Digital Commons Network^™

Geochemical Fate Of Lead In Contaminated Residential Soils Following Application Of Amendments For Lead Immobilization, Hadeer Saleh, Washington Braida, Zhiming Zhang, Rupali Datta, Dibyendu Sarkar

Michigan Tech Publications

Background: Lead (Pb) persists in urban soils, where its partitioning among geochemical fractions governs mobility, bioavailability, and human health risk. These fractions are strongly controlled by soil physicochemical properties, necessitating site-specific remediation strategies. Methods: This study developed a site-specific Pb immobilization framework linking amendment selection to soil geochemistry and sustainability considerations. Pb-contaminated residential soils from three U.S. cities, San Antonio (alkaline), Baltimore (acidic), and Detroit (near-neutral), were treated with gypsum, biochar + lime, and alum, respectively. Changes in Pb speciation were tracked using sequential extraction over 7, 30, and 90 days. Results: All amendments significantly reduced exchangeable Pb (F1) and …

What Goals? Which Point? Whose Purpose? A Critical Engagement With Sport Internalism, Francisco Javier Lopez Frias

Kinesiology and Health Science Faculty Publications

In this article, I critique the dominance of internalism in sport philosophy and outline an alternative theoretical framework that integrates internal and external elements while striving to transcend the dichotomous language used to conceptualize sport. The analysis begins by claiming that internalism conflates three fundamental teleological aspects of sport: goals, point, and purposes. I argue that this conflation limits internalism’s ability to explain the complexity of sporting practices. By carefully distinguishing these elements, I illustrate their distinct roles in shaping sport and explore how they interact. I conclude by proposing that the alternative pluralist framework briefly sketched here enables a …

Cover Crop Functional Groups Controls Decomposition And Nutrient Release In Conservation Tillage-Based Corn Production Systems, Puja Sapkota

Tennessee State University Alumni Theses and Dissertations

Grass-legume cover crop mixtures are promoted to balance ecosystem services, but predicting their decomposition and nutrient release remains a challenge. A two-year litterbag study investigated the decomposition of cereal rye, crimson clover, their field mixture, and a gradient of biomass proportions in a no-till corn system. Monocultures exhibited a strong functional dichotomy where rye decomposed slowly with a large recalcitrant fraction and clover decomposed rapidly. The field mixture yielded high biomass similar to rye and exhibited intermediate decomposition kinetics. Crucially, analysis of non-additive effects revealed a fundamental decoupling as the residue mass loss showed context-dependent synergistic acceleration but nitrogen release …

Nanomedicine Meets Immunotherapy: Transforming Chimeric Antigen Receptor T Cell Treatment For Solid Tumors, Stephen O'Rourke, Nuo Xu, Hongjun Wang, Hexin Chen

Faculty Publications

The emergence of effective immunotherapies has drastically revolutionized clinical management of many cancer types. Among them, chimeric antigen receptor (CAR)-T cell therapy (CTT), as a groundbreaking approach, has been considered as a “living drug,” displaying unprecedented clinical outcomes with hematological malignancies, including B cell leukemia and lymphomas, and multiple myeloma. Despite the high remission rates and improved survival achieved with hematological cancers, the effectiveness of CTT in solid tumors remains largely unsatisfactory. The efficacy of CTT in solid tumors is significantly challenged by multiple factors, including tumor-antigen heterogeneity, limited T cell trafficking and infiltration, a highly immunosuppressive tumor microenvironment, and …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

International Society Of Sports Nutrition Position Stand: Effects Of Dietary Antioxidants On Exercise And Sports Performance, Drew E. Gonzalez, Broderick L. Dickerson, Brandon M. Roberts, Jennifer A. Kurtz, Hunter S. Waldman, Adam M. Gonzalez, Matthew J. Mcallister, Jeffery L. Heileson, Richard J. Bloomer, Shawn M. Arent, Darren G. Candow, Jeffrey R. Stout, Karen A. Hecht, Bill Campbell, Chad Kerksick, Douglas Kalman, Jose Antonio, Richard B. Kreider

