Indenture of Land between Joseph Kingsmill, sheriff and Joseph Augustus Woodruff of the Town of Clifton

Indenture of between Joseph Kingsmill, sheriff and Joseph Augustus Woodruff of the Town of Clifton for 4 acres of land in part of Lot no. 12 in the 5th Concession of Wainfleet – instrument no. 9998, May 23, 1857.

Indenture of assignment of mortgage between Executors of the Zimmerman Estate and the Bank of Upper Canada

Indenture of assignment of mortgage between Executors of the Zimmerman Estate and the Bank of Upper Canada regarding Lot no. 4 in block O in the Town of Elgin – instrument no. 6360, May 14, 1858.

Indenture of bargain and sale between Frederic and Laura Charlotte Davis of the Town of Sarnia to Joseph A. Woodruff of the Town of Clifton

Indenture of bargain and sale between Frederic and Laura Charlotte Davis of the Town of Sarnia to Joseph A. Woodruff of the Town of Clifton for Lot no. 28 on the east side of Front Street in Sarnia. This document is slightly torn. This does not affect the text, Jan. 26, 1859.

Indenture of deed for taxes between Benjamin Walker Smith, sheriff of the County of Simcoe and Joseph A. Woodruff of the Town of Clifton

Indenture of deed for taxes between Benjamin Walker Smith, sheriff of the County of Simcoe and Joseph A. Woodruff of the Town of Clifton for 98 acres in the Township of Tiny in the County of Simcoe, Lot no. 15 in the 18th Concession, Dec. 12, 1861.

Indenture of bargain and sale between Henry and Mary Miller of the Town of Niagara to Joseph Augustus Woodruff of the Town of Niagara

Indenture of bargain and sale between Henry and Mary Miller of the Town of Niagara to Joseph Augustus Woodruff of the Town of Niagara for 50 acres in the east half of Lot no. 15 in the 1st Concession in the Township of Southwold in Elgin County, April 2, 1853.

Indenture between William Dickson and Thomas Clark

Indenture between William Dickson and Thomas Clark (as per the Last Will and Testament of Robert Hamilton) of Niagara to Joseph Gatehill of Grimsby for the Lot lettered G in the Town of Grimsby. The document is torn and slightly stained. This does not affect the text, Aug. 19, 1819.

Indenture of sale (memorial) between the Honourable William Dickson of Galt and A. E. Godfrey of Dumphries

Indenture of sale (memorial) between the Honourable William Dickson of Galt and A. E. Godfrey of Dumphries for 40 acres in Lot no. 37 in the Township of Dumphries. A portion of the lower right hand side of this document is missing. This affects the signatures, April 11, 1829.

Indenture of bargain and sale between Walter Hamilton Dickson and Augusta Maria Dickson of Niagara to Jane Dickson (widow of Robert Dickson), Thomas Clark Street of Stamford and Edward Clarke Campbell of Niagara

Indenture of bargain and sale between Walter Hamilton Dickson and Augusta Maria Dickson of Niagara to Jane Dickson (widow of Robert Dickson), Thomas Clark Street of Stamford and Edward Clarke Campbell of Niagara for 150 acres for the south half of Lot no. 32 in the 7th concession and the north east quarter of Lot no. 22 in the 10th Concession of Dumphries. This was recorded in the County of Halton on the 29th day of January, 1849 in Folio 326, memorial 236, Jan. 12, 1849.

Indenture between James Reid and James Henderson of Toronto

Indenture between James Reid and James Henderson of Toronto for 200 acres on Lot no. 10 in the 19th Concession in the Township of Tiny in Simcoe County. This document is dated Aug. 4, 1854. It is attached to another indenture between James Henderson of Toronto and The Honourable Walter H. Dickson for the aforesaid land. The second document is torn. This does not affect the text, Jan. 1, 1857.

