Life Sciences Commons^™

Mathematical Multi-Compartment Modeling Of Chronic Lymphocytic Leukemia Cell Kinetics Under Ibrutinib, Melanie Schulz, Sanne Bleser, Manouk Groels, Dragan Bošnački, Jan A Burger, Nicholas Chiorazzi, Carsten Marr

Faculty, Staff and Student Publications

The Bruton tyrosine kinase inhibitor ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia (CLL). While it rapidly reduces lymph node and spleen size, it initially increases the number of lymphocytes in the blood due to cell redistribution. A previously published mathematical model described and quantified those cell kinetics. Here, we propose an alternative mechanistic model that outperforms the previous model in 26 of 29 patients. Our model introduces constant subcompartments for healthy lymphocytes and benign tissue and treats spleen and lymph nodes as separate compartments. This three-compartment model (comprising blood, spleen, and lymph nodes) performed significantly better …

From Sampling To Simulating: Single-Cell Multiomics In Systems Pathophysiological Modeling, Alexandra Manchel, Michelle M. Gee, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

As single-cell omics data sampling and acquisition methods have accumulated at an unprecedented rate, various data analysis pipelines have been developed for the inference of cell types, cell states and their distribution, state transitions, state trajectories, and state interactions. This presents a new opportunity in which single-cell omics data can be utilized to generate high-resolution, high-fidelity computational models. In this review, we discuss how single-cell omics data can be used to build computational models to simulate biological systems at various scales. We propose that single-cell data can be integrated with physiological information to generate organ-specific models, which can then be …

Bone-Ivd Crosstalk And The Role Of Rage Signaling In An Ivd Injury Model, Remy Walk

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain (LBP) is the number one musculoskeletal cause of disability with a lifetime prevalence of up to 85%. The causes of LBP are multifactorial with potential contributions from factors such as tissue injury and degeneration as well as social economic and psychological factors. Intervertebral disc (IVD) degeneration is associated with 26-40% of LBP cases and in a 2015 meta-analysis, it was estimated that a total 403 million people suffer from symptomatic IVD degeneration. IVD degeneration is characterized by loss of hydration in the nucleus pulposus (NP), damage accumulation in the annulus fibrosus (AF) and calcification of the cartilaginous …

Quantitative Approaches To Dissect Bivalent Antibody Binding And Detect Viruses From Aerosolized Samples, Ananya Benegal

McKelvey School of Engineering Graduate Student Theses & Dissertations

Influenza A virus (IAV) poses substantial epidemiological burdens around the world, with an estimated annual global mortality rate in the hundreds of thousands. Its rapid rate of mutation gives it a propensity for causing seasonal epidemics and occasional pandemics. As an airborne virus, IAV is most commonly transmitted through droplets and aerosols. Antibodies play a crucial role in the immune defense against IAV infection. By understanding the mechanisms of antibody-mediated defense and the transmission dynamics of IAV, we can better inform strategies for prevention, vaccination, and treatment, ultimately mitigating its impact on public health. The work encompassed in this dissertation …

Bone-Ivd Crosstalk And The Role Of Rage Signaling In An Ivd Injury Model, Remy Walk

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain (LBP) is the number one musculoskeletal cause of disability with a lifetime prevalence of up to 85%. The causes of LBP are multifactorial with potential contributions from factors such as tissue injury and degeneration as well as social economic and psychological factors. Intervertebral disc (IVD) degeneration is associated with 26-40% of LBP cases and in a 2015 meta-analysis, it was estimated that a total 403 million people suffer from symptomatic IVD degeneration. IVD degeneration is characterized by loss of hydration in the nucleus pulposus (NP), damage accumulation in the annulus fibrosus (AF) and calcification of the cartilaginous …

