Digital Commons Network^™

The Role Of Micrornas In The Pathophysiology Of Neonatal Hypoxic-Ischemic Brain Injury, Eric S. Peeples

Theses & Dissertations

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. The subsequent metabolic failure and cellular injury in the brain can be partially attenuated by rapid initiation of therapeutic hypothermia, but even with prompt induction of hypothermia, more than one in four survivors suffer from major developmental disabilities – an indication of the critical need for more effective therapies. MicroRNAs (miRNA) may be able to act as therapeutic targets in neonatal HIBI; however, very little is known about the endogenous expression of miRNAs …

Design And Synthesis Of Small Molecular Probes For Cns And Kidney Disorders, Swagat H. Sharma

Theses & Dissertations

The G protein regulated inwardly rectifying potassium channels (GIRK) are a family of inwardly rectifying potassium channels and are key effectors in signaling pathways. GIRK 1/2 channel subunit, predominantly found in the brain, is involved pathophysiology of various neurological disorders including, but not limited to, epilepsy, anxiety, Parkinson's, pain, reward, and addiction. Previously, our laboratory had identified a series of urea containing molecules as GIRK1/2 preferring activators. Unfortunately, the urea series suffers from significant PK liabilities (solubility, brain penetration and high clearance). The chapter 1 of the dissertation describes our efforts in developing three new series of activators with improved …

Delivery Of Sirna With Drugs Targeting Polyamine Metabolism As Combinational Cancer Treatment, Ao Yu

Theses & Dissertations

Cancer has been a major public health issue worldwide for years and is the second leading cause of death in the United States. Important barrier must be broken to extend the life expectancy in every country. The standard care for cancer causes severe side effects which affects patients’ physical health and quality of life. Polyamines are highly related with the cell proliferation and apoptosis. Dysregulated polyamine metabolism in cancer leads to increased polyamine concentration in neoplastic cells. Thus, polyamine metabolism for cancer therapy can be an intriguing target. However, the heterogeneity affecting key cancer pathways poses significant challenges for effective …

Development Of Polymeric Cxcr4 Targeting Carriers For Sirna Delivery To Treat Acute Kidney Injury, Weimin Tang

Theses & Dissertations

Acute kidney injury (AKI) is a major kidney disease that is characterized by a sudden loss of renal function which manifests by a decrease in urine output and an increase in serum creatinine. AKI is a global healthcare burden associated with high morbidity, mortality, and increasing cost. Currently there are no effective pharmacological treatments available. Apoptosis induced by p53 has been demonstrated as an important pathological mechanism for the development of AKI. Meanwhile, CXCR4/SDF-1 axis has been associated with the inflammation during AKI, and CXCR4 is overexpressed on injured tubules. This dissertation hypothesized that polycations with CXCR4 targeting ability could …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Usp11 And Usp7 Deubiquitinases Regulate Sprtn Auto-Proteolysis And Sprtn-Mediated Dna-Protein Crosslink Repair, Megan C. Perry

Theses & Dissertations

DNA repair pathways that recognize and remove damaged DNA are vital for maintenance of genomic stability and prevention of tumorigenesis. Conversely, these pathways may be robust in tumor cells, thus diminishing the anti-cancer potential of available therapies. DNA-protein crosslinks (DPCs) are particularly deleterious DNA adducts that occur when proteins become irreversibly covalently bound to the DNA. DPCs represent a diverse group of lesions, as any protein can be crosslinked to the DNA duplex by non-specific crosslinking agents like reactive aldehydes and radiation. Additionally, functional DNA-binding proteins such as topoisomerases may become permanently crosslinked to DNA ends by abortive enzymatic processes …

Glad To Be Out. I Was Running Out Of Womb: A Study Of Omega-6 And Omega-3 Fatty Acid Metabolites At Delivery And Their Relationship To Infant Growth, Prematurity, And Admission To The Neonatal Intensive Care Unit, Maranda Thompson

Theses & Dissertations

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled it can lead to poor infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and omega-6 fatty acids have been shown to be metabolized into bioactive metabolites that effect inflammation. The presence and importance of these metabolites at the time of delivery are not well understood. Therefore, the purpose of this dissertation was to first quantify omega-3 and omega-6 metabolites in maternal plasma, cord plasma, and placental tissue. Then the relationships between metabolites and infant outcomes, including birth weight percentile, length percentile, head circumferences …

