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Integrative Single-Cell Genomics And Machine Learning Methods For Tumor Microenvironment Characterization And Survival Prediction, Wenjuan Zhang

Theses and Dissertations

The tumor microenvironment (TME) comprises diverse cell types and plays crucial roles in cancer development and therapeutic response. Single-cell RNA sequencing (scRNA-seq) data quantifies gene expression at the single-cell level, enabling the dissection of heterogeneous cell populations in various biological contexts and diseases. In this work, we developed integrative single-cell genomics and machine learning approaches to characterize the TME and enhance patient survival prediction. We introduced a convolutional neural network (CNN)-based method, cnnImpute, to address the high proportion of missing data in scRNA-seq datasets. cnnImpute effectively imputes missing values while preserving the integrity of cell clusters, achieving superior performance in …

Phylogenomics Of The Tribe Leonureae Reveals A New Genus: Paraleonurus (Lamiaceae, Lamioideae), Mei-Lin Qian, Ya-Ping Chen, Tuncay Di̇rmenci̇, Yue Zhao, Guo-Xiong Hu, Fei Zhao, Ferhat Celep, Bo Li, Chunlei Xiang

Turkish Journal of Botany

With approximately 80 species across six genera (Leonurus, Lagopsis, Panzerina, Lagochilus, Chaiturus, and Loxocalyx), the tribe Leonureae represents one of the most morphologically diverse tribes within the subfamily Lamioideae of Lamiaceae. Previous studies indicated that Leonurus and Lagopsis are not monophyletic, and relationships among and within these genera remain unclear due to limited sampling and DNA markers. In this study, we present the most comprehensive phylogenomic analyses of Leonureae based on complete plastome sequences and 127 nuclear loci retrieved from next-generation sequencing data. Our results provide strong evidence for the monophyly of Leonureae, which can be further divided into six …

Selective Indel Marker Identification Across The Peanut (Arachis Hypogaea L.) Genome Using Ddradseq, Moin Qureshi, Bi̇rgül Guden, Hi̇lal Şule Tosun, Mojtaba Kordrostami, Sunil Shiwaji Gangurde, Bülent Uzun, Engi̇n Yol

Turkish Journal of Botany

The advent of next-generation sequencing technologies, mainly double digest restriction site-associated DNA sequencing (ddRADSeq), has significantly advanced the development of molecular markers for crop genetics. This study used ddRADSeq to identify and develop insertion-deletion (InDel) markers in 25 peanut genotypes from diverse geographic regions. The bioinformatic analysis unveiled 62728 InDels across the peanut genome, predominantly between 1-5 bp, which constituted 96% of the total, while InDels of ≥ 6 bp accounted for 3.96%. We focused on 1013 InDels of at least 10 bp for further analysis, representing 1.61% of the total reads, with a distribution of 832 insertions and 181 …

Exploring The Population Structure And Genetic Diversity In Apple Germplasm Using Ipbs-Retrotransposon Markers, Aigul Madenova, Angsagan Kuan, Amjad Ali, Muhammad Azhar Nadeem, Muhammad Tanveer Altaf, Balnur Kabylbekova, Dinara Kaldybaeva, Ti̇mur Turdi̇yev, Faheem Shahzad Baloch

Turkish Journal of Botany

The apple (Malus domestica [Suckow] Borkh) is economically and culturally significant worldwide, thriving in temperate regions. This study examined genetic variations among 52 apple accessions from three research centers in Kazakhstan using the iPBS-retrotransposons marker system. Out of 35 screened markers, 12 highly polymorphic markers were selected for PCR amplification, resulting in 280 bands, 279 of which were polymorphic, yielding a 99.64% polymorphism rate. Genetic diversity indices showed substantial variation: effective number of alleles (ne=1.655), Shannon's information index (I=0.373), gene diversity (h=0.549), and an average genetic distance of 1.2. The analysis of molecular variance (AMOVA) indicated that 98.80% of the …

Heterologous Expression Of Haloarchaeal Transporter Genes In Nicotiana Tabacum Under Salt And Drought Stresses, Çi̇ğdem Otur, Musa Kavas, Aslihan Kurt Kizildoğan

