Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS -generating agents

A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2·− ), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2·− is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2·− and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2·−, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells. ^

Grand concertante duet : for harp & piano forte on a favorite Irish and Neapolitan air /

Mode of access: Internet.

The epidemic threshold and contact number with implications for optimal vaccination strategies /

Thesis (Ph.D.)--Cornell University, May, 2000.

Progressive architecture.

Editor: 1920-Oct. 1925, Eugene Clute.--Nov. 1925- R.F. Whitehead (with Kenneth Reid, Elizabeth L. Cleaver, June 1926-Jan. 1933)

School of Nursing Class of 2008

Top Row: Therese Adamowski, Anel Adamson, Michelle Ahleman, Brooke Babineau, Jennifer Ballough, Lisa Anne Beckman, Jennifer Bergeren, Tedra Boedigheimer, Mary Bonner, Genevieve Bott, Megan Bouwhuis, Mitchell Bradley, Rachel Brown, Katherine Bulson, Jennifer Calhoun, Carley Cebelak, Sarah Choinard

Row 2: Sarah Clevenger, Elizabeth Anne Conway, Erin Coughlin, Karie Curtis, Stephanie Curtis, Jodi Danhof, Rebecca Debri, Stacie Deleszek, Andrea Dehline, Amanda Devlin, Charlotte Dietrich, Angela Dodge, Elizabeth Dougherty, Ashley Doyle, Lindsay Driver, Nancy Duckworth, Kathy Dunnuck, Jennifer Dziadaio, Ellen English

Row 3: Kelly Esser, Amanda Fender, Lindsey Smith, Andrew Bradburn, Fallon Garfield Turner, Margaret Dembeck, Courtney Van Essen, Jessica paige Smith, Lauren Inouye, Jacqueline Dufek, Emily Klump, Amanda Jones, Tiffany Burrell, Deborah Mitchell, Emily Michel, Michelle Steen, Kirsten Thulin, Emily Hautamaki, Sheila Fender, Keith Ferguson

Row 4: Annie Fields, Jillian Fisher, Erin Flatley, Renee Forma, Aileen Franchi, Lindsey Freysinger, Sarah Fulgenzi, Beth Funnell, Andrea Galaviz, Lacey Garbo, Katherine Garcia, Lynn Garofalo

Row 5: Heather Gehrke, Nicole Genrich, Katie Giordano, Lindsey Glover, Andrea Godfrey, Jocelyn Gossman, Alana Greenberg, Julien Guttman, Sarah Halfmann, Kimberly Hanger, Allison Hanson, Stephanie Hecklin

Row 6: Geri Helminiak, Kristi Hershiser, Erin Hipp, Amanda Hoath, Tracy Hurlbutt, Nadya Indrei, Nisa Joorabchi, Katy Kerrigan, Layne Kiella, Jessica Kim, Samantha Klaiman, Jodi Knight, Laura Kovacic, Alicia Kreger

Row 7: Amanda Kretsch, Kimberly Kurzeja, Julie Lamonoff, Sarah Leirstein, Ashley Labb, Suzanne Loeb, Alessandra Lollini, Heather Loomis, Caroline Luke, Stephanie Maniquis, Elizabeth Mann, LaTasha Marable, Amanda McAdams, Mara McKinley

Row 8: Leah McLaughlin, Erin Migda, Scott Migut, Joane Nwoke, Lazarus Okammor, Brittany Pajewski, Judith Lynch-Sauer, Patricia Coleman-Burns, Bonnie Hagerty, Kathleen Potempa, Carol Loveland-Cherry, Carolyn Sampselle, Joanne Pohl, Sarah Pajtas, Maria Paneda, Jennifer Parker, Carol Peterson, Kimberley Peven, Rachel Poterek, Sarah Poucher

Row 9: Jannet Provost, Jessica Quigley, Nicole Rasmuson, Joanthan Reed, Sharon Reske, John Reves, Amy Riebe, Sara Riegner, Kelly Risicato, Christine Sabado, Stephanie Sargent, Jolene Schaefer, Erin Schroeder, Catherine Scott, Katherine See, Andrea Semaan, Jessica Shantz, Kathryn Sibbold, Kathleen Skendrovic, Aaron Smith, Elizabeth Stanton

