2923 research outputs found
Sort by
Peptide Carriers to Improve Uptake and Functionality and to Cross BBB to Arrest Secondary Injury Post TBI
Get PDFCell-penetrating peptides (CPP) possess the ability to transport different cargos efficiently across the cell membrane. In this study, the ability of a CPP to cross the blood-brain barrier (BBB) and stably carry therapeutic components across the plasma membrane was assessed. The therapeutic efficacies were determined by the ability of the KAFAK conjugated anti-inflammatory peptide drug to inhibit the progression of secondary neuronal damage in a traumatic brain injury (TBI) model at 7-day post-injury (DPI) by inhibiting the production of inflammatory cytokines. A related study with minocycline and PgP-rolipram was conducted to improve the outcome in TBI models at 14 DPI. Similarly, the ability of halloysite nanotubules (HNTs) to cross the BBB was investigated. Improving the BBB-crossing carrier library is the primary objective of this study, which seeks to identify reliable carrier molecules that can transport therapeutic compounds to the brain to treat brain injury and disorders.
Initially, two peptides were synthesized: (1) an anti-inflammatory peptide (AIP-1) that specifically target the MK2 pathway (mitogen-activated protein kinase) to regulate the inflammatory response (control), and (2) KAFAK, a CPP conjugated to AIP-1. The intracellular delivery, therapeutic efficacy, and cytotoxicity of these peptides were compared in rodent primary BBB cells (primary brain microvascular endothelial cells (BMVEC\u27s)) and four cell lines (macrophages (RAW, J774), neuronal cells (SHEP-1), and hepatocytes (HEP G2)). KAFAK did not induce cell toxicity at concentrations below 250 µM in primary BMVEC cells and below 1000 µM in the cell lines. Subsequently, the CPP conjugate was validated in vivo for its uptake and localization in the brain and its therapeutic efficacy in a TBI mouse model following non-invasive intranasal administration for six days. The results showed that KAFAK was primarily localized in the olfactory bulbs. Some diffused throughout the cortex, and it reduced cytokine (IL-1β, IL-6, and TNF-α) production in TBI mice as compared to vehicle-treated mice.
Halloysite nanotubules (HNTs), naturally available nanoparticles, were also explored for their ability to penetrate the BBB. HNTs were loaded with rhodamine isothiocyanate (RITC) to determine their uptake and localization in the brain at 4, 24, and 48 hours after a single noninvasive intranasal administration. Another group of mice received HNTs loaded with diazepam intranasally for six days and was evaluated for behavioral changes versus mice that received HNTs alone. Fluorescence from RITC was observed in the brain tissue of mice treated intranasally with HNTs loaded with RITC but not in mice treated with RITC alone. The intensity of fluorescence decreased over time, and no HNTs-associated behavioral changes were observed. Mice treated with HNT-diazepam exhibited diazepam-associated behavioral changes, indicating that HNTs could penetrate the BBB and release the drug into the brain. In summary, HNTs and CPPs have demonstrated that they have the potential to transport drugs across the BBB
Alternative Approach for Assessment of Hydraulic Design Basis for Pressure Pipe Liners
Get PDFNew product development requires stringent testing to ensure that strength and safety standards are met by the innovative materials. When developing a new pipe material, several factors have to be tested for. In addition to normal material characteristics such as elastic modulus of pipe materials, long-term hydrostatic strength (LTHS) and hydrostatic design basis (HDB) are needed. Tests for typical material characteristics are commonplace and can certainly be conducted in most lab facilities. In contrast, LTHS and HDB as described in ASTM D2992 are two tests that can prove very challenging to conduct. The current method requires a minimum of 18 full pipe specimen be placed under hydrostatic test at various stress levels to produce required failures. Successfully generating these failures can be very hard to achieve with a relatively unfamiliar material. This work suggests a modified method drawing from years of successful ASTM D2990 testing. This method will combine the loading apparatus used for ASTM D2990 creep testing, strain gauges and a new relationship between strain and the typical ductile failures seen in D2992 testing. It is also possible, with existing long-term data, to model the material behavior and reduce time further. The goal of this approach is to increase the volume of testing in order to ensure a higher level of confidence for designers and owners and save clients research funding as well
Atomistic-Informed and Machine Learning-Assisted Crystal Plasticity Modeling for Materials Interface