Faculty Scholarship

Following a comprehensive review, the International Society of Sports Nutrition (ISSN) has developed an official position on the role of dietary antioxidants in exercise and sport. Antioxidants play a complex, context-dependent role in vivo; they can facilitate recovery from exercise but may also hinder training adaptations when consumed at supraphysiological doses. While endogenous antioxidant systems can effectively maintain redox balance, dietary sources, particularly whole foods, can help mitigate excessive oxidative stress following intense/heavy training or inadequate recovery. The influence of dietary antioxidants depend on timing, dosage, type, and individual factors. The ISSN’s official position encompasses the following: (1) Redox balance …

American Kestrel Population Trends And Vital Rates At The Continental Scale, Paige E. Howell, Abigail J. Lawson, Kristin P. Davis, Guthrie S. Zimmerman, Orin J. Robinson, Matthew A. Boggie, Mitchell J. Eaton, Fitsum Abadi, Jessi L. Brown, Julie A. Heath, John A. Smallwood, Karen Steenhof, Ted Swem, Brian W. Rolek, Christopher J.W. Mcclure, Jean Francois Therrien, Karl E. Miller, Brian A. Millsap

Department of Biology Faculty Scholarship and Creative Works

The American kestrel (Falco sparverius, hereafter referred to as kestrel) has declined across much of its North American range since at least the mid-1960s. Kestrel population dynamics have been explored through a multitude of local studies and two broad reviews of available data. Across large geographic extents, however, the demographic cause(s) of kestrel population declines remain(s) largely unknown. As part of a collaborative effort to elucidate the drivers of kestrel population declines, we developed a continental-scale integrated population model using band-recovery data, productivity data, and Breeding Bird Survey indices from 1986 to 2019 to estimate indices of annual population sizes, …

Impact Of Iron-Bearing Fillers On The Mechanical Strength And Chemical Stability Of Magnesium Potassium Phosphate Matrices Incorporating Rhenium, Sergey Sayenko, Volodymyr Shkuropatenko, Hans Conrad Zur Loye, Petr Vecernik, Monika Kiselova, Vlastislav Kašpar, Vlastimil Miller, Petr Bezdicka, Jan Šubrt, Petra Ecorchard, Natalija Murafa, Iva Milisavljevic, Scott T. Misture

Faculty Publications

We report on the study of the immobilization process of non-radioactive rhenium (Re), a chemical analogue of technetium-99 (⁹⁹Tc), in compounds based on magnesium potassium phosphate (MKP), as well as the possibility of enhancing their properties with iron-bearing additives/fillers. Powdered Re2O7 was used as the initial Re-containing source. Because of the solubility and high leachability of Tc (VII), which is also volatile at high temperatures, its immobilization for long-term storage and disposal poses a serious challenge to researchers. Taking this into account, low-temperature stabilization technology based on MKP, a cementitious material, is currently considered promising. We prepared experimental …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

Genomic Comparisons And The Adaptive Basis Of Brain Size Plasticity And Chromosomal Instability In The Eurasian Common Shrew, William R. Thomas, Tanya M. Lama, Cecilia Baldoni, Laia Marín-Gual, Diana Moreno Santillán, Marta Farré, Linelle Abueg, Jennifer Balacco, Olivier Fedrigo, Giulio Formenti, Nivesh Jain, Jacquelyn Mountcastle, Tatiana Tilley, Ying Sims, Alan Tracey, Jo Wood, David A. Ray, Dominik Von Elverfeldt, John Nieland, Angelique P. Corthals, Aurora Ruiz-Herrera, Dina K.N. Dechmann, Erich Jarvis, Liliana M. Dávalos