Province of Upper Canada Grant (vellum) to Thomas Fraser of the Township of Edwardsburgh granted 1 acre in Lot no.9 in the County of Stormont

Province of Upper Canada Grant (vellum) to Thomas Fraser of the Township of Edwardsburgh granted 1 acre in Lot no.9 in the County of Stormont. Signed by William Jarvis, Sir Isaac Brock, Prideaux Selby and John Macdonell. There are some holes in the document and there are small pieces missing on the right hand side. William Jarvis was the Provincial Secretary of the Lt. Governor of Upper Canada; Sir Isaac Brock. Jarvis was an officer in the Queen’s Rangers. He also served as Provincial Secretary of Upper Canada. A partial crown seal is attached, Mar. 26, 1812.

Some Incidents and Circumstances

- The first part of the document traces Mr. Haile’s lineage. His father, James Haile was a farmer. His grandfather, Amos Haile was a sailor for the early part of his life. He was placed on a British man-of- war in about 1758. He escaped and settled in Putney. (p.1) - His father’s mother’s maiden name was Parker. His mother’s maiden name was Campbell. Her father was a captain in the Revolutionary Army. (p.2) - His earliest memories revolve around the death of his aunt and the funeral of General Washington (although he did not witness this). At the time, his father was a Lieutenant in a regiment militia of Light Dragoons who wore red coats. (p.3) - In 1804, an addition was added to the Haile house which necessitated that William was to stay home to help with the building. He continued to study and read on his own. He was particularly interested in Napoleon Bonaparte’s victories. In that same year he was sent to Fairfield Academy where Reverend Caleb Alexander was the principal. (p.4) - On June 1, 1812, William was appointed as an Ensign in the Infantry of the Army of the United States. He was put into the recruiting service at Nassau (20 miles east of Albany) where he remained until September. (p.4) - He was assigned to the 11th Regiment of the W.S. Infantry and directed to proceed to Plattsburgh to report to Colonel Isaac Clark. (p.7) - He was assigned to the company commanded by Captain Samuel H. Halley who was not in the best of health and often absent. For a good part of the time William was in charge of the company. (p.8) - The 11th Regiment was encamped beside the 15th Regiment commanded by Col. Zebulon Montgomery Pike [Pike’s Peak was named after him]. Col. Pike generously drilled and disciplined the 11th Regiment since their officers didn’t seem capable of doing so. (p.8) - The first brigade to which William’s regiment was attached to was commanded by Brigadier General Bloomfield of New Jersey. Brigadier Chandler of Maine commanded the second brigade. (p.9) - At the beginning of November, Major General Dearborn took command of the army. He had been a good officer in his time, but William refers to him as “old and inefficient” earning him the nickname “Granny Dearborn” (p.9) - On November 17th, 1812, General Dearborn moved north with his army. The troops ended up in Champlain. There was no fighting, only a skirmish between a party of men under Colonel Pike and a few British troops who he succeeded in capturing. (p.10) - The troops were moved to barracks for the winter. Colonel Pike’s troops were put into suitable barracks and kept healthy but another part of the army (including the 11th Regiment) were sent to a barracks of green lumber north of Burlington. Disease soon broke out in the damp barracks and the hundreds of deaths soon followed. One morning, William counted 22 bodies who had died the previous night. He puts a lot of this down to an inexperienced commanding officer, General Chandler. (p.11) - At the beginning of 1813, William was stationed as a recruiter on the shore of Shoreham across from Fort Ticonderoga. In February, he returned to Burlington with his recruits. In March he received an order from General Chandler to proceed to Whitehall and take charge of the stores and provisions. In April and May it was decided that his half of the regiment (the First Battalion) should march to Sackett’s Harbour, Lake Ontario. They arrived at Sackett’s Harbour about the 10th of June, a few days after the Battle of Sackett’s Harbour. (p.12) - He was camped near the site of Fort Oswego and got word to head back to Sackett’s Harbour. A storm overtook the schooner that he was on. (p.14) - William was involved in the Battle of Williamsburg (or Chrysler’s Farm) which he calls a “stupid and bungling affair on the part of our generals”.(p. 18) - General Covington was wounded and died a few days after the battle. (p.19) - William speaks of being ill. The troops were ordered to march to Buffalo, but he is able to go to his father’s house in Fairfield where his mother nursed him back to health (p.23) - Upon arrival at Buffalo, the “old fogy Generals” were replaced with younger, more efficient men. (p.25) - On page 27 he sums up a few facts: In 1812, the army was assembled on Lake Champlain with the intention of capturing Montreal, and then Quebec. That year, under General Dearborn the army marched as far as Champlain, then turned back and went into winter quarters. In 1813, the army was assembled at Sackett’s Harbour and that year the campaign ended at French Mills which was 70 or 80 miles from Montreal. In 1814, the army at Buffalo were some 400 miles from Montreal with still the same object in view. - He says that these facts make “a riddle – difficult to explain”. (p.27) - On the evening of July 2nd they embarked on the boats with the objective of capturing Fort Erie. The enemy were all made prisoners of war (p.27) - On July 4th they went to Street’s Creek, 2 miles above the Chippewa [Chippawa] River (p.28) - Page 29 is titled The Battle of Chippewa [Chippawa] - He speaks of 2 drummers who were fighting over the possession of a drum when a cannonball came along and took of both of their heads (p.29) - He proclaims that this was one of the “most brilliant battles of the war”. The battle was fought and won in less than an hour after they left their tents. He credits General Scott with this success and states that was due to his rapid orders and movements. (p.30) - The dead of the battle remained on the field during the night. He describes this as quite gloomy seeing friend and foe lying side by side. At daybreak they set to work digging trenches to bury the dead. (p.31) - Colonel Campbell was wounded and advised to have his leg amputated. He refused, and subsequently died. (p.32) - It is said that the British threw several of their dead into the river and they went over the Falls. (p.32) - His troops repaired the bridge over Chippawa which the enemy had partially destroyed and then pursued the British as far as Queenston Heights. (p.32) - On pages 33 and 34 he speaks about meeting an old friend of his, Philip Harter. - The account ends at Queenston Heights