Understanding The Impact Of Chlamydia Trachomatis Infection On Host Vesicular Trafficking, Lisa M. Jorgenson

Theses & Dissertations

Chlamydia trachomatis is a highly evolved obligate intracellular bacterial pathogen. During infection, organisms reside within a host epithelial cell in a membrane-bound vacuole called the inclusion. The inclusion membrane contains both pathogen and host components, including unique chlamydial type III effector proteins called Incs and host lipids like cholesterol and sphingomyelin. The inclusion membrane serves as the main barrier between the bacteria and the host cytosol, and thus, functions as the platform supporting host-chlamydial interactions. Via the inclusion membrane, C. trachomatis intercepts components of host vesicular traffic including many host SNARE proteins, which are a conserved family of eukaryotic proteins …

Molecular Investigation Into The Biologic And Prognostic Elements Of Peripheral T-Cell Lymphoma With Regulators Of Tumor Microenvironment Signaling Explored In Model Systems, Tyler Herek

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is heterogenous group of mature T-cell neoplasms characterized by distinctive transcriptional and genetic lesions. Herein, we investigated DNMT3A mutations in angioimmunoblastic T-cell lymphoma (AITL, n = 176) and novel molecular subtypes (i.e., PTCL-GATA3, n = 61 and PTCL-TBX21, n = 80) within PTCL- NOS and observed significant biological and prognostic differences associated with DNMT3A mutations. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS; p < 0.005), with DNMT3A mutations (DNMT3A-MT) skewed toward the methyltransferase domain and in the dimerization domain (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8⁺ T-cell cytotoxic gene signatures in the tumor microenvironment of DNMT3A-MT PTCL-TBX21 cases. Genome-wide methylation analysis of DNMT3A-R882/Q886 versus wild-type in PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating T-cytotoxic genes, TCR …

Humanized Mice For Brain Infection Of Emerging Viruses, Edward Makarov

Theses & Dissertations

Studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic development. Humanized mice enable investigation of viral pathogens, including Human immunodeficiency virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV), offering an advanced understanding into the mechanisms of viral perseverance in its natural human host cells and for therapeutic discovery. Realizing the diverse dynamics of various viral infections with the capacity to establish an innovative acuity for therapeutics and mechanics when utilizing humanized mice contributes a formerly inaccessible insight into human-specific viral pathogenesis and treatment. We recently developed …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Sacubitril/Valsartan Versus Angiotensin Inhibitors And Arrhythmia Endpoints In Heart Failure With Reduced Ejection Fraction, Sandra Chaparro

All Publications

No abstract provided.

Spaceflight And Differential Gene Expression Analysis Of Mice Quadriceps Exposed To Microgravity, Tommy Nguyen

Master's Projects

he trip to Mars and back is planned for the next 20 years. Improvement in technology and research has allowed data analysis, at a larger scale, on spaceflight specimen. However, research involving spaceflight is decentralized, as research is spread across laboratories with different methodologies. NASA’S GeneLab is a public repository for spaceflight-related omics data and promotes centralizing spaceflight RNA-Seq studies using NASA’s RNA-Seq pipeline. Jonathan Oribello, a SJSU’s Bioinformatics graduate and now an employee at GeneLab, has implemented Nextflow to NASA’s RNA-Seq pipeline. The Nextflow RNA-Seq pipeline was ran on San Jose State University’s College of Science High Performance Computing …

An Examination Of Bone Loss During Space Travel With Differential Gene Expression Analysis, Claudia Vo

Master's Projects

Spaceflight poses many risks to human health due to the harsh conditions of microgravity, cosmic radiation, and confinement. One of the impacts that spaceflight entails is bone loss, which is a risk to astronauts as future space missions will require long travel durations. To elucidate the role of genetics in spaceflight bone loss, in this study differential gene expression analysis was performed using Nextflow-RCP, an adaptation of NASA Genelab’s RNA-Seq Consensus pipeline. The dataset for this project was GLDS-241, which contained samples from mice femoral skin. To gain a comprehensive understanding of the genes involved in bone loss, the results …

Systems And Methods For Scalable Retinal Screening Programs, Jeremy Richard Benson

Computer Science ETDs

This dissertation addresses gaps in artificial intelligence-based computer vision tasks in the medical image processing field. We demonstrate effective methods for standardizing and augmenting digital fundus photographs so that robust convolutional neural network-based systems can perform high-throughput disease classification and generalize to never-before-seen data from novel camera technologies, scaling with the changing hardware landscape, as well as keeping up with vast amount of incoming data from the ever-increasing population. We also tackle the problem of discovering relevant samples in an unlabeled cohort of image data, thus widening the bottleneck to all downstream supervised machine learning tasks.

