Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes

The genetic basis for virulence in influenza virus is largely unknown. To explore the mutational basis for increased virulence in the lung, the H3N2 prototype clinical isolate, A/HK/1/68, was adapted to the mouse. Genomic sequencing provided the first demonstration, to our knowledge, that a group of 11 mutations can convert an avirulent virus to a virulent variant that can kill at a minimal dose. Thirteen of the 14 amino acid substitutions (93%) detected among clonal isolates were likely instrumental in adaptation because of their positive selection, location in functional regions, and/or independent occurrence in other virulent influenza viruses. Mutations in virulent variants repeatedly involved nuclear localization signals and sites of protein and RNA interaction, implicating them as novel modulators of virulence. Mouse-adapted variants with the same hemagglutinin mutations possessed different pH optima of fusion, indicating that fusion activity of hemagglutinin can be modulated by other viral genes. Experimental adaptation resulted in the selection of three mutations that were in common with the virulent human H5N1 isolate A/HK/156/97 and that may be instrumental in its extreme virulence. Analysis of viral adaptation by serial passage appears to provide the identification of biologically relevant mutations.

Themes, 1795-1797

This is a paper-bound volume of themes White composed on many subjects, including flattery, the human condition, liberty, the importance of sleep and repose, procrastination, honesty, death, labor, justice, the triumph of folly over reason, and the importance of choosing one's friends wisely. On the last page, White copied several passages from Shakespeare's Richard II.

Themes and reviews, 1788-1805

Small notebook with brown paper covers containing handwritten entries noting the essay topics given to students between 1788 and 1805 according to class. The prompts are in both English and Latin and are generally philosophical quotations or verse from poetry that students responded to in short essays. There is a small handwritten chart for "A Scheme for a Lottery for a New College" laid into the back of the volume.

Essays on current themes,

Mode of access: Internet.

Two sketches for string quartet based on Indian themes.

Mode of access: Internet.

Caprice : sur plusieurs themes de la dansomanie : op. 4 /

Mode of access: Internet.

Flower show themes and arrangement classes for developing them /

Includes index.

Guide de la langue espagnole sans maitre a l'usage des français, ou, Abrégé des principales regles pour apprendre la dite langue : augmenté d'une collection d'articles, noms, pronoms, verbes ... suivi d'un petit cours de themes sur les neuf parties du discours /

Mode of access: Internet.

Revival sermons in outline, with thoughts, themes and plans, by eminent pastors and evangelists;

Mode of access: Internet.

The Albert A. Bieber collection of American plays, poetry and songsters; A most unusual gathering of early and modern American literature, covering a variety of themes...

Mode of access: Internet.

A vision of Giorgione; three variations on Venetian themes.

Bound in pale purple paper boards; printed paper labels on front cover and spine; pale purple endpapers. Dust jacket.

Gospel themes; a treatise on salient features of "Mormonism," written for, and dedicated to the High Priests, Seventies and Elders of the Church of Jesus Christ of L.D.S.

Mode of access: Internet.

The Scofield reference Bible. The Holy Bible, containing the Old and New Testaments. Authorized version, with a new system of connected topical references to all the greater themes of Scripture, with annotations, revised marginal renderings, summaries, definitions, and index; to which are added helps at hard places, explanations of seeming discrepancies, and a new system of paragraphs.

Mode of access: Internet.