Photograph - Dorothy Rungeling and others at Airplane Hangar

A photograph of five men and Dorothy Rungeling standing at the entrance of an airplane hangar.

UNDERSTANDING THE RELATIONSHIP BETWEEN ONCOLYTIC AD5 DELETED E1b55KDA LYTIC INFECTION AND P53 IN MAMMALIAN CELLS

Adenoviruses are the most commonly used in the development of oncolytic therapy. Oncolytic adenoviruses are genetically modified to selectivity replicate in and kill tumor cells. The p53 molecule is a tumor suppressor protein that responds to viral infection through the activation of apoptosis, which is inhibited by adenovirus E1B55kDa protein leading to progressive viral lytic cycle. The non-specificity of replication has limited the use of wild type adenovirus in cancer therapy. This issue was resolved by using an E1b deleted Ad that can only replicate in cells with a deficiency in the p53 protein, a common feature of most cancer cells. Although demonstrating a moderate success rate, E1b55kDa deleted Ad has not been approved as a standard therapy for all cancer types. Several studies have revealed that E1b deleted Ad replication was independent of p53 status in the cell, as the virus replicated better in some p53 deficient cancers more than others. However, this mechanism has not been investigated deeply. Therefore, the objective of this study is to understand the relationship between p53 status, levels and functional activity, and oncolytic Ad5dlE1b55kDa replication efficiency. Firstly, five transient p53 expression vectors that contain different regulatory elements were engineered and then evaluated in H1299, HEK293 and HeLa cell lines. Data indicated that vector that contains the MARs and HPRE regulatory elements achieved the highest stability of p53 expression. Secondly, we used these vectors to examine the effect of various p53 expression levels on the replication efficiency of oncolytic Ad5dlE1b55kDa. We found that the level of p53 in the cell had an insignificant effect on the oncolytic viruses’ replication. However, the functional activity of p53 had a significant effect on its replication, as Ad5dlE1b55kDa was shown to have selective activity in H1299 cells (p53-null). In contrast, a decrease in viral replication was found in HeLa cells (p53-positive). Finally, the effect of p53’s functional activity on the replication efficiency of oncolytic Ad5dlE1b55kDa was examined. Viral growth was evaluated in H1299 cells expressing number of p53 mutants. P53-R175H mutant successfully rescued viral growth by allowing the virus to exert its mechanism of selectivity. The mechanism entailed deregulating the expression of specific genes, cell cycle and apoptosis, in the p53 pathway to promote its production leading to efficient oncolytic effect. These results confirmed that oncolytic Ad5dlE1b55kDa sensitivity is mutation-type specific. Therefore, before it is applied clinically as cancer therapy for p53 deficient tumors, the type of p53 mutation must be determined for efficient antitumor effect.

Photograph - Samuel DeVeaux Woodruff in Uniform with others

A photograph of Samuel Deveaux Woodruff in uniform, standing in a garden with three women and a man.

Photograph - Percy Band and others

A photograph of Percy Band and two other men and one woman. They are outside in a field.

Photograph - Percy Band Hunting with others

A photograph of Percy Band with a group of men with a pack of hunting dogs.

Photograph - Percy Band Hunting with others #2

Another photograph of the Percy Band with a group of hunters.

Photograph - Percy Band and others on a Boat

A photograph of Percy Band and two other men on a boat. There are two small children sitting with the men in the boat.

Photograph - Percy Band and Two others

A photograph of Percy Band and two other men. They are dressed in suits and standing together next to a house in the garden.

Psychopathy and the Ability to Detect Cheaters: An Evolutionary Perspective

This research examined psychopathy as an evolutionary adaptation that involves cheating and deception. I theorized that this strategy should be associated with certain abilities. This research examined the association between psychopathic traits and the ability to detect cheaters, altruism, deception, and psychopathic traits. Results indicated that psychopathic traits were not significantly associated with the ability to detect cheaters or altruism. Results indicated that high Factor 1 psychopathy scores, and low Factor 2 psychopathy scores, were indicative of higher ratings of deception when viewing deceptive videos. Conversely, when viewing truthful videos, Factor 1 was a significant predictor of higher ratings of deception. Finally, our results indicated that total psychopathy scores were associated the ability to identify psychopathic traits in others. Taken together the results provide mixed support for the evolutionary perspective of psychopathy.

Indenture of Release between Richard Miller and others

Indenture of release by executors between Richard Miller, John L. Ranney and Richard Woodruff, all of St. Catharines and Joseph A. Woodruff of Clifton, all executors of the will of Samuel Zimmerman of the first part and The Great Western Railway Company of the second part. Parties of the second part have exonerated parties of the first part to undertake and complete the Sarnia branch of the railway. Also, parties of the first part believe they are entitled to compensation as the death of Zimmerman was caused while travelling on one of the carriages belonging to said company. A sum of $150,000 was agreed upon to be paid to the executors by the Great Western Railway Company, September 7, 1858.