Metastasis, or the spread of cancer to a secondary site, is responsible for most cancer-related deaths. The tissue-specific environment that disseminated tumor cells experience influences whether they will proliferate and colonize the tissue, remain dormant, or die. Skeletal muscle (SkM) is one of the rarest sites for metastasis, despite making up nearly half of human body mass. What makes SkM so resistant to metastasis? We set out to test the hypothesis that the mechanical nature of SkM is responsible for the lack of metastases at this site. To do so, we used the mdx mouse model of Duchenne muscular dystrophy to probe if the destruction of SkM structure and function would make it a more hospitable host to disseminated tumor cells. Wild type and mdx mice were intramuscularly injected with EO771 murine mammary tumor cells and monitored for tumor outgrowth using bioluminescent imaging. Preliminary results suggest that tumor growth is increased in dystrophic (e.g. dysfunctional muscle) versus wild-type mice. A complementary and more reductionist approach to test whether mechanics influences tumor colonization of muscle is to employ a culture model that allows tumor cells seeded on top of a SkM layer to experience mechanical stretching akin to the contraction/relaxation movements of muscle. To accomplish this, we constructed a device that applies a cyclic stretch to a 3D organotypic SkM culture model on a flexible silicone plate. We predicted that stretching would reduce tumor cell survival, when compared to no stretching. While these experiments are in progress, we believe that these data may elucidate a relationship between mechanical activity and suppression of tumor outgrowth in SkM. This work will contribute to a more complete understanding of how SkM avoids tumor colonization and could inform future approaches that leverage tissue mechanics to treat or prevent metastasis.

Amidst the turn of the twentieth century, few women were accounted for witnessing the advancement of archaeology, later known as the "Golden Age'' of Egyptology. In fact, much of the source material by women in this period have been misplaced or yet to be published. Mrs. Emma B. Andrews wrote nineteen volumes of diaries while observing the unearthing of over twenty tombs in the Valley of the Kings. The Emma B. Andrews Diary Project seeks to introduce Mrs. Andrews's works—and other unpublished historical documents composed by women during the time—to modern platforms, such as an online reader and social media. The transcribed texts are encoded into XML, using Text Encoding Initiative Guidelines, and the structural and contextual elements are denoted. The TEI documents are currently being used to create a comprehensive database for scholars and students alike to read the compositions of the lesser-known women of Egyptology. Accompanying the transcribed texts are biographies to equip the readers with additional context. However, we interns stepped further into this project by attempting to answer a fundamental question—how did Mrs. Andrews's accounts of her day-to-day interactions reflect the manner she viewed her life, and therefore herself? Guided by this question, we used research methods involving an analysis of Mrs. Andrews's language and identification via XML-TEI of the various contextual elements referenced—the people, places, hotels, and boats she encountered. These components were also cross-evaluated with further sources, including a sentimental analysis tool, to provide supplemental information to our study. After converging Mrs. Andrews's life history with recognized research in memory retrieval, we have noted observations on how her writing reveals her distinct perspective of the world and how her past may have influenced that point of view.

Despite research supporting the efficacy of certain mental health practices, many mental health care providers in community mental health clinics are not utilizing evidence-based practices (EBPs) consistently when treating patients with mental health needs. Clinical supervisors play a critical role in EBP implementation given that they have regular oversight with clinicians and can gauge how often clinicians use EBPs and how effective they are at delivering them. The purpose of our project is to examine the feasibility and self-reported usefulness of case-based consultation for clinical supervisors at child-serving community mental health clinics to support the implementation of EBPs. In our pilot study, nine clinical supervisors and two supervisor consultants were recruited from community mental health clinics to participate in supervisor consultation calls. The purpose of these calls was to improve clinical supervision skills and perceived competencies for clinical supervisors. These calls consisted of: (1) a brief 15-minute didactic lead by the supervisor consultant that covered various content areas relevant to their roles as supervisors; and (2) 45 minutes of case-based consultation among the consultant and the clinical supervisors where they discussed real-life supervision scenarios, barriers and challenges that they faced, and proposed solutions or strategies. Pre and post surveys with clinical supervisor participants showed the consultation calls resulted in greater self-reported supervision competency. To build on the quantitative analyses, my mentors and I have been conducting a qualitative thematic analysis of eleven of the case-based consultation calls, which were recorded and transcribed. We will analyze the qualitative data to identify reoccurring themes discussed on the calls coded as barriers or solutions to supervision and clinical challenges to EBP implementation. This thematic analysis will help us gain insight into one potential support strategy to improve EBP implementation and sustainment to increase the quality of behavioral health care for youth.

Tuberculosis (TB) is one of the top ten causes of death globally. Although it is mostly curable, the antibiotic treatment is long, challenging, and carries dire consequences if discontinued. Patients face many known barriers to treatment adherence, such as traveling to TB clinics, lack of TB knowledge, stigma, and the medication's adverse effects. In response, the TB Treatment Support Tools (TB-TSTs) intervention has been iteratively developed with patients and TB teams to improve treatment outcomes. TB-TSTs is a two-part system. The patient-facing mobile application allows patients to report taking the medication daily, potential medication side effects, submitting a photo of a test strip that detects a TB drug metabolite, asking questions, and interacting with a treatment supporter. The other part of the system is for treatment supporters who can be, for example, social workers, physicians, or nurses to review the daily reports, encourage and support patients through treatment. As part of this larger study, the aim is to improve the treatment supporter interface by analyzing and synthesizing interview transcripts with treatment supporters to provide recommendations for the design team. Interviews were conducted with actual or potential Argentinian treatment supporters and transcribed for qualitative analysis of main themes using Atlas.Ti. In collaboration with research team members, we iteratively developed a codebook. The team identified five main themes and seven sub-themes. Main themes include limitations of the system, what works, design recommendations/features to improve, and subthemes include usability/UI feedback and cultural adaptation. Expanding on patient events (e.g., appointments) and quickly visualize adverse effects are the main recommendations. The main findings were presented to the design team to influence the treatment supporter interface of the TB-TSTs for the next stage of testing. This study will improve the TB-TST, and the larger project presents the usability of future treatment supporter tools for chronic diseases.