What’s so Special About Cyberspace ? Reflections on Elkin-Koren And Salzberger

Un résumé en français est également disponible.

Regulation of the memory T cell development and islet beta-cell survival by DAPK-related apoptosis-inducing protein kinase 2 (Drak2)

Drak2 est un membre de la famille des protéines associées à la mort et c’est une sérine/thréonine kinase. Chez les souris mutantes nulles Drak2, les cellules T ne présentent aucune défectuosité apparente en apoptose induite par activation, après stimulation avec anti-CD3 et anti-CD28, mais ont un seuil de stimulation réduit, comparées aux cellules T de type sauvage (TS). Dans notre étude, l’analyse d’hybridation in situ a révélé que l’expression de Drak2 est ubiquiste au stade de la mi-gestation chez les embryons, suivie d’une expression plus focale dans les divers organes pendant la période périnatale et l’âge adulte, notamment dans le thymus, la rate, les ganglions lymphatiques, le cervelet, les noyaux suprachiasmatiques, la glande pituitaire, les lobes olfactifs, la médullaire surrénale, l’estomac, la peau et les testicules. Nous avons créé des souris transgéniques (Tg) Drak2 en utilisant le promoteur humain beta-actine. Ces souris Tg montraient des ratios normaux entre cellules T versus B et entre cellules CD4 versus CD8, mais leur cellularité et leur poids spléniques étaient inférieurs comparé aux souris de type sauvage. Après activation TCR, la réponse proliférative des cellules T Tg Drak2 était normale, même si leur production d’interleukine (IL)-2 et IL-4 mais non d’interféron-r était augmentée. Les cellules T Tg Drak2 activées ont démontré une apoptose significativement accrue en présence d’IL-2 exogène. Au niveau moléculaire, les cellules T Tg Drak2 ont manifesté une augmentation moins élevée des facteurs anti-apoptotiques durant l’activation; un tel changement a probablement rendu les cellules vulnérables aux attaques subséquentes d’IL-2. L’apoptose compromise dans les cellulesT Tg Drak2 a été associée à un nombre réduit de cellules T ayant le phénotype des cellules mémoires (CD62Llo) et avec des réactions secondaires réprimées des cellules T dans l’hypersensibilité de type différé. Ces résultats démontrent que Drak2 s’exprime dans le compartiment des cellules T mais n’est pas spécifique aux cellules T; et aussi qu’il joue des rôles déterminants dans l’apoptose des cellules T et dans le développement des cellules mémoires T. En outre, nous avons recherché le rôle de Drak2 dans la survie des cellules beta et le diabète. L’ARNm et la protéine Drak2 ont été rapidement induits dans les cellules beta de l’îlot après stimulation exogène par les cytokines inflammatoires ou les acides gras libres et qui est présente de façon endogène dans le diabète, qu’il soit de type 1 ou de type 2. La régulation positive de Drak2 a été accompagnée d’une apoptose accrue des cellules beta. L’apoptose des cellules beta provoquée par les stimuli en question a été inhibée par la chute de Drak2 en utilisant petit ARNi. Inversement, la surexpression de Drak2 Tg a mené à l’apoptose aggravée des cellules beta déclenchée par les stimuli. La surexpression de Drak2 dans les îlots a compromis l’augmentation des facteurs anti-apoptotiques, tels que Bcl-2, Bcl-xL et Flip, sur stimulation par la cytokine et les acides gras libres. De plus, les