Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells.

To determine which features of retroviral vector design most critically affect gene expression in hematopoietic cells in vivo, we have constructed a variety of different retroviral vectors which encode the same gene product, human adenosine deaminase (EC 3.5.4.4), and possess the same vector backbone yet differ specifically in transcriptional control sequences suggested by others to be important for gene expression in vivo. Murine bone marrow cells were transduced by each of the recombinant viruses and subsequently used to reconstitute the hematopoietic system of lethally irradiated recipients. Five to seven months after transplantation, analysis of the peripheral blood of animals transplanted with cells transduced by vectors which employ viral long terminal repeats (LTRs) for gene expression indicated that in 83% (77/93) of these animals, the level of human enzyme was equal to or greater than the level of endogenous murine enzyme. Even in bone marrow transplant recipients reconstituted for over 1 year, significant levels of gene expression were observed for each of the vectors in their bone marrow, spleen, macrophages, and B and T lymphocytes. However, derivatives of the parental MFG-ADA vector which possess either a single base mutation (termed B2 mutation) or myeloproliferative sarcoma virus LTRs rather than the Moloney murine leukemia virus LTRs led to significantly improved gene expression in all lineages. These studies indicate that retroviral vectors which employ viral LTRs for the expression of inserted sequences make it possible to obtain high levels of a desired gene product in most hematopoietic cell lineages for close to the lifetime of bone marrow transplant recipients.

Letter book : manuscript, 1757-1759

Contains chiefly correspondence with Secretary of State William Pitt, including a letter, dated 22 Sept. 1759, describing the fall of Québec and the death of Wolfe.

Réclamations à l'Assemblée-Nationale en faveur des anciens habitans de l'Acadie transportés en France lors de la prise de Louisbourg et particulierement en faveur de ceux débarqués à Cherbourg le 14 janvier 1760: Distribué au profit des acadiens 1790 : manuscript, 1790

Documents concern the landing of Acadian refugees at Cherbourg on 14 Jan. 1760.

India & South Asia, 1752 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Carte de l'Inde : dressée pour la Compagnie des Indes, par le Sr. d'Anville, Sécrétaire de S.A.S. Mgr. le Duc d'Orleans ; [engraved by] Guill.' de-la-Haye. It was published by Jean Baptiste Bourguignon d'Anville in November 1752. Scale [ca. 1:3,100,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the northern portion of the map. Covers India and portions of South Asia. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Kalianpur 1975 India Zone III projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, roads, shoreline features, and more. Relief shown pictorially. Includes insets: Negraïs -- Rivière d'Aracan -- Riv. de Sirian -- Archipel de Merghi -- Environs de Junk Selon -- Environs d'Ashem -- Entréé du Gange -- Environs de Goa. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.