Biological Sciences: Faculty Publications

Sorex araneus, the Eurasian common shrew, has seasonal brain size plasticity (Dehnel's phenomenon) and many intraspecific chromosomal rearrangements. Genomic contributions to these traits, however, remain unknown. We couple a chromosome-scale genome assembly with seasonal brain transcriptomes to discover relationships between molecular evolution and both traits. While Positively Selected Genes (PSGs) enriched the Fanconi anemia DNA repair pathway (FANCI, FAAP100), which is likely involved in chromosomal rearrangements by preventing the accumulation of chromosomal aberrations, genes under positive selection or showing seasonal differential expression in the brain implicate neurogenesis (PCDHA6, SOX9, Notch signaling) and metabolic regulation (VEGFA, SPHK2) as key mechanisms underlying …

Dna Stability In Aqueous Solutions: A Case Study On Poly A - Poly T Duplex Using Molecular Dynamics Simulations, Haripriya Chennuru

Biochemistry and Molecular Biology

This thesis relies on molecular dynamics (MD) simulations, which apply the AMBER software package to analyze the structural stability, energetics, and dynamics of Poly A - Poly T DNA duplexes. This work is mainly concerned with testing configurations of non-bonded interaction cutoffs (12 Å and 15 Å) on the Generalized Born solvation models (IGB1 and IGB2) to determine the most appropriate conditions regarding computation time and physical reliability in DNA molecular dynamics. The solvation models enable effective simulation of solvent effects, facilitating the calculation of simulation parameters to evaluate structural stability within different environmental conditions. Overall, the performance indicates that …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Developing Updated And New Guidance To Promote Reliable Patient Identification, Emma Weatherford, Anne Grauer, Carina Sirochinsky, I-Fong Lehman, Neha Thummala, Miriam Callahan, Dean F Sittig, Hardeep Singh, Hojjat Salmasian, Madison Jurgens, Jason S Adelman

Faculty, Staff and Student Publications

Objectives: To describe the process of updating the Patient Identification Safety Assurance Factors for EHR Resilience (SAFER) Guide and to review new practices and refinements to the Guide.

Materials and methods: We conducted a review of literature on the topic of patient identification in healthcare settings, focusing on papers published after 2016. Titles and abstracts were screened by a team of reviewers, and the full text of retained articles was used to inform the revision.

Results: The updated SAFER Guide strengthens recommendations for displaying patient photographs and using electronic patient identification, including barcoding and radiofrequency identification on patient wristbands. The …

Comparing The Effectiveness Of A Medication Knowledge Base Product As Designed With Real-World Hospital Implementations Using The Leapfrog Group’S Computerized Physician Order Entry (Cpoe/Ehr) Evaluation Tool, Zoe Co, Howard R Strasberg, Bruce R Hanway, Dean F Sittig, David C Classen

Faculty, Staff and Student Publications

Objectives: We sought to compare and analyze the performance of a medication knowledge base (MKB) vendor's (Medi-Span) fully enabled, factory settings product to operational implementations in hospitals using the Leapfrog Group's Computerized Physician Order Entry (CPOE)/electronic health record (EHR) Evaluation Tool.

Materials and methods: We randomly selected a hospital that used the MKB vendor's product to complete the Leapfrog CPOE/EHR Evaluation Tool in 2018 and used this version of the tool to assess the MKB vendor's fully enabled product. Next, we retrospectively evaluated all hospitals, regardless of EHR vendor, that used the MKB vendor's product in the tool from 2017 …

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Melody: Mediation Analysis In Logistic Regression For High-Dimensional Mediators And A Binary Outcome, Sunyi Chi, Xingyu Li, Peng Wei, Xuelin Huang

Faculty, Staff and Student Publications

Mediation analysis is a pivotal tool for elucidating the indirect effect of an environmental factor or treatment on disease through potentially high‐dimensional omics data, such as gene expression profiles. However, traditional mediation analysis methods tailored for binary outcomes often rely on the rare disease assumption in logistic regression and provide inadequate measures of total mediation effect when multiple mediators have effects in different directions. In this paper, we develop a MEdiation analysis framework in LOgistic regression for high‐Dimensional mediators and a binarY outcome (MELODY). It leverages a second‐moment‐based measure analogous to the ��2 for linear models to quantify the total …

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Dissolved Organic Matter Composition In The Laurentian Great Lakes Ice And Its Contribution To Spring Melt, Anthony J. Arsenault, Nolan J.T. Pearce, Ted Ozersky, Sarah C. D’Amario, Kirill Shchapov, Hunter J. Carrick, Trista Vick-Majors, Et Al.

