Second Welland Canal - Book 2, Survey Map 4 - Locks 11, 12, 13, 14 and 15 in Grantham

Survey map of the Second Welland Canal created by the Welland Canal Company showing the Grantham Township along the outskirts of Merritton. Identified structures associated with the Canal include Locks 11, 12, 13, 14, and 15, Lock House Lot, and the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Several stones likely used in the measurements are identified on the map. Local area landmarks are also identified and include streets and roads(ex. Hartzel Road and Macadamized Road), the Great Western Railroad, Swing Bridge, Thorold Station and its structures (ex. freight house, office, water tank, and wood house), Gordon and Mackay Houses, Gordon and Mackay's Cotton Mill, hydraulic race, a wharf, pond, and an unnamed bridge. Properties and property owners of note are: Concession 9 Lots 12 and 13, A. Bradley, John O'Coner, G. Grant, J. Bradley, J. Vanderburgh, O. Clifford and a parcel of land leased Gordon and Mackay.

The production of 4-adminobutyrate in response to treatments reducing cytosolic pH and the regulation of intracellular pH

GABA (4-aminobutyrate) is synthesized through the decarboxylation of LGlu- (L-Glu-+ H+ ---> GABA + C02), and compared to many free amino acids is present in high concentrations in plant cells. GABA levels rise rapidly and dramatically in response to varied stress conditions including anaerobiosis. Recent papers suggest that GABA production and associated H+ consumption are parts of a metabolic pH-stat mechanism which ameliorates the intracellular pH decline associated with anaerobiosis or other treatments. To test this hypothesis GABA production and efflux have been measured in isolated Asparagus sprengeri cells in response to three treatments which potentially cause intracellular acidification. Acid loads were imposed using 60 min of (i) anaerobiosis, (ii) H+/LGlu- cotransport, and (iii) treatment with permeant weak acids (butyric, acetic and propionic). Both intra- and extracellular GABA concentrations increased more than 100% after anaerobiosis, almost 1000% after H+/L-Glu- cotransport (light or dark) and almost 5000/0 after addition of 5 mM butyric acid at pH 5.0. HPLC analysis of amino acids indicates that as GABA concentrations increased in response to butyric acid addition, glutamate concentrations decreased. Time-course studies demonstrated that added butyric acid stimulates GABA production by 2800/0 within 15 seconds. A fluorescent determination of cytosolic pH indicates that addition of butyric or other weak acids resulted in a rapid reduction in cytosolic pH of 0.6 pH units. The half time for the response to butyric acid addition is 2.1 seconds, indicating that the decline in cytosolic pH is rapid enough to account for the rapid stimulation of GABA production. The acid load in response to butyric acid addition was assayed by measurements of 14C-butyric acid uptake. Calculations indicate that GABA production accounted for 45% of the imposed acid load. The biological significance of GABA efflux is not yet understood. The results support the original hypothesis suggesting a role for GABA production in cellular pH regulation.

Second Welland Canal - Book 1, Survey Map 13 - St. Catharines and Locks 4 and 5

Survey map of the Second Welland Canal created by the Welland Canal Company showing the Town of St. Catharines. Identified structures associated with the Canal include Lock 4, Lock House, Lock 5, Small Lock House, the towing path, and Gasometer for Canal. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Geneva Street, Queenston Street, and Academy Street), C. Phelps Mill and Store House, St. Catharines and Welland Canal Gas Works, William Mahony's Tannery, Cooper Shop, a barrel shed, barn, and gas tanks. Properties and property owners of note are: Concession 6 Lots 14, 14, and 16, Concession 7 Lots 14, 15, and 16, C. Phelps, R. M. Clement, Orson Phelps, R. Collier, D. P. Haynes, W. Chace, and John Soper.

The Gleaner and Niagara Newspaper, January 15, 1818

The Gleaner and Niagara Newspaper was a weekly paper in the town of Niagara-on-the-Lake that began publication December 4, 1817 and ceased in 1830. This bound volume has been divided by publication dates. Other dates included in the volume are: 1817 December 18 1817 December 25 1818 January 1 1818 January 8 1818 January 22 There is also a letter that was found inside the bound volume written by Andrew Heron on October 1 1817.

