BASIGIN-2 MEDIATED ACTIVATION OF ERK1/2 SIGNALING IN HUMAN GLIOBLASTOMA MULTIFORME CELLS

Glioblastoma multiforme (GBM) is the most common malignant form of human brain cancer. GBM tumor cells overexpress the protein Basigin (Bsg) at the cell surface where it contributes to malignancy via stimulation of matrix metalloproteinase (MMP) expression in surrounding normal tissues, resulting in the degradation of the extracellular matrix (ECM) surrounding tumors, promoting remodeling of the tumor borders, stimulating growth. In work by Belton et al. (2008), human uterine endometrial cells treated with a recombinant form of human basigin possessing the extracellular domain of the Bsg protein (rBsg-ECD) showed activation of the Mitogen-Activated Protein Kinase (MAPK) signaling pathway proteins, ERK1/2. This effect was mediated by rBsg-ECD binding to the Basigin-2 (Bsg-2) at the cell surface. In this research, U87-MG human GBM cells were treated with purified rBsg-ECD protein to measure changes in the phosphorylation of the ERK1/2 proteins. The results indicate the presence of a signaling loop within GBM tumors where soluble Bsg protein stimulates signal transduction through Bsg-2 at the cell surface. rBsg-mediated ERK1/2 stimulation is inhibited by the antioxidant compound Resveratrol, suggesting that the signaling mechanism through Bsg-2 involves the Epidermal Growth Factor Receptor (EGFR). Taken together, these results indicate that soluble Basigin protein stimulates signaling events through the MAPK signaling pathway by binding to Bsg-2 on the surface of GBM cells

Remnant assessment and soil inoculation to inform large-scale prairie restoration at Eastern Washington University

The Palouse Prairie of Eastern Washington and Western Idaho, characterized by rolling hills of deep loess soil, is one of the most endangered ecosystems in the world, with more than 99% converted to tilled farmland. To mitigate this loss, Eastern Washington University has begun prairie restoration on a tilled wheat field adjacent to campus, in the northern extent of the Palouse Prairie Ecoregion. However, effective restoration requires understanding reference conditions, and there are relatively few studies of remnant prairie plant communities or soils, particularly in the Northern Palouse. From north to south in the Palouse Prairie Ecoregion, there are gradients in precipitation and temperature that affect plant communities. In addition, the Prairie is intersected by Channeled Scablands, which were formed when the ancient Missoula Floods washed away some of the loess hills, leaving exposed basalt. In deeper soil pockets, Channeled Scablands have plant communities overlapping with Palouse Prairie. In prairies, both the plants and the soil microbiome can play crucial structural roles in supporting the ecosystem. Successful restoration of degraded plant communities may rely on restoration of the original soil microbiome. Therefore, my goal was to identify and survey remnant prairie vascular plant communities in the region surrounding Eastern Washington University to understand how they vary from north to south and differ from Channeled Scabland, and to understand the role that intact prairie soils, with their complement of microbial species, can play in native plant growth. This resulted in a two-part thesis, with Chapter 1 documenting remnant plant communities, and Chapter 2 studying the effect of whole soil inoculation with native prairie soils on plant growth. To document how remnant prairie plant communities near EWU differ from sites in the southern Palouse and from Channeled scablands, I identified over 100 remnants from aerial imagery across Whitman and Spokane Counties, and conducted vegetation surveys at thirteen sites, including both Palouse Prairie and Channeled Scabland locations. Palouse Prairie and Channeled Scabland plant communities, while overlapping, had significant differences as indicated by PERMANOVA analysis. Palouse Prairie remnants had relative more native species, such as Symphoricarpos albus and Balsamorhiza sagittata, as indicators, while Channeled Scablands tended to have more invasive species, including invasive annual grasses such as Bromus tectorum and Poa bulbosa. There were also distinctive differences between northern and southern Palouse sites, with northern sites having more Pinus ponderosa and Geum triflorum while southern sites had more Ventenata dubia and Lomatium dissectum. Unlike when all sites were analyzed, Palouse site community composition was correlated with aspect and solar radiation. To determine the effect of the native prairie soil microbiome on native plant growth, I inoculated native and nonnative grass species with soil from native prairies and the restoration site in a greenhouse experiment. The three inoculum sources were Turnbull National Wildlife Refuge, the EWU restoration site, and Kamiak Butte. Plants were grown in unsterilized background soil collected from the EWU restoration site and sterile or unsterile soil inoculum. In general, inoculum source had no effect on either grass species but sterilization of inoculum resulted in increased growth of the native grass especially in soil collected from the EWU restoration. Invasive grass was unaffected by treatment. Results indicate possible nutrient limitation or altered soil microbiome at the EWU restoration site. Overall, my study results provide a better understanding of reference plant and soil communities for the EWU Prairie restoration site

