Metalinear cinematic narrative : theory, process, and tool

Thesis (Ph.D.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 1999.Includes bibliographical references (leaves 207-218).Media entertainment technology is evolving rapidly. From radio to broadcast television to cable television, from motion picture film to the promise of digital video disks, as the media evolves, so do the stories told over these media. We already share many more stories and more types of stories from many more sources than we did a decade ago. This is due in part to the development of computer technology, the globalization of computer networks, and the emerging new medium which is an amalgam of television and the internet. The storyteller will need to invent new creative processes and work with new tools which support this new medium, this new narrative form. This thesis proposes the name Metalinear Narrative for the new narrative form. The metalinear narrative is a collection of small related story pieces designed to be arranged in many different ways, to tell many different linear stories from different points of view, with the aid of a story engine. Agent Stories is the software tool developed as part of this research for designing and presenting metalinear cinematic narratives. Agent Stories is comprised of a set of environments for authoring pieces of stories, authoring the relationships between the many story pieces, and for designing an abstract narrative structure for sequencing those pieces. Agent Stories also provides a set of software agents called story agents, which act as the drivers of the story engine. My thesis is that a writing tool which offers the author knowledgeable feedback about narrative construction and context during the creative process is essential to the task of creating metalinear narratives of significant dimension.by Kevin Michael Brooks.Ph.D

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)