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Effect of Rexinoids on Inducing Effector T Cell Chemotaxis

Description

The retinoid-X receptor (RXR) can form heterodimers with both the retinoic-acid
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,

The retinoid-X receptor (RXR) can form heterodimers with both the retinoic-acid
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.

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2020-05

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A Review of the Human Vermiform Appendix and its Proposed Function

Description

Since its discovery in 1524, many people have characterized the vermiform appendix. Charles Darwin considered the human appendix to be a vestige and a useless structure. Others at the time opposed this hypothesis. However, Darwin's hypothesis became prevalent one until

Since its discovery in 1524, many people have characterized the vermiform appendix. Charles Darwin considered the human appendix to be a vestige and a useless structure. Others at the time opposed this hypothesis. However, Darwin's hypothesis became prevalent one until recently when there became a renewed interest in the appendix because of advancements in microscopes, knowledge of the immune system, and phylogenetics. In this review, I will argue that the vermiform appendix, although still not completely understood, has important functions. First, I will give the anatomy of the appendix. I will discuss the comparative anatomy between different animals and also primates. I will address the effects of appendicitis and appendectomy. I will give background on vestigial structures and will discuss if the appendix is a vestige. Following, I will review the evolution of the appendix. Finally, I will argue that the function of the appendix is as an immune organ, including discussion of gut-associated lymphoid tissue (GALT), development of lymphoid follicles in GALT and their comparison within different organs, Immunoglobulin A (IgA) function in the gut, biofilms as evidence that the appendix is a safe-house for beneficial bacteria, re-inoculation of the bowel, and protection against recurring infection. I will conclude with future studies that should be conducted to further our understanding of the vermiform appendix.

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2018-05

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Development and Evaluation of an Electrical Engineering and Math Curriculum Module for High School Students

Description

Parents in STEM careers are more apt to guide their kids towards STEM careers (Sherburne-Michigan, 2017). There are STEM programs and classes for students who are interested in related fields, but the conundrum is that students need to be interested

Parents in STEM careers are more apt to guide their kids towards STEM careers (Sherburne-Michigan, 2017). There are STEM programs and classes for students who are interested in related fields, but the conundrum is that students need to be interested in order to choose to participate. The goal of this creative project was to introduce engineering concepts in a high school class to reveal and investigate the ways in which engineering concepts can be successfully introduced to a larger student populace to increase interest in engineering programs, courses, and degrees. A lesson plan and corresponding materials - including circuit kits and a simulated ball launching station with graphical display - were made to accomplish this goal. Throughout the lesson students were asked to (1) use given materials to accomplish a goal, (2) predict outcomes based on conceptual understanding and mathematical calculations, (3) test predictions, (4) record data, and (5) analyze data to generate results. The students first created a simple circuit to understand the circuit components and learn general electrical engineering concepts. A simple light dimmer circuit let students demonstrate understanding of electrical concepts (e.g., voltage, current resistance) before using the circuit to a simulated motor in order to launch a ball. The students were then asked to predict the time and height of a ball launched with various settings of their control circuit. The students were able to test their theories with the simulated launcher test set up shown in Figure 25 and collect data to create a parabolic height versus time graph. Based on the measured graph, the students were able to record their results and compare calculated values to real-world measured values. The results of the study suggest ways to introduce students to engineering while developing hands-on concept modeling of projectile motion and circuit design in math classrooms. Additionally, this lesson identifies a rich topic for teachers and STEM education researchers to explore lesson plans with interdisciplinary connections to engineering. This report will include the inspiration for the product, related work, iterative design process, and the final design. This information will be followed by user feedback, a project reflection, and lessons learned. The report will conclude with a summary and a discussion of future work.

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2018-05

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The Development of a Plant-Expressed M2e-Based Universal Influenza Vaccine

Description

Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix

Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.

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2018-05

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Analog-to-Digital Converter Reliability Testing in Hostile Environments

Description

Analog to Digital Converters (ADCs) are a critical component in modern circuit applications. ADCs are used in virtually every application in which a digital circuit is interacting with data from the real world, ranging from commercial applications to crucial military

Analog to Digital Converters (ADCs) are a critical component in modern circuit applications. ADCs are used in virtually every application in which a digital circuit is interacting with data from the real world, ranging from commercial applications to crucial military and aerospace applications, and are especially important when interacting with sensors that observe environmental factors. Due to the critical nature of these converters, as well as the vast range of environments in which they are used, it is important that they accurately sample data regardless of environmental factors. These environmental factors range from input noise and power supply variations to temperature and radiation, and it is important to know how each may affect the accuracy of the resulting data when designing circuits that depend upon the data from these ADCs. These environmental factors are considered hostile environments, as they each generally have a negative effect on the operation of an ADC. This thesis seeks to investigate the effects of several of these hostile environmental variables on the performance of analog to digital converters. Three different analog to digital converters with similar specifications were selected and analyzed under common hostile environments. Data was collected on multiple copies of an ADC and averaged together to analyze the results using multiple characteristics of converter performance. Performance metrics were obtained across a range of frequencies, input noise, input signal offsets, power supply voltages, and temperatures. The obtained results showed a clear decrease in performance farther from a room temperature environment, but the results for several other environmental variables showed either no significant correlation or resulted in inconclusive data.

