Digital Commons Network^™

Targeting A Chemo-Induced Adaptive Signaling Circuit Confers Therapeutic Vulnerabilities In Pancreatic Cancer, Guangsheng Pei, Dadi Jiang, Chao Wang, Zhen Chen, Mi Li, Litong Nie, Yun Xiong, Siting Li, Jeong-Min Park, Huimin Zhang, Min Huang, Klaudia Szymonowicz, Zhongming Zhao, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide a comprehensive and comparative dataset for genetic interactions between the whole-genome protein-coding genes and a panel of tumor suppressor genes, which allows us to uncover known and new high-confidence synthetic lethal interactions. Mining this dataset, we uncover essential paralog gene …

Nadarajah Haghighi Generalised Power Weibull: Properties And Applications, Anuwoje Ida L. Abonongo, Albert Luguterah, Suleman Nasiru

Applied Mathematics & Information Sciences

This study developed the Nadarajah Haghighi generalised power Weibull (NHGPW) distribution by compounding the Nadarajah Haghighi and the generalised power Weibull distribution. Various statistical properties of this new distribution are derived for the new distribution. Estimators of the parameters of the developed distribution are also derived using the maximum likelihood estimation. The hazard rate function of the NHGPW distribution has been shown to be monotonically increasing, monotonically decreasing, constant, bathtub, upside down bathtub (unimodal), modified bathtub or modified unimodal. Its probability density function also exhibits various shapes such as decreasing-increasing, decreasing, increasing, increasing-decreasing, decreasing-increasing- decreasing, increasing-decreasing-increasing, positively skewed among others. …

Data And Algorithmic Modeling Approaches To Count Data, Andraya Hack

Honors College Theses

Various techniques are used to create predictions based on count data. This type of data takes the form of a non-negative integers such as the number of claims an insurance policy holder may make. These predictions can allow people to prepare for likely outcomes. Thus, it is important to know how accurate the predictions are. Traditional statistical approaches for predicting count data include Poisson regression as well as negative binomial regression. Both methods also have a zero-inflated version that can be used when the data has an overabundance of zeros. Another procedure is to use computer algorithms, also known as …

The Development And Characterization Of Piezoelectric- Magnetostrictive Smart Self-Sensing Composites, George Relebohile Qhonosheane

Mechanical and Aerospace Engineering Dissertations - Archive

The composites industry is expanding due to the growing global demand for high-performance materials. How do you ensure the production of composites is as smooth and effective as possible while maintaining the high quality of the material? The key issues in composites include crack occurrence, sticking to molds in the production process, and durability differences during their operation. However, monitoring such cases can be challenging. The industry is in need of a smart solution to be able to obtain accurate data from the raw material. This work focuses on the development of smart composite materials. The word composite comes from …

Synthesis And Function Of Ion-Selective Single-Molecule Fluorescent Imaging Molecules And Materials, Alena A. Denisenko

Chemistry & Biochemistry Dissertations - Archive

Neutrinos are fermion subatomic particles that interact only by weak subatomic forces—making them almost impossible to detect. However, they can be produced in specific radioactive decay reactions, such as beta decay. We hypothesize the detection of double beta decay through the tagging of the Ba2+ daughter ion from 136Xe (136Xe —136Ba2+ + 2ν + 2β). The proposal is to develop single-molecule fluorescence imaging (SFMI) technology to investigate gaseous chemical constituents in high-pressure gases (ca. 30-150 psi) at gas-solid interfaces. To achieve proper SMFI, heterogenous self-assembled monolayers (SAMs) containing fluorophores that operate under dry conditions and are turned on when a …

A Qualitative Study Identifying A School Leadership Model Promoting And Fostering Technology-Enhanced Teaching And Learning, Lisa Flanders-Dick