Baltimore Patriot and Evening Advertiser Vol. 3 No. 89- April 15, 1814

This daily paper, except Sundays, began publication on August 17, 1813 and ceased April 30, 1817. It was also published tri-weekly for a "COUNTRY" edition. The paper later became the Baltimore Patriot. Topics of interest include: Page 1: announcement Capt. M. Simmones Burnbury is seeking men to form a company of Sea Fencibles; Page 2: U.S. Legislature authorizes bill to increase the Marine Corps; U.S. Legislature authorizes bill to purchase vessels captured on Lake Erie; U.S. Senate bill authorizes the appointment of officers for the flotilla service; President of United States authorized to accept service of volunteer corps for defence of United States; Letter from Capt. A. H. Holmes to Lieut. Col. Butler detailing an American victory over the British near Detroit; announcement of British forces building barges for the purpose of attacking Detroit; War sloop Erie returns to Baltimore unable to reach sea due to British forces in the Chesapeake; Page 3: Death notice of Mr. Ward Fairchild of the U.S. Army; Page 4: Commander of the U.S. Flotilla seeks men for the Chesapeake Flotilla.

National Intelligencer Vol. XVI, No. 2193- October 15, 1814

The Intelligencer was an American newspaper that was established, in 1800, in Washington by Samuel Harrison Smith, a young Jeffersonian- Republican from Philadelphia. War of 1812 related content includes: Page 1: Major General Winfield Scott's arrival in Washington escorted by Colonel Laval's cavalry; report from Sackett's Harbour on the American and British navies; a debate on a bill to temporarily remove the seat of government from the City of Washington due to the war; the Military Committee wishing to have the President commission gold medals for distinguished service for Major Generals Brown and Scott and silver medals to Brigadier Generals Ripley, Miller and Porter for their efforts at Chippewa, Erie and Niagara as well as gold medals to Brigadier General Gaines for efforts at Erie and Brigadier General Macomb for efforts at Plattsburg; resolutions of the House on the victory of Commodore Thomas Macdonough at the Battle on Lake Champlain; Page 2: more detail on the proposed removal of the seat of government from Washington; Page 3: a letter from Major General Andrew Jackson to the Secretary of War on repelling the British at Fort Bowyer on the Point of Mobile and naval battle reports on the vessels Hermes, Sophie, and Carron; a letter from Major William Lawrence to Andrew Jackson on the battle at Fort Bowyer; military promotions of Alexander Macomb, Roger Jones, J. Hindman; more on the removal of the seat of government; citizens of Washington offering to volunteer in defense of the city; banks willing to loan the government funds to re-build destroyed government buildings; assignments of Major General Scott, General Winder and Major General Gaines; report of 300 British prisoners from Fort Erie passed through Washington; Montreal newspaper report condemning Provost for his actions at the Battle of Lake Champlain; trouble with stage coaches traveling between New Haven and Bridgeport due to cannon fire; report of a British naval squadron appearing off New Port and by Long Island and New Bedford; report of enemy naval movements from Norfolk; announcement of a book entitled "A Narrative of the Battle of Bladensburg" by and officer of General Smith; Page 4: report on the amassing navy at Kingston under Drummond and the defenses at Sackett's Harbor; report of American and British naval news from Nova Scotia and the east coast; actions of the American sloop of war, The Peacock, in international waters; an enlistment announcement by Captain Perrin Willis of the 2nd Regiment Infantry; listing of American officers and privates released from parole on October 13; Other notices report on stray horses, properties for sale, runaway slaves, imprisonments, missing livestock, medical lectures at the University of Maryland, stage lines, auctions, etc. The paper was a supporter of the Jefferson and Madison administrations until 1810 when it was sold to Joseph Gales Jr. from North Carolina. In 1812 William Seaton joined Gales as a publishing partner. This paper made significant contributions to the nation and wielded considerable influence in political circles during its publication. It has been praised for its "high standard of journalistic excellence and high intellectual level of its contents". (William E. Ames , National Intelligencer: Washington's Leading Political Newspaper) The Intelligencer was, until 1810, named the National Intelligencer, and Washington Advertiser. It was a tri-weekly paper and had a peak circulation of 6, 000. Publication was suspended in 1869.

