Small Molecule Inhibitors of BRD4 for Treatment of Multiple Myeloma

Cancer is a complex disease with distinct hallmarks caused by a variety of factors. Transcription factors that normally control a large array of genes required for cell development can become oncogenes if their transcription is altered. BRD4 is a transcriptional activator that is a member of the bromodomain and extra-terminal (ET) domain (BET) family of proteins. The bromodomains of BRD4 bind to acetylated lysine residues on histones and is common among chromatin binding proteins whereas the ET domain is distinct to the BET proteins. Current BRD4- based therapeutics target the bromodomain using small molecule mimics of acetylated lysine. These inhibitors have limited efficacy because of dose-limiting toxicities due to the inhibitors targeting other proteins with bromodomains. The ET domain interacts with proteins linked to lung, breast, oral, colon, and acute myeloid leukemia (AML) cancers as well as viral integrase (IN) from murine leukemia virus (MLV). Examination of the binding interface between MLV IN and the ET domain allowed for in-silico selection of potential inhibitors. These compounds were screened in leukemia cell lines leading to selection of BETi-10. Multiple myeloma (MM) tumors are located within the bone marrow, making it difficult to treat with limited current therapies. Using a variety of MM cell lines, BETi-10 was tested for efficacy in this hematologic cancer. In addition, a BCL-2 selective inhibitor, venetoclax (ABT-199), was chosen based on its efficacy in hematologic cancers to test synergy with BETi-10. Some MM cell lines are less sensitive to venetoclax, prompting the idea that BETi-10 could increase sensitivity to the inhibitor. While combination of BETi-10 and venetoclax treatment did not increase sensitivity in low responding MM cell lines, a switch from venetoclax-induced necroptosis to apoptosis was observed. After investigation of the effects of BRD4 inhibition on the necroptosis pathway, it was determined that the combination of BETi-10 and venetoclax can decrease the expression of key proteins in the pathway. These results suggest a new role of BETi-10 in the switch from necroptosis to the safer apoptotic route.A three-year embargo was granted for this item.Academic Major: Biochemistr

Council on Academic Affairs: Minutes (March 19, 2025)

Minutes from the Council on Academic Affairs' meeting on March 19, 2025

The Impacts of Plasma Treatment on Airborne Microorganisms for Space Environment Applications

In space environments, microorganisms such as bacteria and fungi exhibit enhanced growth parameters and resilience to antibiotics, complicating mitigation efforts. This behavior increases risks of structural damage to the spacecraft and health issues such as infections and hypersensitivities among astronauts in closed environments such as the International Space Station (ISS). To address this, a cost-effective, low-waste technology called CAFAAI (Cabin Atmosphere Filtration using Ambient Air Ionization) has been developed for continuous microbial neutralization using the generation of negative plasma discharge. CAFAAI is optimized for low- power operation with no moving parts, making it a low-maintenance option. This study evaluated CAFAAI’s effectiveness in neutralizing three microorganisms commonly found on the ISS – Aspergillus (filamentous fungi), Aureobasidium pullulans (polymorphic fungi), and Bacillus atrophaeus (bacterium). Cultures were nebulized and treated under two voltage potentials and two treatment durations, repeated three times. Microbial survival was assessed by collecting samples post-CAFAAI treatment and monitoring growth on agar plates after incubation. Results demonstrated that higher voltages and longer treatment durations enhanced microbial neutralization for all microorganisms tested. Furthermore, a tradeoff between treatment duration and voltage potential was observed; doubling the contact time decreased the colony forming units on the plates 3x more than doubling the voltage potential. CAFAAI’s ability to continuously reduce microbial loads without producing significant waste or requiring moving parts positions it as a promising addition to spacecraft systems. This technology offers a sustainable solution for maintaining healthier and safer environments for astronauts during long-duration missions.A one-year embargo was granted for this item.Academic Major: Aerospace Engineerin

Neural Correlates of the Development of Word Laterality in the Visual Word Form Area (VWFA) During Early Childhood

Introduction: Humans have long been fascinated with how the brain is organized to support complex cognitive functions. One key finding is cortical specialization; the brain harbors many regions specialized to carry out specific cognitive functions. Many of these functional regions display lateralization, meaning they are more specialized to one hemisphere than the other. The Visual Word Form Area (VWFA) is one such region. The VWFA is an area of ventral temporal cortex (VTC) specialized for written scripts, and it develops category selectivity only after literacy. In adults, this word selectivity is dominant on the left. The experience dependent nature of the VWFA makes it a prime opportunity to investigate the development of functional laterality in the human brain, potentially revealing domain general mechanisms also related to the development of other lateralized functions. Therefore, we ask, what neural correlates relate to the development of word laterality in young children? Methods: We tested two potential sources of this word laterality: 1) structural connectivity of the VWFA with the high-level language network in frontal and temporal cortices and 2) activation in these language regions. To do so, we scanned reading children (4-13 years) on a visual fMRI task to define word and face regions as well as a separate auditory fMRI localizer to estimate language responses and collected diffusion-weighted imaging (DWI) to examine white matter connectivity. We defined face, word, and (spoken) language regions for each individual child and independent runs were used to extract activation to each condition to calculate selectivity and laterality; probabilistic tractography was used to quantify white matter connections between these regions. Results: Word selectivity was significantly left lateralized in our sample of young children. The magnitude of word laterality did not correlate with age, indicating variability in word laterality may be driven by other factors. Word laterality was positively and significantly related to laterality of the VWFA’s connectivity with frontal language regions. Additionally, word laterality correlated with auditory language selectivity in both frontal and temporal language regions. Laterality of language selectivity in these same regions was also positively and significantly related to word laterality. Conclusion: Our findings suggest that both connectivity to related regions and activation patterns in those connected regions may play a role in the development of functional laterality. Additionally, our investigations shed further light on the development of the neural circuitry that underlies reading behavior.OSU Center for Cognitive and Behavioral Brain Imaging (CCBBI), 2024 Gibson Research AwardThe College of Arts & Sciences at OSU (Dr. Saygin)The Chronic Brain Injury program at OSU (Dr. Saygin)R01 HD110401-01 (Dr. Saygin)A one-year embargo was granted for this item.Academic Major: Neuroscienc