Turkish Journal of Botany

The objective of the study: Climate change and human activities impose severe biotic and abiotic stresses that threaten plant survival. To cope with these extreme conditions, plants have evolved various resistance mechanisms. In recent years, genetic approaches have been increasingly employed to enhance abiotic stress tolerance and develop stress-resistant plants. In this study, we introduced three transporter-related genes from extreme haloarchaea, which thrive in saturated NaCl environments, into the Nicotiana tabacum genome to improve its salt and drought tolerance mechanisms.E xperimental procedure(s) : The U2845, U3508, and CL165 genes were subcloned into the pIPKb004 vector, which includes the cauliflower mosaic …

Role Of Sulfur Metabolism In Acquiring Of Boron Tolerance In Arabidopsis Thaliana, Seda Yi̇rmi̇beş, Ceyhun Kayihan, Nuran Çi̇çek, Yasemi̇n Ekmekçi̇

Turkish Journal of Botany

The purpose of this study was to assess whether sulfate applications (pre- and combined) caused the changes of tolerance against boron (B) toxicity in Arabidopsis thaliana at physiological, biochemical and molecular levels. Plants were germinated and grown on MS medium for 12 days, and then, sulfate pre-treatment groups (PS-B) were transferred to sulfate-containing media for 3 days. Subsequently, PS-B, combined (S+B) and un-treated application groups were transferred to medium containing 3 and 5 mM B for 10 days. Leaf area, plant biomass and total chlorophyll content decreased significantly depending on the accumulation of B. Toxic levels of B adversely affected …

Gene-Environment Interactions In Non-Alcoholic Fatty Liver Disease: Insights From Mexican American Populations, Eron G. Manusov, Vincent P. Diego, Marcio Almeida, Jacob Galan, Auwal A. Bala, Marco Arriaga, Natasha Garcia-Rodriguez, Renee Hernandez, Satish Kumar, John Blangero, Sarah Williams-Blangero

School of Medicine Publications

Nonalcoholic Fatty Liver Disease (NAFLD) is a prevalent and complex condition influenced by both genetic and environmental factors. This chapter explores the genotype-by-environment interactions that contribute to the development and progression of NAFLD in the Mexican American population. Using advanced genetic epidemiology and bioinformatics approaches, we investigated how specific genetic variants interact with environmental factors such as depression, acculturation stress, and social determinants of health, to influence NAFLD risk and severity. Our findings reveal significant genotype-by-environment interactions for key NAFLD-related traits, including HbA1c, AST/ALT ratio, and steatosis-controlled attenuation parameter (CAP). We also discuss the application of cutting-edge proteomic and transcriptomic …

Probate Standing, David Horton

Michigan Law Review

Few topics in civil justice have sparked as much criticism as the standing doctrine. The U.S. Constitution and some of its state counterparts require plaintiffs to allege that they suffered an “injury-in-fact” that the defendant caused and that a court can redress. A veritable ocean of commentary argues that this requirement [is confusing, ahistorical, and unmoored from its objectives.

Yet a different manifestation of the standing doctrine has long lurked in obscurity. Standing issues are also common in state probate courts, where the transmission of assets from the dead to the living can affect a variety of parties. But in …

Influence Of Demographics, Health, And Self-Objectification On Body Acceptance And Body Appreciation In Older Adults, Heather Russell

Walden Dissertations and Doctoral Studies

Prior research has examined the demographic, health, and activity factors influencing how young people, particularly young women, see themselves concerning body appreciation and acceptance. However, body appreciation and acceptance as perceived by older men and women have not been well-studied. The purpose of the study was to examine the extent to which gender, age, quality of life assessment of physical and mental health, physical activity, and self-objectification influence body acceptance by others and body appreciation in adults ages 55-75. Self-objectification theory (SOT) was the framework used to examine the influence of two aspects of self-objectification (lack of autonomy and invisibility) …

Co-Inhibition Of Tgli1 And Gp130 Using Fda-Approved Ketoconazole And Bazedoxifene Is Synergistic Against The Growth And Metastasis Of Her2-Enriched And Triple-Negative Breast Cancers, Sara Manore, Chuling Zhuang, Mariana K Najjar, Grace L Wong, Shivani Bindal, Kounosuke Watabe, Jiayuh Lin, Hui-Wen Lo

Faculty, Staff and Student Publications

Breast cancer stem cells (CSCs) are resistant to most cancer therapeutics and contribute to tumor recurrence and metastasis. Two breast CSC-promoting transcription factors, truncated glioma-associated oncogene homolog 1 (tGLI1) and signal transducer and activator of transcription 3 (STAT3), have been reported to be frequently co-expressed in HER2-enriched breast cancer and triple-negative breast cancer (TNBC), undergo protein-protein interactions for gene regulation and activation, and functionally cooperate to promote breast CSCs. STAT3 can be activated by activated interleukin-6 receptor/glycoprotein-130 (IL-6R/GP130). Co-targeting of tGLI1 and IL-6R/GP130 has not been investigated in breast cancer or any tumor type. Here, we report that tGLI1 and …

Understanding Sequence Determinants Of Functional Protein Dynamics Using Biophysical Simulations And Experiments, Upasana Lakshmi Mallimadugula

Arts & Sciences Graduate Student Theses and Dissertations

Mutations in the sequence of proteins associated with a disease often increase its risk or severity. They can also be a barrier to developing effective therapeutics for such diseases. One way in which mutations affect function is by altering dynamics that elude structural studies. Observing these changes requires methods that can report on movements of the protein on various timescales and is an ongoing challenge in biophysics and biochemistry. In this study I will use both experimental and computational techniques that can report on such dynamics to explore how small sequence changes shift the conformational landscape and consequently the function …

Seismic Site Response, Liquefaction-Induced Lateral Spreading And Impact Of Seasonal Frost On Pile Foundations In Cold Regions, Yue Zhao

Engineering

Permafrost sites are experiencing significant changes due to anthropogenic activities and climate change, leading to substantial variations in soil dynamic properties and increased seismic risks. The associated geohazards, including differential settlement, slope instability, and liquefaction of degraded, unconsolidated materials in seismically active warm permafrost regions, pose substantial threats to the built infrastructure. This study aims to assess the seismic site response of warm permafrost sites and analyze the impact of seasonal frost on liquefaction-induced lateral spreading and pile foundation behavior in cold regions. Northway Airport, Alaska, was used as the study site to characterize permafrost conditions, while the Slana River …

Uba1 Inhibition Sensitizes Cancer Cells To Parp Inhibitors, Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills, Shannon N Westin, Michael T Lewis, Weiyi Peng, Anil K Sood, Timothy A Yap, S Stephen Yi, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Students Publications

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition …

The C-Terminal Activating Domain Promotes Pannexin 1 Channel Opening, Erik Henze, Jacqueline J Ehrlich, Janice L Robertson, Eric Gelsleichter, Toshimitsu Kawate

2020-Current year OA Pubs

Pannexin 1 (Panx1) constitutes a large pore channel responsible for the release of adenosine triphosphate (ATP) from apoptotic cells. Strong evidence indicates that caspase-mediated cleavage of the C-terminus promotes the opening of the Panx1 channel by unplugging the pore. However, this simple pore-plugging mechanism alone cannot account for the observation that a Panx1 construct ending before the caspase cleavage site remains closed. Here, we show that a helical region located immediately before the caspase cleavage site, referred to as the "C-terminal activating domain (CAD)", plays a pivotal role in facilitating Panx1 activation. Electrophysiology and mutagenesis studies uncovered that two conserved …

Conventional Cytogenetic Analysis Of Solid Tumor Abnormalities: A 25-Year Review Of Proficiency Test Results From The College Of American Pathologists/American College Of Medical Genetics And Genomics Cytogenetics Committee, Rachel K Vanderscheldon, Yang Cao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …

The Pace Of Biological Aging Partially Explains The Relationship Between Socioeconomic Status And Chronic Low Back Pain Outcomes, Edwin N Aroke, Jai Ganesh Nagidi, Vinodh Srinivasasainagendra, Tammie L Quinn, Fiona B A T Agbor, Kiari R Kinnie, Hemant K Tiwari, Burel R Goodin

2020-Current year OA Pubs

INTRODUCTION: Having a lower socioeconomic status (SES) is a predictor of age-related chronic conditions, including chronic low back pain (cLBP). We aimed to examine whether the pace of biological aging mediates the relationship between SES and cLBP outcomes - pain intensity, pain interference, and physical performance.

METHODS: We used the Dunedin Pace of Aging Calculated from the Epigenome (DunedinPACE) software to determine the pace of biological aging in adults ages 18 to 85 years with no cLBP (n = 74), low-impact pain (n = 56), and high-impact pain (n = 77).

RESULTS: The mean chronological age of the participants was …

The Effects Of Dietary Level Of Mulberry Leaf Powder On Growth Performance, Carcass Yields, And Some Serum Lipid Levels In Pradu-Hang-Dam Chickens During Cool And Rainy Seasons, Sarawanee Khunmanee, Thuwanon Boonkerd, Thananon Junsuri, Winai Kaewlamun, Pachara Pearodwong, Kajohn Nitiwararak

The Thai Journal of Veterinary Medicine

This study aimed to determine the optimal concentration of mulberry leaf powder (MLP) supplementation and to evaluate the impact of different seasons on the growth performance, carcass characteristics, and blood lipid levels of Pradu-Hang-Dam chickens. One-week-old chickens were assigned to three groups: a control group (without MLP) and two groups receiving diets supplemented with 0.5% and 1.5% MLP, respectively, over a 10-week period. The results indicated that during the cool season, the control group exhibited the highest feed intake, average daily gain, and superior carcass characteristics (P < 0.05). In the rainy season, chickens supplemented with 1.5% MLP achieved the highest feed intake, while those supplemented with 0.5% MLP showed the highest average daily gain and the lowest feed conversion ratio (P < 0.05). Furthermore, the 1.5% MLP group demonstrated superior carcass characteristics compared to the control group during the rainy season (P < 0.05). Analysis of blood lipid metabolism revealed that the group supplemented with 0.5% MLP during the cool season had the lowest levels of triglycerides, cholesterol, and high-density lipoprotein. In conclusion, the cool season is the most favorable for raising Pradu-Hang-Dam chickens in Thailand. Additionally, supplementing diets with at least 0.5% MLP during the rainy season can improve growth performance, carcass characteristics, and blood parameters.

Investigating The Expression Of C-Myc And Birc5 In Trail And Pbox-15 Treated Metastatic Prostate Cancer Cells, Corinne Kai Leng Chew, Hannah O'Toole, Daniela M. Zisterer, Seema M. Nathwani, Jade K. Pollock

SURE Journal: Science Undergraduate Research Experience Journal

Purpose Metastatic prostate cancer is associated with poor survival rate and limited treatment options. Overexpression of c-Myc and BIRC5 has been reported in prostate cancer cells which contribute to the development of the tumour environment. The specific tumour receptor mechanism of the death ligand TRAIL (tumour necrosis factor related apoptosis inducing ligand) has attracted remarkable therapeutic interest. However, many cancer cells are resistant to TRAIL monotherapy. A novel microtubule-targeting agent, PBOX-15 is known to exhibit anti-tumour activity in cancer cell lines including those with multi-drug resistance. Previous studies demonstrated that PBOX-15 is capable in sensitising cancer cells to TRAIL-mediated cell …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Association Between Body Mass Index, Abdominal Obesity And Menopause-Related Symptoms In Postmenopausal Women, Brianna A. Rice, Patricia Heavey

SURE Journal: Science Undergraduate Research Experience Journal

Abstract: Existing research demonstrates a lack of data on the relationship between body mass index (BMI) and menopause-related symptoms in postmenopausal women, particularly in Ireland. This study aimed to determine whether there is an association between BMI, general abdominal obesity and menopause-related symptoms in postmenopausal women. This should help bridge the data gap regarding postmenopausal women living in Ireland and their symptoms. Introduction: Menopause is defined as the permanent cessation of a woman's menstrual cycle. This is caused by a reduction of the secretion of oestrogen and progesterone, leading to reduced ovarian function. These changes have been attributed …

Reframing The Management Of Irritable Bowel Syndrome: Investigating The Efficacy Of A Modified Low Fodmap Diet Approach On Symptom Response, Tara Howley, Lorraine Cooney, Suzanne L. Doyle

SURE Journal: Science Undergraduate Research Experience Journal

Background/ Objectives: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a multi-faceted pathogenesis. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), known as a low FODMAP diet (LFD), is an effective management option for many, however, it is complex, costly, and restrictive. A milder, modified low FODMAP diet (MLFD) is one suggested alternative, however, data on this approach is lacking. This study aimed to explore the efficacy of a MLFD versus a LFD on symptom improvement in IBS.