Many hats: intra-trial and reward-level dependent bold activity in the striatum and premotor cortex

2012 Spring.Includes bibliographical references.Lesion, drug, single-cell recording, as well as human fMRI studies, suggest dopaminergic projections from VTA/SNc (ventral tagmental area/substantia nigra pars compacta) and cortically driven striatal activity plays a key role in associating sensory events with rewarding actions both by facilitating reward processing and prediction (i.e. reinforcement learning) and biasing and later updating action selection. We, for the first time, isolated BOLD signal changes for stimulus, pre-response, response and feedback delivery at three reward levels. This design allowed us to estimate the degree of involvement of individual striatal regions across these trial components, the reward sensitivity of each component and allowed for a novel comparison of potential (and potentially competing) reinforcement learning computations. Striatal and lateral premotor cortex regions of interest (ROIs) significant activations were universally observed (excepting the ventral striatum) during stimulus presentation, pre-response, response and feedback delivery, confirming these areas importance in all aspects of visuomotor learning. The head of the caudate showed a precipitous drop in activity pre-response, while in the body of the caudate showed no significant changes in activity. The putamen peaked in activity during response. Activation in the lateral premotor cortex was strongest during stimulus presentation, but the drop off was followed by a trend of increasing activity as feedback approached. Both the head and body of the caudate as well as the putamen displayed reward-level sensitivity only during stimulus, while the ventral striatum showed reward sensitivity at both stimulus and feedback. The lack of reward sensitivity surrounding response is inconsistent with theories that the head and ventral striatum encode the value of actions. Which of the three examined reinforcement learning models correlated best with BOLD signal changes varied as a function of trial component and ROI suggesting these regions computations vary depending on task demand

Order Submission Strategy and the Curious Case of Marketable Limit Orders

We provide empirical evidence on order submission strategy of investors with similar com-mitments to trade by comparing the execution costs of market orders and marketable limit orders (i.e., limit orders with the same trading priority as market orders). The results in-dicate the unconditional trading costs of marketable limit orders are significantly greater than market orders. We attribute the difference in costs to a selection bias and provide evidence suggesting the order submission strategy decision is based on prevailing market conditions and stock characteristics. After correcting for the selection bias, the results show the average trader chooses the order type with lower conditional trading costs. I