Who Pays To Clean Up What A Dying Industry Leaves Behind?, Audrey Carleton

Capstones

As the birthplace of oil and gas, Pennsylvania is home to the highest number of orphaned abandoned oil and gas wells in the country — an estimated 300,000 to 500,000 dot the Keystone State, all remnants of a dying industry. These wells emit methane, a potent greenhouse gas, and have, for decades, caused alarm to hundreds of residents, documents obtained in a months-long capstone investigation show. The state is currently plugging 10 to 12 abandoned wells per year, on average, out of hundreds of thousands, in part because it has not collected enough in cleanup funds from producers to fund …

A Protocol For The Induction Of Experimental Necrotizing Enterocolitis In Neonatal Mice, Lila S Nolan, Qingqing Gong, Heather N Hofmeister, Misty Good

Open Access Publications

Recapitulating human NEC using animal models has been insightful in dissecting the signaling pathways, immune-mediated mechanisms, genetic signatures, and the intestinal architecture of NEC. This protocol describes an

Filling Information Gaps In Milwaukee’S Metcalfe Park Neighborhood, Kynala J. Phillips

Capstones

While in the Craig Newmark Graduate School of Journalism’s Engagement Journalism program, I got the chance to work with residents in Milwaukee’s predominantly Black Metcalfe Park neighborhood and the organizations and people that communicate most frequently with its residents.

During these past 18 months, I have practiced deep listening and slow and engaged journalism to build trust with my community. The goal: to create a product that is useful to the residents of Metcalfe Park.

To accomplish this, I joined a small group of journalists and community leaders to produce a print and SMS neighborhood newsletter titled “North 2 Center” …

Poetic Self Expression, Impact, And Activism, Mariah Thomas

Capstones

Poetic Self Expression, Impact, and Activism revolves around Black women activists and how they used poetry to fight against racial and social injustice.

Link: https://medium.com/@mariaht/poetic-self-expression-impact-and-activism-a98c7f3385b2

Ultrasound Modulation Of Macaque Prefrontal Cortex Selectively Alters Credit Assignment–Related Activity And Behavior, Davide Folloni, Elsa Fouragnan, Marco K. Wittmann, Lea Roumazeilles, Lev Tankelevitch, Lennart Verhagen, David Attali, Jean François Aubry, Jerome Sallet, Matthew F.S. Rushworth

School of Psychology

Credit assignment is the association of specific instances of reward to the specific events, such as a particular choice, that caused them. Without credit assignment, choice values reflect an approximate estimate of how good the environment was when the choice was made—the global reward state—rather than exactly which outcome the choice caused. Combined transcranial ultrasound stimulation (TUS) and functional magnetic resonance imaging in macaques demonstrate credit assignment–related activity in prefrontal area 47/12o, and when this signal was disrupted with TUS, choice value representations across the brain were impaired. As a consequence, behavior was no longer guided by choice value, and …

The Analysis Of Microdroplet Arrays, Alex Austin

Mechanical Engineering and Materials Science Independent Study

The primary objective of my research this semester was the investigation into the optimization of the micropillar array both through simulations and physical testing. Where ancillary objectives include the familiarization of SEM imaging, Surface Evolver, and COMSOL. Significant progress has been made in all these objectives. Specifically in the construction of different asymmetrical droplets that were combined to form an array.

Fasting Status Of Steller Sea Lion Pups, Stephanie G. Crawford

Biological Sciences

Following population declines in species of concern, wildlife managers often seek to identify underlying causes to understand and predict population dynamics for better future management. Often, physiological and/or behavioral metrics are measurable markers of decline, and these are often detectable well before declines are measurable through population surveys. During the 1970's, 80's, and 90's Steller sea lion (SSL; Eumetopias jubatus) populations in the western portion of their breeding range declined by ~85%. Though declines in most regions have since stabilized or exhibited modest recovery, some subpopulations breeding in the Aleutian Islands continue to decline. In contrast, SSL subpopulations in eastern …

Naturally Occurring Etiologic Factors Affecting The Health Of Breeding Seabirds In The Bering Sea, Maile Branson