Subjects/ Methods: Routine clinical data collected on individuals with a Rome IV IBS diagnosis between August …

Tension Recordings From Primary Bronchi In Acta2-Gcamp8.1-Mvermilion Transgenic Mice, Qais Khalaf, Srijit Ghosh, Keith Thornbury

SURE Journal: Science Undergraduate Research Experience Journal

Contractions in smooth muscle cells are initiated by elevation of cytosolic Ca²⁺. It is of interest to measure Ca²⁺ signals in these cells. Transgenic Acta2-GCaMP8.1-mVermilion (GCaMP) mice express a genetically encoded intracellular fluorescent Ca²⁺ indicator in smooth muscle cells, have been developed to facilitate the study of Ca²⁺. However, there is a concern that the GCaMP Ca²⁺ indicator might buffer Ca²⁺ and interfere with the signals it is designed to measure. Therefore, the aim of this study was to compare tension responses in GCaMP and wild type (WT) mice to determine if …

Review: Cell Mechanisms In The Control Of Inflammatory Foundations Of Obesity And Secondary Metabolic Disorders, Kristin Goldstone, Keelin Irwin, Ava O' Meara-Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Review: Obesity is a global threat to human health that is precipitating epidemically, with almost 2 billion adults categorised as overweight or obese in 2016. Ireland has one of the highest reports of obesity in Europe with 60% of Irish adults reported as overweight or obese. Inflammation plays an integral role in disease pathogenesis and is a major hallmark of obesity and obesity-related secondary co-morbidities. Obesity-related inflammation can precipitate several diseases, such breast cancer, insulin resistance, type II diabetes and cardiovascular issues. As obesity puts human health at inherent risk, the regulation of obesity-related inflammation is therefore a necessary component …

Investigation Into The Effect Of Aspartame On The Expression Of P53 And Bax In Mouse Stomach Tissue, Angelique Cheryl, Aoife Mac Cooey

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The recent reclassification of aspartame as a Group 2B hazard by the International Agency for Research on Cancer, along with studies suggesting links to cancer, has raised concerns and prompted further investigation. Evidence suggests that aspartame exposure may alter p53 and BAX gene expression, affecting apoptosis in cancer cells. This study aims to examine how aspartame exposure affects p53 and BAX gene expression in normal mouse stomach tissue, shedding light on cellular stress and apoptosis mechanisms.

Methods: Mice were sacrificed, and stomach tissue was excised and divided into control and treatment groups. RNA extraction was carried out in the …

Total Organic Carbon Analysis Of Residual Contaminants In Bioreactor Equipment: A Cleaning Verification Study Using Surface Swabbing, Ciara E. Fitzpatrick, James J. Roche

SURE Journal: Science Undergraduate Research Experience Journal

Contamination is a major issue in the biopharmaceutical industry. Bioreactors must be meticulously cleaned to remove residual impurities and avoid cross-contamination. Cleaning validation is necessary to ensure residual contaminants are reduced to the lowest acceptable limits. Bacterial cells represent the paramount challenge in manufacturing equipment cleaning because they are composed of insoluble organic contaminants. Total organic carbon (TOC) analysis is a fast, highly sensitive, and inexpensive analytical technique commonly used to evaluate the approximate level of organic contamination.

A study was conducted to assess the effectiveness of cleaning procedures in the removal of contaminants from bioreactor equipment by measuring the …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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Proof Of Causation In A Private Action For Acid Rain Damage, Patrick J. Scully

Maine Law Review

The acid rain problem has become one of the major environmental issues of our day. Each new report on the subject is more disturbing than the last, documenting serious and often irreversible effects of acid rain on lakes and streams, fish and other aquatic life, forests, soils, buildings, and even human health. Present federal legislation is inadequate to deal with acid rain effectively. Proposed legislation could help ameliorate the problem, but even if adopted the effects of such proposals will not be felt until early in the next century. Furthermore, the current administration, particularly the Environmental Protection Agency (EPA), has …

Reevaluating The Role Of White Male Professionals In Higher Education: A Transformative Analysis Of Identity Development, Awareness, And Advocacy, Justin Zagorski

MAGIS: Student Development Journal

This article focuses on investigating the systematic privilege afforded to White male professionals in higher education by comparing a researcher’s personal experiences to the findings of a qualitative research study. This reflective piece enables the author to further investigate how White male privilege impacts his practice while linking his journey to the experiences of five White male student affairs administrators. This comparative analysis illustrates a need for White male professionals to transform and commit to a continual process of learning about racial and gender privilege in higher education.

Back Matter

The Journal of Purdue Undergraduate Research

No abstract provided.