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Supplemental Materials for Investigating ruminal resident immune cells in dairy cattle before and after a subacute ruminal acidosis challenge.
No full textImmune cells have been observed in many tissues of the mammal including the gut, liver, adipose, bone, and neural tissue. Our objective was to demonstrate whether immune cells are present within the stratified rumen epithelium of healthy lactating dairy cattle. We hypothesized that immune cells would be found in the rumen tissue and that the total amount of leukocytes present would increase during a ruminal acidosis challenge. We conducted a 2-phase experiment with 9 rumen-cannulated lactating Holstein cows. During phase 1, cows were fed a diet containing 31% NDF, 24% forage NDF and 27% starch (CON) for 14 d. The starch sources were corn silage and dry ground corn. During phase 2, cows were fed a diet with 28% NDF, 16% forage NDF, and 32% starch (SARA) for 7 d. The SARA starch sources were corn silage, dry ground corn, ground wheat, and ground barley. During both phases, rumen fluid, fecal, blood, and rumen tissue samples were collected. Feed intake and milk yield were recorded each day and milk samples were collected at each milking during the final 2 d of each period. Data were analyzed with mixed models that included the fixed effect of phase (CON or SARA) and the random effect of cow. The SARA diet reduced rumen pH and increased area under the curve for rumen pH beneath 5.8 and 5.6. Feed intake, milk yield, and milk protein yield increased for SARA. Phase did not affect ruminal immune cell phenotype proportions or total presence. Most immune cells observed were CD3+ (T-cells) for both CON and SARA. The ruminal immune cells were located within the lamina propria, stratum basale, and stratum spinosum of the rumen papillae. Our data demonstrate that T lymphocytes are prominent in rumen tissue. Understanding the role of ruminal leukocytes may yield new insights into ruminant gut health, function, development, and maintenance.USDA AFRI Education and Workforce Development Predoctoral Fellowship program (award #2022-11331
The Design and Synthesis of Small Molecule Therapeutics and Vaccine Prophylactics as Medical Solutions for Organophosphorus Exposure
Get PDFOrganophosphorus (OP) compounds pose a serious health risk to humans through the inhibition of acetylcholinesterase (AChE). AChE is a vital enzyme responsible for hydrolyzing the neurotransmitter acetylcholine (ACh), which plays the primary role in muscle contraction and nerve signaling. OP compounds inhibit AChE through the phosphylation of the catalytic serine residue, preventing hydrolysis of ACh, leading to cholinergic crisis and death. Current therapeutics include oxime moieties that operate via a nucleophilic attack on the phosphylated serine residue of some OP-inhibited forms of AChE, a process which has been coined reactivation. However, oximes are limited by a lack of broad-scope reactivation, and they are ineffective at crossing the blood-brain barrier due to their permanent positive charge, thus limiting reactivation of AChE within the central nervous system (CNS). OP-inhibited AChE can also undergo a spontaneous O-dealkylation process, coined aging, in which current therapeutics do not offer any recovery.
In 2018, the Hadad lab reported a class of quinone methide precursors (QMPs) that were the first therapeutics to show evidence of recovery of the OP-aged form of the enzyme in a process termed resurrection. These QMPs have since been iterated and are able to recover both the inhibited and aged forms of AChE. Furthermore, due to being neutral, these QMP compounds have been shown to penetrate the BBB, increasing therapeutic efficacy compared to oximes. However, despite these strides toward better therapeutics, these QMPs still lack broad-scope reactivation and resurrection efficacy, and thus more research is being performed to optimize their activities. Herein, we report a novel library of 4-pyrrolylphenol and 6-pyrrolylpyridinol QMPs that show broad-scope reactivation of several OP-inhibited forms and resurrection of several OP-aged forms of AChE.
Following the discussion of QMPs, the design and synthesis of antigenic determinants as a method of prophylactic treatment to produce catalytic antibodies against OP compounds is discussed.Joint Science and Technology Office (CB10791 MCDC1905-006)Joint Science and Technology Office (CB10898 MCDC1906-005)No embargoAcademic Major: Neuroscienc
Implementation of an Evidence-Based LVAD Patient and Family Advisory Council
No full textIntroduction: A Left Ventricular Assist Device (LVAD) program was not receiving sufficient patient feedback from satisfaction surveys to enable leaders to improve the quality of the program and to meet the regulatory standard set forth by The Joint Commission to utilize patient satisfaction data for performance improvement activities.