Doctoral Dissertations

Technology-enhanced teaching and learning (TETL) is the integration of technology into teaching and learning practices to improve the quality of learning outcomes. This is an essential strategy for improving educational quality. School leaders significantly affect the integration of effective TETL in the classroom. The International Society for Technology in Education (ISTE) provides Standards for Leaders that serve as a framework for innovation in education. Situational Leadership Theory contends that one leadership style cannot be applied to all leadership tasks. This study expands upon the current use of SLT to help derive characteristics needed to develop a school leadership model that …

The Ruinous Northern Frontier: The Decline And Collapse Of Frontier And Roman Civilizational Integrity On The Danube, A.D. 370 - 500, James Knight

Masters Theses

The imperial Roman advance to and entrenchment along the Danube from the times of Augustus to Aurelian, mirrored by the slow development of various Germanic peoples beyond the 1,700-mile river’s northern bank, set the stage for a series of climactic engagements between the late Roman Empire and their various barbarous neighbors along what had quickly become the Empire’s most important and unstable frontier. The immigration and settlement of Goths from the Pontic Steppe, fleeing the Huns as they emerged from Central Asia, within the Roman Balkans undermined the Danube frontier, eviscerated the Eastern Roman field army, and enabled Alaric’s role …

Recruiting And Retaining Generation Z, Dylan Klim

Faculty and Staff Publications & Presentations

No abstract provided.

Nonlinear Optical Microscopy Assessment Of Tissue Structure And Chondrocyte Viability Of Articular Cartilage, Michael Le

All Theses

Articular cartilage functions to protect the ends of bones by providing a surface that can withstand compressive forces and minimize friction during movement. Collagen fibers form the organizational backbone of the extracellular matrix (ECM) in cartilage. Proteoglycans within the ECM function to retain water and provide the tissue with the swelling pressure needed to withstand compressional forces. Chondrocytes, the only type of cell found in articular cartilage, produces these collagen fibers and proteoglycans to maintain the tissue structure and function. Significant injuries to articular cartilage can damage the chondrocytes and disrupt their ability to maintain homeostasis in the tissue. Therefore, …

Biophysical Insights Into The Transport Properties Of Lysenin Channels, Andrew Merlin Bogard

Boise State University Theses and Dissertations

The defense work focused on deciphering novel functionalities of lysenin channels with respect to adjustment of their regulation and transport properties in response to environmental changes. Lysenin is a pore-forming toxin extracted from the earthworm E. fetida, which self-assembles into large pores in artificial and natural lipid membranes containing sphingomyelin. Prior investigations on their functionality identified strong regulation by voltage and ligands as fundamental traits of lysenin, similar to ion channels. In addition, stochastic sensing, controlled switching, and hysteretic conductance have been added to the list of intricate biophysical properties of lysenin channels as potential enablers of biotechnological and biomedical …

Synthesis And Characterization Of Organometallic Complexes For Biological Imaging, Emily Stumbo

Honors Theses

Luminescent transition metal complexes are of interest for biological imaging applications due to their unique photophysical properties including large Stokes shift, long fluorescence lifetimes, and tunable emission. Altering ligand structure is a useful way to manipulate the charge transfer (CT) and mixed character states that give these complexes their photophysical properties. A series of organometallic complexes containing ligands with externally facing nitrogens has been prepared and synthesized. Complexes of the form Pt (II)(tbbpy)(C2-py), Re(CO)3(N^N), Ir(C^N)2(N^N), and Ir(C^N)2(N^O) have been studied for their potential application as biological imaging agents. The goal of this project is to compare the properties of these …

Identifying Psychological Mental Disorders Through Machine Learning, Mohammad Al Abdooli

Theses

Psychology is the Study of Human Behavior and the various ways of thinking in it’s both consciousness and unconsciousness mind as this field is still growing to various fields such as Sports, Criminal and even Administrative Psychology through, Furthermore, This Study aims to shape and accommodate both fields of Sciences together, There are very few Scholars and Researches done on Medical Mental Health from a Data Analytics perspective, examining the datasets of the patients ICD-11 or DSM-5 scores and correlating it with the patients well-being, family medical history or any accident the patient have been through, so the current study …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations and Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

Computer Vision And Machine Learning Applications In Cellular Images And Clinical Data, Guochang Ye

Theses and Dissertations

With the progressive development of artificial intelligence (AI), automated analysis has been explored for substituting tedious manual methods in cellular image analysis. Additionally, medical information not included in the conventional statistical methods is now being reconsidered with AI-based personalized medicine. The adaptivity and flexibility of AI ensure its efficiency and accuracy. In this work, computer vision and machine learning (ML) methods under the scope of AI are explicitly investigated and applied to cellular images and clinical data for cytological analysis and to provide diagnosis-based assistance/predictions. Firstly, novel computer vision algorithms achieve cell detection and differentiation estimation on phase-contact microscopic images …

Mathematical Modeling Of Potassium Modulated Viral Infection, Zaira Elizabeth Mather

Open Access Theses & Dissertations

In recent years, there is a growing interest in the investigation of using potassium to treat virus infections. In the region of infection, there is a biological observation of extracel- lular potassium level being typically very low whereas the intracellular potassium levels are much higher. There are numerous biological studies showing that elevated potassium levels in the extracellular membrane tends to block virus infections. A recent effort in this direction is a collaborative research conducted by mathematicians and biologists from the University of Texas at El Paso, New Mexico State University, and the University of New Mexico, where we develop …

Hold That Pose: Capturing Cervical Dystonia's Head Deviation Severity From Video, Zheng Zhang, Joel S Perlmutter, Et Al

2020-Current year OA Pubs

OBJECTIVE: Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system-the Computational Motor Objective Rater …

Modeling And Analysis Of Subcellular Protein Localization In Hyper-Dimensional Fluorescent Microscopy Images Using Deep Learning Methods, Yang Jiao

UNLV Theses, Dissertations, Professional Papers, and Capstones

Hyper-dimensional images are informative and become increasingly common in biomedical research. However, the machine learning methods of studying and processing the hyper-dimensional images are underdeveloped. Most of the methods only model the mapping functions between input and output by focusing on the spatial relationship, whereas neglect the temporal and causal relationships. In many cases, the spatial, temporal, and causal relationships are correlated and become a relationship complex. Therefore, only modeling the spatial relationship may result in inaccurate mapping function modeling and lead to undesired output. Despite the importance, there are multiple challenges on modeling the relationship complex, including the model …

Describing Bacterial Mutagenic Hotspots And Signatures Along With The Factors That Drive Them, Carmen Vallin

UNLV Theses, Dissertations, Professional Papers, and Capstones

In my dissertation work, I investigated bacterial mutagenesis. I asked: where do mutations occur in the bacterial genome? What types of mutations occur? What factors promote or prevent mutations? And lastly, how do the answers to these questions change depending on the bacterial life cycle (When)? I used Bacillus subtilis, a Gram-positive bacterium belonging to the phylum Firmicutes, and Escherichia coli, a Gram-negative bacterium belonging to the phylum Proteobacteria, to answer these questions. B. subtilis and E. coli are model systems that have been used to gain insights into fundamental processes of mutations and evolution for nearly ~8 decades. Here, …

Biological Sex Differences In The Monodelphis Domestica: Investigating Behavioral Responses In Environmental Enrichment And Conditioned Place Preference Paradigms, Katelynn M. Renteria

Theses and Dissertations

The Monodelphis domestica, commonly known as the grey short-tailed opossum, has become an increasingly frequented animal model for areas of psychological study, including comparative psychology. Despite the growing interest in utilizing the Monodelphis as an animal model, several areas of research remain limited in what has been studied. This includes associative learning and the effects of environmental enrichment on the Monodelphis. This study novelly incorporates the two using environmental enrichment with the conditioned place preference (CPP) paradigm to both diversify associative learning literature and expand existing knowledge on the Monodelphis domestica. The CPP paradigm included interactive objects as environmental …

Removal Of Arsenic (Iii) And Arsenic (V) From Aqueous Solution Via Common Sunflower Helianthus Annuus By Phytoremediation, Irving A. Vazquez Hurtado

Theses and Dissertations

Phytoremediation provides a cost-effective, non-invasive technique to remove contaminants from the soil and groundwater. Sunflowers are fast growing and have a showed effective at removing various pollutants from soil, including lead and other heavy metals. Health issues related to arsenic are mainly attributed to exposure of arsenite, whereas arsenate is much less toxic. The common sunflower Helianthus annuus was the species used to remove both arsenic (III) and As(V) ions from hydroponics solutions. In the present study sunflower seeds were germinated for a week, placed under the sun for a day and subsequently placed in a nutrient solution to aid …

Book Reviews, Florida Historical Society

Florida Historical Quarterly

Garrigus and Morris, eds., Assumed Identities: The Meanings of Race in the Atlantic World. by Light T. Cummins; Evans, A "Topping People": The Rise and Decline of Virginia's Old Elite, 1680-1790. by Ronald L. Hatzenbuehler; Ashton, I Belong to South Carolina: South Carolina Slave Narratives. by Carmen V. Harris; Kennedy, Born Southern: Childbirth, Motherhood, and Social Networks in the Old South. by Blain Roberts; Pickenpaugh, Captives in Gray: The Civil War Prisons of the Union. by Jeremy Taylor; Martin, Benching Jim Crow: The Rise and Fall of the Color Line in Southern College Sports, 1890-1980. by Michael Oriard; Keirn and …

Young Children’S Tv Show Preferences And Perceptions Of Women In Stem, Lauren Berck

Undergraduate Theses

Women are joining STEM fields at higher rates, yet the stereotype of math and science being for men is still reinforced to children by their parents, their teachers, and especially what they watch. Children tend to trust characters of their same gender and are more likely to retain the lessons from the characters they trust. Since most of the shows children watch tend to display gender stereotypes, especially the stereotype of men being good in STEM, children are likely to enforce these stereotypes. The increase of women in STEM has increased interest in STEM for girls, but boys still tend …

Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …

Cngpld: Case-Control Copy-Number Analysis Using Gaussian Process Latent Difference, Kim-Anh Do, Shiaw-Yih Lin, Scott L Carter

Faculty, Staff and Student Publications

MOTIVATION: Cross-sectional analyses of primary cancer genomes have identified regions of recurrent somatic copy-number alteration, many of which result from positive selection during cancer formation and contain driver genes. However, no effective approach exists for identifying genomic loci under significantly different degrees of selection in cancers of different subtypes, anatomic sites or disease stages.

RESULTS: CNGPLD is a new tool for performing case-control somatic copy-number analysis that facilitates the discovery of differentially amplified or deleted copy-number aberrations in a case group of cancer compared with a control group of cancer. This tool uses a Gaussian process statistical framework in order …

The Role Of Mink1 In Congenital Heart Disease: Regulation Of Spemann Organizer Cell Fate And Multiciliated Cell Specification, Vaughn Colleluori

Yale Graduate School of Arts and Sciences Dissertations

Congenital Heart Disease (CHD) is the most common birth defect and leading cause of infant mortality, yet molecular mechanisms explaining CHD remain mostly unknown. Sequencing studies are identifying CHD candidate genes at a brisk rate including MINK1, a serine/threonine kinase. However, a plausible molecular mechanism connecting CHD and MINK1 is unknown. Here, we reveal that mink1 is required for proper heart development due to its role in left-right patterning. Mink1 regulates canonical Wnt signaling to define the cell fates of the Spemann organizer and the Left-Right Organizer, a ciliated structure that breaks bilateral symmetry in the vertebrate embryo. To identify …

The Parkinson’S Gene Vps13c Encodes An Er-Lysosome Lipid Transfer Protein Linking Lysosomal Lipid Homeostasis And Cgas/Sting-Mediated Innate Immunity, William Franklin Hancock-Cerutti

