Modulation Of Hiv Protease Flexibility By The T80n Mutation,
2016
Northeastern University
Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski
Celia A. Schiffer
The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the …
A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro,
2016
University of North Carolina at Chapel Hill
A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom
Celia A. Schiffer
Though the steps of human immunodeficiency virus type 1 (HIV-1) virion maturation are well documented, the mechanisms regulating the proteolysis of the Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) remain obscure. One proposed mechanism argues that the maturation intermediate p15NC must interact with RNA for efficient cleavage by the PR. We investigated this phenomenon and found that processing of multiple substrates by the HIV-1 PR was enhanced in the presence of RNA. The acceleration of proteolysis occurred independently from the substrate's ability to interact with nucleic acid, indicating that a direct interaction between substrate and RNA is not …
A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance,
2016
University of Massachusetts Medical School
A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon
Celia A. Schiffer
The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, …
Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172,
2016
University of Massachusetts Medical School
Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer
Celia A. Schiffer
Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound …
Dietary Supplementation With Organoselenium Accelerates Recovery Of Bladder Expression, But Does Not Improve Locomotor Function, Following Spinal Cord Injury,
2016
University of Kentucky
Dietary Supplementation With Organoselenium Accelerates Recovery Of Bladder Expression, But Does Not Improve Locomotor Function, Following Spinal Cord Injury, Carolyn A. Meyer, Ranjana Singh, Mackenzie T. Jones, Chen-Guang Yu, Ronan F. Power, James W. Geddes
Spinal Cord and Brain Injury Research Center Faculty Publications
Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. …
The Real Footprint Of Electric Vehicles, And What That Could Mean For Our Future,
2016
Colby College
The Real Footprint Of Electric Vehicles, And What That Could Mean For Our Future, Krista Brown
Journal of Environmental and Resource Economics at Colby
This paper looks at the impact of electric vehicles on CO2 emissions specifically based on the type of electricity used in each New England state analyzed. The research looks at the question of whether or not emissions will in fact be lowered as electric cars start to take the majority of vehicles used instead of the conventional cars that take up a much larger percent of the motor vehicles used today. Taking into account the use of electricity and how many sources of electricity also release a substantial amount of emissions, we see how valid the public opinion of electric …
The Effect Of Information On Avoidance Behavior And Bicycle Transportation: A Study Of “Spare The Air” And Bay Area Bikeshare,
2016
Colby College
The Effect Of Information On Avoidance Behavior And Bicycle Transportation: A Study Of “Spare The Air” And Bay Area Bikeshare, Paige W. Whistler
Journal of Environmental and Resource Economics at Colby
This paper seeks to address the effect of “Spare the Air” pollution control alerts in the San Francisco Bay Area in California on the use of Bay Area BikeShare as a form of transportation. By observing the daily alerts on the duration of rides using BikeShare, this paper observes if STA ozone alerts are effective in changing human behavior. The results show that only as a subscriber to the BikeShare program and on an alert day does duration decrease whereas customers regardless of if it is an alert day will ride more often and at longer distances. The results contradict …
Socioeconomic Attributes’ Relationship To Green Commercial Office Buildings,
2016
Colby College
Socioeconomic Attributes’ Relationship To Green Commercial Office Buildings, Tianyang Zhou
Journal of Environmental and Resource Economics at Colby
This paper examines the relationship between the socioeconomic attributes of a state and its green commercial office space adaptation. I hypothesize that a state with high socioeconomic status will have a high green building adoption. Additionally, the high socioeconomic status states may be more likely to invest in green commercial buildings with higher LEED certification levels, and various types of LEED commericial office projects are affected by the socoeconomic attributes differently.
Do Peers Get Punished: Stock Market Effect Of Bp Oil Spill On Peers,
2016
Colby College
Do Peers Get Punished: Stock Market Effect Of Bp Oil Spill On Peers, Yuga Koda
Journal of Environmental and Resource Economics at Colby
This paper examines the stock market reaction to the British Petroleum oil spill on April 20, 2010. This event study looks at different sectors that may be affected by the oil spill. It finds that different industries do not have significant abnormal returns, with two exceptions. First, utilities companies have a very small positive abnormal return for a short period of time after the incident. Second, when only looking at BP's direct competitors, there is a statistically significant negative abnormal return, implying that BP's competitors are punished for BP's mishap.
Media Effects On Solar Panel Installations Across 20 States,
2016
Colby College
Media Effects On Solar Panel Installations Across 20 States, Casey Romeo
Journal of Environmental and Resource Economics at Colby
This paper looks at the relationship between media coverage of solar power and the solar panel installation at a state level. Specifically, it aims to find if more newspaper articles cause more households to adopt solar energy. Use data from 20 states from 2009 to 2014. I find that there is a modest, yet positive and statistically significant relationship between newspaper articles and installations, which suggests that the media does influence the decision to install solar panels. There is possible endogeneity between these two variables. Disentangling this endogeneity is beyond the scope of this research and would be a topic …
Renewable Energy Consumption: Initiatives In Colorado And Washington,
2016
Colby College
Renewable Energy Consumption: Initiatives In Colorado And Washington, Robin K. Doroff
Journal of Environmental and Resource Economics at Colby
This paper examines the use of policy mechanisms to increase renewable energy consumption within the United States. In order to effectively measure the change of renewable energy consumption, I analyze two initiatives that promote energy consumption from renewable sources and overall increases in energy conservation. Colorado and Washington had approved initiatives in the years 2004 and 2006, respectively. Although the results are not entirely statistically significant, I find that the initiatives lead to increases in total renewable energy consumption and decreases in total energy use.