Biological Sciences

Seabird populations across the globe have experienced both significant instability and consistent overall declines in recent history. Seabirds in the Bering Sea of Alaska, USA appear to be severely affected by environmental changes, exhibiting large-scale shifts in behavior and distribution and increases in unusual mortality events (UMEs) in recent years. I analyze a selection of the naturally occurring pathogenic and toxicological factors affecting breeding seabirds in the Bering Sea region using an approach focusing on zoonoses and bioaccumulating toxins. Specimens were collected at three breeding colonies in the Bering Sea in 2018 and 2019, and were evaluated for the presence …

Rooted In Environmental Justice: Phytogeography And Ethnoecology Of Serianthes, Else Demeulenaere

Biological Sciences

Serianthes Benth. (Fabaceae) is one of the most endangered plant genera in the world, with 12 of the 18 species listed on the IUCN Red List of Threatened Species. Serianthes trees are culturally important to island communities of the Indo-Pacific region for canoes, boats, traditional houses, and medicine. Habitat loss and ecosystem degradation increased pressure on these trees, also threatening its Indigenous cosmology and traditional practices. This interdisciplinary study integrated genomic, biogeographic and ethnoecological approaches to develop appropriate policies that protect the Indigenous biocultural diversity of Serianthes. Phylogenomics of 401 nuclear exons and non-coding flanking regions using both a multi-species …

Air Quality And Mental Health: Evidence, Challenges And Future Directions, K Bhui, J Newbury, R Latham, M Ucci, Z Nasar, B Turner, C O'Leary, Hl Fisher, E Marczylo, P Douglas, S Stansfeld, S Jackson, S Tyrrel, A Rzhetsky, R Kinnersley, P Kumar, C Duchaine, F Coulon

School of Biomedical Sciences

No abstract provided.

Coyote Management In San Francisco, Matthew Greer

Master's Projects and Capstones

As cities in North America grow, coyotes have become progressively more important species in urban ecosystems. Moreover, as coyotes increasingly use these urban spaces, human-coyote conflicts have become more common, creating a need for new management strategies. This paper will explore how the city of San Francisco could create a new coyote management plan for its highly visible coyote population. San Francisco has had a persistent coyote population since the early 2000s (Todd, 2018). Currently, the coyote population is close to 100 individuals and is still growing (J. Young, Presidio Trust, pers. comm.). To explore this topic a literature review …

The Feasibility Of Industrial Wastewater Reuse Onsite In The Tri-City Area, Shayla Bergeron

Master's Projects and Capstones

Industries typically discharge wastewater to a centralized wastewater treatment plant, but given ongoing water scarcity from repeated droughts, onsite wastewater reuse within the industrial facility’s plant is an attractive alternative. However, information on economic and technical feasibility on wastewater reuse onsite is limited. A literature review showed that membrane bioreactors are a promising wastewater reuse treatment technology due to their reduced footprint and high quality produced effluent. A watershed assessment of the Tri-City area was conducted to evaluate future water supply. A case study was then performed on industrial dischargers in the Tri-City area applying this technology. Finally, the costs …

Utility Of S100a12 As An Early Biomarker In Patients With St-Segment Elevation Myocardial Infarction, Xiaolin Zhang, Minghui Cheng, Naijing Gao, Yi Li, Chenghui Yan, Xiaoxiang Tian, Dan Liu, Miaohan Qiu, Xiaozeng Wang, Bo Luan, Jie Deng, Shouli Wang, Hongyan Tian, Geng Wang, Xin-Liang Ma, Gregg W Stone, Yaling Han

Department of Emergency Medicine Faculty Papers

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.

Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).

Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.

Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral …

Influence Of Grassland Management And Grazing By Different Farm Animals On Animal Performance And Flora Alterations, W. Jentsch, H.-D. Matthes, A. Admasu, H. Möhring

IGC Proceedings (1977-2023)

The objectives of this study were to test the possibilities of using different farm animals for landscape care on extensive pasture, taking into account their particular performance, and to analyse alterations of the flora in consequence of grazing by different animals and various pasture management. Salers had the highest (836g/d) and Galloways (584g/d) the lowest live weight gain as compared with the other breeds (771g/d). Lambs had higher live weight when grazing together with cattle and horses (mixed grazing) than under one species grazing. The number of legume increased and that of grass decreased. Following 3 years the grazing animals …