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Date Created
2019-05

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Development of Nanozymes from 2D Materials for Optical Detection of Neurotransmitters

Description

This paper discusses the possibility of utilizing 2D molybdenum disulfide (MoS2) as a nanozyme to detect dopamine colorimetric assays, first by detecting color change in liquid solutions due to oxidation and then second on paper-based assays. MoS2 samples dispersed in

This paper discusses the possibility of utilizing 2D molybdenum disulfide (MoS2) as a nanozyme to detect dopamine colorimetric assays, first by detecting color change in liquid solutions due to oxidation and then second on paper-based assays. MoS2 samples dispersed in methylcellulose (MC) solution were prepared using liquid-phase exfoliation through sonication. The dopamine (DOPA) and hydrogen peroxide (H¬¬2O2) solutions were prepared separately in specific concentrations. The solutions were mixed in a well plate and colorimetric results were analyzed by a plate reader, revealing a quantitative relationship between dopamine concentration and absorbance. Subsequent testing was conducted using paper assays, where combined solutions of DOPA and H2O2 were dropped onto paper with printed wax wells that contained dried MoS2. An analysis of the color change was conducted using a smartphone application called Color Grab to detect the red, green, and blue (RGB) values. Plotting the RGB results across the dopamine concentrations revealed a positively correlated relationship between the two factors, suggesting that a predictive model could be developed to predict dopamine concentrations based on measured colorimetric values.

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2019-05

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Predicting Mechanical Failure of Vacuum Pumps Using Accelerometer Data

Description

The objective of this paper is to find and describe trends in the fast Fourier transformed accelerometer data that can be used to predict the mechanical failure of large vacuum pumps used in industrial settings, such as providing drinking water.

The objective of this paper is to find and describe trends in the fast Fourier transformed accelerometer data that can be used to predict the mechanical failure of large vacuum pumps used in industrial settings, such as providing drinking water. Using three-dimensional plots of the data, this paper suggests how a model can be developed to predict the mechanical failure of vacuum pumps.

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2019-05

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Around the Corner Imaging: Developing a Graphical User Interface

Description

This Creative Project was carried out in coordination with the capstone project, Around the Corner Imaging with Terahertz Waves. This capstone project deals with a system designed to implement Around the Corner, or Non Line-of-Sight (NLoS) Imaging. This document discusses

This Creative Project was carried out in coordination with the capstone project, Around the Corner Imaging with Terahertz Waves. This capstone project deals with a system designed to implement Around the Corner, or Non Line-of-Sight (NLoS) Imaging. This document discusses the creation of a GUI using MATLAB to control the Terahertz Imaging system. The GUI was developed in response to a need for synchronization, ease of operation, easy parameter modification, and data management. Along the way, many design decisions were made ranging from choosing a software platform to determining how variables should be passed. These decisions and considerations are discussed in this document. The resulting GUI has measured up to the design criteria and will be able to be used by anyone wishing to use the Terahertz Imaging System for further research in the field of Around the Corner or NLoS Imaging.

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2019-05

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Worker Policing Mechanisms in Ponerine Ant Species

Description

For colonies of ponerine ant species, sterility regulation after a founding queen's death is not totally achieved in the worker caste, and the possibility of sexual reproduction is opened to workers. The persisting survival of these colonies is dependent on

For colonies of ponerine ant species, sterility regulation after a founding queen's death is not totally achieved in the worker caste, and the possibility of sexual reproduction is opened to workers. The persisting survival of these colonies is dependent on capturing the optimal reproductive ratio; yet, an informational gap bounds the mechanisms detailing the selection of new reproductives and the suppression of ovarian development in rejected reproductives. We investigated the mechanisms of worker policing, one of the primary methods of ovarian suppression, through continuous video observation for a period of five days at the start of colony instability. Observations suggest policing in H. saltator is performed by a majority of a colony, including potential reproductives, and requires multiple events to fully discourage ovarian growth.

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2018-12

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A protocol for Resolving Indeterminate Blood Phenotypes in Rhesus (Macaca mulatta) and Cynomolgus Macaques (M. fascicularis)

Description

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune responses. While most macaques can be efficiently and accurately phenotyped using a DNA-based assay, we have identified some animals that are unable to be classified as type A, B, or AB and therefore exhibit an indeterminate phenotype. The purpose of this study was to develop a protocol for resolving indeterminate blood group phenotypes and consequently determine if these animals do indeed belong to an O blood phenotype. We attempted both direct and cloning-based sequencing of 21 animals phenotyped as A, B, AB, or indeterminate in order to assess variation at the functional mutation site in exon 7 of the macaque ABO gene. Although direct-from-PCR Sanger sequencing was unable to generate reliable sequence results, our cloned plasmid protocol yielded high quality sequences consistent with known blood group-specific alleles and as such can be used to identify informative polymorphisms at this locus.

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2018-05