Spatial Insight Of Kidney Sex-Dimorphism And Tumor Evolution, Chia-Kuei Mo

McKelvey School of Engineering Graduate Student Theses & Dissertations

The landscape of spatial biology research has transformed drastically in recent years allowing a comprehensive understanding of cellular organization and molecular mechanisms in various biological context. This thesis presents three complementary studies that advance our understanding of spatial organization in normal tissue biology and tumor evolution, utilizing cutting-edge spatial multi-omics approaches. The first study presents a comprehensive investigation of kidney sexual dimorphism across the lifespan, integrating six distinct technological platforms: single-nucleus transcriptomics, epigenomics, Visium spatial transcriptomics, Xenium single-cell resolution spatial transcriptomics, conventional immunofluorescence imaging, and co-detection by indexing (CODEX) multiplexed protein imaging. This multi-modal approach reveals that proximal tubules exhibit …

Characterization Of Tfiie-Regulated Genes By Transcriptome Analysis, Serdar Baysal

Turkish Journal of Biology

RETRACTED: This article has been retracted. Please see the Retraction Notice for details. An Expression of Concern was previously published.

Previous studies on GTF2E showed that it has association with certain group of diseases such as colon cancer and trichothiodystrophy but what is the global effect of GTF2E on cellular processes is not widely characterized. In this regard, this study aimed to investigate and characterize the affect of GTF2E on transcription level of genes and identify the cellular processes and diseases associated with GTF2E. The HCT116 cell line was used in the study and transfected at 30 nM concentration with …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Chilling- And Dark-Regulated Photoprotection In Miscanthus, An Economically Important C4 Grass, Jared Haupt, Katarzyna Glowacka

Department of Biochemistry: Faculty Publications

Tolerance of chilling dictates the geographical distribution, establishment, and productivity of C4 crops. Chilling reduces enzyme rate, limiting the sink for the absorbed light energy leading to the need for quick energy dissipation via non-photochemical quenching (NPQ). Here, we characterize NPQ upon chilling in three Miscanthus accessions representing diverse chilling tolerance in C4 grasses. High chilling tolerant accessions accumulate substantial amounts of zeaxanthin during chilling nights in both field and growth chamber settings. Chilling-induced zeaxanthin accumulation in the dark enhances rate of NPQ induction by 66% in the following morning. Based on our data, the emerging ways for the unique …

Exploring Nutrition Teachers' Perspectives Of Enacted Nutrition Policies To Address Childhood Obesity In The Bahamas, Shondell M. De Velde

Doctoral Dissertations and Projects

The purpose of this phenomenological study was to gain a comprehensive understanding of nutrition teachers' perspectives on enacted nutrition policies aimed at combating childhood obesity in The Bahamas. The central phenomenon of the study is teachers' perspectives of enacted nutrition policies to address childhood obesity in The Bahamas. The Health Belief Model (HBM) developed by Irwin M. Rosenstock in the 1950s was used to provide a theoretical framework, that can be used to understand nutrition teachers' perceptions and actions related to enacted nutrition policies. The HBM delves into an individual’s motivation to accept healthy behavior and is thus constructed to …

A Quantitative Approach To Determining The Reduction Rate Of Cassette Labeling Errors Within A Surgical Pathology Diagnostic Laboratory, Kiaya Symonné Pruitt

Doctoral Dissertations and Projects

Cassette labeling errors within a surgical pathology laboratory can affect patient safety variously, including invalid patient results. In order to diminish these errors, automated systems have been placed in surgical pathology laboratories. However, there is no current research on reducing cassette labeling errors within a surgical pathology laboratory that possesses a partial automated system without a LIS connection. Therefore, the current study aimed to determine if there is a statistically significant reduction in pathology cassette labeling errors during different phases of the barcode system (an automated system) implementation for cassette creation. A nonexperimental correlational design was used for the current …

The Proteomics Of T-Cell And Early T-Cell Precursor (Etp) Acute Lymphocytic Leukemia: Prognostic Patterns In Adult And Pediatric-Etp All, Fieke W Hoff, Lourdes Sriraja, Yihua Qiu, Gaye N Jenkins, David T Teachey, Brent Wood, Meenakshi Devidas, Shaina Shockley, Mignon L Loh, Evangelia Petsalaki, Steven M Kornblau, Terzah M Horton