Memory and Identity on Display in a “Family Museum”: A Video Poster

The things we save of our everyday lives are not always considered “museum pieces,” but these items often find their ways into meaningful displays throughout the home. These objects become expressions of identity and memory. In Art as Experience, Dewey (1934), comments on the role of expressive objects as the tangible things of the world which represent meaning and experience. These objects are not simply mementoes or souvenirs of things past, but rather, emotional conduits that integrate and unify the sense of self; things from the past “become co-efficients in new adventures and put on a raiment of fresh meaning” (Dewey, 1934, p. 60). We are surrounded by these objects in all aspects of our lives, but it is not until they are assembled, or collected, in one place that the value and significance of these objects becomes clear. Vernacular museums, those which are set in “non-museum spaces,” are places that demonstrate a “connectedness between consumption, history, individuality, and place… [and which] allow people to discuss heritage without breaking from daily activities” (Gordon, 2012, p. 76).These settings provide an opportunity for exploration of stories of the past. A particular form of vernacular museum, what is best described as a “family museum,” represents a unique perspective on the meaning of objects as they interconnect with family and community history. The interdisciplinary approach to this study of material culture, experience, and family history encompasses a humanities research approach--posing questions about common assumptions, uncovering new meanings in the artifacts of human life, and finding new ways to understand cultural interactions. For this study in particular, the objects on display in the family museum and the way that they are displayed become a locus for the study of human experience. The poster presentation uses digital storytelling techniques to examine “The Loft,” a part of the Pierce Homestead in Mount Desert, ME, a family museum representing the collective material history of five generations of an American family. Digital storytelling is an emergent practice that incorporates traditional narratives with digital imagery, text, audio and video. Burgess (2006) suggests that the strategies of digital storytelling are fundamentally community oriented and represent “a field of cultural practice: a dynamic site of relations between textual arrangements and symbolic conventions, technologies for production and conventions for their use; and collaborative social interaction that takes place in local and specific contexts” (p.7). The opportunity to study and document vernacular museums like The Loft provides an important avenue for better understanding the personal connections that museums can build between visitors and objects, as well as ways memory, identity and sense of family. Each of thee artifacts in The Lof is a possession of the family as a whole, and “take their value from their association to events that are constitutive of the person or of the family history” (Marcoux, 2001, p. 72). Members of the family can point to and interpret their life events of the time, and connect this to the history and continuity of the family and community context, all through their relationship to the artifacts in The Loft. References Burgess, Jean (2006) Hearing Ordinary Voices: Cultural Studies, Vernacular Creativity and Digital Storytelling. Continuum: Journal of Media & Cultural Studies 20(2):pp. 201-214. Dewey, J. (1934). Art as experience. New York: Perigree Books. Gordon, T.S. (2011). Private history in public exhibition and the settings of everyday life. Lanham, MD: AltaMira. Marcoux, J-S. (2001). The refurbishment of memory. In D. Miller (Ed.)., Home possessions: Material culture behind closed doors (pp. 69-86). Oxford, England: Berg

Design of Sequences with Good Folding Properties in Coarse-Grained Protein Models

Background: Designing amino acid sequences that are stable in a given target structure amounts to maximizing a conditional probability. A straightforward approach to accomplish this is a nested Monte Carlo where the conformation space is explored over and over again for different fixed sequences, which requires excessive computational demand. Several approximate attempts to remedy this situation, based on energy minimization for fixed structure or high-$T$ expansions, have been proposed. These methods are fast but often not accurate since folding occurs at low $T$. Results: We develop a multisequence Monte Carlo procedure, where both sequence and conformation space are simultaneously probed with efficient prescriptions for pruning sequence space. The method is explored on hydrophobic/polar models. We first discuss short lattice chains, in order to compare with exact data and with other methods. The method is then successfully applied to lattice chains with up to 50 monomers, and to off-lattice 20-mers. Conclusions: The multisequence Monte Carlo method offers a new approach to sequence design in coarse-grained models. It is much more efficient than previous Monte Carlo methods, and is, as it stands, applicable to a fairly wide range of two-letter models.Comment: 23 pages, 7 figure

Physical Computing for Materials Acceleration Platforms

A ''technology lottery'' describes a research idea or technology succeeding over others because it is suited to the available software and hardware, not necessarily because it is superior to alternative directions--examples abound, from the synergies of deep learning and GPUs to the disconnect of urban design and autonomous vehicles. The nascent field of Self-Driving Laboratories (SDL), particularly those implemented as Materials Acceleration Platforms (MAPs), is at risk of an analogous pitfall: the next logical step for building MAPs is to take existing lab equipment and workflows and mix in some AI and automation. In this whitepaper, we argue that the same simulation and AI tools that will accelerate the search for new materials, as part of the MAPs research program, also make possible the design of fundamentally new computing mediums. We need not be constrained by existing biases in science, mechatronics, and general-purpose computing, but rather we can pursue new vectors of engineering physics with advances in cyber-physical learning and closed-loop, self-optimizing systems. Here we outline a simulation-based MAP program to design computers that use physics itself to solve optimization problems. Such systems mitigate the hardware-software-substrate-user information losses present in every other class of MAPs and they perfect alignment between computing problems and computing mediums eliminating any technology lottery. We offer concrete steps toward early ''Physical Computing (PC) -MAP'' advances and the longer term cyber-physical R&D which we expect to introduce a new era of innovative collaboration between materials researchers and computer scientists