Row 10: Mary Stewart, Ashley Strotbaum, Danielle Swartz, Janet Trost, Elizabeth Underwood, Lauren Underwood, Allison Vanhall, Brian Velker, Kristen Wells, Ryan Werblow, Jennifer Werden, David Westrin, Mallory Wiesen, Karen Wingrove, Amy Wright, Carrie Wright, Emily Wright, Minou Xie, Charles Zimmerman

Herbivore and nutrient impact on primary producer assemblages in a tropical marine environment

Globally, human populations are increasing and coastal ecosystems are becoming increasingly impacted by anthropogenic stressors. As eutrophication and exploitation of coastal resources increases, primary producer response to these drivers becomes a key indicator of ecosystem stability. Despite the importance of monitoring primary producers such as seagrasses and macroalgae, detailed studies on the response of these benthic habitat components to drivers remain relatively sparse. Utilizing a multi-faceted examination of turtle-seagrass and sea urchin-macroalgae consumer and nutrient dynamics, I elucidate the impact of these drivers in Akumal, Quintana Roo, Mexico. In Yal Ku Lagoon, macroalgae bioindicators signified high nutrient availability, which is important for further studies, but did not consistently follow published trends reflecting decreased δ 15N content with distance from suspected source. In Akumal Bay, eutrophication and grazing by turtles and fishes combine to structure patches within the seagrass beds. Grazed seagrass patches had higher structural complexity and productivity than patches continually grazed by turtles and fishes. Results from this study indicate that patch abandonment may follow giving-up density theory, the first to be recorded in the marine environment. As Diadema antillarum populations recover after their massive mortality thirty years ago, the role these echinoids will have in reducing macroalgae cover and altering ecosystem state remains to be clear. Although Diadema antillarum densities within the coral reef ecosystem were comparable to other regions within the Caribbean, the echinoid population in Akumal Bay was an insufficient driver to prevent dominance of a turf-algal-sediment (TAS) state. After a four year study, declining coral cover coupled with increased algal cover suggests that the TAS-dominated state is likely to persist over time despite echinoid recovery. Studies on macroalgal diversity and nutrients within this same region of echinoids indicated diversity and nutrient content of macroalgae increased, which may further increase the persistence of the algal-dominated state. This study provides valuable insight into the variable effects of herbivores and nutrients on primary producers within a tropical coastal ecosystem. Results from this work challenge many of the currently accepted theories on primary producer response to nutrients and herbivory while providing a framework for further studies into these dynamics.

Mitigating Social Risk in the Extractive Sector: Developing Intercultural Competence as a Tool for Negotiating Western-Indigenous Perspectives within the Undergraduate Mining Engineering Curriculum

Drawing upon critical, communications, and educational theories, this thesis develops a novel framing of the problem of social risk in the extractive sector, as it relates to the building of respectful relationships with indigenous peoples. Building upon Bakhtin’s dialogism, the thesis demonstrates the linkage of this aspect of social risk to professional education, and specifically, to the undergraduate mining engineering curriculum, and develops a framework for the development of skills related to intercultural competence in the education of mining engineers. The knowledge of social risk, as well as the level of intercultural competence, of students in the mining engineering program, is investigated through a mixture of surveys and focus groups – as is the impact of specific learning interventions. One aspect of this investigation is whether development of these attributes alters graduates’ conception of their identity as mining engineers, i.e. the range and scope of responsibilities, and understanding of to whom responsibilities are owed, and their role in building trusting relationships with communities. Survey results demonstrate that student openness to the perspectives of other cultures increases with exposure to the second year curriculum. Students became more knowledgeable about social dimensions of responsible mining, but not about cultural dimensions. Analysis of focus group data shows that students are highly motivated to improve community perspectives and acceptance. It is observed that students want to show respect for diverse peoples and communities where they will work, but they are hampered by their inability to appreciate the viewpoints of people who do not share their values. They embrace benefit sharing and environmental protection as norms, but they mistakenly conclude that opposition to mining is rooted in a lack of education rather than in cultural values. Three, sequential, threshold concepts are identified as impeding development of intercultural competence: Awareness and Acknowledgement of Different Forms of Knowledge; Recognition that Value Systems are a Function of Culture; Respect for varied perceptions of Social Wellbeing and Quality of Life. Future curriculum development in the undergraduate mining engineering program, as well as in other educational programs relevant to the extractive sector, can be effectively targeted by focusing on these threshold concepts.