Chemoenzymatic Total Synthesis of Morphine alkaloids: Synthesis of Dihydrocodeine and Hydrocodone via a Double Claisen Strategy and ent-Hydromorphone via an Oxidative Dearomatization/intramolecular [4+2] Cycloaddition

This thesis describes the chemoenzymatic synthesis of three morphine alkaloids. The total synthesis of dihydrocodeine and hydrocodone was accomplished starting from bromobenzene in 16 and 17 steps, respectively. The key steps included a microbial oxidation of bromobenzene by E. coli JM109 (pDTG601A), a Kazmaier-Claisen rearrangement of glycinate ester to generate C-9 and C-14 stereo centers, a Johnson-Claisen rearrangement to set the C-13 quaternary center, and a C-10/C-11 ring closure via a Friedel-Crafts reaction. In addition, the total synthesis of ent-hydromorphone starting from β-bromoethylbenzene in 12 steps is also described. The key reactions included the enzymatic dihydroxylation of β-bromoethylbenzene to the corresponding cis-cyclohexadienediol, a Mitsunobu reaction, and an oxidative dearomatization followed by an intramolecular [4+2] cycloaddition.

Role of Phosphorylation of the Oxysterol Binding Protein (OSBP) in (PI(4)P) and Sterol-Containing Membrane Recognition and Binding

Studies have demonstrated that the oxysterol binding protein (OSBP) acts as a phosphatidylinositol phosphate (PIP)-sterol exchanger at membrane contact sites (MCS) of the endoplasmic reticulum (ER) and Golgi. OSBP is known to pick up phosphatidylinositol-4-phosphate (PI(4)P) from the ER, transfer it to the trans-Golgi in exchange for a cholesterol molecule that is then transferred from the trans-Golgi to the ER. Upon further examination of this pathway by Ridgway et al. (1), it appeared that phosphorylation of OSBP played a role in the localization of OSBP. The dephosphorylation state of OSBP was linked to Golgi localization and the depletion of cholesterol at the ER. To mimic the phosphorylated state of OSBP, the mutant OSBP-S5E was designed by Ridgway et al. (1). The lipid and sterol recognition by wt-OSBP and its phosphomimic mutant OSBP-S5E were investigated using immobilized lipid bilayers and dual polarization interferometry (DPI). DPI is a technique in which the protein binding affinity to immobilized lipid bilayers is measured and the binding behavior is examined through real time. Lipid bilayers containing 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and varying concentrations of PI(4)Ps or sterols (cholesterol or 25-hydroxycholesterol) were immobilized on a silicon nitride chip. It was determined that wt-OSBP binds differently to PI(4)P-containing bilayers compared to OSBP-S5E. The binding behavior suggested that wt-OSBP extracts PI(4)P and the change in the binding behavior, in the case of OSBP-S5E, suggested that the phosphorylation of OSBP may prevent the recognition and/or extraction of PI(4)P. In the presence of sterols, the overall binding behavior of OSBP, regardless of phosphorylation state, was fairly similar. The maximum specific bound mass of OSBP to sterols did not differ as the concentration of sterols increased. However, comparing the maximum specific bound mass of OSBP to cholesterol with oxysterol (25-hydroxycholesterol), OSBP displayed nearly a 2-fold increase in bound mass. With the absence of the wt-OSBP-PI(4)P binding behavior, it can be speculated that the sterols were not extracted. In addition, the binding behavior of OSBP was further tested using a fluorescence based binding assay. Using 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (22-NBD cholesterol), wt-OSBP a one site binding dissociation constant Kd, of 15 ± 1.4 nM was determined. OSBP-S5E did not bind to 22-NBD cholesterol and Kd value was not obtained.