Matching Items (287)

132342-Thumbnail Image.png

Optimization of a Blood-Based Tuberculosis Diagnostic Assay for the Developing World-with a focus on Sub-Saharan Africa

Description

The optimization of a blood-based assay for diagnosing tuberculosis which has been developed and validated in Dr. Hu’s lab, at Arizona State University, is important for ensuring its successful translation

The optimization of a blood-based assay for diagnosing tuberculosis which has been developed and validated in Dr. Hu’s lab, at Arizona State University, is important for ensuring its successful translation to a resource-limited setting of the developing world. Tuberculosis is most prevalent in the developing world with Sub-Saharan Africa having the highest cases of HIV/TB coinfections. The implementation of a blood-based assay for diagnosing Tuberculosis in the sub-Saharan would significantly improve the diagnosis and treatment monitoring of tuberculosis thereby managing or eliminating the pandemic altogether. The World Health Organization has called for robust diagnostic technologies that would resolve the shortfalls of the current technologies which include GeneXpert, X-ray, and smear microscopy. The blood-based diagnostic methodology heavily relies on Mass-spectrometry, a technology which could be entirely novel and expensive to implement in most laboratories in the Sub-Saharan. Despite virtual challenges in implementing the technology, the assay has demonstrated high specificity and sensitivity to HIV/TB coinfected patients and children in comparison to the available TB diagnostic assays. This study endorses the Blood-based Mass Spectrometry assay as one of the promising technologies to effectively improve the diagnosis of TB. The performance of the assay on detecting TB antigens was tested using different methods and materials. In the end, the use of DBS and miniaturized mass spectrometers have been discussed as possible routes for translating the assay to the developing world

Contributors

Agent

Created

Date Created
  • 2019-05

132188-Thumbnail Image.png

UTILIZING A NOVEL 3D BREAST TUMOR MODEL TO STUDY COMBINATORIAL DRUG TREATMENT EFFICACY

Description

Stromal cells play an important role in facilitating disease progression of ductal carcinoma. Cancer associated fibroblasts (CAFs) are an important component of the extracellular matrix (ECM) which constitutes the microenvironment

Stromal cells play an important role in facilitating disease progression of ductal carcinoma. Cancer associated fibroblasts (CAFs) are an important component of the extracellular matrix (ECM) which constitutes the microenvironment of breast tumor cells. They are known to participate in chemotherapeutic drug resistance by modulating various biochemical and biophysical factors that contribute to increased matrix stiffness and collagen I density of the tumor-adjacent stroma. To address these issues in terms of patient treatment, anti-cancer drug regimes have been assembled to incorporate both chemotherapeutic as well as anti-fibrotic drugs to both target tumor cells while also diminishing the elastic modulus of the microenvironment by targeting CAFs. The quantitative assessment of these drug regimes on tumor progression is missing in terms of CAFs role alone.

A high density 3D tumor model was utilized to recapitulate the tumor microenvironment of ductal carcinoma in vitro. The tumor model consisted of MDA-MB-231 tumors seeded within micromolded collagen wells, chemically immobilized upon a surface treated PDMS substrate. CAFs were seeded within the greater collagen structure from which the microwells were formed. The combinatorial effect of anti-fibrotic drug (Tranilast) and chemotherapy drug (Doxorubicin) were studied within 3D co culture conditions. Specifically, the combinatorial effects of the drugs on tumor cell viability, proliferation, and invasion were examined dynamically upon coculture with CAFs using the microengineered model.

The results of the study showed that the combinatorial effects of Tranilast and Doxorubicin significantly decreased the proliferative ability of tumor cells, in addition to significantly decreasing the ability of tumor cells to remain viable and invade their surrounding stroma, compared to control conditions.

Contributors

Agent

Created

Date Created
  • 2019-05

132190-Thumbnail Image.png

Germ Cell Specific Safety Switches: Cell Isolation

Description

The process of spermatogenesis, the differentiation of sperm stem cells into spermatozoa, produces a diverse array of descendent cells which express varied morphological and genetic traits throughout their maturation. Beginning