Purpose: The purpose of this evidence-based quality improvement initiative was to implement an LVAD Patient and Family Advisory Council (PFAC) in a large urban academic Midwestern medical center to obtain meaningful patient satisfaction feedback.
Methods: LVAD patients and their support persons participated in one of three monthly PFAC sessions to share their experiences within the healthcare system, with a facilitated discussion soliciting feedback on potential areas for improvement. Audio recordings of the meetings were converted to written transcripts. Patient/family comments were separated into two categories, potentially actionable or not actionable, based on whether they contained information that could inform improvement initiatives. The potentially actionable comments were then categorized into themes.
Outcomes: Three PFAC sessions hosted 42 percent of the LVAD population, with 25 patients and 17 support persons in attendance. There were 266 comments received pertaining to the LVAD program and care, and 78 were potentially actionable with four themes: education, support, healthcare system gaps, and communication. From these comment themes, four improvement initiatives were identified for the program.
Conclusions: Implementing a PFAC for an LVAD patient population is one model to increase patient engagement. This inaugural LVAD PFAC was successful in soliciting meaningful feedback to make programmatic improvements.A five-year embargo was granted for this item
Flexible Multimodal Prediction of Alzheimer's Disease Progression with Deep Learning
Get PDFBackground: Alzheimer’s disease (AD) is a neurodegenerative disease with no known cure. AD progression has a high inter-patient variance, with some patients slowly progressing from mild cognitive impairment (MCI) to dementia while others demonstrate more rapid cognitive decline. AD progression prediction with deep learning is best informed by multiple medical data modalities, but existing multimodal models are limited by their inability to make accurate predictions when some modalities are missing during inference.
Methods: The state of the art in flexible multimodal fusion, Flex-MoE, was modified by replacing its single gating network in the sparse mixture-of-experts layer with independent gating networks for each neuroimaging modality. The resulting method is referred to as Per-Modality Mixture-of-Experts, abbreviated as PerMod-MoE. T1-weighted MRI, FLAIR, amyloid beta PET, and tau PET neuroimaging data were obtained for 469 patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Flex-MoE and PerMod-MoE were evaluated along with unimodal neuroimaging models on predicting two-year change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).
Results: PerMod-MoE achieves 8%, 4%, and 4% improvements in RMSE over Flex-MoE when evaluated on observations with only FLAIR, amyloid beta PET, and tau PET, respectively. Further, per-modality routing demonstrates competitive performance with Flex-MoE when more modalities are available. PerMod-MoE boasts an average 13% improvement in RMSE for patients with an initial CDR-SB greater than five and an average 16% improvement for patients with an observed two-year CDR-SB change of 0.5 or 1.
Conclusions: PerMod-MoE, with its addition of independent, modality-specific routers in a sparse mixture-of-experts layer, improves performance on AD progression prediction when modality availability is limited during inference.No embargoAcademic Major: Data Analytic
Design, Simulation, and Manufacturing of a Tendon Driven Compliant Robotic Gripper for Space Applications
Get PDFFirst Place in Engineering at Denman ForumSatellites can be utilized for many purposes including weather forecasting, internet communications, data services, and research gathering. Satellites have a limited lifespan often because of hardware failure including Central Processing Units (CPUs), which are responsible for the operation of control systems, navigation, data processing, communication, and other essential requirements of satellites. Because there is currently no method of performing maintenance tasks on satellites while they are in orbit, integrating robotic systems into future satellites has the potential to increase satellite lifespan by allowing for the replacement of fragile hardware. Compliant robotics, which are robotics designed with deformable materials, offer a promising solution for in-orbit maintenance tasks on spacecraft because of their flexibility, lightweight construction, energy-absorbing characteristics, and adaptability to various maintenance scenarios. The objective of this research is to design and analyze the performance of a tendon-driven compliant robotic gripper optimized for fragile hardware replacement tasks where precise and delicate manipulation is necessary, while minimizing electrical and mechanical demands. To evaluate the performance of the gripper, three methods were utilized including using the pseudo-rigid body model (PRBM), computational simulations in ANSYS Mechanical, and experimental testing. Deformable materials including 90A TPU were used for the joints while PLA was used for the rigid gripper segments. To analyze the gripper performance, the joints were specifically investigated because they are responsible for the overall deflection of the gripper. Theoretical calculations of joint stiffness, torque, and angular deflection were determined by implementing the PRBM using MATLAB. ANSYS Mechanical simulations were used to model the gripper and analyze stresses, strains, and deformations under applied loads utilizing various different joints composed of materials of various stiffnesses. Experimental tests measured the actual forces and joint deflections to validate the computational and simulation results. The findings demonstrate that a 50% decrease in joint thickness and a 20% increase in length is associated with a 86% decrease in required torque for actuation. Therefore, thinner, longer compliant joints reduce electrical costs and enable the use of smaller, more efficient motors. Additionally, the findings indicate materials with a lower Young’s modulus reduce the required torque for actuation where 60A TPU had a 20% decrease in required torque compared to 90A TPU. The results highlight the agreement between the PRBM, simulation, and experimental methods. This research contributes to the advancement of compliant robotics for aerospace applications, offering insights into the design of energy-efficient, durable, and adaptable robotic systems for in-orbit satellite maintenance and other space-related tasks. The methodology and results serve as a foundation for future developments in compliant robotic systems.Sierra LoboNo embargoAcademic Major: Aerospace Engineerin
Impacts of Drainage Water Management on Nutrient Runoff from Agricultural Fields in the Western Lake Erie Basin
No full textAlgal blooms in the Western Lake Erie Basin are a massive environmental problem fueled by nutrient pollution from agricultural runoff. In efforts to reduce the blooms, different best management practices (BMPs) have been implemented, such as drainage water management. This paper evaluates the impact of drainage water management on legacy phosphorus (P) loads on two fields, an experimental and control site, in the Maumee River Watershed. dissolved reactive P (DRP), total P (TP), nitrate-nitrogen (N-NO3), and total nitrogen (TN) areal loading rates and concentrations, as well as discharge, are evaluated.
The nutrients are evaluated based on site, management status, storm event size, and season. Storm event sizes were created based on precipitation amounts in the storms corresponding to each discharge event (small (≤0.35 inches), medium (0.35<x ≤0.75), and large (0.75<x ≤3.15)). The results show evidence that on these fields, subsurface areal loading rates of P are higher during large storm events than medium and small ones, but drainage water management reduces the increase between medium and large events. Overall, nitrogen (N) areal loading rates are higher with drainage water management than without it. Seasonally, loads are highest during March 1 to July 31, sometimes referred to as Lake Erie spring. Drainage water management can reduce the increase between the loads in other seasons and spring loads.No embargoAcademic Major: Environmental Scienc
Analysis of Thrombus Composition and Architecture in a High-Shear vs Low-Shear Stress Environment
No full textIntroduction
Thrombotic diseases—including acute ischemic stroke (AIS) and venous thromboembolism (VTE)—are major global health burdens with current therapies limited by narrow time windows, bleeding risks, or infrastructure barriers. While arterial thrombi are often labeled “white clots” rich in platelets and venous thrombi as “red clots” rich in RBCs and fibrin, this dichotomy lacks thorough validation in human tissue. Understanding thrombus composition and architecture under different shear stress conditions may uncover novel and translatable therapeutic targets, especially for patients ineligible for standard thrombolytics.
Methods
Thrombi were collected from AIS and VTE patients under IRB protocol and processed for immunofluorescent staining. Markers for von Willebrand Factor (VWF), fibrin, CD42b (platelets), glycophorin A (RBCs), PAI-1, and NETs markers (Cit-H3, MPO, NE) were quantified by percent positive area using ImageJ segmentation. Morphology was classified as peripheral, clustering, diffuse, or mixed. A two-tailed unpaired T-test compared percent area, and Z-tests assessed morphological distribution differences between arterial (n=74) and venous (n=31) thrombi.
Results
RBCs had significantly greater percent area in venous thrombi (p=0.0039), while fibrin content was paradoxically lower in venous thrombi (p=0.0128). No significant differences were observed for VWF, platelets, PAI-1, or NETs markers. Morphologically, venous thrombi demonstrated decreased clustering and increased mixed morphologies across nearly all markers. NETs markers were predominantly diffuse in both thrombus types. VWF and fibrin exhibited substantial peripheral localization. Despite expectations, VWF levels were not significantly lower in venous thrombi, suggesting that shear stress alone does not dictate its distribution.
Conclusion
These results challenge the conventional “white vs red clot” model by revealing that fibrin is more abundant in arterial thrombi and that platelet content is not significantly reduced in venous thrombi. Elevated PAI-1 and a shell-like fibrin structure suggest thrombolytic resistance, while VWF and NETs may prove to be efficacious therapeutic targets due to their widespread presence in both AIS and VTE. This work underscores the need to revise simplistic thrombus classifications and supports targeted therapeutic innovation.A three-year embargo was granted for this item.Academic Major: Biomedical Scienc
Novel Device for Intermediate Strain Rate (ISR) Testing
Get PDFDue to the strain rate sensitivity of materials, it is necessary to have reliable dynamic data, in order to calibrate material models used in Computer Aided Engineering. The difficulty of testing intermediate strain rates (ISR) arises from the oscillations and ringing produced during testing, as inertia manifesting itself as reflected elastic waves negatively affects the quality of test data. Additionally, intermediate strain rates are too slow for traditional high rate dynamic testing apparatuses, such as the Split Hopkinson Bar (SHB), as the duration of the test is limited by the length of the transmitter bar. Current approaches to testing at ISRs utilize a modified SHB, consisting of a high speed hydraulic actuator, and a very long transmitter bar, in order to eliminate unwanted oscillations from the data. To address the impractical size and complexity of existing ISR testing devices, the need for a more accessible test device arises. The topic of this research will explore a solution to this shortcoming by presenting a new ISR testing configuration consisting of an in-line spring-viscous damper mechanical element, in order to eliminate the need for a long transmitter bar or data filter. The design of the element will be informed by analytical and numerical modeling and existing hardware will be modified to test the concept experimentally.College of EngineeringNo embargoAcademic Major: Aerospace Engineerin
Exploration and Explanation of Variations in Efficacy between Self-identified Religious Terrorist Organizations and Secular Terrorist Organizations
Get PDFThis thesis examines the relationship between religious ideology and the effectiveness of terrorist organizations, assessing whether groups that incorporate religious frameworks into their objectives, structures, and leadership are more or less effective than their secular counterparts. Effectiveness is measured using a framework adapted from Risa Brooks' (2007) Creating Military Power: The Sources of Military Effectiveness, which evaluates military systems based on integration, responsiveness, quality, and skill (Brooks, 2007). To investigate the relationship between religious affiliation and effectiveness, a comparative case study approach is applied to four terrorist organizations: two with explicitly religious identification - the Islamic State of Iraq and Syria (ISIS) and Al Qaeda - and two with no explicit religious identification - the Liberation Tigers of Tamil Eelam (LTTE) and the Irish Republican Army (IRA). By analyzing these organizations' structures, ideological commitments, strategic adaptations, and operational outcomes, this study seeks to determine whether religious ideology plays a significant role in shaping terrorist group effectiveness.
Findings suggest that religiously self-affiliated groups like Al Qaeda and ISIS often face limitations in adaptability due to their rigid ideological frameworks, hindering their long-term success. In contrast, secular or nationalist groups exhibit greater flexibility, which allows them to adjust strategies and engage in political negotiations, leading to more sustainable outcomes. Ultimately, while religious self-identification can enhance group cohesion and commitment, it also reinforces inflexibility, making it a liability for organizations seeking to maintain operational success over time. The findings emphasize the importance of understanding the balance between ideological commitment and strategic adaptability for both counterterrorism efforts and the long-term sustainability of terrorist organizations.No embargoAcademic Major: Political Scienc
Alternative Education During the Holocaust
Get PDFThroughout WWII, the Nazis attacked Jewish students’ right to education in Germany and all occupied territories. This project focuses on the ways in which Central and Eastern European Jewish communities, primarily in Poland, attempted to circumvent Nazi legislation and continue to educate their children. Using primarily diaries and memoirs from Holocaust-era children, this project analyzes when and how students continued to study despite Nazi oppression. While research has been conducted on underground schools, this thesis discusses individualized alternative education which does not resemble a traditional schooling center. Alternative education began even before schools shut down with community members creating study groups and privately tutoring students. More alternative education appeared in the ghettos than among children in hiding due to the presence of a larger community; although, as conditions worsened, educational responsibility transferred from adult community members to the students themselves. Late in the war, students self-studied without the structure of formal education. There were limited examples of education in the concentration and extermination camps as well. These findings illustrate how the Holocaust should be included in the history of alternative and home education. This project also reveals how ghetto environments could result in unique educational opportunities for students and demonstrates that children were the main agents in their own educational journeys.No embargoAcademic Major: Histor