Michigan Tech Publications

Dissolved organic matter (DOM) plays a vital role in lakes, but its behavior in winter is poorly understood. This study examined the differences in DOM between lake ice and the upper water column across 18 sites in the Laurentian Great Lakes, integrating in situ sampling and remotely sensed ice data to create a mass budget model to estimate basin-scale DOM storage and release from ice. We found that the composition of the DOM pool in ice varied based on ice thickness, water DOM composition, nutrients, and dissolved organic carbon concentrations. Calculations of protein-like, microbial humic-like, and terrestrial-like DOM storage in …

Cleavage And Polyadenylation Specificity Factor Subunit 5 Regulates Pulmonary Artery Smooth Muscle Expansion And Hypoxic Response, Scott D Collum, Lisha Zhu, Tingting W Mills, Rene Girard, Jamie Tran, Tinne C J Mertens, Cory Wilson, Nancy Wareing, Erik E Suarez, Howard J Huang, Rahat Hussain, Bindu Akkanti, Wenjin J Zheng, Hari K Yalamanchili, Bela Patel, Eric J Wagner, Sandeep Agarwal, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results …

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Somatosensory Cortex Responses To Illusory Touch In A Visual-Tactile Integration Task, Aditi Surendra Pawar

Dissertations, Theses, and Capstone Projects

Perceptual illusions arising from multisensory integration reveal how the brain constructs subjective experience from sensory input, and provide a powerful means of allowing the investigation of neural processes that track perceptual interpretation rather than physical stimulation alone. While visual illusions induced by auditory or tactile stimuli have been fairly well studied, the neural mechanisms underlying visually-induced illusory touch remain unclear. This study investigated whether illusory tactile perception engages the somatosensory cortex in a manner similar to veridical touch. Twenty healthy adults participated in an event-related functional magnetic resonance imaging (fMRI) study while performing a tactile numerosity judgment task. Each trial …

How To Search For The Engram: Optogenetics And Network Dynamics, Claudia Garcia Jou

Dissertations, Theses, and Capstone Projects

Memories are thought to be encoded by ensembles of neurons called "engram cells", because their artificial activation with optogenetics leads to the behavioral expression of a memory. However, the physiological mechanisms that mediate this process remain unknown. In this thesis, I investigate how optogenetic stimulation of memory-tagged cells changes neuronal firing, spatial coding, and the geometry of neural manifolds. I used an active place avoidance task and a foraging task to label engram cells in the dorsal hippocampus with Channelrhodopsin2 (ChR2). I then recorded the hippocampal activity response to optogenetic stimulation in mice under anesthesia, head-fixed, or freely moving. I …

Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain

Dissertations, Theses, and Capstone Projects

Chapter 1: A glycan detection platform comprised of synthetic carbohydrate receptors (SCRs) immobilized onto polymer brushes was prepared. SCR043, an alkene-containing SCR, was incorporated into grafted-from polymer brushes using hypersurface photolithography, resulting in microarrays of SCR043-functionalized polymer brushes, where brush height (h) and SCR grafting density (Γ) is controlled precisely at each feature in the array. The influence of h and Γ on the binding to five fluorescently labelled monosaccharides – α-glucose (α-Gluc-FL), α-galactose (α-Gal-FL), α-mannose (α-Man-FL), β-glucose (β-Gluc-FL), and β-galactose (β-Gal-FL) – in aqueous buffer …