High-risk human papillomavirus (HR HPV) can establish a persistent infection in epithelial cells through its ability to evade immune detection. HR HPV type E6 is an oncogenic protein that is known to downregulate the innate immune response in human keratinocytes. Previous studies have shown that NFX1-123, an endogenously expressed epithelial protein, acts as a novel binding a partner for HR HPV type 16 E6 (16E6). We examined whether or not NFX1-123 also plays a role in the repression of the innate immune response in human foreskin keratinocytes (HFKs) transduced with HR HPV type 16E6. By stimulating the immune response with Poly(I:C) or double stranded DNA in HFKs, cells with overexpressed levels of NFX1-123 (FWT), and cells with endogenous levels of NFX1-123 (LXSN), we demonstrated that stimulation occurs both at the RNA and protein levels. We found, however, that the immune response of 16E6 HFKs with overexpressed levels of NFX1-123 were more downregulated than those with endogenous levels, confirming the protein’s association with 16E6 in the repression of the innate immune response. By understanding the roles of 16E6 and NFX1-123, we will further understand how together they cause a persistent infection, which can ultimately lead to cancer.

Little is known about mammalian diversity in North America during the mid-Cretaceous (Albian-Cenomanian, 120-90 mya). This was an important interval in mammalian evolutionary history, during which metatherian (including marsupials) and eutherian (including placentals) mammals first appeared in North America and multituberculates (a now-extinct group of mammals) began to radiate. Unfortunately, our understanding of this period is poor because mid-Cretaceous mammal-bearing fossil localities are sparse in North America. Accordingly, each newly discovered specimen from this interval could provide important insights into therian and multituberculate diversity and their early stages of evolution. Recent paleontological fieldwork in the mid-Cretaceous (ca. 100 mya) Wayan Formation of eastern Idaho has led to the recovery of 30 mammalian specimens, including 15 metatherians and 13 multituberculates. These specimens, all isolated teeth, were discovered in situ and in the lab. Previous work by myself and other members of the Wilson Lab has focused on describing three metatherian species from this sample, as well as documenting a new occurrence of the genus Targheedelphys. Here, I focus on describing the multituberculates and analyzing their taxonomic diversity, as well as comparing them to those from a larger, contemporaneous sample from the Mussentuchit member of the Cedar Mountain formation of central Utah. Some of the Wayan specimens are attributed to new species and others are referred to previously known species. Current results indicate that multituberculate and metatherian diversity is approximately equal, with three species observed in each group, and each occupying close to fifty percent of the local fauna. The similarities and differences in taxonomic composition and diversity between these two localities will give us important insight about mid-Cretaceous mammalian evolution in North America. Additionally, this information fills a gap in the timeline of mammalian evolution that will further our understanding of mammal evolution through the K-Pg and onward into the Cenozoic.

In order to understand the paleoecology of extinct animals, it is useful to look at extant species for comparison. Due to the shared ancestry between the modern opossum, Didelphis virginiana, and the extinct marsupialiform, Didelphodon vorax, the opossum is often used as an analog for understanding the life history of D. vorax. Didelphodon vorax, which was the largest mammal from the latest Cretaceous of North America (~66 million years ago), is thought to have had an ovivorous (egg eating) or durophagous (hard-shelled eating) diet; however, little is known about its ontogenetic patterns and ecology. Therefore, we aim to construct an age series of D. vorax to gain insight into diet changes throughout its life. A mandibular bending strength analysis investigates the level of force the mandible is capable of withstanding during biting in both dorsoventral and labiolingual directions. Additionally, we can use it to determine variation in bending strength along the body of the jaw, which allows us to further explore feeding behavior. Here, we illuminate cranial ontogenetic patterns in D. vorax by examining different development stages to determine diet variation based on mandibular strength profiles. We analyzed mandibular cross-sectional properties and applied beam theory to 15 D. virginiana and seven D. vorax specimens. Each individual used in the study resulted with a relative force greater than one, which is indicative of an adaptation toward exerting forces directly on prey, whereas a ratio less than one would indicate an adaptation toward withstanding struggling motions or transverse stresses. Finally, we find similar patterns of ontogeny for both species at different tooth positions, which supports the notion that diet changes throughout ontogeny of these marsupials. Thus, comparison of mandibular bending strength between extinct and extant mammals has the ability to gain insight into their feeding behavior and morphological adaptations.