expériences in vivo ont démontré que les souris Tg Drak2 étaient sujettes au diabète de type 1 dans un modèle de diabète provoqué par de petites doses multiples de streptozotocine et qu’elles étaient aussi sujettes au diabète de type 2 dans un modèle d’obésité induite par la diète. Nos données montrent que Drak2 est défavorable à la survie des cellules beta. Nous avons aussi étudié la voie de transmission de Drak2. Nous avons trouvé que Drak2 purifiée pouvait phosphoryler p70S6 kinase dans une analyse kinase in vitro. Lasurexpression de Drak2 dans les cellules NIT-1 a entraîné l’augmentation de la phosphorylasation p70S6 kinase tandis que l’abaissement de Drak2 dans ces cellules a réduit la phosphorylation. Ces recherches mécanistes ont prouvé que p70S6 kinase était véritablement un substrat de Drak2 in vitro et in vivo. Cette étude a découvert les fonctions importantes de Drak2 dans l’homéostasie des cellules T et le diabète. Nous avons prouvé que p70S6 kinase était un substrat de Drak2. Nos résultats ont approfondi nos connaissances de Drak2 à l’intérieur des systèmes immunitaire et endocrinien. Certaines de nos conclusions, comme les rôles de Drak2 dans le développement des cellules mémoires T et la survie des cellules beta pourraient être explorées pour des applications cliniques dans les domaines de la transplantation et du diabète.

The Quest for Hegemony Among Countries and Global Pollution

This paper builds on the assumption that countries behave in such a way as to improve, via their economic strength, the probability that they will attain the hegemonic position on the world stage. The quest for hegemony is modeled as a game, with countries being differentiated initially only by some endowment which yields a pollution free flow of income. A country's level of pollution is assumed directly related to its economic strength, as measured by its level of production. Two types of countries are distinguished: richly-endowed countries, for whom the return on their endowment is greater than the return they can expect from winning the hegemony race, and poorly-endowed countries, who can expect a greater return from winning the race than from their endowment. We show that in a symmetric world of poorly-endowed countries the equilibrium level of emissions is larger than in a symmetric world of richly-endowed countries: the former, being less well endowed to begin with, try harder to win the race. In the asymmetric world composed of both types of countries, the poorly-endowed countries will be polluting more than the richly endowed countries. Numerical simulations show that if the number of richly-endowed countries is increased keeping the total number of countries constant, the equilibrium level of global emissions will decrease; if the lot of the poorly-endowed countries is increased by increasing their initial endowment keeping that of the richly-endowed countries constant, global pollution will decrease; increasing the endowments of each type of countries in the same proportion, and hence increasing the average endowment in that proportion, will decrease global pollution; redistributing from the richly-endowed in favor of the poorly-endowed while keeping the average endowment constant will in general result in an increase in the equilibrium level of global pollution.