Exposure to arsenic (As) through contaminated drinking water is a far-reaching problem in Washington State, as well as the entire United States. There is a demand for novel approaches to arsenic remediation as current technologies prove to be either too expensive or ineffective at lower arsenic concentrations. Periphyton is a community of different organisms, including blue-green algae, bacteria, fungi, plant detritus and animals. In addition to providing dissolved oxygen and soil to its environment, periphyton has been shown to accumulate arsenic at far higher concentrations than the water around it. Our lab aimed to discover if bacteria were in fact responsible for the uptake of arsenic observed in periphyton. So far, we have isolated several species of the Pseudomonas and Janithobacterium genera that are resistant to high levels of arsenic. We further isolated species contained within the periphyton, and then determined that these organisms are metabolizing arsenic. We investigated the genetic basis of the arsenic resistance in our isolates by generating targeted deletions of known arsenic metabolism genes and through a genetic screen of a pool of transposon insertional mutants for gain of arsenic sensitivity. With these identified genes linked to arsenic transformation and resistance of arsenic toxicity, it will then become possible to alter, repress, or enhance these processes. In the future this data may provide utility in arsenic remediation.

Porphyromonas gingivalis is a bacterium that is often present in the gum pockets of people who have gum disease. Research has indicated that P. gingivalis is able to avoid detection by a host’s immune system by modifying the lipid A structure on its outer membrane. Our research has examined the effect of lipid A modifications on outer membrane vesicle production. Outer membrane vesicles (OMVs) are formed when the outer membrane of the bacterium bends out into a tight bubble-like shape and pinches off from the membrane completely. As this happens, contents within the membrane space can be packaged inside of the vesicle. OMVs may contain toxins or misfolded proteins for expulsion from the bacterium, or they can package DNA which enables horizontal gene transfer. It is known that OMVs are common in Gram-negative bacteria, but the exact mechanism of how they are formed is not yet well understood. To better understand OMV production, I have performed assays to quantify the OMV production of several different strains of P. gingivalis. Mutant strains provided to our lab had their lipid A protein mutated as follows: dephosphorylated and tetra-acylated (wild type), phosphorylated at the C4 position (Δ1587), phosphorylated at the C1 position (Δ1773), and penta-acylated (Δ1123). Assay results indicated that when compared to wild type, phosphorylation of the C4 position (present in Δ1587) inhibits OMV production, and yet phosphorylation of the C1 position (present in Δ1773) enhances OMV production. Whether lipid A has 4 or 5 acyl chains (Δ1123), the difference appears to have no significant effect on OMV production. The logical next step is to identify which proteins are causing these differences by their varying interactions with lipid A. Identifying these proteins will contribute to the larger scientific quest of understanding how outer membrane vesicles are formed.

HSV-2 is a sexually transmitted disease of global importance, with an estimated infected global population of over 500 million people, as estimated by the WHO. HSV-2 is a lifelong infection which results in painful, recurrent lesions in the genital area. Previous research has shown that high numbers of regulatory T cells (suppressive immune cells important for maintaining tolerance) are present in the mucosal tissue alongside traditional CD4+ and CD8+ T cells (T cells important for an adaptive immune response), and their role is not fully understood. The reporter strain “Nedel” is a strain of HSV-2 with an inserted mNeonGreen fluorescent marker, allowing us to visualize HSV-2 infection. Our current project is to characterize the viral kinetics of the reporter strain of HSV-2 and compare it with WT HSV-2, as well as visualize the virus in infected cells via immunofluorescence and flow cytometry. We have infected mice intravaginally with both strains of virus, collected vaginal washes for plaque assays (to determine viral load) and harvested their vaginal tracts for flow cytometry. Our first round of experiments have shown that while the general frequency of immune cells were comparable, there was significantly lower activation of these cells in the Nedel-infected mice as compared with the WT-infected mice. In ongoing experiments, we have infected the mice with a higher dose of Nedel virus in an effort to make infection more comparable to WT, and we will be harvesting vaginal tracts for flow cytometry analysis to see whether we can visualize the mNeonGreen. Our overall goal is to utilize the Nedel HSV-2 strain to investigate the role of regulatory T cells in modulating anti-viral immune response, with a broader goal of finding treatments and an effective vaccine for HSV-2.

Extreme precipitation events have the potential to threaten physical infrastructure, property, and human lives, and are predicted to become heavier due to climate change. Understanding past, present, and future precipitation is important in analyzing how precipitation risks change spatially and temporally. The observational record, from which point precipitation frequency estimates such as NOAA Atlas-14 are derived, is limited by its lack of spatial coverage and it represents just one realization of past climate. When using a high-resolution large ensemble global climate model, we have multiple realizations of climate, consistent spatial coverage, and the added benefit of being able to incorporate climate change scenarios into precipitation risk analysis. Here, we use the GFDL (Geophysical Fluid Dynamics Laboratory) 50-km horizontal atmospheric resolution global SPEAR (Seamless System for Prediction and EArth System Research) 30-member ensemble to analyze how U.S. 24-hour precipitation extremes at various return periods change over the 1921-2100 time period. We quantify extreme precipitation risks across the U.S. and locally under different climate change scenarios (SSP2-4.5, SSP5-8.5, and natural forcings alone). With the large ensemble, we are also able to explore methodology and uncertainties in characterizing extreme precipitation risks.