Faculty, Staff and Student Publications

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Methods: Protein expression was assessed using RPPA methodology for 321 target proteins in 361 T-ALL patient samples from 292 pediatrics and 69 adults, …

Author Correction: Single-Cell And Spatial Proteo-Transcriptomic Profiling Reveals Immune Infiltration Heterogeneity Associated With Neuroendocrine Features In Small Cell Lung Cancer, Ying Jin, Yuefeng Wu, Alexandre Reuben, Liang Zhu, Carl M Gay, Qingzhe Wu, Xintong Zhou, Haomin Mo, Qi Zheng, Junyu Ren, Zhaoyuan Fang, Teng Peng, Nan Wang, Liang Ma, Lungevity Panshi Initiative Consortium, Yun Fan, Hai Song, Jianjun Zhang, Ming Chen

Faculty, Staff and Student Publications

No abstract provided.

Enhancer Reprogramming Underlies Therapeutic Utility Of A Smarca2 Degrader In Smarca4 Mutant Cancer, Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

Faculty, Staff and Student Publications

Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes …

Mechanism Of Impaired Cd8+ T Cell Activation During Ross River Virus Infection, Christopher Bullock

Arts & Sciences Graduate Student Theses and Dissertations

Ross River virus (RRV) is a mosquito transmitted virus endemic to Australia that infects humans and causes acute symptoms of rash, fever, myalgia, and fatigue. Although systemic viral infection subsides within a few weeks, joint pain lingers in many patients for months. Active viral replication is not readily detected in this chronic phase, although persistent viral RNA has been found in the synovial fluid of patients. This can be studied in mice, which can be productively infected with RRV when inoculated in the foot. Like in humans, in the chronic phase of disease, viral RNA is still present in the …

Cytoplasmic And Mitochondrial Calcium Influences Retinal Ganglion Cell Survival To Axon Injury, Sean Mccracken

Arts & Sciences Graduate Student Theses and Dissertations

Retinal Ganglion Cell (RGC) death is the final outcome in optic neuropathies like glaucoma and traumatic optic nerve injury, which represent the leading cause of irreversible blindness worldwide. There are currently no treatments for these diseases targeting RGCs directly, and mechanisms underlying RGC death are unclear. Calcium ion (Ca2+) dysregulation occurs in almost all neurodegenerative conditions, including glaucoma, which has been studied in rodents using a robust injury model of traumatic axon injury, optic nerve crush (ONC). However, the impact of homeostatic Ca2+ regulation in RGCs response to glaucoma or ONC is unknown. Furthermore, while some mechanisms that regulate Ca2+ …

Studying The Dynamics Of Neuromodulators In The Brain By Fluorescence Lifetime Imaging, Pingchuan Ma

Arts & Sciences Graduate Student Theses and Dissertations

Neuromodulators in the brain are fundamental to neuronal functions and animal behaviors in health and diseases. The modulatory actions of neuromodulators highly rely on their spatiotemporal dynamics. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic and phasic neuromodulator release. However, no traditional methods could simultaneously record both types of dynamics. Fluorescence lifetime of optical reporters could offer a solution because it both allows high temporal resolution and is impervious to sensor expression differences across chronic periods. Nevertheless, no fluorescence lifetime change across the entire classes of neuromodulator sensors was previously …

Exploring The Homeostatic Functions And Driving Forces Of Lymphatic Outflow Pathways From The Central Nervous System, Zachary Matthew Papadopoulos

Arts & Sciences Graduate Student Theses and Dissertations

Lymphatic drainage from the central nervous system (CNS) has been noted and described for several hundred years, yet its physiological roles have remained unclear. The fluid homeostasis of the CNS has long stood as an area of scientific interest due to primary disorders including hydrocephalus. However, the early days of neuroimmunology leaned on the lack of lymphatic vasculature in the CNS as a contributing explanation for ‘immune privilege’ in the CNS. As a result, the importance of lymphatics in CNS homeostasis has remained poorly understood and controversial. Following a renaissance in interest in the contribution of lymphatics to CNS homeostasis, …

