Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human α1-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3–5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes.

Student notebook of Marston Cabot, ca. 1720-1735

This leather-bound volume contains excerpts copied by Marston Cabot from books he read while he was a student at Harvard in 1723. The volume includes extracts from Charles Morton's 1687 Compendium Physicae (titled "of Phisicks" by Cabot), Dr. Adriani Heereboord (Adrianus Heereboord), Philosophia Naturalis and Johanne-Henrico Alstedio’s (John Henry Alsted) geometry text Compendium Geometria. The excerpts from Compendium Geometria include both figures and text, primarily in Latin with some Greek. The volume also includes “Theses quaedam extractae potissimum ex Enchiridio Metaphysico Domini Johannis Clerici" a précis of Jean Le Clerc's Ontologia et Pneumatologia made by Jonathan Remington, a Harvard Tutor from 1703 to 1711, to serve in place of printed textbooks. The names Jonathan Jackson and Edward Jackson are written on the inside cover, suggesting the book may have been handed down to Edward Jackson (Class of 1726) and his son Jonathan Jackson (Class of 1761). The text of the volume is in Marston Cabot's hand.

Central Europe Region, 1720-1729 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Tabula novissima totius Germaniae praecipue ex designatione viri celeberrimi D[om]ini Johannis Caspari Eisenschmidii. It was published by in lucem edita a Johanne Baptista Homanno, between 1720 and 1729. Scale [ca. 1:1,270,000]. Covers the Central Europe region. Map in Latin. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic 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, territorial and administrative boundaries, shoreline features, and more. Relief shown pictorially.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.

Étude de la migration des populations de lymphocytes B du sang de patients infectés par le virus d’immunodéficience humaine (VIH)

La dérégulation du compartiment de cellules B est une conséquence importante de l’infection par le virus de l’immunodéficience humaine (VIH-1). On observe notamment une diminution des nombres de lymphocytes B sanguins ainsi qu’une variation des fréquences relatives des différentes populations de lymphocytes B chez les individus infectés par rapport aux contrôles sains. Notre laboratoire a précédemment démontré l’implication des cellules dendritiques dans la dérégulation des lymphocytes B via la roduction excessive de BLyS/BAFF, un stimulateur des cellules B. De plus, lors l’études menées chez la souris transgénique présentant une maladie semblable au SIDA, et chez la souris BLyS/BAFF transgénique, l’infection au VIH-1 fut associée à une expansion de la zone marginale (MZ) de la rate. De façon intéressante, nous observons chez les contrôleurs élites une diminution de la population B ‘mature’ de la MZ. Il s’agit du seul changement important chez les contrôleurs élites et reflète possiblement un recrutement de ces cellules vers la périphérie ainsi qu’une implication dans des mécanismes de contrôle de l’infection. Pour tenter d’expliquer et de mieux comprendre ces variations dans les fréquences des populations B, nous avons analysé les axes chimiotactiques CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 et CCL25-CCR9. L’étude longitudinale de cohortes de patients avec différents types de progression clinique ou de contrôle de l’infection démontre une modulation des niveaux plasmatiques de la majorité des chimiokines analysées chez les progresseurs rapides et classiques. Au contraire, les contrôleurs élites conservent des niveaux normaux de chimiokines, démontrant leur capacité à maintenir l’homéostasie. La migration des populations de cellules B semble être modulée selon la progression ou le contrôle de l’infection. Les contrôleurs élites présentent une diminution de la population B ‘mature’ de la MZ et une augmentation de la fréquence d’expression du récepteur CXCR7 associé à la MZ chez la souris, suggérant un rôle important des cellules de la MZ dans le contrôle de l’infection au VIH-1. De façon générale, les résultats dans cette étude viennent enrichir nos connaissances du compartiment de cellules B dans le contexte de l’infection au VIH-1 et pourront contribuer à élaborer des stratégies préventives et thérapeutiques contre ce virus.

Opus regale in quo continentur infrascripta opuscula ...

Contiene según consta en port.: Epistola consolatoria in qua tria optima remedia ad repelle[n]du[m] omnes causas tristicie aperiuntur. Prea[m]bulu[m] seque[n]tis opusculi in quo agit[ur] de officio pietatis in defunctos ... Tractatus aureus de pugna partis sensitiuae el intellectiue ... Epistola ... in qua multa curiosa sub breuibus tanguntur ... Tractatus ... de laudib[us] ... lilio[rum] que in scuto regis xpianissmi figuran. ...

Historiae Societatis Jesu prouinciae Bohemiae : Pars primae ab anno Christi MDLV ad annum MDXCII /

Mode of access: Internet.

Opus sermonum de aduentu ... /

CCBE S. XVI,

Tertia pars totius su[m]me maioris beati Antonini.

Es parte de: Prima pars totius summe maioris beati Antonini.

Sermones quadragesimales /

Adams, G-1276.