Engineering Commons^™

Long-Acting Antituberculous Therapeutic Nanoparticles Target Macrophage Endosomes, Benson J. Edagwa, Dongwei Guo, Pavan Puligujja, Han Chen, Joellyn Mcmillan, Xinming Liu, Howard Gendelman, Prabagaran Narayanasamy

Nebraska Center for Biotechnology: Faculty and Staff Publications

Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl- INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

A Highly Adaptive And Cost Effective Second Generation Incubator (Sgi) Towards Educational, Research And Clinical Processes, Yassir H. Al-Sayagh

Department of Biological Systems Engineering: Dissertations and Theses

Today´s rising demand for more reliable and affordable alternatives to organ transplant has led to a growing market for in vitro tissue culture systems. The main objective of tissue engineering as a whole is to employ human tissue equivalents for commercial use. The state-of-the-art processes for producing these so called tissue models are still very expensive, difficult to produce and time-consuming.

To engineer tissues, in vitro, a three-dimensional support structure commonly termed scaffold is needed. Stem cells are then added to the scaffold. In order for tissue to materialize, the scaffold and the cells must be incubated (cultured) at a …

Applications Of Novel Mri Technologies In Tissue Engineering And Disease Diagnosis, Vahid Khalilzad-Sharghi

Department of Biological Systems Engineering: Dissertations and Theses

Magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE) are increasingly under investigation to explore their potential role in establishing effective evaluation methods for the procedure of tissue regeneration carried out in vitro, in vivo, and in disease diagnosis. To this end, there is a continuous pursuit of novel tools both in vitro and in vivo. For instance, there is a great need for the development and evaluation of an MR-compatible incubation system that enables simultaneous monitoring and culturing of cell and tissue constructs using MRI techniques. Such an imagingcompatible incubation system eliminates exposing the culture to the risks of …

Virus-Host Mucosal Interactions During Early Siv Rectal Transmission, Wuxun Lu, Fangrui Ma, Alexander Churbanov, Yanmin Wan, Yue Li, Guobin Kang, Zhe Yuan, Dong Wang, Chi Zhang, Jianqing Xu, Mark Lewis, Qingsheng Li

Nebraska Center for Biotechnology: Faculty and Staff Publications

To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggests that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into …

Implementation And Validation Of Aortic Remodeling In Hypertensive Rats, Shijia Zhao, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

A computational framework was implemented and validated to better understand the hypertensive artery remodeling in both geometric dimensions and material properties. Integrating the stress-modulated remodeling equations into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both arterial thickening and stiffening effects were captured and visualized. An adaptive material remodeling strategy combined with the element birth and death techniques for the geometrical growth were implemented. The numerically predicted remodeling results in terms of the wall thickness, inner diameter, and the ratio of elastin to collagen content of the artery were compared with and fine-tuned by …

Implementation And Validation Of Aortic Remodeling In Hypertensive Rats, Shijia Zhao, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

A computational framework was implemented and validated to better understand the hypertensive artery remodeling in both geometric dimensions and material properties. Integrating the stress-modulated remodeling equations into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both arterial thickening and stiffening effects were captured and visualized. An adaptive material remodeling strategy combined with the element birth and death techniques for the geometrical growth were implemented. The numerically predicted remodeling results in terms of the wall thickness, inner diameter, and the ratio of elastin to collagen content of the artery were compared with and fine-tuned by …

An Experimental Study Of The Implementation Of A Fluid Diode Inside A Sano Shunt, Patrick Austin Lane

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Fluid diodes are fluidic devices that enhance fluid flow in a particular direction while inhibiting it in the opposite direction without the use of moving parts. This is accomplished through the use of nozzle shaped geometry on one side of the diode, and cusp shaped geometry on the opposing side. Fluid meets very little resistance as is travels though the nozzle side of the diode. The cusps on the other side of the diode reduce the effective flow area, thereby inhibiting flow. The objective of this study is to determine the effectiveness of a fluid diode installed in a reconstructed …

Design And Development Of A Miniature In Vivo Surgical Robot With Distributed Motor Control For Laparoendoscopic Single-Site Surgery, Eric J. Markvicka

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Paradigm shifts in invasiveness, recovery time, cosmesis, and cost have been seen within the field of general surgery through major advances in surgical technology. Some of the most advanced types of general surgery now include Minimally Invasive Surgery (MIS), LaparoEndoscopic Single-Site (LESS) surgery, and Natural Orifice Translumenal Endoscopic Surgery (NOTES). One of the newest and rapidly developing catalysts is robotic platforms. Such platforms have improved ergonomics and control, increased workspace and dexterity, and have surpassed the efficacy of many non-robotic platforms such as traditional laparoscopic surgical tools. This thesis presents the design and development of a four-degree-of-freedom (4- DOF) miniature …

Fluid Powered Miniature In-Vivo Robots For Minimally Invasive Surgery (Mis), Abolfazl Pourghodrat

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Minimizing the invasiveness of surgery is believed to improve patient outcomes. Bleeding, infection, and pain are major concerns in surgery afflicting patients for decades. Minimally invasive techniques have come into play to reduce these concerns and smooth the evolution of abdominal surgery to a scarless process where nearly all surgeries can be performed without a skin incision. Technology continually advances the frontier of development of novel surgical devices to implement less invasive surgical techniques.

Fusion of robotics and Minimally Invasive Surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems …

Experimental And Numerical Investigation Of The Mechanism Of Blast Wave Transmission Through A Surrogate Head, Yi Hua, Praveen Akula, Linxia Gu, Jeff Berg, Carl A. Nelson

Department of Mechanical and Materials Engineering: Faculty Publications

This work is to develop an experiment-validated numerical model to elucidate the wave transmission mechanisms through a surrogate head under blast loading. Repeated shock tube tests were conducted on a surrogate head, i.e., water-filled polycarbonate shell. Surface strain on the skull simulant and pressure inside the brain simulant were recorded at multiple locations. A numerical model was developed to capture the shock wave propagation within the shock tube and the fluid-structure interaction between the shock wave and the surrogate head. The obtained numerical results were compared with the experimental measurements. The experiment-validated numerical model was then used to further understand …

Preliminary Test Of A Real-Time, Interactive Silent Speech Interface Based On Electromagnetic Articulograph, Jun Wang, Ashok Samal, Jordan R. Green

CSE Conference and Workshop Papers

A silent speech interface (SSI) maps articulatory movement data to speech output. Although still in experimental stages, silent speech interfaces hold significant potential for facilitating oral communication in persons after laryngectomy or with other severe voice impairments. Despite the recent efforts on silent speech recognition algorithm development using offline data analysis, online test of SSIs have rarely been conducted. In this paper, we present a preliminary, online test of a real-time, interactive SSI based on electromagnetic motion tracking. The SSI played back synthesized speech sounds in response to the user’s tongue and lip movements. Three English talkers participated in this …

Developing Defined And Scalable 3d Culture Systems For Culturing Human Pluripotent Stem Cells At High Densities, Yuguo Lei, Daeun Jeong, Jifang Xiao, David V. Schaffer

Department of Chemical and Biomolecular Engineering: Faculty Publications

Human pluripotent stem cells (hPSCs)—including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)—are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation. Here, we describe additional design rationale and characterization of this …

Fluid Flow-Induced Mesenchymal Stem Cell Migration: Role Of Fak And Rock Mechanosensors, Brandon D. Riehl

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

The study of mesenchymal stem cell (MSC) migration under mechanical stimulation conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcomes in stem cell-based regenerative medicine. MSCs having multipotent regenerative capability exist in niches in the bone marrow, muscle, vasculature, and in other tissues throughout the body, and their migration through tissues and vasculature for the repair of damaged tissue is a key process of cell and tissue homeostasis, remodeling, and regeneration. While cell migration in response to cytokines and other chemo-attractants is relatively well understood, little is revealed in regard to the effect …

Application Of Limited Mixing In The Hele-Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Characterization Of Extraction Methods To Recover Phenolic-Rich Antioxidants From Blue Green Algae (Spirulina) Using Response Surface Approaches, Ahmad Salamatullah

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Blue green algae (spirulina) is a dietary system that is widely consumed as a whole food or as a supplement in many Asian countries where populations are mostly unaffected by many of the diseases currently afflicting western societies, such as cancer, heart disease and arthiritis. Indeed, spirulina is a rich source of antioxidants with the phenolic compounds playing a significant role. As components of a complex dietary system, phenolic compounds can act alone or through synergistic mechanisms to impart a greater biologic effect than can be elicited by a sum of the individual parts. Therefore, an understanding of the antioxidative …

Head Impact Exposure In Male And Female Collegiate Ice Hockey Players, Bethany J. Wilcox, Jonathan G. Beckwith, Richard M. Greenwald, Jeffrey J. Chu, Thomas W. Mcallister, Laura A. Flashman, Arthur C. Maerlender, Ann-Christine Duhaime, Joseph J. Crisco

Department of Psychology: Faculty Publications

The purpose of this study was to quantify head impact exposure (frequency, location and magnitude of head impacts) for individual male and female collegiate ice hockey players and to investigate differences in exposure by sex, player position, session type, and team. Ninety-nine (41 male, 58 female) players were enrolled and 37,411 impacts were recorded over three seasons. Frequency of impacts varied significantly by sex (males: 287 per season, females: 170, p < 0.001) and helmet impact location (p < 0.001) but not by player position (p = 0.088). Head impact frequency also varied by session type; both male and female players sustained more impacts in games than in practices (p < 0.001), however the magnitude of impacts did not differ between session types. There was no difference in 95th percentile peak linear acceleration between sexes (males: 41.6 g, females: 40.8 g), but 95th percentile peak rotational acceleration and HITsp (a composite severity measure) were greater for males than females (4424, 3409 rad/s2, and 25.6, 22.3, respectively). Impacts to the back of the helmet resulted in the greatest 95th percentile peak linear accelerations for males (45.2 g) and females (50.4 g), while impacts to the side and back of the head were associated with the greatest 95th percentile peak rotational accelerations (males: 4719, 4256 rad/sec², females: 3567, 3784 rad/sec², respectively). It has been proposed that reducing an individual’s head impact exposure is a practical approach for reducing the risk of …

Physiological And Transcriptional Memory In Guard Cells During Repetitive Dehydration Stress, Laetitia Virlouvet, Michael E. Fromm

Nebraska Center for Biotechnology: Faculty and Staff Publications

Arabidopsis plants subjected to a daily dehydration stress and watered recovery cycle display physiological and transcriptional stress memory. Previously stressed plants have stomatal apertures that remain partially closed during a watered recovery period, facilitating reduced transpiration during a subsequent dehydration stress. Guard cells (GCs) display transcriptional memory that is similar to that in leaf tissues for some genes, but display GC-specific transcriptional memory for other genes. The rate-limiting abscisic acid (ABA) biosynthetic genes NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) and ALDEHYDE OXIDASE 3 (AAO3) are expressed at much higher levels in GCs, particularly during the watered recovery interval, relative to their low …

The Pseudomonas Syringae Type Iii Effector Hopd1 Suppresses Effector-Triggered Immunity, Localizes To The Endoplasmic Reticulum, And Targets The Arabidopsis Transcription Factor Ntl9, Anna Block, Tania Y. Toruno, Christian G. Elowsky, Chi Zhang, Jens Steinbrenner, Jim Beynon, James R. Alfano

Nebraska Center for Biotechnology: Faculty and Staff Publications

Pseudomonas syringae type III effectors are known to suppress plant immunity to promote bacterial virulence. However, the activities and targets of these effectors are not well understood. We used genetic, molecular, and cell biology methods to characterize the activities, localization, and target of the HopD1 type III effector in Arabidopsis. HopD1 contributes to P. syringae virulence in Arabidopsis and reduces effector-triggered immunity (ETI) responses but not pathogen-associated molecular pattern-triggered immunity (PTI) responses. Plants expressing HopD1 supported increased growth of ETI-inducing P. syringae strains compared with wild-type Arabidopsis. We show that HopD1 interacts with the membrane-tethered Arabidopsis transcription factor NTL9 and …