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Development of Pharmaceutical Inhibitors Targeting nNOS for Melanoma Treatment
No full textInterferon-gamma (IFN-γ), a well-studied pro-tumorigenic cytokine in melanoma, has been shown to upregulate programmed death‐ligand 1 (PD‐L1) on the melanoma cell. The interaction between PD-L1 and its receptor PD-1 inactivates T-lymphocytes, allowing melanoma cells to escape from immune surveillance. Immune checkpoint inhibitors targeting PD-1/PD-L1 have been shown to prevent immunosuppression and exhibited significant clinical benefits in improving patient survival across a broad range of cancer types including melanoma. Of note, our preliminary RPPA study showed that one of the significantly upregulated genes induced by IFN-γ was cyclooxygenase-2 (COX-2). COX-2 catalyzes the first rate-limiting step in the conversion of arachidonic acid to prostaglandins, including PGE2 which leads to inflammation. It is well documented that COX-2 plays an important role in tumor development and progression in many cancers. Particularly, studies have demonstrated that COX-2 expression in melanoma tumors positively correlates with PD-L1 expression. In this study, we first determined the role of COX-2- mediated PGE2 production in IFN-γ-induced melanoma progression and PD-L1-mediated immunosuppression.
Moreover, our previous studies demonstrated that novel nNOS inhibitor HH044, effectively inhibited IFN-γ-induced PD-L1 expression both in vitro and in vivo. Another objective of this study was to determine whether nNOS-mediated nitric oxide (NO) signaling interacts with the COX-2-PGE2-PD-L1 signaling axis in melanoma. Our overall hypothesis is that in combination with COX-2 inhibitors, nNOS inhibitors may synergistically reduce melanoma tumor growth and extend mouse survival. In addition, the translational potential of our novel nNOS inhibitor in clinical practice and the effects on nNOS inhibition on the melanoma tumor microenvironment were further assessed.
In summary, this study determined the underlying mechanisms by which IFN-γ stimulates melanoma progression and examined the anti-melanoma activity of novel combination therapy using nNOS inhibitors with COX-2 inhibitors and immunotherapy for melanoma treatment
Innovative Soil Classification Approach for Achieving Global Biodiversity Framework Utilizing Integrated Data Fusion of EMIT and Multispectral Satellite Observations: Case Study of Imam Turki bin Abdullah Royal Reserve, Kingdom of Saudi Arabia
Get PDFSoil classification is essential for sustainable land management, ecological conservation, and combating desertification, particularly in arid and semi-arid regions. This study integrates hyperspectral data from the Earth Surface Mineral Dust Source Investigation (EMIT) and multispectral imagery from Sentinel-2 to achieve accurate soil classification for the Imam Turki bin Abdullah Royal Reserve (ITBA) in Saudi Arabia. Using advanced Machine Learning (ML) techniques, including Extreme Gradient Boosting (XGBoost), the study highlights the power of data fusion in addressing the limitations of standalone remote sensing methods. The integration of hyperspectral and multispectral data combines the spectral richness of hyperspectral imaging with the spatial resolution of multispectral data, providing detailed insights into the region\u27s heterogeneous soil types. The Gram-Schmidt fusion technique enhanced spatial resolution, enabling precise identification of inter-dune soils, linear dunes, and rocky outcrops. The resulting soil classification map achieved an accuracy of 93 %, outperforming traditional methods and existing maps. Inter-dune soils, characterized by their loamy-skeletal texture and superior moisture retention, were identified as critical for supporting vegetation and afforestation efforts. This research also developed a suitability map for afforestation by incorporating weighted overlays of soil fertility, moisture retention, and vegetation indices. These findings directly contribute to global biodiversity priorities, supporting the Convention on Biological Diversity (CBD) and the associated Global Biodiversity Framework (GBF) targets such as reducing biodiversity loss (Target 1), restoring ecosystems effectively (Target 2), minimizing the impacts of climate change (Target 8), and enhancing sustainable agriculture (Target 10). Furthermore, the study utilizes these advancements in addressing land degradation and achieving the United Nations Sustainable Development Goals (SDGs), including Zero Hunger (SDG 2), Climate Action (SDG 13), and Life on Land (SDG 15). By integrating soil classification with afforestation strategies through remote sensing and advanced data sciences approaches, this research demonstrates a robust, scalable and precise solution to support biodiversity conservation, land management, and climate resilience in arid environments
Highly Targeted Metabolomics Coupled With Gene Expression Analysis by RT–qPCR Improves Beef Separation Based on Grass, Grain, or Grape Supplemented Diet
Get PDFThe objective of this study was to use a multi-omics (i.e., gene expression quantification, metabolomics, and fatty acid [FA] profiling) approach to separate and authenticate beef from three different dietary groups. In this 2-year study, Red Angus steers (n = 54) were randomly allocated to one of three treatments: (1) complex biodiverse pasture (GRASS), (2) total mixed ration (TMR) in feedlot (GRAIN), or (3) TMR in feedlot supplemented with 5% (dry matter) grapeseed extract for the last 30 days (GRAPE). FAs were measured by gas chromatography-mass spectrometry (GC–MS), secondary metabolites were identified using ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS), and gene expression analysis was performed using quantitative reverse transcription polymerase chain reaction (RT–qPCR). All target genes were upregulated in beef from GRASS compared to the other two groups. Multivariate analyses showed that long-chain n-3 polyunsaturated FAs, the n-6:n-3 ratio, vitamin E, organic acids, amino acid derivatives, and the nephronectin isoform X1 (NPNT-1) gene were the most important compounds for group separation. These compounds, considered to be beneficial for human health, showed higher concentrations in beef from GRASS. The success of beef separation by dietary treatment was highlighted by the 90.4% prediction accuracy of the random forest model, with beef from GRASS being 100% accurately predicted and beef from GRAPE being 94.4% accurately predicted. Beef from GRAIN was 76.5% accurately predicted. In conclusion, coupling gene expression analysis to metabolomics and FA profiling allowed for the separation of beef samples from varying dietary backgrounds with a high degree of confidence
Bibliography for Japanese Language Display
Get PDFA bibliography created to support a display about the Japanese language in May 2025 at the Leatherby Libraries at Chapman University
Tracing Anti-Communist Nation-Building in South Korea
Get PDFAnti-communism has always been the cornerstone of South Korea’s national identity. The Rhee government, the very first of the post-Independence era, created the basis for anti-communist state-building. This thesis focuses on how the South Korean and the U.S. governments succeeded in internalizing anti-communism among ordinary civilians through critical historical incidents and cultural policies. By tracing the Yeosu-Suncheon incident and the Korean War, this thesis investigates how the Korean peninsula – which in the immediate wake of liberation from Japanese colonial rule was a relatively open space in ideological terms – shifted to a closed-off and exclusionary space, only allowing anti-communism. This thesis argues that war and state violence instilled fear among South Korean civilians and provided the critical momentum for the internalization of anti-communism into society. After the war, governments utilized soft power to accelerate the internalization of anti-communism. Specifically, the Rhee government utilized a “carrots and sticks” approach; they provided incentives to creators who followed the state apparatus while imposing penalties on those who did not follow. The U.S. government employed financial and cultural support, with idealization of consumer goods, to induce and maintain South Korean anti-communism and pro-Americanism
The Effects of Cyclic Peptide [R4W4] in Combination with First-line Therapy on the Survival of \u3cem\u3eMycobacterium avium\u3c/em\u3e
Get PDFBackground: Mycobacterium avium (M. avium) is a nontuberculous mycobacterium (NTM) that can cause pulmonary and extrapulmonary infections mostly in immunocompromised individuals, such as those with HIV and diabetes. Traditionally, rifampicin (RIF) and azithromycin (AZ) have been used for a 12-month duration as first-line antibiotics against M. avium. Due to the increased multidrug resistance, novel ways, such as enhancement of macrophages response, are needed to provide adequate immune response required to clear M. avium infection.
Methods and findings: In this study, we aim to study the effects of using THP-1 cells, which are monocyte-like cells, to induce a macrophage response and control M. avium infection when used in combination with traditional treatments such as RIF and AZ in free and liposomal forms. Traditional treatments’ effects are studied when used alone and in combination therapy with cyclic peptide [R4W4] (liposomal encapsulated and liposomal combination). Colony-forming units (CFU) counts were assessed for all samples 3 hours, 4 days, and 8 days post-treatment. A significant reduction in the intracellular viability of M. avium was observed when THP-1 cells were treated with liposomal combination [R4W4]+RIF and liposomal combination [R4W4]+AZ compared to when treated with liposomal RIF or liposomal AZ alone, respectively.
Conclusion: Our findings show that liposomal combination [R4W4] is a promising adjuvant therapy to increase M. avium susceptibility to known antibiotics
Homesick for You: An Archival Analysis of Love Letters from World War II
No full textIn this project, I cherish and explore a collection of correspondence exchanged between a married couple during World War II. Applying an embodied research approach that incorporates archival, historical, and cultural studies, I analyze key elements of these letters with special attention for themes of love and family, valuing their insights to touching personal stories that nuance the dominant narratives of history. I contend for the preservation and discussion of these letters and similar artifacts, advocating for their lasting significance within both past and present contexts and their irreplaceable contributions to the cultivation of collective memory and empathy across generations
Pinky\u27s Dance Hall
No full textPinky\u27s Dance Hall is a novel in progress that tells the story of several bartenders who work at a failing music venue in Columbus Ohio, and the escalation of cult-like abuse that is inflicted upon these bartenders by the venue\u27s owner. Going back and forth in time, the narrative is built around events that lead up to the owner having his own bar set on fire during a crowded show. As I write this book, I hope to question the ways in which a toxic workplace can mirror the patterns of other types of abusive relationships