What Drives Parental Concerns about their 18-Month-Olds at Familial Risk for Autism Spectrum Disorder?

Thesis (Master's)--University of Washington, 2016-08

Descendants of Richard and Elizabeth (Ewen) Talbott of Poplar Knowle, West River, Anne Arundel County, Maryland /

Edition of 350 copies. No. 170.

Quarter sessions from Queen Elizabeth to Queen Anne; illustrations of local government and history, drawn from original records (chiefly of the county of Devon)

Mode of access: Internet.

Elizabeth Reid, Delegate from Australia at UN women demonstration

General note: Title and date provided by Bettye Lane.

Three Hundred Years in Annapolis: Phase III Archaeological Investigations of the Anne Arundel County Courthouse Site (18AP63), Annapolis, Maryland

During the summer of 1994, Archaeology in Annapolis conducted archaeological investigations of the city block bounded by Franklin, South and Cathedral Streets in the city of Annapolis. This Phase III excavation was conducted as a means to identify subsurface cultural resources in the impact area associated with the proposed construction of the Anne Arundel County Courthouse addition. This impact area included both the upper and lower parking lots used by Courthouse employees. Investigations were conducted in the form of mechanical trenching and hand excavated units. Excavations in the upper lot area yielded significant information concerning the interior area of the block. Known as Bellis Court, this series of rowhouses was constructed in the late nineteenth century and was used as rental properties by African-Americans. The dwellings remained until the middle of the twentieth century when they were demolished in preparation for the construction of a Courthouse addition. Portions of the foundation of a house owned by William H. Bellis in the 1870s were also exposed in this area. Construction of this house was begun by William Nicholson around 1730 and completed by Daniel Dulany in 1732/33. It was demolished in 1896 by James Munroe, a Trustee for Bellis. Excavations in the upper lot also revealed the remains of a late seventeenth/early eighteenth century wood-lined cellar, believed to be part of the earliest known structure on Lot 58. After an initially rapid deposition of fill around 1828, this cellar was gradually covered with soil throughout the remainder of the nineteenth century. The fill deposit in the cellar feature yielded a mixed assemblage of artifacts that included sherds of early materials such as North Devon gravel-tempered earthenware, North Devon sgraffito and Northem Italian slipware, along with creamware, pearlware and whiteware. In the lower parking lot, numerous artifacts were recovered from yard scatter associated with the houses that at one time fronted along Cathedral Street and were occupied by African- Americans. An assemblage of late seventeenth century/early eighteenth century materials and several slag deposits from an early forge were recovered from this second area of study. The materials associated with the forge, including portions of a crucible, provided evidence of some of the earliest industry in Annapolis. Investigations in both the upper and lower parking lots added to the knowledge of the changing landscape within the project area, including a prevalence of open space in early periods, a surprising survival of impermanent structures, and a gradual regrading and filling of the block with houses and interior courts. Excavations at the Anne Arundel County Courthouse proved this to be a multi-component site, rich in cultural resources from Annapolis' Early Settlement Period through its Modern Period (as specified by Maryland's Comprehensive Historic Preservation Plan (Weissman 1986)). This report provides detailed interpretations of the archaeological findings of these Phase III investigations.

Anne McPherson family fonds, 1852-2011 [non-inclusive]

