c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1.

Two genetic events contribute to the development of endemic Burkitt lymphoma (BL) infection of B lymphocytes with Epstein-Barr virus (EBV) and the activation of the protooncogene c-myc through chromosomal translocation. The viral genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for transformation of primary human B cells by EBV in vitro; however, these genes are not expressed in BL cells in vivo. To address the question whether c-myc activation might abrogate the requirement of the EBNA2 and LMP1 function, we have introduced an activated c-myc gene into an EBV-transformed cell line in which EBNA2 was rendered estrogen-dependent through fusion with the hormone binding domain of the estrogen receptor. The c-myc gene was placed under the control of regulatory elements of the immunoglobulin kappa locus composed a matrix attachment region, the intron enhancer, and the 3' enhancer. We show here that transfection of a c-myc expression plasmid followed by selection for high MYC expression is capable of inducing continuous proliferation of these cells in the absence of functional EBNA2 and LMP1. c-myc-induced hormone-independent proliferation was associated with a dramatic change in the growth behavior as well as cell surface marker expression of these cells. The typical lymphoblastoid morphology and phenotype of EBV-transformed cells completely changed into that of BL cells in vivo. We conclude that the phenotype of BL cells reflects the expression pattern of viral and cellular genes rather than its germinal center origin.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Urban penalty: nuevas hipótesis y caso español (1860-1920)

El término urban penalty fue en principio utilizado para definir la sobremortalidad urbana durante la revolución industrial. Los antropómetras lo emplearon más tarde para definir un hecho simultáneo: el descenso de la estatura urbana con respecto a la rural. En la primera parte del trabajo proponemos tres nuevas hipótesis sobre ese castigo urbano: a) incorporar las aportaciones de la Teoría Económica sobre fallos de mercado al análisis de la sobremortalidad urbana; b) explicar la urban penalty mediante el modelo que Floud, Fogel, Harris y Chul Hong han elaborado recientemente para Gran Bretaña y c) sugerir respuestas a una pregunta que debe ser avalada o desmentida por investigaciones de ámbito municipal: ¿por qué los políticos españoles de la restauración tardaron décadas en acometer la reforma sanitaria de las ciudades? En la segunda parte del trabajo ofrecemos información que demuestra que España padeció sobremortalidad urbana derivada de fallos de mercado. Los datos de estatura rural y urbana evidencian por el contrario que, salvo excepciones, el país no experimentó urban penalty. El trabajo termina tratando de explicar esta particularidad y sosteniendo que el modelo de Floud, Fogel, Harris y Chul Hong puede aplicarse a esas excepciones.

Letter to the Selectmen of Charlestown, 1785 January 13

Three-and-a-half-page handwritten letter from "FM Dana by order &c," to the Selectmen of Charlestown. Dana is presumably speaking on behalf of the Selectmen of Cambridge and provides an extensive response to the Charlestown Selectmen about increased ferry fares that is critical of the demands of the Harvard Corporation.

Die Naturgeschichte des Thierreichs / von C.G. Giebel.

bd. 3

Journal of Charles Coffin and David Gurney, 1781-1785

This diary appears to have been kept by two different students, both members of the Harvard College class of 1785. The first two pages contain entries made by a student named David, believed to be David Gurney because the entries relate to the freshman curriculum and Gurney was the only student named David who was a freshman in 1781. Gurney originally titled the volume "A Journal or Diary of my concerns in College of important matters." He made entries from August 28 through October 21, 1781, recording his lessons on Virgil, Tully, Homer, the Greek Testament, Hebrew grammar, English author John Ash's "Grammar," and a text called "The Art of Speaking." At the top of one of the pages recounting these studies, Gurney wrote in large, bold letters: "About how I misspent my precious time." Charles Coffin's entries begin on October 25, 1781 and fill the bulk of the journal. Coffin kept this diary while a student at Harvard College from 1781 to 1785. Although most of Coffin's entries are written in Latin, an account of his July 1781 examination for admission to the College is in English.

Worcester, Massachusetts, ca. 1860 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the city of Worcester, Mass. : from actual surveys under the direction of P. Ball, C.E. It was published by Smith & Mc.Kinney, between 1850 and 1860. Scale [ca. 1:3,600]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001) 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 roads, railroads and stations, drainage, public buildings, schools, industry locations (e.g. mills, factories, etc.), selected private buildings with names of property owners, town and ward boundaries, cemeteries, and more. Includes also engravings of important buildings and advertisements in margins. 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.