A Meta-Analysis Of Seafood Species Mislabeling In The United States, Sarah Ahles, Christina A. Mireles Dewitt, Rosalee S. Hellberg

Food Science Faculty Articles and Research

Seafood is vulnerable to mislabeling due to complex global supply chains, varying prices, and the similar appearance of species. While numerous studies have been published on seafood mislabeling, the focus is often on species known to be commonly substituted. Therefore, the overall mislabeling rates of seafood sold in the U.S. remain unknown, especially for the most consumed species. The objective of the current study was to compile the results of seafood mislabeling studies into a single resource to provide informative statistics on U.S. seafood mislabeling. A meta-analysis was conducted on U.S. seafood mislabeling studies that tested commercial samples of bony …

Deep And Continuous Root Development In Ameliorated Soil Improves Water And Nutrient Uptakes And Wheat Yield In Water-Limited Conditions, Gaus Azam, Kanchana Wickramarachchi, Craig Scanlan, Yinglong Chen

Grain and Other Field Crops Research Articles

Background and aims

Despite the widespread co-occurrence of subsoil acidity and compaction, the interaction between these factors and their combined effects on root system development under water-limited conditions is poorly understood. This study aimed to investigate how the removal of soil strength and acidity influenced root development and examine relationships between root system properties and shoot growth under field conditions.

Methods

Images of root growth were obtained in situ by using rhizotron facilities to assess the temporal effects of soil improvement through loosening and lime incorporation on wheat root development in the 2018 season. Following this, we examined the relationship …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

Administering Tolfenamic Acid To Gilts And Sows Before Artificial Insemination Did Not Improve Litter Size But Tended To Reduce Post-Service Serum Prostaglandin F2Α Levels, Pachara Pearodwong, Nithitad Jiebna, Padet Tummaruk

The Thai Journal of Veterinary Medicine

This study examined the impact of intramuscular administration of tolfenamic acid 10 min before artificial insemination (AI) on serum PGF2α levels and reproductive performance in gilts and sows. In Experiment I, 20 gilts were divided into two groups: control (n = 10) and treatment (n = 10). Serum samples were collected 30 min before and after insemination to measure PGF2α levels. In Experiment II, 175 gilts and sows were divided into control (25 gilts and 56 sows) and treatment (16 gilts and 78 sows) groups. In both experiments, the treatment group received an intramuscular injection of 2 mg/kg tolfenamic acid …

Star-Studded Stingers: Fluorescent Sensilla On The Scorpion Aculeus (Arachnida: Scorpiones), Graeme Lowe

Euscorpius

The aculeus of the scorpion telson was studied by UV fluorescence microscopy. Numerous brightly fluorescent punctae were observed on the non-fluorescent distal aculeus, including the tip region. The punctae were identified as aculear sensilla coeloconica (ASC), and were connected to fluorescent canals running through the cuticle. ASC were present in both sexes, and in adults and immatures as early as the second juvenile instar, but were absent from the first instar. The distal aculeus was found to be encased in a thick, non-fluorescent dark exocuticle (DX), covering an underlying thin, fluorescent hyaline exocuticle (HX). Fluorescent ASC were recorded from 183 …

Quality And Sensory Characteristics Of Selected Freeze-Dried Foods After 50 Years Storage, Prithiviraj Jegannathan

Theses and Dissertations

Freeze-drying is a dehydration process that uses low temperature and pressure to remove moisture from food. With an annual market value of over $35 billion in 2023, freeze-dried foods are widely used in various situations requiring long-term storage such as military rations, emergency food supplies, and space exploration. Freeze-dried foods are becoming more popular for their quality, light weight, easy storage at room temperature, and quick rehydration. Moreover, many freeze-dried food manufacturers claim that their freeze-dried food products can last for 25 years or more. However, there are currently no published studies supporting such claims. Chemical, physical, and sensory properties …

Hyperglycemia Causes Differential Change In Macrophage Population In The Lacrimal Gland, Conjunctiva And Cornea, Saleh Alfuraih, Amy Tran, Lois Kim, Rais Ansari, Ajay Sharma

Pharmacy Faculty Articles and Research

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines.

