Doctor of Philosophy / Department of Chemical Engineering / Stefan H. Bossmann / Both chemotherapy for cancer treatment and antibiotic therapy for bacterial infections require systemic applications of the drug and a systemic application is always linked to a number of disadvantages. To circumvent these a targeted drug delivery system was developed. It utilizes the ability of phagocytes from the hosts own immune system to recognize and internalize antigens. Deactivated M. luteus, a non-pathogenic gram positive bacteria was loaded with high concentrations (exceeding the IC50 at least 60 fold in local intracellular concentration) the chemotherapeutics doxorubicin or DP44mt or with the bactericidal chlorhexidine. The modified bacteria is fed to phagocytes (Monocytes/Macrophages or neutrophils) and serves as protective shell for the transporting and targeting phagocyte. The phagocyte is recruited to the tumor site or site of infection and releases the drug along with the processed M. luteus via the exosome pathway upon arrival. The chlorhexidine drug delivery system was successfully tested both in vitro and in vivo, reducing the pathogen count and preventing systemic spread of a F. necrophorum infection in a mouse model. The doxorubicin drug delivery system reduced the viability of 4T1 cancer cells to 20% over the course of four days in vitro.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Raymond R. R. Rowland / Interferons (IFNs) comprise a group of antiviral cytokines; however, their expression at the porcine maternal-fetal interface and in fetal tissues has not previously been investigated. The purpose of this study was to analyze the expression of type I IFNs and their receptors in maternal and fetal tissues from sows infected with PRRSV. The approach was to use real-time RT-PCR to identify the expression of different subtypes of type I IFN genes. The results show that the constitutive gene expression of some subtypes including IFN-[alpha] and IFN-[alpha][omega] were detected in fetal lymphoid nodes (IFN-[alpha][omega]), placenta (several IFN-[alpha] subtypes and IFN-[omega]5) and particularly, thymus (multiple IFN-[alpha], IFN-[delta] and IFN-[omega]5). The results demonstrate that porcine type I IFNs are differentially expressed at the maternal-fetal interface and in fetal tissues in response to PRRSV infection.

Master of Science / Department of Electrical and Computer Engineering / Steven Warren / The continuous and autonomous real-time monitoring of cattle state of health can provide major benefits for the U.S. livestock industry and lead to a higher quality beef product. Complete real-time monitoring could not only lead to earlier detection of disease in individual animals and reduce the spread of disease to a larger herd, but it could ultimately reduce the cost and frequency of on-site veterinary consultations. This thesis details a wearable device that is mounted on cattle to collect data from a network of internal and external sensors. In addition to the basic data collection, this thesis will describe the infrastructure to communicate these data sets to a central database for permanent storage and future analysis. Physiological, ambient environment, and physical activity data are acquired by the various sensors to give a good indication of the state of health of an animal wearing the device. The communication of data from internal sensors to an external wearable receiver is of particular interest since tissue is not an ideal medium for radio-frequency data transmission. Past research has attempted to use such links with little success due to large signal attenuation at high frequencies and a package that becomes much too large to be usable at low frequencies. As a result, a wireless communications method employing magnetic inductance at relatively low frequencies over short distances is described here.

Master of Science / Department of Electrical and Computer Engineering / Steven Warren / Polysomnography is a method to obtain physiological signals from individuals with potential sleep disorders. Such physiological data, when acquired from children with autism spectrum disorders, could allow caregivers and child psychologists to identify sleep disorders and other indicators of nighttime well-being that affect their quality of life and ability to learn. Unfortunately, traditional polysomnography is not well suited for children with autism spectrum disorder because they commonly have an aversion to unfamiliar objects – in this case, the numerous wires and electrodes required to perform a full polysomnograph. Therefore, an innovative, unobtrusive method for gathering relevant physiological data must be designed. This report discusses several methods for obtaining a ballistocardiogram (BCG), which is a representation of the ballistic forces created by the heart during the cardiac cycle. A ballistocardiograph design is implemented using an electromechanical film placed under the center of a bed sheet. While an individual sleeps on the bed, the circuitry attached to the film extract and amplify the BCG data, which are then streamed to a computer through a LabVIEW interface and stored in a text file. These data are analyzed with a MATLAB algorithm which uses autocorrelation and linear predictive coding in the time domain to sharpen the signal. Frequency-domain peaks are then extracted to determine average heart rate every ten seconds. Initial tests involved four participants (student members of the research team) who laid in four positions: on their back, stomach, right side, and left side, yielding 16 unique data sets. Each participant laid in at least one position that allowed for accurate tracking of heart rate, with seven of the 16 signals demonstrating heart rates with less than 2% error when compared to heart rates acquired with a commercial pulse oximeter. The stomach position appeared to offer the lowest total error, while lying on the right side offered the highest total error. Overall, heart rates acquired from this initial set of participants exhibited an average error of approximately 2.5% for all four positions.

