Let\u27s Talk Science

The focus of our senior thesis, “Let\u27s Talk Science! , was to increase the exposure of elementary school-aged students to science. In particular, we focused on increasing the students’ opportunity to experience fun science experiments that still presented a strong take-home lesson. In doing this, our goal was to increase the students’ interest in science, technology, engineering, and math (STEM) careers. We coordinated our outreach program with the Waverly After-School Program, a student organization that operates through the University of South Carolina Honors College in Columbia, South Carolina. Through the Waverly After-School Program, we were able to carry out our senior thesis experiments with St. Lawrence Place. St. Lawrence Place is a facility for families as they make their way from homelessness to home. Many of the families residing at St. Lawrence Place have young children; these children need somewhere to spend their afternoons while their parents are at work. St. Lawrence Place has an activities center that the children visit after they arrive home from school. This grants the children the opportunity to complete their homework and have fun with their peers. Waverly is directly involved in this after-school center; volunteers from the program work with students each day, helping them with homework and reading. Our goal for developing this science outreach program was to show these kids how fun and exciting science can be, as well as teaching them important scientific concepts. The strategy for the program was initially to visit twice a week (Mondays and Wednesdays) for eight weeks for a total of sixteen different experiments. After three experiments, it was suggested that, instead of doing two different experiments with all of the kids (about 25 in total) in one week, we should divide the kids into two groups (a Monday group and a Wednesday group) and do the same experiment on both Monday and Wednesday. This changed our strategy for the program; instead of doing sixteen different experiments, we would only perform ten. This was a wonderful change to the program as we were able to better assist the kids with their experiments, and it allowed us to have an active discussion about the topic of that day’s experiment. Throughout the course of the program, we asked the kids to write in their laboratory notebooks. This was a great element of the program, because it allowed the kids to process the topics discussed and then put them down in writing. It was our hope that, by working with the kids for eight weeks, we would spark an interest in STEM-related careers. After we finished our thesis, we reflected on our personal experiences. Furthermore, we asked those that supported us, our partners at Waverly and St. Lawrence Place, to reflect on their experience. While we cannot confirm that we made a student want to become a doctor, we hope that we had a positive impact on the children’s interest in science

Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma

Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM

IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium

Mucosal delivery of IL-27 has been shown to have a therapeutic benefit in murine models of inflammatory bowel disease (IBD). The IL-27 effect was associated with phosphorylated STAT1 (pSTAT1), a product of IL27 receptor signaling, in bowel tissue. To determine whether IL-27 acted directly on colonic epithelium, murine colonoids and primary intact colonic crypts were shown to be unresponsive to IL-27 in vitro and to lack detectable IL-27 receptors. On the other hand, macrophages, which are present in inflamed colon tissue, were responsive to IL-27 in vitro. IL-27 induced pSTAT1 in macrophages, the transcriptome indicated an IFN-like signature, and supernatants induced pSTAT1 in colonoids. IL-27 induced anti-viral activity in macrophages and MHC Class II induction. We conclude that the effects of mucosal delivery of IL-27 in murine IBD are in part based on the known effects of IL27 inducing immunosuppression of T cells mediated by IL-10. We also conclude that IL-27 has potent effects on macrophages in inflamed colon tissue, generating mediators that in turn act on colonic epithelium

The Apache Point Observatory Galactic Evolution Experiment (APOGEE)

The Apache Point Observatory Galactic Evolution Experiment (APOGEE), one of the programs in the Sloan Digital Sky Survey III (SDSS-III), has now completed its systematic, homogeneous spectroscopic survey sampling all major populations of the Milky Way. After a three-year observing campaign on the Sloan 2.5 m Telescope, APOGEE has collected a half million high-resolution (R ~ 22,500), high signal-to-noise ratio (>100), infrared (1.51–1.70 μm) spectra for 146,000 stars, with time series information via repeat visits to most of these stars. This paper describes the motivations for the survey and its overall design—hardware, field placement, target selection, operations—and gives an overview of these aspects as well as the data reduction, analysis, and products. An index is also given to the complement of technical papers that describe various critical survey components in detail. Finally, we discuss the achieved survey performance and illustrate the variety of potential uses of the data products by way of a number of science demonstrations, which span from time series analysis of stellar spectral variations and radial velocity variations from stellar companions, to spatial maps of kinematics, metallicity, and abundance patterns across the Galaxy and as a function of age, to new views of the interstellar medium, the chemistry of star clusters, and the discovery of rare stellar species. As part of SDSS-III Data Release 12 and later releases, all of the APOGEE data products are publicly available

The Effect of Vector Silencing during Picornavirus Vaccination against Experimental Melanoma and Glioma.

Virus vector-based vaccination against tumor-specific antigens remains a promising therapeutic approach to overcome the immune suppressive tumor microenvironment. However, the extent that the desired CD8 T cell response against the targeted tumor antigen is impacted by the CD8 T cell response against the virus vector is unclear. To address this question, we used picornavirus vaccination with Theiler's murine encephalomyelitis virus (TMEV) as our vector against tumor-expressed ovalbumin (OVA257-264) antigen in both the B16-OVA murine melanoma and GL261-quad cassette murine glioma models. Prior to vaccination, we employed vector silencing to inhibit the CD8 T cell response against the immunodominant TMEV antigen, VP2121-130. We then monitored the resulting effect on the CD8 T cell response against the targeted tumor-specific antigen, ovalbumin. We demonstrate that employing vector silencing in the context of B16-OVA melanoma does not reduce tumor burden or improve survival, while TMEV-OVA vaccination without vector silencing controls tumor burden. Meanwhile, employing vector silencing during picornavirus vaccination against the GL261-quad cassette glioma resulted in a lower frequency of tumor antigen-specific CD8 T cells. The results of this study are relevant to antigen-specific immunotherapy, in that the virus vector-specific CD8 T cell response is not competing with tumor antigen-specific CD8 T cells. Furthermore, vector silencing may have the adverse consequence of reducing the tumor antigen-specific CD8 T cell response, as demonstrated by our findings in the GL261-quad cassette model

Competition among epitope-specific CD8 T cells occurs in the central nervous system following acute infection with TMEV-OVA.

<p>Mice were administered E7_49-57 (n = 2) or VP2_121-130 (n = 4) peptide i.v. one day prior to i.c. injection of TMEV-OVA. After one week, brain-infiltrating lymphocytes were harvested and stained for surface markers and peptide:MHC tetramer. (A) Representative flow cytometry plots and (B, C) quantified peptide:MHC tetramer⁺ cells of CD8α⁺CD45^hi cells per brain demonstrate a significant decrease in CD8 T cells recognizing VP2_121-130 upon vector silencing. An increase in peptide:MHC tetramer staining for OVA_257-264 is also observed. (D) Number of total CD8 T cells infiltrating the brain was not significantly different. Data are shown as mean±SEM. * denotes p<0.05, n.s. indicates no significant difference.</p