Methods: Mouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm …

Capacity-Weighted Figures-Of-Merit For Battery Transport Metrics, Cj Sturgill, Christopher Sutton, Julian Schwenzel, Morgan Stefik

Faculty Publications

New battery materials with improved transport are needed. Typical measurements yield widely varying voltage-dependent diffusivities and reporting practices are diverse. Some materials (e.g. first-order phase change) have most redox occur at a specific voltage and may be sufficiently represented by singular transport metrics. Many rapid intercalation materials, however, exhibit second-order phase transitions with redox over a broad voltage range. How should such cases be compared? The use of capacity-weighted average values is suggested where voltage-dependent metrics are consolidated into representative descriptors as figures-of-merit. Examples are elaborated where differential capacity (dQ/dV) is used to derive a …

Tree Rings Reveal Mixtures Of Aspen And Spruce Exhibit Greater Drought Resilience In A Planted Field Experiment, Jéssica Chaves Cardoso, Linhao Wu, Marcel Schneider, Charles A. Nock

Aspen Bibliography

Boreal forests provide a wealth of ecosystem services, many of which are linked to forest productivity. Climate change is expected to increase the frequency, duration, and severity of drought, and undermine the productivity of western boreal forests. Favouring species mixtures has emerged as a potential strategy to increase forest resilience to drought. To test the hypothesis that mixtures of trembling aspen and white spruce were more productive than pure stands because they were more resistant and resilient to drought, we analyzed community and species responses to drought utilizing measurements of annual growth obtained from stem disc samples from a planted …

Nexus Between Rural Agricultural Land Ownership And Agricultural Credits Access: A Case Of Tanzania, Gelas Rubakula

Journal of Humanities and Social Sciences

Agricultural investment in low- and middle-income countries faces credit access challenges. Several financial institutions, particularly banks, normally impose some conditions where the possession of a land title deed is required to access agricultural credits. This paper examines whether, and to what extent, rural agricultural land ownership influences agricultural credit access for rural farmers in Tanzania. The study focuses only on rural farmers and tries to find out whether these smallholder farmers can use their land, which is largely unformalized, as a collateral for credit access. The study survey was cross-sectional, using quantitative data collected in December 2017 to March 2018 …

Social Learning And Cultural Enrichment For Fish Welfare, Chiawen Chiang, Becca Franks

Animal Sentience

This commentary examines how understanding animal culture—shared behaviors and knowledge transmitted through social learning—plays a role in advancing welfare practices for captive fishes. Despite extensive evidence of fishes' complex sociocultural capacities, their psycho-social needs remain underestimated and unmet in zoos and aquaria. We explore what considering fish culture might mean for welfare practices: diverse social learning opportunities, cultural development, and thoughtful group management. More knowledge about wild fishes' lives will help bridge the gap between their full, complex lives and current captive welfare practices.

Sensitivity Of Difficult-To-Control Palmer Amaranth Accessions To Fluridone And Diflufenican, Maria Carolina Souza, Matthew Coleman Woolard, Jason K. Norsworthy, Tristen H. Avent, Tristen H. Avent, Tom Barber, Rodrigo Botelho

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Palmer amaranth (Amaranthus palmeri S. Watson) has evolved resistance to herbicides targeting nine sites of action. Phytoene desaturase-inhibiting herbicides remain among the few sites of action that are still effective in controlling Palmer amaranth. Greenhouse experiments were conducted to evaluate the effectiveness of fluridone and diflufenican in controlling difficult-to-control Palmer amaranth accessions collected in Arkansas from 2016 to 2022, to quantify the response of three accessions that exhibited low sensitivity to both herbicides, and to evaluate the effectiveness of photosystem II inhibitors alone and with fluridone or diflufenican on three accessions. At 14 days after a preemergence application, Palmer …