The process of spermatogenesis, the differentiation of sperm stem cells into spermatozoa, produces a diverse array of descendent cells which express varied morphological and genetic traits throughout their maturation. Beginning with primordial germ cells, these sperm progenitors experience twelve stages of differentiation before maturation into their final stage. During their differentiation, these cells reside in the seminiferous tubules within the testes. These tubules are surrounded by somatic cells, primarily Sertoli, Leydig, myoid, and epithelial cells. These cells provide the germ cells with necessary signaling proteins for their progression as well as protection from exterior toxins through the formation of the blood-testis barrier (BTB). However, their close association with germ cells makes extracting these sperm progenitors difficult. Here, I convey the results for an initial trial of harvesting germ cells from two mice. Due to inconclusive qRT-PCR amplification data from the first experiment, future iterations of this harvest will explore other previously published methods. These will include Magnetic-Activated Cell Sorting which will target individual sperm progenitor populations using cell-surface receptors such as GFRα-1 and THY1 to obtain sperm stem cells. Additionally, Fluorescence-Activated Cell Sorting may be useful for obtaining multiple groups of meiotic cell types from a heterogenous cell suspension harvested from the seminiferous tubules through the use of Hoechst 33342 staining. Finally, extraction of spermatozoa from the Cauda Epididymis, a storage site for these mature sperm, can be performed either in conjunction with testes collection during necropsy or as an in vivo technique intended for serial sampling of sperm cells over time. Regardless, it is necessary for these methods to produce populations from spermatogonia to spermatozoa with high purity in order to produce representative qRT-PCR results downstream, indicating either presence or lack of genetic mutation enacted by future CRISPR-Cas9 experiments.

Contributors

Agent

Created

Date Created
  • 2019-05

132198-Thumbnail Image.png

The feasibility, development, and accuracy of a re-instrumented force sensing retracting suction neurosurgical tool

Description

This thesis investigates the feasibility, development, and accuracy of implementing two inline sets of uniaxial strain gauges for a neurosurgical force sensing suction and retraction (FSSR) instrument to determine force

This thesis investigates the feasibility, development, and accuracy of implementing two inline sets of uniaxial strain gauges for a neurosurgical force sensing suction and retraction (FSSR) instrument to determine force metrics such as magnitude, location, and orientation of applied force in real time. Excess force applied during a neurosurgery could lead to complications for the patient during and after surgery, thus there is clinical need for a quantitative real time tool-tissue feedback for various surgical tools. A force-based metric has been observed to be highly correlated to improving not only surgical training but also the outcome of surgical procedures. Past literature and previous studies attempted to design a force sensing retractor. Although previous investigations and prototypes have developed methods and protocols to detect small magnitude forces applied, they lacked the ability to detect the magnitude of force without knowing the distance of the applied force. This is a critical limitation because the location of a net applied force can vary along a retractor during surgery and is often unseen and cannot be measured during surgery. The main goal of this current investigation is to modify the previous design of the force sensing suction retractor (FSSR) device with a new placement of strain gauges, utilizing a novel configuration of an aligned pair of strain gauge arrangement with only knowing the distance between the pair of gauge sets and the strain data collected. The FSSR was a stainless steel suction tube retrofitted with 8 gauges: two sets of 4 gauges aligned and separated radially by 90 degrees within each set. Calibrations test and blind load tests were conducted to determine accuracy of the instrument for detecting the force metrics. It was found that a majority of 40 variations for the calibration tests maintained a percent difference under 10% when comparing actual and calculated values. Specifically, using calibration test 2 for blind test 2 the orientation yielded a calculated value that was 2.1 degrees different. Blind test 2 for the magnitude yielded a calculated value that was .135 N different, which is a 9.104 % difference. Also, blind test 2 set 1 and set 2 for the location of applied load from set 1 and set 2 yielded a calculated value that was 7.334 mm different, which is an 8.95 % difference for set 1 and a 15.63 % difference for set 2. Possible limitations and errors in the protocol that may have increased the discrepancy between actual and calculated values include how accurate the strain gauges were placed in terms of both alignment and radial orientation. Future work in regards to improving the new FSSR prototype, is to first develop a better method to ensure accurate placement of gauges, both in paired alignment between sets and radial separation within sets. Overall, the clinical considerations for a force sensing tool is aimed at minimizing patient injury during surgery, devices such as the force sensing suction retractor is an example of novel technology that could become a standard technology within the operating room.

