Economic Impacts of Montgomery County’s Parks

Final project for ENSP400: Capstone in Environmental Science (Fall 2017). University of Maryland, College Park.This project’s goal is to analyze how the presence and quality of local parks and open spaces affects adjacent property values and the local economy, and to gauge the public perception of parks in Montgomery County to better understand public opinion and concerns surrounding parks. This project will also recommend how those concerns can be addressed to make stakeholder groups more likely to support the activities of the County’s Department of Parks. We assessed opinions of property owners, businesses, developers, and residents in Montgomery County and beyond through on-line and in person surveys. Respondents were asked to assess park amenities by personal preference, state their willingness to pay a premium to live and work near a public park, and share other information on their perceptions of public green spaces in their area. Using these survey result as well as literature reviews, we found a trend of increasing property values near parks, a perception of increasing business activity due to the presence of parks, and an increased attraction of visitors and residents to an area because of parks. We also determined that parks benefit the natural ecosystem in a way that offers significant monetary value and that can benefit the local economy in the form of saved public utility costs and personal health benefits. The surveys also provided information on trends in public opinion about parks. The most favored park amenity was paved trails, while the least favored amenity was skateparks. Overall, respondents’ opinions were quite positive and any concerns they had were related to safety in parks. Our research and surveys enabled us to determine four distinct recommendations for the Department of Parks. The first is to implement popular amenities. The surveys showed that paved trails were the most popular amenity, followed by family-oriented activities and dog parks, and these amenities can greatly help to generate a more positive perception of parks. The second recommendation is to create educational programs to help people better understand the economic and social benefits parks can provide, especially their benefits to the natural ecosystem. When people better understand those benefits, they will be less likely to oppose new park plans. The third recommendation is to continue to develop a safe atmosphere within parks. One of the main concerns is that parks can foster crime, so if the Department of Parks were to heavily advertise their safety measures, such as displaying signs about security camera systems or advertising that the parks are under constant surveillance, people may feel safer and be less concerned about a park in their neighborhood. Finally, more surveys should be conducted. By continuing to survey the public’s perception of their parks, the Department will be able to tailor services to residents and visitors as preferences and demographics change. We believe that following these suggestions will increase the economic benefits of parks in Montgomery County.Montgomery Count

The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage

Flavonol Specific 3-O Glucosyltransferase (Cp3GT) Mutant S20G+T21S: Enzyme Structure and Function

Flavonols are a major subclass of flavonoids and are considered the most abundant subclass of flavonoids. Flavonols are classified as having a hydroxyl group on the 3rd carbon of the C ring. The most prevalent modification to flavonols is glucosylation. The flavonol specific 3-O glucosyltransferase (Cp3GT) enzyme from grapefruit (Citrus paradisi) is the topic of this research and specifically adds glucose to flavonols at the 3-OH position. The level of activity varies depending on the flavonol structure. This makes Cp3GT an ideal model system for studying the structure/function relationship of Cp3GT using site-directed mutants. S20G+T21S is a mutant form of Cp3GT. As compared to the wild type Cp3GT, S20G+T21S has significantly higher activity with kaempferol, quercetin, and gossypetin. Another interesting difference of S20G+T21S is its ability to add glucose to the 7-OH position of the flavanone naringenin, thus showing a change in flavonoid class specificity as well as regiospecificity for position of glucose attachment. The S20G+T21S mutant was first made by site-directed mutagenesis and verified by DNA sequencing. The linearized pPICZa plasmid containing S20G+T21S was then transformed into Pichia pastoris via electroporation. Transformation was verified by colony PCR and DNA sequencing and a time course analysis of methanol-induced expression conducted to identify optimal expression. Optimal expression was identified at 24 hours and was verified by SDS-page gel and a western blot. S20G+T21S was purified by IMAC column in preparation for crystallization