Doctor of Philosophy / Department of Grain Science and Industry / Xiuzhi Susan Sun / Om Prakash / Rational design of peptide molecules to undergo spontaneous organization as a higher-ordered supramolecular structure is an attractive and fast-growing field for developing new functional biomaterials. Hydrogel, with its high water content and three-dimensional architecture, is formed by a self-assembling peptide and has great potential for broad biomedical applications. The key challenge in controlling the functional properties of final biomaterials can be met by designing the peptide primary structure carefully at the beginning and developing a comprehensive understanding of peptide self-assembly pathways. In this study, we first designed a Ca2+ responsive peptide (eD2) using identified functional native domains from a spider flagelliform silk protein and the Ca2+ binding domain of lipase Lip A from Serratia marcescens. Instead of directly linking the two peptide sequences, we rationally inserted the ion-binding motif into the silk structure sequence and made the new peptide inherit the physical characteristics of both model sequences and assemble into nanofibers when triggered by Ca2+. Next, we introduced the amphiphilic property to the eD2 peptide by conjugating its N-terminus with a strong hydrophobic sequence from a trans-membrane segment of human muscle L-type calcium channel. This self-assembly peptide, called h9e, was responsive to Ca2+, solution pH, and selected proteins for hydrogel formation. Interestingly, the turning segment GSII of h9e was considered to play a critical role in construction of the finial matrix. This hypothesis was further demonstrated by exploiting a series of amphiphilic diblock model peptides with different conformational flexibility. The kinetic rate of peptide assembly was suggested as one of the key influences for peptide supramolecular assembly morphology. To better understand the peptide self-assembly process during hydrogel formation, the conformational, morphological, and mechanical properties of h9e molecules in different dimethylsulfoxide/H2O solutions were monitored by 1D and 2D proton nuclear magnetic resonance (NMR), electron microscopy, and a rheometer. The h9e peptide hydrogel formed with Ca2+ and albumin exhibited superior physiological and specific injectable properties, which provides a more realistic tool for 3D cell culture and drug delivery. This study generates new knowledge and contributes to the field by leading to a better understanding the self-assembly hydrogel formation and designing peptides with unique properties for biomedical applications such as cell culture, drug delivery, and tissue engineering.

Master of Science / Department of Electrical and Computer Engineering / Steven Warren / Handgrip contractions are a useful exercise for assessing muscle fatigue in the forearm musculature. Most conventional hand-forearm ergometer systems require the researcher to manually guide subject activity, collect subject data, and assess subject fatigue after it has occurred. Since post-processing tools are not standardized for this type of experiment, researchers resort to building their own tools. This process can make comparing results between research groups difficult. This thesis presents updates to a hand-forearm ergometer system that automate the control, data-acquisition, and data-analysis mechanisms. The automated system utilizes a LabVIEW virtual instrument as the system centerpiece; it provides the subject/researcher interfaces and coordinates data acquisition from both traditional and new sensors. The system also processes the hand-forearm data within the LabVIEW environment as the data are collected. This allows the researcher to better understand the onset of subject fatigue while an experiment is in progress. System upgrades relative to prior work include the addition of new parameters to the researcher display, a change in the subject display from a binary up-down display to a sliding bar for better control over subject grip state, and a software update from a simple data acquisition and display system to a real-time processing system. The toolset has proven to be a viable support resource for experimental studies performed in the Kansas State University Human Exercise Physiology Laboratory that target muscle fatigue in human forearms. Initial data acquired during these tests indicate the viability of the system to acquire consistent and physiologically meaningful data while providing a useable toolset for follow-on data analyses.

Doctor of Philosophy / Department of Electrical & Computer Engineering / Steve Warren / The U.S. health care system is one of the most advanced and costly systems in the world. The health services supply/demand gap is being enlarged by the aging population coupled with shortages in the traditional health care workforce and new information technology workers. This will not change if the current medical system adheres to the traditional hospital-centered model. One promising solution is to incorporate patient-centered, point-of-care test systems that promote proactive and preventive care by utilizing technology advancements in sensors, devices, communication standards, engineering systems, and information infrastructures. Biomedical devices optimized for home and mobile health care environments will drive this transition. This dissertation documents research and development focused on biomedical device design for this purpose (including a wearable wireless pulse oximeter, motion sensor, and two-thumb electrocardiograph) and, more importantly, their interactions with other medical components, their supporting information infrastructures, and processing tools that illustrate the effectiveness of their data. The GumPack concept and prototype introduced in Chapter 2 addresses these aspects, as it is a sensor-laden device, a host for a local body area network (BAN), a portal to external integration frameworks, and a data processing platform. GumPack sensor-component design (Chapters 3 and 4) is oriented toward surface applications (e.g., touch and measure), an everyday-carry form factor, and reconfigurability. Onboard tagging technology (Chapters 5 and 6) enhances sensor functionality by providing, e.g., a signal quality index and confidence coefficient for itself and/or next-tier medical components (e.g., a hub). Sensor interaction and integration work includes applications based on the GumPack design (Chapters 7 through 9) and the Medical Device Coordination Framework (Chapters 10 through 12). A high-resolution, wireless BAN is presented in Chapter 8, followed by a new physiological use case for pulse wave velocity estimation in Chapter 9. The collaborative MDCF work is transitioned to a web-based Hospital Information Integration System (Chapter 11) by employing database, AJAX, and Java Servlet technology. Given the preceding sensor designs and the availability of information infrastructures like the MDCF, medical platform-oriented devices (Chapter 12) could be an innovative and efficient way to design medical devices for hospital and home health care applications.