Contributors

Agent

Created

Date Created
  • 2019-05

Optimizing Recombinant Protein Production for Domain Antibodies: Proof-of-Concept

Description

Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics

Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics is attractive for a number of reasons, yet, the production pipeline for high yield and consistent bioactive recombinant proteins remains a major obstacle. Previous studies for recombinant protein production has utilized gram-negative hosts such as Escherichia coli (E. coli) due to its well-established genetics and fast growth for recombinant protein production. However, using gram-negative hosts require lysis that calls for additional optimization and also introduces endotoxins and proteases that contribute to protein degradation. This project directly addressed this issue and evaluated the potential to use a gram-positive host such as Brevibacillus choshinensis (Brevi) which does not require lysis as the proteins are expressed directly into the supernatant. This host was utilized to produce variants of Stock 11 (S11) protein as a proof-of-concept towards this methodology. Variants of S11 were synthesized using different restriction enzymes which will alter the location of protein tags that may affect production or purification. Factors such as incubation time, incubation temperature, and media were optimized for each variant of S11 using a robust design of experiments. All variants of S11 were grown using optimized parameters prior to purification via affinity chromatography. Results showed the efficiency of using Brevi as a potential host for domain antibody production in the Stabenfeldt lab. Future aims will focus on troubleshooting the purification process to optimize the protein production pipeline.

Contributors

Agent

Created

Date Created
  • 2019-05

134495-Thumbnail Image.png

Comparative Analysis of Interprofessional Clinic Models: Recommendations for Best Practice Implementation

Description

As the complexity of healthcare continues to rise, the need for change in healthcare delivery is more prominent than ever. One strategy identified by the World Health Organization (WHO) for

As the complexity of healthcare continues to rise, the need for change in healthcare delivery is more prominent than ever. One strategy identified by the World Health Organization (WHO) for responding to these increasing complexities is the use of interprofessional practice and education to improve patient outcomes, reduce costs, and enhance the patient experience of care (Triple Aim). Interprofessional collaboration among diverse disciplines is evident on the Phoenix Biomedical Campus, integrating a wide variety of institutions and multiple health profession programs; and at the Student Health Outreach for Wellness (SHOW) free clinic, -- a successful tri-university, student-led, faculty mentored, and community-based model of interprofessional learning and care -- based in downtown Phoenix. This project conducted a comparative analysis of interprofessional components of 6 different clinical models in order to provide recommendations for best practice implementation. These models were chosen based on availability of research on interprofessionalism with their clinics. As a result, three recommendations were offered to the SHOW clinic for consideration in their efforts to improve both patient and educational outcomes. Each recommendation was intentionally formulated for its capacity to increase: interprofessionalism and collaboration between multiple disciplines pertaining to healthcare, among healthcare professionals to promote positive patient and educational outcomes. These recommendations include implementing an interprofessional education (IPE) course as a core component in an academic program's curriculum, offering faculty and professional development opportunities for faculty and mentors immersed in the interprofessional clinics, and utilization of simulation centers. Further studies will be needed to evaluate the impact these specific interventions, if adopted, on patient and educational outcomes.

Contributors

Agent

Created

Date Created
  • 2017-05

134441-Thumbnail Image.png

Utilization of Electrochemical Impedance Spectroscopy for the Detection of QSOX1 and CEA

Description

Improved pancreatic cancer diagnostic technology has the potential to improve patient prognosis by increasing cancer screening rates and encouraging early detection of the cancer. To increase the sensitivity and specificity

Improved pancreatic cancer diagnostic technology has the potential to improve patient prognosis by increasing cancer screening rates and encouraging early detection of the cancer. To increase the sensitivity and specificity while decreasing the cost and time investment, the emerging detection method of electrochemical impedance spectroscopy (EIS) was tested to detect two pancreatic cancer specific biomarkers. The antibodies of carcinoembryonic antigen and quiescin sulfhydryl oxidase 1 were immobilized individually to gold disk electrodes and tested for binding to their respective antigens. An AC signal of varying potential and a wide frequency sweep was applied to the electrode system and the resulting imaginary impedance values were analyzed. Based off of the highest slope and R-squared values of the collected impedance values, the optimal binding frequencies of QSOX1 and CEA with their antibodies was determined to be 97.66 Hz and 17.44 Hz, respectively. EIS was also used to test for potential multimarker detection by coimmobilizing anti-CEA and anti-QSOX1 to the surface of gold disk electrodes. Each system's impedance response was correlated to the physiological concentration range of CEA and QSOX1 individually. The resulting impedance and concentration calibration curves had R-squared values of 0.78 and 0.79 for the calculated QSOX1 and CEA, respectively. Both markers showed similar trends between the calculated and actual calibration curves for each marker. The imaginary impedance output lacks two independent peaks for the distinct optimal binding frequencies of both biomarkers after signal subtraction and show a large shift in optimal frequencies. From analyzing the co-immobilization data for the calculated and experimentally determined calibration curves of CEA and QSOX1, both curves had different correlation values between imaginary impedance values and concentration. Add and subtracting the experimental and calculated co-immobilization, QSOX1, and CEA signals suggest an oversaturation of QSOX1 used during the experiments.