The Cretaceous-Paleogene (K-Pg) mass extinction and resulting biotic recovery mark a pivotal moment in mammal evolution. The recovery period, which spanned about 1 million years from the Puercan North American Land Mammal Age (NALMA) to the Torrejonian NALMA, represents a transition from species-poor “disaster” faunas directly following the extinction event to species-rich “recovery” faunas. Though previous research has broadly studied the faunal dynamics of the early Paleogene, the exact mode and tempo of the biotic recovery has not been well examined. To investigate the ecological trends of the “disaster” to “recovery” faunal transition, specifically changes in diet, we analyzed dental evolution within the periptychid and arctocyonid “archaic ungulate” lineages over a time period that spans from the Puercan NALMA to the Torrejonian NALMA. We measured relief index (RFI), a metric that determines the ratio between the 2D and 3D area of mammal teeth, on both the “archaic ungulates” and a set of ecologically diverse extant mammals to identify the dietary ecologies of the extinct mammals. Previous research has demonstrated a correlation between RFI and diet in extant mammals; high RFI values correspond to herbivory and insectivory, while low RFI values correspond to omnivory and frugivory. Our preliminary results suggest an increase in dietary diversity and an overall decrease in RFI during the biotic recovery. This reduction in RFI reflects a trend in “archaic ungulate” dietary preference from insectivory in the Puercan NALMA to omnivory and frugivory in the Torrejonian NALMA. The results of our study will help scientists understand how ecosystems recover from catastrophic events, such as mass extinctions, on large timescales.

Conjugated polymer semiconductors have received substantial attention for providing a path to low cost manufacturing of electronics such as organic field-effect transistors, light emitting diodes, and solar cells. This work explores the electronic and structural effects of doping colloidal poly(3-hexlythiophene) (P3HT) nanofibers in non-aqueous solution. Doping injects charge carriers into the organic semiconductor and allows for modulation of electrical and optical properties. In solution, increasing dopant concentration also typically leads to uncontrolled polymer aggregation. In this work, we will demonstrate that doping and colloidal stability can be obtained for self-assembled P3HT nanofibers. This work characterizes the conductivity, structure, and optical properties of P3HT nanofibers as a function of dopant concentration and dopant molecular structure. These findings contribute to improved development of transparent thin films for organic electronics by achieving both solution stability and increased conductivity.

The Cretaceous-Paleogene (K/Pg) mass extinction event (~66 million years ago) was a seminal episode in Earth's history. This event resulted in the extinction of up to 76% of all species and led to new evolutionary opportunities for the survivors (e.g., mammals). Accordingly, study of fossils spanning the K/Pg boundary is critical to understanding the dynamics of the extinction and resulting biotic recovery. However, K/Pg sections with vertebrate faunas are presently known only in North America. The Indian subcontinent was geographically isolated from approximately 88 MYA until 55-50 MYA, during which time massive volcanic eruptions (the Deccan Traps) occurred in western India during a four million year span across the K-Pg boundary. These eruptions and their effects have been implicated as causal mechanisms of the K-Pg mass extinction, but few studies have directly tested this hypothesis. Numerous vertebrate fossil localities have been found in India in the sedimentary rocks below (infratrappean) and between (intertrappean) the volcanic basalt flows. Historically, these fossil localities have been considered latest Cretaceous in age, but recent work has refined the stratigraphic and temporal relationships of the fossil localities. This allows us to track species diversity through time during the volcanic eruptions and leading up to and across the K-Pg boundary. In turn, these data can be compiled to determine the timing and magnitude of the extinctions within the context of Deccan volcanism and the mass extinction itself. We have compiled published records of over 1,653 fossil specimens from infra- and intertrappean localities throughout India. From the literature, we recorded demographic and locality information for our database. We will then use this database to characterize vertebrate faunal changes during the volcanic eruptions and across the K-Pg boundary in India, as well as compare the effects of the mass extinction in India with other parts of the world.

Continued advances in energy technologies have allowed for the increased utilization of renewable energy sources. However, energy storage is needed to provide power during peak hours. Flow batteries offer a convenient solution to the problem of storing large amounts of energy while remaining relatively cost efficient. One of the most expensive parts of a flow battery is the proton conducting membrane that separates the two halves of the battery cell. The current state-of-the-art membrane is Nafion, which can be expensive to produce. The goal of this project is to create a membrane with characteristics that can rival those of Nafion but that can be produced using cheaper materials. Towards this end we are utilizing sodium silicate solutions to create flow battery membranes. Two main characteristics of these membranes were studied: 1) proton conductivity, which is essential to current flowing through the battery and 2) ion permeability, which dictates the rate at which the ions in the two halves of the battery cell mix and the battery quality deteriorates. Initial testing for proton conductivity revealed that the experimental membranes were performing within the same order of magnitude as Nafion. However, the experimental membranes showed high permeability relative to Nafion. Future work will focus on isolating variables that affect pore size and polydispersity in the synthesized membranes in order to size exclude redox ions from permeating the membrane while retaining effective proton conductivity.

The Cretaceous-Paleogene (K-Pg) mass extinction event was a pivotal episode in the evolution of mammals. It is widely held that the extinction of non-avian dinosaurs allowed mammals to evolve rapidly into ecological niches previously occupied by dinosaurs. Studies of successive mammalian faunas from northeastern Montana have detailed this pattern, showing that (1) the earliest Paleogene (Puercan 1) ‘survival’ fauna from within 80,000 years of the K-Pg boundary was species poor and included many immigrant taxa and (2) full recovery and expansion of mammalian diversity only occurred 600 to 700 thousand years after the K-Pg event. To better resolve our view of the immediate aftermath following this mass extinction event, previous studies by myself and the Wilson Lab have analyzed a mammalian fossil assemblage from the Constenius locality (UWBM C1665), which documents a ‘survival’ fauna. The Constenius locality is bracketed to within 20,000 years after the K-Pg boundary, thus providing a time-constrained view into which mammals survived the mass extinction and how quickly immigrant taxa invaded this area. Here, I add to our understanding of this fossil assemblage by identifying and describing 23 newly recovered mammalian specimens from the Constenius locality. These specimens, which include isolated teeth and jaw fragments, were discovered in situ in the field and in the lab after screen washing more than 100 kg of bulk sediment. I compared the taxonomic composition and species richness of the Constenius mammalian assemblage to those from the Worm Coulee 1 locality (UWBM C1369), which is bracketed to within 80,000 years of the K/Pg boundary and likely represents a slightly younger assemblage. The results so far indicate that species richness and relative abundance is highest in archaic ungulates and lowest in multituberculates which is consistent and further strengthens previous research done at the Worm Coulee 1 locality within 80,000 years after the extinction event.

Coordination of the initiation of flowering with the optimum season is important for plants in both natural and agricultural systems. In the model plant, Arabidopsis thaliana, timing of flowering is strongly regulated by photoperiod. The main factors important for flowering are CONSTANS (CO) protein, which is an activator of flowering in response to photoperiod and FLOWERING LOCUS T (FT), the direct target of CO. FT protein is a mobile factor which can initiate flowering. Additionally there is a family of repressor transcription factors, the CYCLING DOF FACTOR (CDF) transcription factors that are able to limit the timing of both CO and FT expression so that flowering is repressed during short days. Functionally, CDF expression is controlled by the circadian clock so that their effect is constrained to the morning period of the day. In the afternoon of long days, CDF protein is degraded, enabling CO and FT to promote flowering. Recently, our laboratory has determined that CDFs may require a co-repressor protein, TOPLESS (TPL) to form a repressor complex to regulate flowering genes. To explore the importance of this repressor complex on flowering time, I observed how FT, CO, and other flowering genes expression levels change over the course of development in several genetic backgrounds. To remove TPL function where flowering time genes are expressed, we created a transgenic plant that expresses a dominant negative mutant of TPL in phloem companion cells. We hypothesized that this mutant would resemble a CDF loss of function, so I compared these lines and wild type plants over developmental time. Additionally, I am investigating the genetic interactions and epistasis of TPL with other flowering time pathway components by checking the flowering time and gene expression of transgenic plants which express mutated TPL and harbor mutations in other flowering time genes.