Old Irish and Latin Codeswitching in the St. Gall Priscian Glosses

Codeswitching, as both a rule-governed linguistic phenomenon and an insight into the sociolinguistic interaction of speakers of different languages, has for many years now been of interest to linguists. However, there has been comparatively little investigation into the patterns of written codeswitching and what it can tell us about historical situations of language contact. This paper looks at one of these cases of historical codeswitching which has been recorded in writing: that of Old Irish and Latin among the monastic communities of early medieval Ireland. In particular, I focus on the Old Irish and Latin glosses to the St. Gall manuscript of Priscian’s Ars Grammatica (Stiftsbibliothek, MS 904). I describe the sociohistorical context in which the text was created as well as the linguistic context created by the text itself. I then present examples of several patterns of codeswitching within the glosses. From these examples the comfort of at least some members of the community with bilingualism can be seen, along with some of their bilingual standards. This situation also illustrates ways in which written codeswitching is necessarily distinct from oral codeswitching.No embargoAcademic Major: Linguistic

Synthesis of a Two-dimensional van der Waals Frustrated Antiferromagnet: Mn2Al2S5

There has been significant interest in the discovery of new two-dimensional (2D) van der Waals (vdW) materials which exhibit magnetic phenomena at thin layers, as these materials can prove to be useful as magnetic building blocks. Here, we report a new 2D vdW phase, Mn2Al2S5, and explore its magnetic, physical, and structural properties. We establish a route towards growing powders of this new material by combining stoichiometric equivalents of MnS and Al2S3 in sealed quartz tube synthesis. The Mn2Al2S5 phase consists of AlS4 tetrahedra which tops double-octahedral thick MnS6 layers. Diffuse reflectance absorbance measurements show this material’s band gap is 1.43 eV. Due to the double layering of metals, there is a competing magnetic interaction between them and the Mn2Al2S5 phase is magnetically frustrated. It shows antiferromagnetic characteristic, and a magnetic transition temperature at 10 K, compared with a Weiss constant of -328 K, producing a frustration index of 32.8. Overall, the Mn2Al2S5 phase as a 2D vdW material proves to show interesting and useful characteristics due to its frustrated magnetic structure.OSU Research FoundationNational Science Foundation - Materials Science & Engineering CentersNo embargoAcademic Major: Chemistr

Recession Rates of Zirconium Carbide and Zirconium Diboride During Ultra-High Temperature Oxidation

This research project aims to compare the oxidation kinetics and microstructure development of zirconium carbide (ZrC) and zirconium diboride (ZrB2) at temperatures between 1600 and 2400°C. ZrC and ZrB2 are ultra-high temperature ceramics (UHTCs), which are a class of ceramic material with melting points above 3000°C. A mix of covalent and metallic bonding makes them thermally and chemically resilient with high thermal and electrical conductivities. Studies have shown that ZrB2 is favored over ZrC at temperatures below 1200°C, but not above because the protective liquid layer of boria (B2O3) evaporates, leaving the material exposed, causing it to oxidize very quickly. These materials are of interest for use in leading-edge surfaces of hypersonic aircraft, but due to difficulty of testing, a direct comparison of the oxidation behavior of ZrC and ZrB2 has not been done at predicted service temperatures in publicly available research. This research hypothesizes that ZrB2 will oxidize faster than ZrC above the temperature that boria boils. This experiment compares the oxidation rates at a realistic range of operating temperatures by measuring the rate of recession of the unoxidized base material. The boiling point of boria was calculated with FactSage thermodynamic software to be around 1780°C. This project uses the microplasma resistive heating system at the University of Virginia (UVA) to oxidize ZrC and ZrB2 at 1800-2200°C for 1-7 minutes in an ambient pressure Ar atmosphere with 1% O2. The microstructure and recession rate were analyzed with scanning electron microscopy (SEM) and image processing. Analysis indicates that at 1800-1900°C, ZrB2 oxidizes slower. The recession rate for 2000-2200°C was not able to be calculated because all samples either fully oxidize or vaporize in under 1 minute.Rapp Visiting Scholar FundUndergraduate Research ScholarshipNo embargoAcademic Major: Materials Science and Engineerin

Prediction of Optimal Parameters for Wire-Arc DED Welding Using a Multilayer Perceptron Trained on Synthetic Data Generated by a Generative Adversarial Network

The global demand for 3D printing technologies has grown significantly, influencing various industries and extending into the welding sector through additive manufacturing (AM). In welding, AM involves constructing metal parts layer by layer using wire or powder feedstock. This method offers advantages such as material efficiency and design flexibility. However, bead overlapping between layers often results in defects like surface irregularities and weakened structural integrity. This paper presents an automated approach to optimize welding parameters using a multi-layer perceptron (MLP) neural network. Traditional methods for selecting parameters such as current, voltage, and wire feed rate are time-consuming and resource-intensive. To address limited data availability, synthetic data were generated using a generative adversarial network (GAN). By training the MLP on this expanded dataset, the system predicts parameters that improve bead quality and inter-layer bonding. This AI-driven approach reduces the need for extensive physical experimentation, minimizes material waste, and shortens development cycles.No embargoAcademic Major: Computer and Information Scienc