Doctor of Philosophy / Department of Electrical and Computer Engineering / William B. Kuhn / Balasubramaniam Natarajan / Wireless body area networks (WBANs) are an important part of the developing internet of things (IOT). NASA currently uses space suits with wired sensors to collect limited biomedical data. Continuous monitoring and collecting more extensive body vital signs is important to assess astronaut health. This dissertation investigates wireless biomedical sensor systems that can be easily incorporated into future space suits to enable real time astronaut health monitoring. The focus of the work is on the radio-wave channel and associated antennas. We show that the space suit forms a unique propagation environment where the outer layers of the suit’s thermal micrometeoroid garment are largely radio opaque. This environment can be modeled as a coaxial one in which the body itself plays the role of the coax center conductor while the space suit shielding materials play the role of the outer shield. This model is then validated through simulations and experiments. Selecting the best frequency of operation is a complex mixture of requirements, including frequency allocations, attenuation in propagation, and antenna size. We investigate the propagation characteristics for various frequency bands from 315 MHz to 5.2 GHz. Signal attenuation is analyzed as a function of frequency for various communication pathways through 3D simulations and laboratory experiments. Small-scale radio channel results indicate that using lower frequency results in minimal path loss. On the other hand, measurements conducted on a full-scale model suggest that 433 MHz and 2400 MHz yield acceptable path loss values. Propagation between the left wrist and left ankle yielded the worst overall path loss, but signals were still above –100 dBm in raw measurements for a 0dBm transmission indicating that the intra-suit environment is conducive to wireless propagation. Our findings suggest that the UHF bands are best candidate bands since there is interplay between the body conductivity favoring lower frequencies, and the difficulty of coupling RF energy into and out of the channel using suitably sized antennas favoring higher frequencies. Finally, a new self-shielded folded bow-tie antenna is proposed that can be a promising choice for the general area of WBAN technologies as well as potential new space suit environments.

Master of Science / Department of Electrical & Computer Engineering / Steve Warren / Handgrip contractions are a standard exercise modality to evaluate muscular system performance. Most conventional ergometer systems that collect handgrip contraction data are manually controlled, placing a burden on the researcher to guide subject activity while recording the resultant data. Further, post-processing tools for this type of experiment are not standardized within the domain, which requires investigators to process their data with multiple tool sets and often create custom tool sets for that purpose. This can make experimental data difficult to compare and correlate, even within the same research group. This thesis presents updates to a hand-forearm ergometer system that automate the control and data-acquisition processes as well as provide a tool set to post process hand contraction data. The automated system utilizes a LabVIEW virtual instrument as the system centerpiece; it provides the subject/researcher interfaces and coordinates data acquisition from both traditional and new sensors. The tool set also incorporates a collection of MATLAB scripts that allow the investigator to post process these data in a standard way, such as automating the processes of noise floor removal, burst start/stop time identification, and mean/median frequency calculation in electromyograms (EMGs). The tool set has proven to be a viable support resource for experimental studies performed by the Kansas State University Human Exercise Physiology lab that target muscle fatigue in human forearms. Initial data acquired during these tests indicate the viability of the system to acquire consistent and physiologically meaningful data while providing a usable tool set for follow-on data analyses.

Master of Science / Department of Industrial and Manufacturing Systems Engineering / Chih-Hang John Wu / The University of Kansas Medical Center’s Emergency Department is adopting a new residency program. In the past, generalized Residents have supported attending physicians during a required three month rotation in the Emergency Department. As of July 2010, the University of Kansas Medical Center’s Emergency Department has switched to a dedicated Emergency Medicine Residency program that allows recently graduated physicians the opportunity enter the field of Emergency Medicine. This thesis shows that although not initially a dedicated residency program provides an advantage to the Emergency Department. Discrete Event Simulations have been used to predict changes in processes, policies, and practices in many different fields. The models run quickly, and can provide a basis for future actions without the cost of actually implementing changes in policies or procedures. This thesis applies a learning curve in a Simulation Model in order to provide data that the University of Kansas Medical Center’s Emergency Department can utilize to make decisions about their new Residency Program. A generalized learning curve was used for the base model and compared to all alternatives. When it was compared with an alternative curve following a Sigmoid Function (Logistic Function), there were no significant differences. Ultimately, a Gompertz Curve is suggested for hospitals attempting to develop or improve their residency programs using learning curves because it is easily fitted to their desired shape. This thesis shows the effect that Residents have on the performance of the Emergency Department as a whole. The two major components examined for the generalized learning curve were the initial position for first year residents determined by the variable [alpha], and the shape of the curve determined by the variable [beta]. Individual changes the value of [alpha] had little effect. Varying values of [beta] have shown that smaller values elongate the shape of the curve, prolonging the amount of time it takes for a resident to perform at the level of the attending physician. Each resident’s personal value of [beta] can be used to evaluate the performance in the emergency department. Resident’s who’s [beta] value are smaller the emergency department’s expected value might have trouble performing.