A Generational Divide: The Reconstruction of American Party Politics, 1865-1912

American historians have traditionally divided the late nineteenth and early twentieth centuries into Reconstruction, the Gilded Age, and the Progressive Era; however, this arbitrary periodization obscures more than it reveals. My dissertation argues that the Republican and Democratic Parties—like the American nation—passed through a period of reconstruction. Using the four-way presidential elections of 1860 and 1912 as bookends, I examine national politics through the lens of the two generations of politicians—the Civil War and Progressive generations—who oversaw the United States’ transition from an agricultural to an industrial political economy. The Civil War generation’s inability to address the excesses of industrialization called into question classical liberalism’s emphasis on unfettered individualism for competing visions of a regulatory state. Touching off an internecine intergenerational struggle that spread from Democrats, in 1896, to Republicans, in 1912, both parties coalesced around competing visions of a federal regulatory state that took shape, ultimately establishing the ideological foundation of moder

Flavonol Specific 3-O Glucosyltransferase (Cp3GT) Mutant S20G+T21S: Enzyme Structure and Function

Flavonoids have multiple subclasses. A major subclass of flavonoids is flavonols. Flavonols are the most abundant subclass of flavonoids and are widely spread throughout nature. Flavonols are identified as having a hydroxyl group in the 3rd position of the C ring. The most prevalent modification to flavonols is glucosylation which adds glucose to an acceptor molecule. The flavonol specific 3-O glucosyltransferase (Cp3GT) enzyme from grapefruit (Citrus paradisi) is the topic of this research and specifically adds glucose to flavonols at the 3-OH position. The level of activity with Cp3GT and a flavonol varies depending on the flavonol structure. Since there is varying activity with Cp3GT, Cp3GT is an ideal model system for studying the structure/function relationship of Cp3GT site-directed mutants. Multiple mutants of Cp3GT were created by site directed mutagenesis. The mutant of study is S20G+T21S. As compared to the wild type Cp3GT, S20G+T21S has significantly higher activity with kaempferol, quercetin, dihydroquercetin, and naringenin. One of the more striking difference of S20G+T21S is its ability to add a glucose molecule to the 7-OH position of naringenin. Naringenin is a flavanone and indicates that S20G+T21S has a change in flavonoid class specificity as well as regiospecificity for the addition of glucose. The S20G+T21S mutant was first verified in E. coli via DNA sequencing. Next, S20G+T21S was transformed into Pichia pastoris by linearizing S20G+T21S DNA using Sac I, phenol chloroform purification, and electroporation. Transformation was verified by colony PCR and DNA sequencing. After verification, a time course analysis of expression conduction was completed. Optimal expression was concluded to be 24 hours and was verified by SDS-Page gel and western blot. In preparation for crystallization, S20G+T21S was purified using an IMAC infinity column. Purification was verified using a western blot, Coomassie blue, and silver stain. Progress on optimizing the crystallization conditions for S20G+T21S will be reported

TP-0903 Is Active in Preclinical Models of Acute Myeloid Leukemia with <i>TP53</i> Mutation/Deletion

Acute myeloid leukemia (AML) with mutations in the tumor suppressor gene TP53 confers a dismal prognosis with 3-year overall survival of TP53 mutant cancers, this strategy has not been evaluated in mutant TP53 AML. Previously, we demonstrated that TP-0903 is a novel multikinase inhibitor with low nM activity against AURKA/B, Chk1/2, and other cell cycle regulators. Here, we evaluated the preclinical activity of TP-0903 in TP53 mutant AML cell lines, including a single-cell clone of MV4-11 containing a TP53 mutation (R248W), Kasumi-1 (R248Q), and HL-60 (TP 53 null). TP-0903 inhibited cell viability (IC50, 12–32 nM) and induced apoptosis at 50 nM. By immunoblot, 50 nM TP-0903 upregulated pChk1/2 and pH2AX, suggesting induction of DNA damage. The combination of TP-0903 and decitabine was additive in vitro, and in vivo significantly prolonged median survival compared to single-agent treatments in mice xenografted with HL-60 (vehicle, 46 days; decitabine, 55 days; TP-0903, 63 days; combination, 75 days) or MV4-11 (R248W) (51 days; 62 days; 81 days; 89 days) (p TP53 mutant AML