Antibiotic resistance is an increasingly critical concern for the treatment of bacterial infections, rendering new therapy options progressively more necessary. Gram positive bacteria are common infectious agents in skin and soft tissue infections, pneumonia, urinary tract infections, bacteremia, and more. A novel antibiotic candidate, MRS-2541 has been demonstrated to inhibit Gram positive methionyl-tRNA synthetase and decrease bacterial loads of both methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes in mouse thigh infections to the same degree as currently recommended therapy. This study aims to further characterize the activity of MRS-2541 against Gram positive bacteria including Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus saprophyticus, Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus salivarius. I conducted this study by first determining the preliminary minimum inhibitory concentration of MRS-2541 in growth media against each of the aforementioned organisms. I then use these results to guide time kill assays that characterize MRS-2541’s synergy with another antibiotic often used to treat Gram positive infections outside of the United States. Preliminary results demonstrate that MRS-2541 inhibits the above-mentioned organisms. Synergy experiments with MRS-2541 and existing antibiotics will be performed and results will be presented at the symposium. These results will further define the spectrum of activity as well as synergy of MRS-2541, allowing new insight into its candidacy for clinical trials. As a novel antibiotic candidate, the development of MRS-2541 will help address the increase in antibiotic resistance among Gram positive bacterial infections.

Bronchoscopy with bronchoalveolar lavage (BAL) is a common approach to assess the graft in lung transplant recipients. However, bronchoscopy is an invasive approach that carries procedural risks. Identifying plasma biomarkers levels which correlate with those measured in BAL fluid enables less invasive investigations. This study aims to determine the correlation between biomarkers measured from plasma and BAL fluid. We analyze paired plasma and BALF (BAL fluid) samples collected from lung transplant recipients undergoing for-cause bronchoscopy (n = 95 individuals and inclusive of 164 encounters). Researchers collect paired samples from each participant within a two-hour timeframe. Researchers measure a panel of 39 biomarkers in samples using electrochemiluminescence assays. We evaluate plasma/BAL correlation data using Pearson correlation coefficients on log-transformed concentrations. Among participants, the average age is 61 years, 74% are male, 93% are white, with Restrictive lung disease (60%) being the most common pre-transplant pulmonary disease. The median time from transplant to bronchoscopy is 412 days (IQR: 194-741). Results indicate that correlational data is highly variable. The two most highly correlated biomarkers are IL-12/IL-23p40 (r = 0.67) and CXCL10 (r = 0.64). There are no biomarkers that have significant inverse correlations. The levels of 11 out of the 39 measured biomarkers show moderate correlation, ranging from r = 0.20 to r = 0.45. Many of these biomarkers are chemokines related to immune cell migration to the lung (e.g., CCL2, CCL3, CCL4, and CCL22). A key implication of this finding is that researchers should exercise caution when extrapolating alveolar biology from circulating (plasma) samples. Future analyses will test whether the ratio between paired BALF and plasma biomarker levels provides biological or clinical insight beyond using these biomarkers measured in isolation.

America as a whole is facing a housing affordability crisis. The US faces a deficit of 8 million affordable units available for the 18.9 million renter households that earn under 50% of their area median income (AMI). Due to this shortage, 56% of households considered very low-income (30% > 50% AMI) and extremely low-income (less than 30% AMI) are severely cost-burdened, spending over 50% of their annual income on housing and utility costs. Cities across the country engage in different efforts to combat this issue, this project answers one question: how can adaptive reuse, specifically non-residential to residential building conversions, be effectively applied as an affordable housing solution? This report begins with a literature review that compiles the history of adaptive reuse, strategies to produce more affordable housing and how they are being applied to adaptive reuse projects, and outlines a framework for evaluating successful adaptive reuse projects as they apply to affordable housing. This preliminary research is further supported by informational interviews conducted with industry professionals in affordable housing and adaptive reuse, coupled with a series of case studies that measure the effectiveness of several adaptive reuse projects in generating affordable housing. Finally, the results will inform a series of industry best practices that outline optimal building types for adaptive reuse projects, cost-reduction strategies, and recommendations for policy and zoning changes that can better facilitate the application of adaptive reuse. The best practices outlined in this paper will help developers implement adaptive reuse more effectively in affordable housing projects, ensuring the efficient transformation of vacant buildings into livable spaces. Additionally, these guidelines will inform policymakers of the necessary regulations and incentives to support and facilitate adaptive reuse, ultimately contributing to the expansion of affordable housing options and revitalizing underutilized properties.

We analyzed the effects of marine heatwaves on primary production in the Northern California Current from 1997 to 2023, a productive ecosystem that has been impacted by intense and long-lasting heatwaves, most notably the 'Blob' (2014-2016) and the 'Blob 2.0' (2019). Using Copernicus Marine Service's Global Ocean Colour and NOAA's Optimum Interpolation Sea Surface Temperature (SST) products, we analyzed chlorophyll and temperature bounded by the Columbia River and the Strait of Juan de Fuca. Heatwave metrics were compared to chlorophyll concentrations before and after events, and dynamic linear models (DLMs) were used to determine the changing regression slopes between temperature and primary production for six areas on and off the continental coast. We then used self-organizing maps (SOMs) to analyze spatiotemporal variation in phytoplankton blooms during heatwave years. Chlorophyll decreased during heatwaves for all six locations (p<0.05) and DLMs showed increasingly negative correlations between SST and chlorophyll during heatwaves for the two locations closest to the Strait of Juan de Fuca. Phenological analysis showed that the spring blooms occurred significantly earlier and with lower peaks (p<0.05) during most heatwave years. We conclude that marine heatwaves negatively affect primary production in this region, especially near the Strait of Juan de Fuca. Heatwaves also shifted the timing of spring blooms, indicating possible ecosystem impacts from mismatched phenology. Further analysis is needed to determine the mechanisms of these effects through covariates such as nutrient availability and mixed layer depth.

Cardiopulmonary bypass (CPB) is essential for most cardiac surgeries but often leads to systemic inflammation and multiorgan dysfunction in neonatal and pediatric patients. These adverse inflammatory responses are driven by severe shear stress on the blood, contact with plastic tubing, and rapid cooling/rewarming. However, the molecular mechanisms underlying these complications are poorly understood, creating a significant barrier in improving clinical outcomes. The Nigam Lab has identified Interleukin 8 (IL-8) and Tumor Necrosis Factor alpha (TNF-α) as inflammatory cytokines upregulated in blood cells in response to CPB-associated shear stress. We hypothesize that Lamins (LMNA) play a key role in driving these transcriptional responses, as these structural proteins form the nuclear lamina and can sense mechanical forces acting on the cell. To investigate this, we performed in-vitro experiments using THP-1 human monocytic cells to simulate bypass conditions, applying shear stress and collecting samples at various time points to study the cells’ response and recovery from CPB. Using mass spectrometry-based proteomics (MS), we have identified changes in LMNA phosphorylation between sheared and static cells, providing insight into the mechanisms driving LMNA modifications under CPB conditions. We are also employing techniques such as proximity-dependent biotin identification (BioID) to explore kinase interactions with LMNA. Furthermore, to understand how LMNA influences chromatin organization, transcription factor binding, and regulation of inflammatory genes, we will perform greenCUT&RUN to map LMNA localization on chromatin in both sheared and static THP-1 cells. We aim to uncover the specific molecular mechanisms by which LMNA is altered under shear stress and how it influences chromatin dynamics and transcription of inflammatory genes during CPB. Ultimately, this research will help us understand the underlying causes of systemic inflammation post-CPB and inform novel drug targets and therapeutics to enhance the quality of life for pediatric patients undergoing cardiac surgery.

Every spring, a small population of less than 20 gray whales (Eschrichtius robustus), referred to as “Sounders,” migrate to northern Puget Sound (NPS), Washington State. They stay in this region for two to three months, often leaving before June, to continue their migration to Alaska. In contrast to gray whales in other locations, NPS gray whales primarily forage on ghost shrimp (Callianassa californiensis). These small crustations live in the sediment in the intertidal to shallow subtidal zones, so gray whales must wait for higher tides to feed. Although there have been recurring studies of NPS gray whales since 1990, sighting data have not been analyzed for spatiotemporal trends, apart from a few select years. The purpose of this research is to identify how NPS gray whales are distributed within the NPS throughout the foraging season and between years. I used ArcGIS to analyze sightings data collected by Cascadia Research Collective from 1990 to 2023 for spatial and temporal trends. In NPS, gray whale abundance and time spent in the region have been increasing, especially during gray whale unusual mortality events which are likely caused by reduced prey abundance due to environmental anomalies and decreased upwelling. I hypothesized that increases in the population widened their distribution in the region to accommodate for more individuals. Implications of this research include a better understanding of the areas that may be more frequented by Sounders, which could help decrease negative interactions between marine vessels and whales. In addition, these areas could indicate places for further research to better understand increased gray whale presence on the ecosystem as a whole. Future research may also include the distribution and habitat preference of individual whales, and associations between certain whales.

Core needle biopsy tissue samples were prepared manually with 10% Formalin fixation followed by Hematoxylin & Eosin (H&E) staining in clinical laboratories worldwide, a gold standard for biopsy tissue preparation. The prepared samples were then sent to pathologists for analysis. The goal of this research project is to develop an automated H&E stain dispensing system capable of preparing diagnosable biopsy tissue samples in minutes, and to be integrated onto an automated core needle biopsy diagnosis medical equipment using Fluorescence Imitating Bright field Imaging (FIBI) method. This automated process reduces the time needed for the diagnosis process from days to hours. For many African countries that lack trained personnel and infrastructure, the time reduction is from a month to within a day. The reduction of cost and time makes early stage cancer diagnosis much more affordable and accessible to patients, especially in low-and-middle income countries (LMICs). This early diagnosis of cancer allows patients to start treatment earlier with projected improvement of cancer survival. The research mainly focuses on methods of H&E stain distribution and controlling stain uptake time on 1mm diameter x 16mm long biopsy tissue samples without damaging the sample using various protocols. This project also investigates whether the system should dispense hydrogen peroxide to remove excess blood on tissue specimens and Triton X-100 as a surfactant to permeabilize cell membranes for a fast stain uptake. Large volume of imaging results from automated system prepared tissue samples will be compared with results from manually prepared samples to determine the quality and reliability of the automated staining system.