Yale Graduate School of Arts and Sciences Dissertations

Biallelic loss-of-function mutations in VPS13C cause early-onset Parkinson’s Disease (PD), and the VPS13C locus is a GWAS hit for sporadic PD risk. VPS13C is a member of the VPS13 family, which in humans contains three other proteins, VPS13A, VPS13B, and VPS13D, all with ties to neurological diseases. Mutations in VPS13A cause chorea-acanthocytosis a Huntington’s like syndrome with dysmorphic erythrocytes, mutations in VPS13B cause the neurodevelopmental disorder Cohen syndrome, and mutations in VPS13D cause spastic ataxia with varying presentation. The molecular function of these proteins, why their loss cause neurological diseases, and why they are each associated with distinct diseases despite …

Riboswitches As Versatile Scaffolds For Ligand Recognition And As Tools For Drug Discovery, Harini Sadeeshkumar

Yale Graduate School of Arts and Sciences Dissertations

Riboswitches are highly structured, noncoding RNAs that bind specific ligands to regulate gene expression. To date, over fifty riboswitch classes have been validated to control fundamental biological processes and recognize various coenzymes, nucleotides, signaling molecules, ions, and other important ligands. As described in Chapter 1, careful study of these various riboswitches reveals an incredible diversity in their structural and biochemical characteristics as well as their function. Herein is detailed the efforts to validate long-standing orphan riboswitch classes involved in essential cellular functions such as maintaining nucleotide pools, managing ion toxicity, osmoregulation, and ATP production.The ykkC family of riboswitches are a …

Engineering Functional Distal Lung Epithelium, Katherine Leiby

Yale Graduate School of Arts and Sciences Dissertations

The potential for lung tissue engineering to generate lung tissue capable of gas exchange ultimately rests upon the ability to reconstitute a functional barrier between the air and blood spaces in the engineered lung alveolus. The success of this endeavor will rely in large part on the recapitulation of an alveolar epithelium, comprising alveolar epithelial type 1 cells (AEC1s) and type 2 cells (AEC2s), which provides a surface for gas diffusion, actively maintains critical features of blood-gas barrier function, and comprises resident AEC2 stem cells for ongoing maintenance and repair of the distal lung. Yet, since the beginning of this …

Molecular Mechanisms Of Atg-9 Localization And Function In Neurons, Sisi Yang

Yale Graduate School of Arts and Sciences Dissertations

Autophagy is a cellular degradation pathway essential for neuronal health andfunction. Autophagosome biogenesis occurs at synapses, is locally regulated and increases in response to neuronal activity. The mechanisms that couple autophagosome biogenesis to synaptic activity remain unknown. In my thesis work, I determine that trafficking of ATG-9, the only transmembraneprotein in the core autophagy pathway, links the synaptic vesicle cycle with autophagy. ATG-9-positive vesicles in C. elegans are generated from the trans-Golgi network via AP- 3-dependent budding and delivered to presynaptic sites. At presynaptic sites, ATG-9 undergoes exo-endocytosis in an activity-dependent manner. Mutations that disrupt endocytosis, including a lesion in …

Studies Towards The Synthesis Of Diaporthein B And Studies Towards The Synthesis Of Darobactin A, Ian Tingyung Hsu

Yale Graduate School of Arts and Sciences Dissertations

In the first chapter of this thesis, I describe the development of two convergent, fragment-based strategies to prepare the oxidized carbon scaffold of diaporthein B (1). Diaporthein B (1), initially isolated from the fungal genus Diaporthe, is an antimycobacterial pimarane diterpene that exhibited a minimum inhibitory concentration (MIC) of 3.1 µg⋅mL–1 against M. tuberculosis, as well as half-maximal inhibitory concentrations of 1.5–3 µM against HCT and LoVo colon cancer cell lines. The first synthetic approach towards diaporthein B (1) furnished the tricyclic carbon skeleton 154 in 9 steps from (R)-carvone through a diastereoselective 1,2-addition between two elaborated cycloalkenones, a novel …