Frank C. (Case) McCordick (1873-1946) was the son of William Henry (1849-1930) and Emily D. Howell (1851-1927) McCordick. William H. McCordick was in the coal business. The McCordick family included Frank Case, Mabel Gertrude, Ethel Howell and Arthur Stanley. Frank C. McCordick was educated in St. Catharines, and worked with his father in the coal business and eventually opened up a leather tanning operation. McCordick was active in the Lincoln Regiment and in 1906 was promoted to captain and in command of Company A, 19th Regiment. He was promoted to major and at the outbreak of war he was sent overseas as a commander of the 35th Battalion of the Canadian Expeditionary Forces (CEF). Upon arrival in France he was made officer commanding the 15th Battalion, King’s Own Yorkshire Light Infantry (KOYLI). After the war and his return to Canada he continued to play an active role in the local military units in the area as well as in Hamilton. After his retirement from the military in 1927 McCordick served as alderman and then mayor of St. Catharines from 1930 to 1931. He was a member of a large number of civic clubs, including St. Catharines Chamber of Commerce, Y.M.C.A., Lion’s Club, St. Catharines Golf Club, Detroit Boat Club, the St Catharines Club, as well as a member of several Masonic lodges. He continued to operate McCordick Tannery and other local investments. In 1903 Frank C. McCordick married May Beatrice Simson, daughter of Thomas E. Simson of Thorold. They had three children, E. (Edward) Frank McCordick, Bruce McCordick and (Margaret) Doris McCordick (m. Hubert Grigaut, d. 1977). The McCordick family resided at 82 Yates Street, near Adams Street. May Simson McCordick (b. 1873) was the daughter of Thomas Edward (1836-1908) and Julia Headlam (1844-1887) Simson of Thorold. Her siblings included: Edward, Frances, John, Augusta, Georgia and Gertrude. E. (Edward) Frank McCordick (1904-1980) was born in St. Catharines, Ont., attended Lake Lodge School in Grimsby, Ridley College in St. Catharines, Beechmont Preparatory School in England, Upper Canada College in Toronto and graduated from Royal Military College in Kingston, Ont. in 1925. Upon graduation he was made a lieutenant in the 10th (St. Catharines) Field Battery. In 1929 he married Helen Stanley Smith, daughter of Stanley George and Mary Walker Smith of St. Catharines. Col. McCordick, now promoted to Major, played an active role in the 10th (St. Catharines) Field Battery, being officer commanding the battery. In late 1939 McCordick headed to England for artillery tactical training and on December 6, 1939 the battery began the long trek overseas. McCordick saw action in Italy and in Holland. Upon his return to Canada at the end of the war he was the Liberal candidate in the federal election for Lincoln County. He remained active in the local military serving as honorary lieutenant-colonel of the 56th Field Regiment (ARCA) and in 1976 as the honorary colonel of the regiment. Col. McCordick held the Efficiency Decoration, the Order of the British Empire, granted in 1945 and was made an officer in the Order of St. John in 1978. He continued to serve his community in various capacities, including the Unemployment Insurance Canada Board, Royal Trust Company and the St. John Ambulance Society. He remained an active member of the alumni of Royal Military College, editing and compiling a newsletter and organizing reunion weekends. He kept in close contact with many of his classmates. Helen Stanley Smith McCordick lived in St. Catharines, Ont., attended Robertson School, and graduated from the University of Toronto in 1926 with a Bachelor of Arts degree in Modern Languages. During the war years (1939-1945) Helen was active in the Transport division of the local branch of the Canadian Red Cross and the Women’s Auxiliary of the 10th Field Battery. In 1932 E. Frank and Helen McCordick welcomed their only child, (Catharine) Anne McCordick. Helen continued to play an active role in her community until her passing in 1997. Stanley George Smith (1865-1960) was born in St. Catharines, Ont., the only child of William Smith (d. June 16, 1876) a native of Edinburgh, Scotland and his wife Hannah Louisa Maria Bulkeley a native of Fairfield, Connecticut. Stanley George Smith married Mary Walker of Guelph, Ont.(d. 1956) Mary was the daughter of Hugh and Elizabeth (d. 1924) Walker. Her siblings included Margaret, Agnes, Jessie, Isabella, Lorne, Ada, Alice, Eva, Alexander and George. Hugh Walker was a prominent fruit and vegetable merchant in Guelph. On 1904 their only child, Helen Stanley Smith was born. He was a post office clerk, and the treasurer for the James D. Tait Co. Ltd., a clothing and dry goods retailer in St. Catharines. The family lived at 39 Church Street in St. Catharines, Ont.

Ethics at War: Review of Elizabeth Scannell-Desch and Mary Ellen Doherty, Nurses in War: Voices from Iraq and Afghanistan

Compte-rendu / Review