The Shifting Meaning of the Richmond-Lynchburg Stage Road

This post is part of a series featuring behind-the-scenes dispatches from our Pohanka Interns on the front lines of history this summer as interpreters, archivists, and preservationists. See here for the introduction to the series. The part of the Richmond-Lynchburg Stage Road running through Appomattox Court House holds various meanings for those that have used it through the years. The early 19th-century inhabitants of Appomattox Court House viewed it as the source of prosperity for the town. By connecting the two wealthy cities of Richmond and Lynchburg, it ensured a steady flow of traffic that would spur construction of the town’s first building, the Clover Hill Tavern, in 1819. Without the road, many of the non-agricultural businesses in the community could not function, thus making the road instrumental to the town’s success. In 1854, a railroad stop was established 3 miles west of the town. The road which had once been a source of prosperity spelled the town’s death sentence as people chose faster and smoother train travel over the stage road. Taverns went out of business and the population of 100 people in the 1860s decreased to just 10 by the 1890s. [excerpt

Illusions of Grandeurs: Washingtonian Architecture as Seen by White and Black People of the Early Nineteenth Century

In the early nineteenth century, George Washington and Thomas Jefferson built a classically inspired capital designed to legitimize American republican ideals. White interpretations of the architecture gradually aligned more with the founders’ intentions, especially following its reconstruction after the 1814 conflagration. Enslaved and free black observers recognized their exclusion from the message of freedom and equality. Rather than finding their identity through federal buildings, they established their communities within churches, houses, and businesses owned by black people. The varied reactions to Washington’s and Jefferson’s designs demonstrated how the aesthetic idealization of republicanism revealed incongruities in the new capital

Expansion and Acquisition: The Built Environment Under Gettysburg College President, Gordon Haaland, 1990 to 2004

Gordon Haaland presided over Gettysburg College from 1990 to 2004. His goals included improving the national status of the college by increasing the student body, developing the academic departments, and creating a dynamic campus community. This paper outlines Haaland\u27s attempts to fulfill these goals through a plethora of construction projects, ranging from building a state of the art science center and extensively renovating a historic theater, to updating dormitories and revitalizing the appearance of campus. Some of the construction included projects that were planned under the previous president and carried out by Haaland, as well as scandals that accompanied these efforts. In addition, the paper covers the fundraising and planning processes, as well as the campus and community reactions to the building projects. Ultimately, this paper weighs the successes and challenges of Haaland\u27s construction plans during his highly productive presidency

An Augustan Accident: The Paradox of Augustan Sex and Marriage Laws and Augustan Ideology

Augustus, born Gaius Octavius, curated a specific image of himself and his purpose for the Roman people, starting with his rise to power following his victory at Actium in 31 B.C.E. and culminating in his later construction projects. Augustus was generally successful at crafting a Pax Romana in which the people were fed, the Empire’s borders expanded, and the armies at peace. However, Augustus was fallible. When promoting themes of fertility, he enacted laws to actualize his ideology, restricting marriage based on class, ordering a minimum number of children per couple, and condemning adulteresses. Never before had state law punished citizens for sexual deviance and so plainly distinguished the bottom of moral hierarchy. In creating a model of moral behavior through law, Augustus also necessitated the existence of its antithesis, the prostitute. Additionally, Augustus put himself at odds not only with the sexual desires of the aristocracy but also with his own ideology. He attempted to hold the past as a golden standard to which Rome ought to return. Yet, many of Rome’s ancestors would have been criminals under Augustus’s sex laws. Ultimately, Augustus’s laws did more to damage his own ideology than consolidate his power and control the aristocracy

Letter from the Editors

Even amid the Covid-19 pandemic, The Gettysburg Historical Journal has not forgotten its commitment to publishing the best of undergraduate research. We are heartened to witness students’ continued dedication to excellent work in an array of historical topics. Despite the difficulties we still face—mental and emotional exhaustion, shuttered archives, limited in-person research opportunities—we received a particularly high volume of submissions this year. We are proud to present work from our peers at Gettysburg and around the world in this twentieth edition of our journal. Through the stories we encounter in the past, we gain insight into the human experience in a variety of contexts and receive the tools to work towards a better present and future

Letter from the Editors

In the midst of social unrest and a global pandemic, we, the editors of the Gettysburg Historical Journal, could not forget our duty to publish undergraduate academic scholarship. Although this task may seem trivial considering greater issues, historical discourse deserves its place

Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19

Background While inflammatory and immune responses to SARS-CoV-2 infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished COVID-19 severity categories, and relate these to disease progression and peripheral inflammation. Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalised with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days post-symptom onset) or late (6-20 days post-symptom onset). Results Patients that survived severe COVID-19 showed IFN-dominated mucosal immune responses (IFN-γ, CXCL10 and CXCL13) early in infection. These early mucosal responses were absent in patients that would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by IL-2, IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions Defective early mucosal anti-viral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival