 1.2 x 10 ...


Unravel The Cellular Biophysical Dynamics Of Spatial Constraint-Induced Membrane Blebbing And 3d Migration Using A Microfluidic Platform And Data-Driven Mathematical Modeling, Yu Huang 2019 Utah State University

Unravel The Cellular Biophysical Dynamics Of Spatial Constraint-Induced Membrane Blebbing And 3d Migration Using A Microfluidic Platform And Data-Driven Mathematical Modeling, Yu Huang

Funded Research Records

No abstract provided.


Justrun - Social Gps Running Game, Riley Bergin, Maggie Cai, Simran Judge, Grace Ling 2019 Santa Clara University

Justrun - Social Gps Running Game, Riley Bergin, Maggie Cai, Simran Judge, Grace Ling

Interdisciplinary Design Senior Theses

With advances in technology allowing people to live more sedentary lives, more and more people are struggling to live a healthy active lifestyle. In the efforts to combat unhealthy styles of living, we wish to introduce a mobile app that takes advantage of motivational game mechanics to motivate players will make go on runs regularly.


Epic: Examining Patch Impedance Characteristics, Shane Buck, Jyotsna Gopinath, Kyle Markfield 2019 Santa Clara University

Epic: Examining Patch Impedance Characteristics, Shane Buck, Jyotsna Gopinath, Kyle Markfield

Interdisciplinary Design Senior Theses

In the United States, approximately one in 4 adults have at least one chronic illness, making up approximately 84% of US Healthcare Spending. Unfortunately, 50% of patients with chronic diseases do not take their medication properly and as such spend more money trying to get better – approximately $100 billion in annual preventable costs. One solution to this issue is digital medicine as it allows for the monitoring of patient medicine consumption.

Our industry partner has developed a three-part digital medicine system with the aim of allowing patients with chronic health issues to better reach their health goals through monitoring of ...


Challenges Of Erau’S First Suborbital Flight Aboard Blue Origin’S New Shepard M7 For The Cell Research Experiment In Microgravity (Crexim), Pedro Llanos, Kristina Andrijauskaite, Vijay V. Duraisamy, Francisco F. Pastrana, Erik Seedhouse, Sathya Gangadharan, Leonid Bunegin, Mariel Rico 2019 Embry-Riddle Aeronautical University - Daytona Beach

Challenges Of Erau’S First Suborbital Flight Aboard Blue Origin’S New Shepard M7 For The Cell Research Experiment In Microgravity (Crexim), Pedro Llanos, Kristina Andrijauskaite, Vijay V. Duraisamy, Francisco F. Pastrana, Erik Seedhouse, Sathya Gangadharan, Leonid Bunegin, Mariel Rico

Pedro J. Llanos (www.AstronauticsLlanos.com)

Cell Research Experiment In Microgravity (CRExIM) was launched aboard Blue Origin’s New Shepard suborbital vehicle on Tuesday, December 12, 2017, from the West Texas Launch Site in Van Horn, Texas. One of the aims of this science experiment was to assess the effects of microgravity on murine T-cells during suborbital flight. These cells were placed in a NanoLab with a data logger that sensed the acceleration, temperature, and relative humidity during preflight, flight, and postflight operations. Some discrepancies in sensor measurement were noticed, and these errors were attributed partly to the difference in sampling rates and partly to the ...


Anti-Infective Mechanism-Based Drug Discovery Via Sortase A, Huong Chau, Alice Matsuda, Leepakshi Johar 2019 Santa Clara University

Anti-Infective Mechanism-Based Drug Discovery Via Sortase A, Huong Chau, Alice Matsuda, Leepakshi Johar

Bioengineering Senior Theses

Sortase A is a transmembrane protein prominent in gram-negative bacterial strains. It is a virulence factor that anchors other proteins, which facilitate MRSA infections. In the long term, we plan to utilize this protein to create anti-infective drugs as antibiotic resistance continues to become a global health issue. Starting with five NIH drug candidates, we decided to first study Sortase A with B12 due to its historical past of ancient civilizations using natural sources of B12 to treat infections. Our senior design is further centered around understanding how vitamin B12 interacts with Sortase A in vitro, particularly the binding affinity ...


Developing A Control System To Better Understand The Effects Of Pyruvate Decarboxylase Activity On Clostridium Thermocellum Metabolism, Nicholas Cervenka 2019 Dartmouth College

Developing A Control System To Better Understand The Effects Of Pyruvate Decarboxylase Activity On Clostridium Thermocellum Metabolism, Nicholas Cervenka

ENGS 88 Honors Thesis (AB Students)

In order for cellulosic biofuels from Clostridium thermocellum to be commercially viable, the ethanol yield and titer of the microbe must be increased. To accomplish this, it has been suggested to introduce the Pyruvate Decarboxylase (PDC) enzyme into C. thermocellum. In order to demonstrate effects on ethanol production by PDC prior to genetic modification, a cell free system (CFS) has been developed. A purified enzyme system was developed with the CFS to function as a control. Using the purified enzyme system, PDC from Saccharomyces cerevisiae was demonstrated to be a good candidate for further testing in the CFS.


A Physical And Computational Reverse-Engineering Approach To Determine Dimensional Change And Its Relationship To Oxidation In Retrieved Orthopedic Implants, Josephine Kalshoven 2019 Dartmouth College

A Physical And Computational Reverse-Engineering Approach To Determine Dimensional Change And Its Relationship To Oxidation In Retrieved Orthopedic Implants, Josephine Kalshoven

ENGS 88 Honors Thesis (AB Students)

Oxidation of the Ultra-High Molecular Weight Polyethylene (UHMWPE) tibial inserts of total knee arthroplasty devices is a major factor underlying multiple modes of failure for these devices, including delamination, wear, and fracture. Previous research has demonstrated that oxidation of UHMWPE is driven by a high concentration of free radicals in the polyethylene. However, even new devices created with undetectable amounts of free radicals are oxidizing in vivo. One theory is that, in the absence of residual free radicals, oxidation is facilitated by absorbed species (e.g. lipids, ROS) delivered or exacerbated by contact stress. However, no method exists to comprehensively ...


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