Flowering time in plants is imperative to reproductive viability and is controlled by a variety of molecular regulatory systems drawing upon internal and external stimulus. We use Arabadopsis thaliana as a model to determine how plants incorporate photoperiodic sunlight cues in the production of flowers. Through the transcriptional regulation of certain molecular factors, plants are able to effectively control the temporal expression of the FT (FLOWERING LOCUS T) gene, FT protein is in leaves and then moves up the shoot apex to initiate flowering. Expression of the FT gene is initiated by a transcription factor called CO (CONSTANS) and suppressed by a protein called CDF1 (CYCLING DOF FACTOR 1) that are controlled by sunlight and the plant’s endogenous circadian clock. CDF1 inhibits CO transcription by binding to a series of four identical upstream DNA binding sites and is thought to do so in conjunction with a corepressor protein called TPL (TOPLESS). In this experiment we created a mutant background that was deficient in TPL activity in conjunction with a synthetic CO promoter fused to the bioluminescent enzyme firefly luciferase (LUC). We use this tool to assay if changes in binding site number and orientation in the presence or absence of TPL change the sensitivity of the promoter to photoperiodic sunlight inputs. We hypothesize that the removal of TPL will increase early-day CO expression regardless of daylength but CO expression will be unaffected by the amount of binding sites. We also expect that loss of TPL function attenuates CDF1 dependent repression of flowering, such that differences in CDF1 repression between different binding site architectures types will be unchanged in the absence of the corepressor. This would corroborate results from previous experiments. Should we obtain other results we might be made to reevaluate the role TPL plays in florigenesis in Arabidopsis.

The Veterans Health Administration teledermatology program is designed to expand access to dermatological care for veterans. This study seeks to evaluate the quality of the store-and-forward teledermatology (SFTD) care provided to veterans in the VISN 20 (Pacific Northwest) region. SFTD incorporates imaging technology to remotely and asynchronously provide dermatology for patients who experience barriers to care. When a patient sees their primary care provider (PCP) with a suspicious skin lesion, they may initiate a SFTD consult. PCPs are trained to evaluate and treat many skin conditions, but a suspicious lesion may require consultation. The suspicious lesion is photographed by a trained imager and the pictures are sent via secure communication to a consulting dermatologist. Within days, the dermatologist assesses the lesion and provides a differential diagnosis and treatment plan. Melanoma, a serious form of skin cancer, was used as an indicator for quality of care. Melanomas found in regional SFTD patients between 2009 and 2011 were extracted from existing datasets. Chart reviews were conducted of these cases to understand how melanomas were handled. Melanomas that were mishandled by SFTD were classified as misdiagnosed, mismanaged, incidental, or a combination. If "melanoma" or "lentigo maligna" was not in the SFTD differential diagnosis, then it was classified as misdiagnosed. If the melanoma was not biopsied on the first encounter, it was classified as mismanaged. If the melanoma was not imaged as a suspicious lesion by the PCP, it was classified as incidental. Of the 7964 patients seen by SFTD between 2009 and 2011, there were 69 diagnosable melanomas. 6 of these were classified as incidental, 16 were classified as misdiagnosed, and 4 were considered mismanaged. These results are far below those predicted by previous studies about the quality of SFTD care.