Contributors

Agent

Created

Date Created
  • 2017-05

Biomedical Engineering Workforce Competencies for 21st Century Healthcare Technology Product Development Teams: A BME Student Cohort Perspective

Description

The importance of efficient design and development teams in in 21st century is evident after the compressive literate review was performed to digest various aspects of benefits and foundation of

The importance of efficient design and development teams in in 21st century is evident after the compressive literate review was performed to digest various aspects of benefits and foundation of teamwork. Although teamwork may have variety of applications in many different industries, the new emerging biomedical engineering is growing significantly using principles of teamwork. Studying attributes and mechanism of creating successful biomedical engineering teams may even contribute more to the fast paste growth of this industry. In comprehensive literate review performed, general importance of teamwork was studied. Also specific hard and soft attributes which may contribute to teamwork was studied. Currently, there are number of general assessment tools which assists managements in industry and academia to systematically bring qualified people together to flourish their talents and skills as members of a biomedical engineering teams. These assessment tools, although are useful, but are not comprehensive, incorporating literature review attributes, and also doesn't not contain student perspective who have experience as being part of a design and development team. Although there are many scientific researches and papers designated to this matter, but there is no study which purposefully studies development of an assessment tool which is designated to biomedical engineering workforce and is constructed of both literature, current assessment tools, and also student perspective. It is hypothesized that a more comprehensive composite assessment tool that incorporate both soft and hard team attributes from a combined professional and student perspective could be implemented in the development of successful Biomedical Engineering Design and Development teams and subsequently used in 21st century workforce.

Contributors

Agent

Created

Date Created
  • 2017-05

133991-Thumbnail Image.png

Flicker: A Climate Fiction Novella and Analysis

Description

The novella Flicker by Rachel Ponstein is a climate fiction story. It draws influence from the post-apocalyptic and dystopian genres as well as classic gothic literature. The story utilizes elements

The novella Flicker by Rachel Ponstein is a climate fiction story. It draws influence from the post-apocalyptic and dystopian genres as well as classic gothic literature. The story utilizes elements of gothic literature including Freud's Uncanny, uneven framing, and bildungsroman. It also utilizes subhuman species to incite conversation about the importance of perspective and the use of an alternative lens on the post-Reckoning world. The disaster story is ambiguous to focus the reader on the importance of the characters and their progress throughout the journey rather than the overall plotline. The analysis below serves as an explanation for the intentional decisions made to fit a sub-genre and engage the reader in an intellectual conversation about the issues broached.

Contributors

Agent

Created

Date Created
  • 2018-05

133841-Thumbnail Image.png

The Effects of Human Hairless Gene Overexpression on U87 MG Glioblastoma Cell Function

Description

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with a median prognosis of 14 months. Human hairless protein (HR) is a 130 kDa nuclear transcription factor that plays a

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with a median prognosis of 14 months. Human hairless protein (HR) is a 130 kDa nuclear transcription factor that plays a critical role in skin and hair function but was found to be highly expressed in neural tissue as well. The expression of HR in GBM tumor cells is significantly decreased compared to the normal brain tissue and low levels of HR expression is associated with shortened patient survival. We have recently reported that HR is a DNA binding phosphoprotein, which binds to p53 protein and p53 responsive element (p53RE) in vitro and in intact cells. We hypothesized that HR can regulate p53 downstream target genes, and consequently affects cellular function and activity. To test the hypothesis, we overexpressed HR in normal human embryonic kidney HEK293 and GBM U87MG cell lines and characterized these cells by analyzing p53 target gene expression, viability, cell-cycle arrest, and apoptosis. The results revealed that the overexpressed HR not only regulates p53-mediated target gene expression, but also significantly inhibit cell viability, induced early apoptosis, and G2/M cell cycle arrest in U87MG cells, compared to mock groups. Translating the knowledge gained from this research on the connections between HR and GBM could aid in identifying novel therapies to circumvent GBM progression or improve clinical outcome.

Contributors

Agent

Created

Date Created
  • 2018-05