Digital Commons Network^™

The Evolving Privacy And Security Concerns For Genomic Data Analysis And Sharing As Observed From The Idash Competition, Tsung-Ting Kuo, Xiaoqian Jiang, Haixu Tang, Xiaofeng Wang, Arif Harmanci, Miran Kim, Kai Post, Diyue Bu, Tyler Bath, Jihoon Kim, Weijie Liu, Hongbo Chen, Lucila Ohno-Machado

Faculty, Staff and Student Publications

Concerns regarding inappropriate leakage of sensitive personal information as well as unauthorized data use are increasing with the growth of genomic data repositories. Therefore, privacy and security of genomic data have become increasingly important and need to be studied. With many proposed protection techniques, their applicability in support of biomedical research should be well understood. For this purpose, we have organized a community effort in the past 8 years through the integrating data for analysis, anonymization and sharing consortium to address this practical challenge. In this article, we summarize our experience from these competitions, report lessons learned from the events …

Tumor-Intrinsic Sirpa Promotes Sensitivity To Checkpoint Inhibition Immunotherapy In Melanoma, Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V Kumar, Rehan Akbani, Yiling Lu, Han Liang

Faculty, Staff and Student Publications

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8+ T cells in a co-culture …

The Genome Of Orychophragmus Violaceus Provides Genomic Insights Into The Evolution Of Brassicaceaepolyploidizationandits Distinct Traits, Kang Zhang, Yinqing Yang, Xin Zhang, Lingkui Zhang, Yu Fu, Zhongwei Guo, Shumin Chen, Jian Wu, James C. Schnable, Keke Yi, Xiaowu Wang, Feng Cheng

Department of Agronomy and Horticulture: Faculty Publications

Orychophragmus violaceus, referred to as ‘‘eryuelan’’ (February orchid) in China, is an early-flowering ornamental plant. The high oil content and abundance of unsaturated fatty acids in O. violaceus seeds make it a potential high-quality oilseed crop. Here, we generated a whole-genome assembly for O. violaceus using Nanopore and Hi-C sequencing technologies. The assembled genome of O. violaceus was ~1.3 Gb in size, with 12 pairs of chromosomes. Through investigation of ancestral genome evolution, we determined that the genome of O. violaceus experienced a tetraploidization event from a diploid progenitor with the translocated proto-Calepineae karyotype. Comparisons between the reconstructed subgenomes …

Piglet Cardiopulmonary Bypass Induces Intestinal Dysbiosis And Barrier Dysfunction Associated With Systemic Inflammation, Jeffrey D. Salomon, Haowen Qiu, Dan Feng, Jacob Owens, Ludmila Khailova, Suzanne Osorio Lujan, John Iguidbashian, Yashpal S. Chhonker, Daryl J. Murry, Jean-Jack Riethoven, Merry L. Lindsey, Amar B. Singh, Jesse A. Davidson

Nebraska Center for Biotechnology: Faculty and Staff Publications

The intestinal microbiome is essential to human health and homeostasis, and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery postoperatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB is necessary. We used a piglet model of CPB with two groups, CPB (n=5) and a control group with mechanical ventilation (n=7), to evaluate changes to the microbiome, …

Running Out Of Oxygen: Revealing The Interannual And Intra-Annual Dynamics Of Bottom Water Hypoxia In A Great Lakes Estuary Using Time-Series Observations, Experiments, And Analyses, Nate M. Dugener

Masters Theses

Bottom water hypoxia, a condition of low dissolved oxygen in the bottom waters, negatively effects lakes and freshwater and marine coastal estuaries globally. As climate change shifts climatological and ecological patterns, hypoxia continues to shift in duration and severity. In Muskegon Lake, Michigan, hypoxia occurs annually, restricting fish habitat, increasing cyanobacteria blooms, and disrupting ecological and socioeconomic prosperity. In the current study, we examined the duration and severity of hypoxia over a 11 years (2011-2021) utilizing data from the Muskegon Lake Observatory buoy (MLO, https://www.gvsu.edu/wri/buoy/). During 2021, we analyzed the dissolved oxygen (DO) concentrations observed by the MLO, conducted biweekly …

Progression Of Functional And Structural Glaucomatous Damage In Relation To Diurnal And Nocturnal Dips In Mean Arterial Pressure, Jesus D. Melgarejo, Jan V. Eijgen, Dongmei Wei, Gladys E. Maestre, Lama A. Al-Aswad, Chia-Te Liao, Luis J. Mena, Thomas Vanassche, Stefan Janssens, Peter Verhamme

School of Medicine Publications

Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP.

Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic …

Medicc2: Whole-Genome Doubling Aware Copy-Number Phylogenies For Cancer Evolution, Tom L Kaufmann, Marina Petkovic, Thomas B K Watkins, Emma C Colliver, Sofya Laskina, Nisha Thapa, Darlan C Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi, Roland F Schwarz

Faculty, Staff and Student Publications

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.

Reproduction In Relation To Heavy-Metal Contamination Along An Urbanization Gradient In Aninvasive Florida Lizard Species (Anolis Sagrei), Elizabeth Hauck

USF Tampa Graduate Theses and Dissertations

Environmental contamination is accumulating rapidly worldwide due to increasing urbanization rates. Heavy metals are known to be particularly toxic to organisms, to accumulate in biological systems, and to be found in higher concentrations in animals located in areas of high urban levels. However, the physiological impacts of these toxic heavy metals in wildlife remain largely unknown. Lizards are excellent bioindicator species for environmental contaminants due to their trophic level as mesopredators and their susceptibility of exposure via air, water, diet, and soil through egg deposition. To assess the impacts heavy-metal contamination has on reproductive parameters in lizards and how these …

L-Ergothioneine Treatment In Old Cba/Caj Male Mice Slows The Progression Of Age-Related Hearing Loss, Mark A. Bauer

USF Tampa Graduate Theses and Dissertations

The naturally occurring amino acid, L-Ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, suggesting that it is highly conserved, to be utilized by cells as an antioxidant and anti-inflammatory, particularly under stressed conditions. In our current study, EGT was administered over a period of 6 months to 25-26 month old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis and chronic …

Microbiome Insights Into Pediatric Familial Adenomatous Polyposis., Thomas M. Attard, Seth Septer, Caitlin E. Lawson, Mark I. Attard, Sonny T M Lee, Shahid Umar

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Individuals with familial adenomatous polyposis (FAP) harbor numerous polyps with inevitable early progression to colon cancer. Complex microbiotic-tumor microenvironment perturbations suggest a dysbiotic relationship between polyp and microbiome. In this study, we performed comprehensive analyses of stool and tissue microbiome of pediatric FAP subjects and compared with unaffected cohabiting relatives through 16S V4 region amplicon sequencing and machine learning platforms.

RESULTS: Within our FAP and control patient population, Firmicutes and Bacteroidetes were the predominant phyla in the tissue and stool samples, while Proteobacteria dominated the polyp/non-polyp mucosa. A decline in Faecalibacterium in polyps contrasted with a decline in Bacteroides …

Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean

Faculty, Staff and Student Publications

Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the …

Copy Number Variants Are Ovarian Cancer Risk Alleles At Known And Novel Risk Loci, Amber A Devries, Joe Dennis, Jonathan P Tyrer, Pei-Chen Peng, Simon G Coetzee, Alberto L Reyes, Jasmine T Plummer, Brian D Davis, Stephanie S Chen, Felipe Segato Dezem, Katja K H Aben, Hoda Anton-Culver, Natalia N Antonenkova, Matthias W Beckmann, Alicia Beeghly-Fadiel, Andrew Berchuck, Natalia V Bogdanova, Nadja Bogdanova-Markov, James D Brenton, Ralf Butzow, Ian Campbell, Jenny Chang-Claude, Georgia Chenevix-Trench, Linda S Cook, Anna Defazio, Jennifer A Doherty, Thilo Dörk, Diana M Eccles, A Heather Eliassen, Peter A Fasching, Renée T Fortner, Graham G Giles, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Opal Study Group, Aocs Group, Niclas Håkansson, Michelle A T Hildebrandt, Chad Huff, David G Huntsman, Allan Jensen, Siddhartha Kar, Beth Y Karlan, Elza K Khusnutdinova, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Nhu D Le, Jan Lubiński, Taymaa May, Usha Menon, Roger L Milne, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Kunle Odunsi, Håkan Olsson, Celeste L Pearce, Tanja Pejovic, Susan J Ramus, Elio Riboli, Marjorie J Riggan, Isabelle Romieu, Dale P Sandler, Joellen M Schildkraut, V Wendy Setiawan, Weiva Sieh, Honglin Song, Rebecca Sutphen, Kathryn L Terry, Pamela J Thompson, Linda Titus, Shelley S Tworoger, Els Van Nieuwenhuysen, Digna Velez Edwards, Penelope M Webb, Nicolas Wentzensen, Alice S Whittemore, Alicja Wolk, Anna H Wu, Argyrios Ziogas, Matthew L Freedman, Kate Lawrenson, Paul D P Pharoah, Douglas F Easton, Simon A Gayther, Michelle R Jones

Faculty, Staff and Student Publications

BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.

METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.

RESULTS: We identified …

Numerical Investigation Of Heat Generation And Accumulation Contributing To Elevated Temperature In Msw Landfills, Alborz Fathinezhad

LSU Doctoral Dissertations

Landfills are complex geostructures which contains organic and inorganic municipal, and in some cases industrial, wastes and are expected to remain operational for long times. Due to the complex nature of physical, chemical, biological, and thermal reactions that carry on within the depths of a landfill, unexpected incidents such as elevated temperatures could become inevitable. While uncommon to happen, elevated temperatures cause health and environmental issues such as odors, rapid settlements, slope instabilities. In addition, elevated temperatures can negatively impact engineered components in composite bottom liners, cover systems, leachate collection, and gas extraction and recovery systems.

Air intrusion into municipal …

Inhibiting Ack1-Mediated Phosphorylation Of C-Terminal Src Kinase Counteracts Prostate Cancer Immune Checkpoint Blockade Resistance, Dhivya Sridaran, Surbhi Chouhan, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Shambhavi Bhagwat, Melissa Reimers, Eric H Kim, Manish K Thakur, Muhammad A Saeed, Russell K Pachynski, Markus A Seeliger, W Todd Miller, Felix Y Feng, Nupam P Mahajan

2020-Current year OA Pubs

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8

Region-Specific Denoising Identifies Spatial Co-Expression Patterns And Intra-Tissue Heterogeneity In Spatially Resolved Transcriptomics Data, Linhua Wang, Mirjana Maletic-Savatic, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Spatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring …

The Legal Framework Applicable To Intrusive Intelligence, Surveillance, And Reconnaissance Operations In The Air And Maritime Domains, Raul (Pete) Pedrozo

International Law Studies

The validity of intrusive intelligence, surveillance, and reconnaissance (ISR) operations in the maritime and air domains depends on the location from which the operation is conducted. Intrusive ISR conducted beyond the territorial sea and national airspace is considered an internationally lawful use of the sea that is not subject to coastal State jurisdiction or interference. Efforts by a handful of States to regulate ISR operations in and over the exclusive economic zone are clearly inconsistent with a plain reading of the United Nations Convention on the Law of the Sea and the Convention on International Civil Aviation (and their negotiating …

Conformational Motions And Ligand-Binding Underlying Gating And Regulation In Ip3r Channel, Guizhen Fan, Mariah R Baker, Lara E Terry, Vikas Arige, Muyuan Chen, Alexander B Seryshev, Matthew L Baker, Steven J Ludtke, David I Yule, Irina I Serysheva

Faculty, Staff and Students Publications

Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP3 and Ca2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP3R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP3 binding relies upon intrinsic flexibility of the ARM2 domain in the …

Applications Of Covalent Chemistry In Targeted Protein Degradation, Dong Lu, Xin Yu, Hanfeng Lin, Ran Cheng, Erika Y Monroy, Xiaoli Qi, Meng C Wang, Jin Wang

Faculty, Staff and Students Publications

Proteolysis-targeting chimeras (PROTACs) and targeted covalent inhibitors (TCIs) are currently two exciting strategies in the fields of chemical biology and drug discovery. Extensive research in these two fields has been conducted, and significant progress in these fields has resulted in many clinical candidates, some of which have been approved by FDA. Recently, a novel concept termed covalent PROTACs that combine these two strategies has emerged and gained an increasing interest in the past several years. Herein, we briefly review and highlight the mechanism and advantages of TCIs and PROTACs, respectively, and the recent development of covalent PROTACs using irreversible and …

High Throughput Sequencing For Clinical Tuberculosis: An Overview, Tara E Ness, Andrew Dinardo, Maha R Farhat

Faculty, Staff and Students Publications

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field.

Chimes: November 14, 2022, Calvin University

Chimes

Teams sweep MIAA tournament, ready for NCAA tournament by Lauren Nyong

New program aims to increase retention of under-represented employees by Ezra Craker

Changes to course release costs aim to increase research opportunities by Savannah Shustack & Grace Buller

SAO gets creative in wake of low ticket sales by Katie Rodendale

SAO, coaches hope new sports teams will bring more energy to campus life by Emily Thomas

Pastoral Partners provide presence and care post-COVID by Gabriel Choi

Professor releases trailer for independent film; several students involved by Kipp De Man

School Knights to the rescue by Maya Oeverman

Eating is …

Extension Of Fundamental Transversals And Euler’S Polyhedron Theorem, Joy Marie D'Andrea

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

An Integral Projection Modeling Approach To Understanding Demographic Effects Of Multispecies Mutualisms, Alexandra Campbell

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Comparison Of Assessment And Teaching Modalities For A Quantitative Biology Course, Dmitry Kondrashov

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Humanizing Mathematical Biology Research And Education, Carrie Diaz Eaton, Ognyan Simeonov

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Ceramic Matrix Composites Ii: Science And Technology Of Materials, Design, Applications, Performance And Integration, Ram Darolia, Rishi Raj, Yutaka Kagawa, Jon Binner, Dietmar Koch, Gerard Vignoles

Ceramic Matrix Composites II: Science and Technology of Materials, Design, Applications, Performance and Integration

No abstract provided.

A Molecular Chemodosimeter To Probe “Closed Shell” Ions In Kidney Cells, Rashid Mia

Faculty Publications

Two quinidine-functionalized coumarin molecular probes have been synthesized and have been found to bind metal cations (Cd2+, Co2+, Cu2+, Fe2+, Hg2+, Ni2+, and Zn2+) with high affinity in organic–aqueous media (DMSO–HEPES). The chemodosimeters coordinate with the Zn2+ ions in a two-to-one ratio (molecular probe : Zn2+) with a log β of 10.0 M−2. Upon the addition of the closed-shell metal ions studied, a fluorescence turn-on via an excimer formation is seen at 542 nm due to the quinaldine moiety adopting a syn arrangement when coordinated to the metal Zn2+ ions. Confocal microscopy monitored free Zn2+ ions in the Human Embryonic …

Big Data Affirmative Action, Peter N. Salib

Northwestern University Law Review

As a vast and ever-growing body of social-scientific research shows, discrimination remains pervasive in the United States. In education, work, consumer markets, healthcare, criminal justice, and more, Black people fare worse than whites, women worse than men, and so on. Moreover, the evidence now convincingly demonstrates that this inequality is driven by discrimination. Yet solutions are scarce. The best empirical studies find that popular interventions—like diversity seminars and antibias trainings—have little or no effect. And more muscular solutions—like hiring quotas or school busing—are now regularly struck down as illegal. Indeed, in the last thirty years, the Supreme Court has invalidated …

Spatiotemporal Transcriptome Diversity And Responses To Salinity Tolerance In The Extremophyte Schrenkiella Parvula, Chathura Wijesinghege

LSU Doctoral Dissertations

Schrenkiella parvula is an extremophyte model related to the most widely studied plant model, Arabidopsis thaliana and Brassica crops in the mustard family (Brassicaceae). It can thrive in highly saline environments where the soil is enriched in Na⁺, K⁺, Li⁺, borates, and chlorides. Understanding how this extremophyte can survive high salinity with genomic adaptations can provide insight into developing stress resilient crops in the future. Gene expression of S. parvula in response to salt has been investigated using shoot and root tissue from mature vegetative-phase plants. However, prior studies have not examined the transcript …

Novel Single-Nucleotide Variants For Morpho-Physiological Traits Involved In Enhancing Drought Stress Tolerance In Barley, Ibrahim S. Elbasyoni, Shamseldeen Eltaher, Sabah Morsy, Alsayed M. Mashaheet, Ahmed M. Abdallah, Heba G. Ali, Samah A. Mariey, P. Stephen Baenziger, Katherine Anna Frels

Department of Agronomy and Horticulture: Faculty Publications

Barley (Hordeum vulgare L.) thrives in the arid and semi-arid regions of the world; never-theless, it suffers large grain yield losses due to drought stress. A panel of 426 lines of barley was evaluated in Egypt under deficit (DI) and full irrigation (FI) during the 2019 and 2020 growing seasons. Observations were recorded on the number of days to flowering (NDF), total chlorophyll content (CH), canopy temperature (CAN), grain filling duration (GFD), plant height (PH), and grain yield (Yield) under DI and FI. The lines were genotyped using the 9K Infinium iSelect single nucleotide polymorphisms (SNP) genotyping platform, which …

High School Course-Completion Trajectories And College Pathways For All: A Transcript Analysis Study On Elective Computer Science Courses, Hsun-Yu Chan, Ting-Lan Ma, Guan K. Saw, Yen-Ming Huang

Faculty Publications

Abstract: Whereas researchers regard high school math and science coursework as the best indicator of college readiness for students in the United States, computer science coursework and its relationship to college attendance, particularly for minoritized students, have not received due attention despite its root in the mathematical and scientific reasoning ability. We examined students’ high school course completion patterns across subjects and grade levels with a special focus on elective computer science courses and whether the coursework pattern transitions worked differently for minoritized students in Texas, USA. Latent profile analysis and latent transition analysis revealed multiple patterns of coursework, including …