Stock Market Reactions To The Iarc Announcement Linking Red Meat And Processed Meat To Cancer,
2016
Colby College
Stock Market Reactions To The Iarc Announcement Linking Red Meat And Processed Meat To Cancer, Scott B. Lehman
Journal of Environmental and Resource Economics at Colby
This study investigates how food companies were affected by the International Agency for Research on Cancer’s report that linked processed meat and red meat consumption to increased risk of cancer. The results indicate that neither fast food companies nor meat producers were greatly affected by the announcement in the days immediately following the release.
Property Value Changes From Public Transportation: How The Greenbush Commuter Line Affected Property Values,
2016
Colby College
Property Value Changes From Public Transportation: How The Greenbush Commuter Line Affected Property Values, Sarah C. Evans
Journal of Environmental and Resource Economics at Colby
Prior studies have investigated the impact on property values to the proximity of established public transportation stations. Public transportation is thought to increase value of towns and properties, giving residents more options for transportation to and around the city. Both benefits and consequences of public transportation exist, allowing for either a raise or lower of property values in towns with stops. This paper analyzes the Greenbush Commuter line in Massachusetts, seeing if the proximity to the stops has an affect on the property of values in the towns. A difference – in – difference model is used to investigate a …
The Effectiveness Of The Colby College Electricity Competition On Promoting Electricity Conservation To Students,
2016
Colby College
The Effectiveness Of The Colby College Electricity Competition On Promoting Electricity Conservation To Students, Jeff Vaz
Journal of Environmental and Resource Economics at Colby
This paper examines the effectiveness of the Colby College electricity reduction competition in altering students’ behavior to conserve electricity. The Colby College electricity reduction competition is an information-based policy that Colby implemented to promote the conservation of electricity, which are a major contributor to greenhouse gas (GHG) emissions in the United States. The study analyzes if different residence halls reduce electricity consumption by different amounts during the competition period. Results indicate that only 4 of 22 residence halls reduced electricity usage during competition periods in a statistically significant manner. The study concludes that the electricity competition at Colby College is …
Invited Introduction To Jerec,
2016
Yale University and NBER
Invited Introduction To Jerec, Matthew Kotchen
Journal of Environmental and Resource Economics at Colby
No abstract provided.
Welcome By The Editor,
2016
Colby College
Welcome By The Editor, Nathan W. Chan
Journal of Environmental and Resource Economics at Colby
No abstract provided.
Investigating The Suitability Of The Crayfish Metabolome As A Bioindicator Of Stream Conditions,
2016
The University of Western Ontario
Investigating The Suitability Of The Crayfish Metabolome As A Bioindicator Of Stream Conditions, Natalie M. Izral
Electronic Thesis and Dissertation Repository
The suitability of the crayfish metabolome as a bioindicator of stream conditions was investigated because there is a need for fast responding, sensitive, diagnostic, and ecologically relevant bioindicators. A laboratory study assessed Procambarus clarkii metabolome sensitivity to six different treatments of food or DO stress. A field study in subcatchments of the Red River Valley, Manitoba, Canada assessed the effects of land-use type (reference, agriculture, wastewater effluent) on the Orconectes virilis metabolome. Crayfish were sacrificed, and hepatopancreas, gill, and tail tissues were dissected. Analyses found the metabolome was sensitive enough to potentially diagnose food and DO stress in P. clarkii …
Drug Eluding Stents For Malignant Airway Obstruction: A Critical Review Of The Literature,
2016
University of Erlangen
Drug Eluding Stents For Malignant Airway Obstruction: A Critical Review Of The Literature, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Georgia Pitsiou, Bernd Linsmeier, Drosos Tsavlis, Ioannis Kioumis, Eleni Papadaki, Lutz Freitag, Theodora Tsiouda, J. Francis Turner, Robert Browning, Michael Simoff, Nikolaos Sachpekidis, Kosmas Tsakiridis, Bojan Zaric, Lonny Yarmus, Sofia Baka, Grigoris Stratakos, Harald Rittger
Internal Medicine Faculty Publications
Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin …
Novel Approaches For Assessment Of Copper Toxicity: Fast Scan Cyclic Voltammetry And Optical Bioassays,
2016
Wayne State University
Novel Approaches For Assessment Of Copper Toxicity: Fast Scan Cyclic Voltammetry And Optical Bioassays, Annette R. Tremonti
Wayne State University Dissertations
Anthropogenic activities negatively impact fresh water ecosystems through toxic contaminants that are released into the environment. Copper (Cu) is a water contaminant that is fundamentally persistent once introduced into the environment that has the potential for bioaccumulation. Although Cu toxicity has been studied for decades, there is still a continuing problem with new sources and pathways. New approaches are needed to understand distribution and transport of Cu and its potential for complex biological impacts beyond the simple assessment of lethality. Several novel approaches were used in this research project to advance our understanding of Cu toxicity, including fast scan cyclic …
Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents,
2016
Trinity College Dublin, Ireland
Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle
Articles
Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …
