Hermeneutics, accreting receptions, hypermedia: A tool for reference versus a tool for instruction

We provide a select overview of tools supporting traditional Jewish learning. Then we go on to discuss our own HyperJoseph/HyperIsaac project in instructional hypermedia. Its application is to teaching, teacher training, and self-instruction in given Bible passages. The treatment of two narratives has been developed thus far. The tool enables an analysis of the text in several respects: linguistic, narratological, etc. Moreover, the Scriptures' focality throughout the cultural history makes this domain of application particularly challenging, in that there is a requirement for the tool to encompass the accretion of receptions in the cultural repertoire, i.e., several layers of textual traditions—either hermeneutic (i.e., interpretive), or appropriations—related to the given core passage, thus including "secondary" texts (i.e., such that are responding or derivative) from as disparate realms as Roman-age and later homiletics, Medieval and later commentaries or supercommentaries, literary appropriations, references to the arts and modern scholarship, etc. in particular, the Midrash (homiletic expansions) is adept at narrative gap filling, so the narratives mushroom at the interstices where the primary text is silent. The genealogy of the project is rooted in Weiss' index of novelist Agnon's writings, which was eventually upgraded into a hypertextual tool, including Agnon's full-text and ancillary materials. Those early tools being intended primarily for reference and research-support in literary studies, the Agnon hypertext system was initially emulated in the conception of HyperJoseph, which is applied to the Joseph story from Genesis. Then, the transition from a tool for reference to an instructional tool required a thorough reconception in an educational perspective, which led to HyperIsaac, on the sacrifice of Isaac, and to a redesign and upgrade of HyperJoseph as patterned after HyperIsaac.

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pH-dependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of (125)I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3h) and ISA1 dose (0.04-100mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed approximately 60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10mg/kg to 100mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.