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Statistical Methods For Assessing Structural Change In Human & Microbial Genomes, Xuan Zhu

Dissertations and Theses (Open Access)

Genetic sequencing has been recognized as an effective approach to accurately address biological problems, such as clinical detection of disease, mutation discovery, and targeting specific biomarkers associated with complex diseases. Compared with conventional Sanger sequencing, next-generation sequencing costs much less due to massively parallel high-throughput sequencing. However, due to large numbers of short read sequences, the accuracy of high-throughput sequencing data remains a challenge in that the data obtained from next-generation sequencing often has higher error rates, which may impact downstream genomic analysis. Even if the downstream genomic analysis performs well, the quality of the result will still be impacted …

Characterizing The Source Of Neutrophil Elastase And Proteinase 3 Cross-Presentation In B-Cell Acute Lymphoblastic Leukemia, Selena Carmona

Dissertations and Theses (Open Access)

Discovery of tumor-associated antigens is an important step in designing effective antigen-targeting immunotherapies. PR1 is a nonameric human leukocyte antigen (HLA)-A2 restricted leukemia-associated antigen derived from serine proteases neutrophil elastase (NE) and proteinase 3 (P3). NE and P3 are primarily expressed in cells of myeloid lineage including granulocytes, bone marrow progenitors and myeloid leukemia. Our lab reported that NE and P3 are cross-presented by antigen presenting cells (APCs) and solid tumors, a mechanism whereby exogenous antigens are endocytosed and presented on HLA class I molecules, inducing a cytotoxic T lymphocyte (CTL)-mediated immune response. Therefore, identifying non-myeloid tumors capable of PR1 …

Undergraduate Student Perceptions And Awareness Of Genetic Counseling, Amanda Gerard

Dissertations and Theses (Open Access)

Genetic counseling (GC) is a rapidly expanding field, and the supply of certified genetic counselors is currently unable to keep up with job demand. Research is fairly limited regarding the awareness and perceptions potential genetic counseling program applicants have of the field and what factors most influence their interest in the field. This study aimed to examine some of these topics. The current study includes data collected from 1,389 undergraduate students in the sciences at 23 universities across the United States who were surveyed regarding information related to their awareness, perceptions, knowledge, and interest in GC. Data analysis was performed …

Attitudes Of Clinicians To Wards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations and Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations and Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …

Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia

Dissertations and Theses (Open Access)

Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …

Characterization Of The Ubiquitin Ligase, Ube4b, In Endocytic Trafficking, Natalie Sirisaengtaksin, Natalie Sirisaengtaksin

Dissertations and Theses (Open Access)

Endocytosis is a process by which cells internalize membrane proteins to remove them from the plasma membrane, allowing cells to regulate the cell surface expression of transmembrane proteins. In this manner, cellular responses to extracellular cues may be tuned by limiting the number of proteins available at the cell surface. One particular class of proteins, receptor tyrosine kinases (RTK), is internalized upon binding to extracellular ligands during their residence at the cell surface. The epidermal growth factor receptor (EGFR) is an RTK whose trafficking through the endocytic pathway through the cell is well-documented. Stimulation of EGFR with its cognate ligand, …

Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors, Hui Ju Hsieh

Dissertations and Theses (Open Access)

Cell cycle checkpoints determine whether cells meet requirements to progress through the next stage. In response to DNA damage, how cells activate checkpoints have been well studied, but little is known about checkpoint deactivation (recovery), which directly impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required for checkpoint recovery or adaptation after DNA damage.

To achieve this goal, we performed a multidisciplinary study combining reverse …

Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors, Hui-Ju Hsieh

Dissertations and Theses (Open Access)

Cell cycle checkpoints determine whether cells meet requirements to progress through the next stage. In response to DNA damage, how cells activate checkpoints have been well studied, but little is known about checkpoint deactivation (recovery), which directly impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required for checkpoint recovery or adaptation after DNA damage.

To achieve this goal, we performed a multidisciplinary study combining reverse …

The Role Of Adenosine Signaling In Mature Erythrocytes And Erythroid Progenitors, Hong Liu

Dissertations and Theses (Open Access)

Adenosine is a ubiquitous nucleoside in almost all the cells throughout our bodies. It is highly induced particularly under hypoxia or energy depletion conditions. Adenosine functions as a critical ligand, after binding to membrane-associated adenosine receptors, adenosine initiates a downstream signaling cascade and subsequently contributes to functions of nervous system, immune response, vascular function and even metabolism.

Hypoxia is a condition with limited O₂ availability in the whole body or a region of the body. It is a major consequence of many respiratory and cardiovascular diseases, as well as for people living and working at high altitudes or other …

Cd47+ Exosomes Facilitate Effective Targeting Of Oncogenic Kras In Pancreatic Cancer, Sushrut Kamerkar

Dissertations and Theses (Open Access)

Despite the current standard of care, the prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) remains dismal. Genetic analyses of PDAC show that mutations in the GTPase KRAS are encountered in the majority of patients that present with the disease, and are key drivers of cancer initiation, progression and metastasis. However, while it is recognized that the Ras mediated signaling pathway is a key mediator of PDAC progression, a direct and specific targeting of Ras has been elusive. Therefore, due to the indisputable evidence for the causal functional role of RAS in the biology of PDAC, new approaches to specifically …

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …

Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan

Dissertations and Theses (Open Access)

Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …

Stromal Fibroblasts Restrain The Rate Of Colon Cancer Progression And Metastasis By Suppressing Regulatory T Cells And Colon Cancer Stem Cells, Changsoo Kwak

Dissertations and Theses (Open Access)

The initiation, progression, and metastasis of tumors involve not only cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory cells, fibroblasts, endothelial cells, and extracellular matrix components (ECM). Fibroblasts are ubiquitous stromal cells that can influence other neighboring cell types through the secretion of chemokines, cytokines, ECM, ECM remodeling enzymes, and other metabolites. Myofibroblasts are a distinct subtype of fibroblasts characterized by expression α-smooth muscle actin (αSMA). These cells are a dominant component of the microenvironment, and a FSP1 and FAP could be a different clone of fibroblasts. Myofibroblasts also have been known to contribute to …

Characterization Of The Role Of The Pkm101-Encoded T4ss Outer Membrane Core Complex In Substrate Transfer, Pilus Biogenesis, And Recipient Cell Contact, Jay E. Gordon

Dissertations and Theses (Open Access)

The bacterial type IV secretion systems (T4SS) encoded on the Escherichia coli pKM101 and R388 conjugative plasmids and the Agrobacterium tumefaciens virB operon are composed of 12 subunits arranged in an architecturally similar fashion. Structural studies of the T4SS from R388 (Trw_R388) highlighted the presence of a distinct outer membrane core complex (OMCC) and inner membrane complex (IMC) joined together by a central stalk. This thesis is focused on the development of the pKM101 model system and the role of an OMCC cap region formed by alpha helical antenna projections (AP) found in VirB10 and TraF_pKM101. …

Detecting And Evaluating Therapy Induced Changes In Radiomics Features Measured From Non-Small Cell Lung Cancer To Predict Patient Outcomes, Xenia J. Fave

Dissertations and Theses (Open Access)

The purpose of this study was to investigate whether radiomics features measured from weekly 4-dimensional computed tomography (4DCT) images of non-small cell lung cancers (NSCLC) change during treatment and if those changes are prognostic for patient outcomes or dependent on treatment modality. Radiomics features are quantitative metrics designed to evaluate tumor heterogeneity from routine medical imaging. Features that are prognostic for patient outcome could be used to monitor tumor response and identify high-risk patients for adaptive treatment. This would be especially valuable for NSCLC due to the high prevalence and mortality of this disease.

A novel process was designed to …

Ms171: Interview With Diana Chow, Diana Shu-Lian Chow Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

Diana Shu-Lian Chow, Ph.D., is an outstanding researcher at the University of Houston College of Pharmacy, where she began her career in 1981. She has authored or co-authored more than 50 peer-reviewed journal articles, three book chapters and more than 200 abstracts presented at national and international scientific conference or meetings. She is the editor of the British Journal of Pharmacology, editorial board member for the Journal of Drug Development and Industrial Pharmacy and a reviewer for more than a dozen journals.

She holds more than 10 U.S. and international patents, and in 2009, the Houston Intellectual Property Law Association …

Ms171: Interview With Margaret Carter Mcneese, Margaret Carter Mcneese M.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Margaret Carter McNeese about her career in the Department of Pediatrics at the Univeristy of Texas Health Science Center at Houston Medical School.

Dr. McNeese’s undergraduate years were spent at Mary Baldwin College in Staunton, Virginia. She went to medical school at The University of Texas Medical Branch at Galveston, where she began her career as a physician and pediatrician. She has been a recipient of many awards, among them the UT Health Science Center at Houston’s President’s Award for Mentoring Women; the Catholic Charity Guild Award for service at the San Jose Clinic, the …

Ms171: Interview With Kathryn Peek, Kathryn Elaine Peek Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Kathryn Elaine Hickman Peek about her career as a biomedical administrator and educator at many institutions in the Texas Medical Center.

Kathryn Elaine Peek, Ph.D. completed her bachelor’s degree in English and embarked on a first career as a public school teacher. She obtained master’s degrees in biology and behavioral sciences at the University of Houston and UH Clear Lake during two stays in the Houston area. She entered the University of Texas Graduate School of Biomedical Sciences at what is now the McGovern Medical School at the age of 39. She graduated with a …

Understanding Patient Safety Reports Via Multi-Label Text Classification And Semantic Representation, Chen Liang

Dissertations and Theses (Open Access)

Medical errors are the results of problems in health care delivery. One of the key steps to eliminate errors and improve patient safety is through patient safety event reporting. A patient safety report may record a number of critical factors that are involved in the health care when incidents, near misses, and unsafe conditions occur. Therefore, clinicians and risk management can generate actionable knowledge by harnessing useful information from reports. To date, efforts have been made to establish a nationwide reporting and error analysis mechanism. The increasing volume of reports has been driving improvement in quantity measures of patient safety. …

Ms171: Interview With Melinda Perrin, Melinda H. Perrin, Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Melinda Perrin about her career in the Texas Medical Center and work on the board of Hermann Hospital and later Memorial Hermann Healthcare System.

Melinda Hill Perrin was born into a family known for the leadership it has provided both the city of Houston and the state of Texas. Her father John Hill served as the Texas’ secretary of state, then attorney general and finally Chief Justice of the state Supreme Court. Her work in the community and the non-profit sector led to her selection as a member of the Board of Hermann Hospital during …

Ms171: Interview With Millicent Goldschmidt, Millicent Goldscmidt Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Millicent Goldschmidt about her career at University of Texas Health Science Center at Houston (UTHealth) where she has held faculty positions in the Department of Diagnostic and Biomedical Sciences at UTHealth School of Dentistry, UTHealth Medical School, and the Graduate School of Biomedical Sciences.

Millicent Edna Goldschmidt, Ph.D., came to the Texas Medical Center after an educational journey that included parental objections and a husband’s ethical concerns about research.

Once in Houston, her professional journey took her to almost every institution in the Texas Medical Center – from Baylor College of Medicine to The University …

The Significance Of So-Called Equivocal Immunohistochemical Staining For Cytomegalovirus In Colorectal Biopsies, David A Johnson, Philip O Katz, David Armstrong, Henry Cohen, Brendan C Delaney, Colin W Howden, Peter Katelaris, Radu I Tutuian, Donald O Castell

Faculty, Staff and Student Publications

The availability of over-the-counter (OTC) proton pump inhibitors (PPIs) for the short-term (2 weeks) management of frequent heartburn (≥2 days/week) has increased markedly, yet evidence-based recommendations have not been developed. A panel of nine international experts in gastroesophageal reflux disease developed consensus statements regarding the risks and benefits of OTC PPIs using a modified Delphi process. Consensus (based on ≥80% approval) was reached through multiple rounds of remote voting and a final round of live voting. To identify relevant data, the available literature was searched and summarized. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system terminology was used to …

What Makes A Medical Journal Successful? Five Crucial Components, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Prolonged Sinus Pauses Upon Termination Of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic And Electroanatomic Findings, Zhengyu Bao, Hongwu Chen, Bing Yang, Michael Shehata, Weizhu Ju, Fengxiang Zhang, Gang Yang, Kai Gu, Mingfang Li, Kejiang Cao, Xunzhang Wang, Minglong Chen

The Texas Heart Institute Journal

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients.

Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs …

A Rare Case Of Vascular Ring And Coarctation Of The Aorta In Association With Charge Syndrome, Jonathan B Wagner, Joshua Q Knowlton, Peter Pastuszko, Sanket S Shah

The Texas Heart Institute Journal

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring—consisting of a right aortic arch with retroesophageal brachiocephalic artery—combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution.

To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case …

Transcatheter Aortic Valve Implantation In A Patient With Unicuspid Aortic Valve, Angelo Nascimbene, Pranav Loyalka, Igor D Gregoric, Ricardo Bellera, Maan Malahfji, Marija Petrovic, Biswajit Kar

The Texas Heart Institute Journal

Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valves has been successfully performed, but there is a lack of published experience in percutaneous treatment of patients with unicuspid valves and severe aortic stenosis. We describe a case of TAVR in such a patient.

A 31-year-old woman with Turner syndrome—who had undergone coarctation repair via subclavian flap at age 7 days and an aortic valvotomy at age 6 weeks—presented with severe symptomatic aortic stenosis. She was deemed inoperable because of her severe pulmonary hypertension and numerous comorbidities; consequently, a 20-mm Edwards Sapien 3 Transcatheter Heart Valve was offered for …

Nina Braunwald: A Female Pioneer In Cardiac Surgery, Nikhil Sabharwal, Harmanjit Dev, Hassiba Smail, David C Mcgiffin, Pankaj Saxena

The Texas Heart Institute Journal

Nina Starr Braunwald, the first female cardiac surgeon, made headlines during a time when almost all specialty surgeons were men.

Women have typically been deterred from entering surgical specialties, in part because of their traditional dual burden of managing their households and careers. Instead, female medical students and junior doctors have tended to be more attracted to medical specialties. This was the reality during Dr. Braunwald's venture into medicine in 1949. However, she never allowed negative ideas to keep her from joining a surgical training program.

Under the mentorship of the prominent cardiac surgeons Charles Hufnagel and Andrew Morrow, Dr. …

Ten Keyword Tips For Digitalcommons@Tmc, Laurel Sanders

Library Staff Publications

This document contains guidelines for selecting keywords for DigitalCommons contributors.

A Controlled Comparison Trial Of The Collaborative Assessment And Management Of Suicidality (Cams) In An Inpatient Setting: Outcomes At Discharge And Six-Month Follow-Up, Thomas E Ellis, Katrina A Rufino, Jon G Allen

Staff and Researcher Publications

This controlled comparison trial evaluated a suicide-specific intervention, the Collaborative Assessment and Management of Suicidality (CAMS), in an extended-stay psychiatric inpatient setting. Multiple outcomes were examined for 104 patients, half of whom received individual therapy from therapists trained in CAMS. The comparison group was selected from a larger pool through Propensity Score Matching to ensure comparability on age, sex, treatment program, number of prior suicide attempts, and severity of suicidal ideation. Results showed that a) all patients improved significantly across a wide range of measures, including depression, suicidal ideation, functional disability, and well-being; b) these gains were durable over a …