Portland & Rochester Railroad, New England, 1860 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map showing the Portland & Rochester railroad and its connections, prepared by G.W. & C.B. Colton & Co. It was published in 1860. Scale [ca. 1:900,000]. Covers Vermont, New Hampshire, Massachusetts, Connecticut, Rhode Island, and portions of New York, Maine, and the provinces of Quebec and New Brunswick, Canada.The image inside the map neatline is georeferenced to the surface of the earth and fit to the USA Contiguous Albers Equal Area Conic projection (Meters). 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, or other information associated with the principal map. This map shows features such as railraods, principal and proposed railroad connections, drainage, state, county, and town boundaries, and more. Relief shown by hachures. Includes table of distances and inset: [Northeastern United States]. Scale [ca. 1:7,600,000].This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Munich, Germany, 1860 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: München, augefertigt v. J. Heyberger. It was published by Friedrich Bruckmann's Verlag in 1860. Scale 1:12,000. Covers Munich, Germany. Map in German. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Deutsches Hauptdreiecksnetz (DHDN) Gauss Kruger Zone 4, Rauenberg Datum' 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 roads, railroads and stations, drainage, built-up areas and selected buildings, ground cover, parks, and more. Relief shown by shading. Includes indexes and inset: Umgebung von München. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Maine, 1798 Raster Image

This layer is a digitized geo-referenced raster image of a 1798 map of Maine drawn by D.F. Sotzmann. These Sotzmann maps (10 maps of New England and Mid-Atlantic states) typically portray both natural and manmade features. They are highly detailed with symbols for churches, roads, court houses, distilleries, iron works, mills, academies, county lines, town lines, and more. Relief is usually indicated by hachures and country boundaries have also been drawn. Place names are shown in both German and English and each map usually includes an index to land grants. Prime meridians used for this series are Greenwich and Washington, D.C.

New Hampshire, 1796 Raster Image

This layer is a digitized geo-referenced raster image of a 1796 map of New Hampshire drawn by D.F. Sotzmann. These Sotzmann maps (10 maps of New England and Mid-Atlantic states) typically portray both natural and manmade features. They are highly detailed with symbols for churches, roads, court houses, distilleries, iron works, mills, academies, county lines, town lines, and more. Relief is usually indicated by hachures and country boundaries have also been drawn. Place names are shown in both German and English and each map usually includes an index to land grants. Prime meridians used for this series are Greenwich and Washington, D.C.

Vermont, 1796 Raster Image

This layer is a digitized geo-referenced raster image of a 1796 map of Vermont drawn by D.F. Sotzmann. These Sotzmann maps (10 maps of New England and Mid-Atlantic states) typically portray both natural and manmade features. They are highly detailed with symbols for churches, roads, court houses, distilleries, iron works, mills, academies, county lines, town lines, and more. Relief is usually indicated by hachures and country boundaries have also been drawn. Place names are shown in both German and English and each map usually includes an index to land grants. Prime meridians used for this series are Greenwich and Washington, D.C.

Massachusetts, 1797 Raster Image

This layer is a digitized geo-referenced raster image of a 1797 map of Massachusetts drawn by D.F. Sotzmann. These Sotzmann maps (10 maps of New England and Mid-Atlantic states) typically portray both natural and manmade features. They are highly detailed with symbols for churches, roads, court houses, distilleries, iron works, mills, academies, county lines, town lines, and more. Relief is usually indicated by hachures and country boundaries have also been drawn. Place names are shown in both German and English and each map usually includes an index to land grants. Prime meridians used for this series are Greenwich and Washington, D.C.

Rhode Island, 1797 Raster Image

This layer is a digitized geo-referenced raster image of a 1797 map of Rhode Island drawn by D.F. Sotzmann. These Sotzmann maps (10 maps of New England and Mid-Atlantic states) typically portray both natural and manmade features. They are highly detailed with symbols for churches, roads, court houses, distilleries, iron works, mills, academies, county lines, town lines, and more. Relief is usually indicated by hachures and country boundaries have also been drawn. Place names are shown in both German and English and each map usually includes an index to land grants. Prime meridians used for this series are Greenwich and Washington, D.C.