Synthesis of 4-Thiazolidinone Small Molecules as Potential Inhibitors of the Arp2/3 Complex

Life-essential cellular processes such as endocytosis, motility, and division rely on a cell’s ability to precisely regulate construction of actin filaments in response to external factors and signals. Intrinsically involved in this process is the Actin Related Protein 2/3 (Arp2/3) Complex, a seven-subunit ATPase that functions by nucleating a daughter branch of actin from the side of a pre-existing microfilament. Active Arp2/3 complex is necessary for the proliferation of certain metastatic cancers, and inhibition of Arp2/3 complex is emerging as a potentially useful treatment strategy for such cancers. We describe synthesis and in vitro assays of 4-thiazolidinones predicted by computational methods to inhibit of Arp2/3 Complex strongly, and therefore serve as potential lead compounds for drug development. Known Arp2/3 inhibitor CK-869 serves as the starting point for derivative synthesis. We discuss the efforts towards the synthesis of new compounds and the biochemical data collected about their potency

The Nation Before Taste: The Challenges of American Culinary History

Food is material and familiar, and because it is, we are often overconfident about our ability to understand the culinary past. It is easy to believe that if we can discover the recipe for some forgotten dish, the history of the dish becomes intelligible. When it does not, it tempts those who consume culinary history to impose modern sensibilities on our predecessors. The Nation before Taste argues that historians and museum curators must be especially vigilant when presenting the history of food. Reviewing a series of historical challenges that stemmed from studying the United States in the late nineteenth and early twentieth centuries, the author suggests three strategies for grounding food history in the past: recognizing that taste is constructed and temporal; engaging with material and social contexts, especially physiology, class, and gender; and admitting to our audiences that not all culinary mysteries have immediate or simple answers

The Relationship of the Battles in Zechariah 12 through 14

The relationship of the battle sequences in Zechariah 12-14 has divided scholars for centuries. Jerusalem, besieged by the nations, will be the location of both battles. The nations will be defeated by a divine plague in both battles. Finally, the battles will both result in the establishment of Yahweh\u27s kingdom. There are several important differences between the battle sequences. Zechariah 14 specifically identifies the day of the conflict as the Day of the Lord. Chapters 12-13 do not. Chapter 14 describes the judgment of Jerusalem while chapters 12-13 do not. Finally, chapter 14 presents a thorough description of the battle while narrating the events of the conflict. In contrast, chapters 12-13 use a series of similes establishing the power of Yahweh while mostly ignoring the action of the battle. The dispensational position associated the fulfillment of these battles with Armageddon and the establishment of the Millennial Reign. Dispensational scholars like Charles Feinberg and George Klein therefore suggest that Zechariah 12-14 is describing identical battles in consecutive sequences. It is difficult, however, to find investigation of any length actually linking the battles within a dispensational framework while also explaining the differences between the sequences. This thesis affirms the dispensational position that Zechariah 12-14 is prophesying about the same conflict in consecutive sequences after (1) a study of the historical setting and the apocalyptic genre; (2) an exegesis of chapters 12-14 and the three important motifs established through the exegesis: Zion and its related theology, the Day of the Lord, and Yahweh as the Divine Warrior; and (3) an examination of the differing judgment focus of each conflict and its impact on understanding the differences between the battles

Social Indicators for Arctic Mining

This paper reviews and assesses the state of the data to describe and monitor mining trends in the pan-Arctic. It constructs a mining index and discusses its value as a social impact indicator and discusses drivers of change in Arctic mining. The widely available measures of mineral production and value are poor proxies for economic effects on Arctic communities. Trends in mining activity can be characterized as stasis or decline in mature regions of the Arctic, with strong growth in the frontier regions. World prices and the availability of large, undiscovered and untapped resources with favorable access and low political risk are the biggest drivers for Arctic mining, while climate change is a minor and locally variable factor. Historical data on mineral production and value is unavailable in electronic format for much of the Arctic, specifically Scandinavia and Russia; completing the historical record back to 1980 will require work with paper archives. The most critically needed improvement in data collection and reporting is to develop comparable measures of employment: the eight Arctic countries each use different definitions of employment, and different methodologies to collect the data. Furthermore, many countries do not report employment by county and industry, so the Arctic share of mining employment cannot be identified. More work needs to be done to develop indicator measures for ecosystem service flows. More work also needs to be done developing conceptual models of effects of mining activities on fate control, cultural continuity and ties to nature for local Arctic communities

Halo Properties from Observable Measures of Environment: I. Halo and Subhalo Masses

The stellar mass - halo mass relation provides a strong basis for connecting galaxies to their host dark matter halos in both simulations and observations. Other observable information, such as the density of the local environment, can place further constraints on a given halo's properties. In this paper, we test how the peak masses of dark matter halos and subhalos correlate with observationally-accessible environment measures, using a neural network to extract as much information from the environment as possible. For high mass halos (peak mass $>10^{12.5} M_{\odot}$), the information on halo mass contained in stellar mass - selected galaxy samples is confined to the $\sim$ 1 Mpc region surrounding the halo center. Below this mass threshold, nearly the entirety of the information on halo mass is contained in the galaxy's own stellar mass instead of the neighboring galaxy distribution. The overall root-mean-squared error of the best-performing network was 0.20 dex. When applied to only the central halos within the test data, the same network had an error of 0.17 dex. Our findings suggest that, for the purposes of halo mass inference, both distances to the $k$th nearest neighbor and counts in cells of neighbors in a fixed aperture are similarly effective measurements of the local environment.Comment: Accepted to the Open Journal of Astrophysics; 17 pages, 20 figures; revised versio

APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination

John Rector Interview 2016

Professor John Rector describes his career at Western Oregon University, the experiences he has had, the programs he has been a part of, and what he hopes to see at Western Oregon University in the future