Evaluation of oxytocin pharmacokinetic : pharmacodynamic profile and establishment of its cardiomyogenic potential in swine

La thérapie cellulaire est une avenue pleine de promesses pour la régénération myocardique, par le remplacement du tissu nécrosé, ou en prévenant l'apoptose du myocarde survivant, ou encore par l'amélioration de la néovascularisation. Les cellules souches de la moelle osseuse (CSMO) expriment des marqueurs cardiaques in vitro quand elles sont exposées à des inducteurs. Pour cette raison, elles ont été utilisées dans la thérapie cellulaire de l'infarctus au myocarde dans des études pre-cliniques et cliniques. Récemment, il a été soulevé de possibles effets bénéfiques de l'ocytocine (OT) lors d’infarctus. Ainsi, l’OT est un inducteur de différenciation cardiaque des cellules souches embryonnaires, et cette différenciation est véhiculée par la voie de signalisation du monoxyde d’azote (NO)-guanylyl cyclase soluble. Toutefois, des données pharmacocinétiques de l’OT lui attribue un profil non linéaire et celui-ci pourrait expliquer les effets pharmacodynamiques controversés, rapportés dans la lttérature. Les objectifs de ce programme doctoral étaient les suivants : 1) Caractériser le profil pharmacocinétique de différents schémas posologiques d'OT chez le porc, en développant une modélisation pharmacocinétique / pharmacodynamique plus adaptée à intégrer les effets biologiques (rénaux, cardiovasculaires) observés. 2) Isoler, différencier et trouver le temps optimal d’induction de la différenciation pour les CSMO porcines (CSMOp), sur la base de l'expression des facteurs de transcription et des protéines structurales cardiaques retrouvées aux différents passages. 3) Induire et quantifier la différenciation cardiaque par l’OT sur les CSMOp. 4) Vérifier le rôle du NO dans cette différenciation cardiaque sur les CSMOp. Nous avons constaté que le profil pharmacocinétique de l’OT est mieux expliqué par le modèle connu comme target-mediated drug disposition (TMDD), parce que la durée du séjour de l’OT dans l’organisme dépend de sa capacité de liaison à son récepteur, ainsi que de son élimination (métabolisme). D'ailleurs, nous avons constaté que la différenciation cardiomyogénique des CSMOp médiée par l’OT devrait être induite pendant les premiers passages, parce que le nombre de passages modifie le profile phénotypique des CSMOp, ainsi que leur potentiel de différenciation. Nous avons observé que l’OT est un inducteur de la différenciation cardiomyogénique des CSMOp, parce que les cellules induites par l’OT expriment des marqueurs cardiaques, et l'expression de protéines cardiaques spécifiques a été plus abondante dans les cellules traitées à l’OT en comparaison aux cellules traitées avec la 5-azacytidine, qui a été largement utilisée comme inducteur de différenciation cardiaque des cellules souches adultes. Aussi, l’OT a causé la prolifération des CMSOp. Finalement, nous avons observé que l'inhibition de la voie de signalisation du NO affecte de manière significative l'expression des protéines cardiaques spécifiques. En conclusion, ces études précisent un potentiel certain de l’OT dans le cadre de la thérapie cellulaire cardiomyogénique à base de cellules souches adultes, mais soulignent que son utilisation requerra de la prudence et un approfondissement des connaissances.