No full textThis dissertation presents a comprehensive study that addresses two critical challenges in the field of computational materials science and engineering from nano- to mesoscale. First, to overcome the well-acknowledged length scale limitation associated with atomistic simulations, a novel two-step approach is introduced for a probabilistic prediction of stress-strain curves in terms of material volume. The method combines Molecular Dynamics (MD) simulations and a multioutput Gaussian process (MOGP) with Bayesian analysis to model stress-strain behavior and predict stress and strain values. The model effectively captures the intricate three-stage curve shape exhibited in stress-strain plots, discerning key points such as yielding, hardening, and failure. Through crucial pre-processing steps involving logarithmic transformation and standardization of input and output values, the MOGP model mitigates the impact of outliers, ensures model stability, and facilitates meaningful comparisons among different variables. The model’s accuracy and reliability are rigorously validated through Leave-One-Out Cross-Validation (LOOCV) and in-depth analysis of error metrics. The research findings demonstrate that the developed MOGP model provides highly accurate predictions of stress-strain behavior for various material sizes, thus contributing invaluable insights to materials science and engineering while offering a versatile tool for designing materials with superior mechanical properties. The integration of uncertainty estimates enables precise forecasting of stress-strain behavior beyond the typical size limitations of MD simulations, offering a versatile tool applicable to various materials. Second, to address the limited predictive capability of the existing Crystal Plasticity (CP) method in interface modeling, this work establishes a new sequential multiscale method that incorporates interfacial parameters generated from Molecular Dynamics (MD) simulations into the continuum level Crystal Plasticity Finite Element Analysis (CPFEA) model. The simulation results, as validated by experiments in the literature, acknowledge the significant influence of interface properties on material behaviors. Specifically, the flow parameter of the finite-thickness interface is first obtained by MD simulations; the Nucleation Theory with the nudged elastic band (NEB) technique is then employed to bridge the temporal domains of the atomistic and continuum models, which extrapolates the low-strain-rate yield stresses from the high-strain-rate MD results. To address length scale limitations, the above-mentioned MOGP-based machine learning model is harnessed as a robust tool for accurately forecasting stress-strain curves of materials at larger sizes, with the training data of MD simulations of materials of varying dimensions. The integrated flow parameters and extrapolated yield stresses are then incorporated into the CPFEA model, allowing for grain-level CP simulations over extended time scales. The validation of the CPFEA model against experimental results demonstrates its accuracy in describing material behavior. Additionally, the interfacial parameters obtained from MD simulations using the NEB method offer valuable insights into dislocation nucleation from interfaces. Determination of the athermal component of the yield stress and an intrinsic thermally activated portion through calculations based on Fisher plots enhances the understanding of material behavior, facilitating the development of advanced materials with improved mechanical properties. With the successful development and demonstration of these two novel methodologies, this dissertation contributes to the field of materials science and engineering by enabling precise probabilistic predictions of stress-strain behavior beyond the typical size of atomistic simulations and enhancing the capability of CP simulations for materials with interfaces. The research findings offer valuable insights and pave the way for designing materials with enhanced mechanical properties for various engineering applications
A Help or Hindrance? Team Leader Behaviors and the Team Climate of Innovation
Get PDFWhile the nature of teamwork in organizations is ever-evolving, the utilization of teams in some form has continued to increase over the past several decades. While creativity is generally regarded as an individual-level phenomenon, innovation tends to occur as an emergent process at the team level, so rather than only hiring and rewarding star performers, organizations should cultivate and protect the team’s climate for innovation. A particularly impactful contextual factor in team climate is the team leader’s behavior. Therefore, the team leader’s contribution to the climate should work to promote innovation rather than discourage it. A cross-sectional, correlational study surveyed participants who identified as part of a work-related team. They were asked about the motivational states their team leaders encourage (the motivational micro-climate created by the leader) and about their team’s climates of innovation and psychological safety. A regression-based analysis found the relationship between a psychologically diverse micro-climate encouraged by the team leader and the team’s climate of innovation to be significant (B = 0.11, 95.00% CI [0.10, 0.13], p \u3c .001). The analysis also considered the potential mediating role of psychological safety, and a significant indirect effect was found (β = 0.037, 95.00% CI [0.012, 0.07]). Additional relationships between selected aspects of the motivational micro-climate (specifically, purpose and change orientation) and selected factors of innovation (specifically, team orientation and vision) were examined with a moderated mediation model through conditional process analysis. Notable findings here were a positive relationship between the leader micro-climate of. iv change orientation and the team climate of innovation (B = 0.09, 95.00% CI [0.05, 0.13], p \u3c .001), that was partially mediated by the team climate of innovation factor, task orientation (B = 0.10, 95.00% CI [0.06, 0.13], p\u3c .001)
Our Pearls Matter: PCOS through the Lens of Women of Color and White Women
Get PDFThe prevalence of PCOS is increasing and due to the associated health complications, it is important to understand how higher-risk populations (women of color) cope with said condition. Analyzing current symptom management and treatment could help develop more practical resources and treatment strategies to help improve healthcare expectations and quality of life.
Ten women aged 22-38 with PCOS participated in comprehensive individual interviews with goal-oriented, semi-structured questions. A 27-question survey was also completed. Sampling was continued until data saturation was reached. The data was analyzed using the grounded theory technique which codes emergent themes with keywords and phrases which ultimately are used as the basis of the development of a new theory.
The data analysis aided in finding the main themes of the research (1) Age of diagnosis (2) Symptoms (3) Body Fat Discrimination (4) Dismissiveness/Symptoms Triage (5) Poor Guidance (6) Life Impact (7) Mental Health (8) Support Symptoms (9) Religion/Spirituality (10) Cultural Comparisons and Differences.
In this study, the women with PCOS showed similarities with symptoms, symptom management, and experiences with healthcare providers regardless of race. However, there was an expression from several participants that racial discrimination could play a role in receiving inadequate care. Recognizing potential biases with race, body size, and female reproductive health and staying current in PCOS symptom management and available resources could help provide more inclusivity, guidance, and support leading to a better quality of life and better healthcare experiences for women with PCOS
Case Study of the Contexts in Which Inclusive Leaders Learn Essential Knowledge, Skills, and Dispositions to Lead Inclusive Schools
Get PDFThis case study was implemented to better understand how leaders of inclusive schools develop the knowledge, skills, and dispositions necessary to improve schooling for all students. Inclusive leaders find that leadership preparation programs provide theoretical knowledge that is only minimally useful to them when they are faced with the day-to-day complexities of leading inclusive schools. The most important learning takes place through “trial by fire” on the job. They learn through experiencing critical incidents which occur over both the short and long term. These critical incidents have been categorized through this study as acute and chronic critical incident. Additionally, significant learning occurs through mentorship with seasoned leaders who have themselves learned to successfully lead inclusive schools
Effects of Topography on Tornado Paths Using Navier Stokes Equations
Get PDFTornadoes are relatively common in Louisiana with an average of 55 tornadoes per year. Predicting tornado paths has been extremely challenging due to the many factors that play into the formation of a tornado. According to NASA/ADS topography can have significant influence on tornado direction. The main goal of this research is to analyze tornado patterns and to determine if local topography has an effect on tornadic activity. Navier-Stokes partial differential equations will be used to model the data that is collected from the national weather service and a finite difference method will be used to solve the equations. Data will be analyzed in excel to find trends in the tornadic activity around Mount Driskill
Cobalt Nanowire Catalyst for Fischer-Tropsch Reaction
Get PDFThe Fischer Tropsch reaction is a long-standing chemical reaction that enables the generation of hydrocarbons from hydrogen and carbon monoxide. Funding for research in this field has varied over the years due to the economics of producing synthetic fuel versus processing crude oil. The development of new reactors and catalysts has increased the viability of this process, but it still isn’t enough. Presented in this thesis is a novel nanowire catalyst that is not structured in the same manner as conventional catalysts. In this work it is our goal to compare the nanowire catalyst with a traditional catalyst on the basis of activity with respect to metal surface area, hydrocarbon C5+ selectivity, and catalyst longevity. The results from this work indicate that nanowire catalyst activity and C5+ selectivity are similar to traditional catalysts. However, the catalyst activity measured over time indicates that the nanowire catalyst has a far superior longevity when compared to traditional catalyst
Silicon Nitride and Metalized Halloysite Nanotube for Enhanced Bacteriostatic Activity, Wound Healing, and Tissue Regeneration
Get PDFMetals such as titanium have been used in implants, but there are often cases of infection and rejection of the implant from the body. In the past decade, the use of metal nanoparticles has seen increasing demand as an alternative treatment for reducing microbial infections, leading to progress in orthopedic surgery and wound healing. Recent investigations have developed new biomaterial bone substitutes with novel structural, biological, and mechanical properties. Advanced ceramic materials, such as Si3N4, may fulfill all the requirements above and represent a promising alternative to metals or polymers. However, the above mentioned materials have limitations because they are not biodegradable, not biocompatible, and do not contain inherent antimicrobial properties. This research is subdivided into three projects. First, it aims to introduce antibacterial properties into fabricated 3D implants by combining antimicrobial and base polymer powders before processing, which will make the material biocompatible and biodegradable. Second, it aims to fabricate multifunctional antimicrobial blow-spun nanocomposite fiber to facilitate wound healing and reduce microbial infection. Third, it aims to fabricate a biodegradable nanocomposite hydrogel patch for the development of chronic wound healing treatment.
A patented electrodeposition process was used to coat magnesium (Mg) on the HNT outer surfaces to add additional antimicrobial properties. Gentamicin sulfate was vacuum loaded into the lumen of the HNTs, which had already been coated with Mg. Si3N4 was added to the gentamicin-loaded MgHNT to promote cell adhesion and differentiation, and the resulting composite was then 3D printed/blow-spun into the required shapes according to the testing protocol.
FTIR, XRD, and SEM images showed the presence of magnesium on halloysite. cytotoxicity tests show that the fabricated nanocomposites were not toxic to mammalian cells. The results of the antimicrobial activity showed a pronounced inhibition of bacterial growth in all fabricated nanocomposites. Cell proliferation assays showed that Si3N4 enhanced proliferation in all nanocomposites. The porosity test showed that the addition of Si3N4 does not affect the porosity and the cell attachment. The histological staining showed an increase in both calcium and mucopolysaccharides. The nanocomposite shows excellent mechanical properties and a lower contact angle after surface coating with protein. Nanocomposites degraded slowly during the biodegradation test, enabling the growth of new bone cells. Si3N4 gives the cellular surface roughness structure, hydrophilicity, and protein adsorption capability
Firefighter Safety
Get PDFThere are close to 1.2 million career and volunteer firefighters across the United States. In the year 2020 alone 62 of these firefighters died and 64,875 were injured. The following research was performed to determine if the firefighter profession has become safer due to new standards and regulations. Each year the National Fire Protection Agency(NFPA) and the Federal Emergency Management Agency(FEMA) collect data on the number of firefighter deaths and injuries, in order to determine if the standards and regulations are keeping firefighters safe. Statistical hypothesis testing and linear regression were performed on the data to show if in fact the profession is safer. This paper seeks to prove using a t-distribution hypothesis test on the correlation coefficient and the slope parameter, that over the last 40 years there has been a significant decrease in career and volunteer firefighter deaths and injuries