Learning from the social construction of environmental indicators: From the retrospective to the pro-active use of SCOT in technology development

This article explores the challenges, advantages and limitations of the pro-active use of the social construction of technology (SCOT) to improve the methods applied in the development of technology for use by a broad range of actors. Our example is the development of environmental indicators for buildings (EIFOBs). We compare the pro-active use of SCOT with both the ‘traditional’ use of SCOT and with the ‘traditional’ way of developing EIFOBs. pro-actively applying SCOT in developing EIFOBs has the potential of bridging some of the communication gaps at the boundaries between the various professional groups in a multi-actor decision-making process. Using SCOT in a pro-active way means the research becomes action research and the researcher goes beyond the role of a mere observer and becomes an actor too. This means the researcher has to consider the criteria for valid action research when designing and carrying out the research.     

Fabrication of Fischer–Tropsch Catalysts by Deposition of Iron Nanocrystals on Carbon Nanotubes

The fabrication of supported catalysts consisting of colloidal iron oxide nanocrystals with tunable size, geometry, and loading—homogeneously dispersed on carbon nanotube (CNT) supports—is described herein. The catalyst synthesis is performed in a two‐step approach. First, colloidal iron and iron oxide nanocrystals with a narrow size distribution are produced. Second, the nanocrystals are attached to CNT grains serving as support structure. Important features, like iron loading and nanocrystal density on the CNT support, are controlled by changing the nanocrystal concentration and ligand concentration, respectively. The Fischer–Tropsch performance reveals these new materials to be active, selective toward lower olefins (60% C of hydrocarbons produced in the absence of promoters), and remarkably stable against particle growth.     

A role of Hsp60 in autoimmune diabetes: analysis in a transgenic model

A pathogenic role for self-reactive cells against the stress protein Hsp60 has been proposed as one of the events leading to autoimmune destruction of pancreatic beta cells in the diabetes of nonobese diabetic (NOD) mice. To examine this hypothesis, we generated transgenic NOD mice carrying a murine Hsp60 transgene driven by the H-2E alpha class II promoter. This would be expected to direct expression of the transgene to antigen-presenting cells including those in the thymus and so induce immunological tolerance by deletion. Detailed analysis of Hsp60 expression revealed that the endogenous gene is itself expressed strongly in thymic medullary epithelium (and weakly in cortex) yet fails to induce tolerance. Transgenic mice with retargeted Hsp60 showed overexpression of the gene in thymic cortical epithelium and in bone marrow-derived cells. Analysis of spontaneous T-cell responses to a panel of self and heterologous Hsp60 antigens showed that tolerance to the protein had not been induced, although responses to an immunodominant 437-460 epitope implicated in disease were suppressed, probably indicating an epitope shift. This correlated with changes in disease susceptibility: insulitis in transgenic mice was substantially reduced so that pathology rarely progressed beyond periislet infiltration. This was reflected in a substantial reduction in hyperglycemia and disease. These data indicate that T cells specific for some epitopes of murine Hsp60 are likely to be involved in the islet-cell destruction that occurs in NOD mice.     

Studies in the thermal degradation of poly(vinyl chloride)

Thermal degradation of poly(vinyl chloride) (PVC) was studied in nitrogen atmosphere in the presence of rubber seed oil and epoxidized rubber seed oil, barium and lead soaps of rubber seed oil, and epoxidized seed oil at various temperatures. The rate of dehydrochlorination at 1% degradation and the time required to attain 1% degradation were used to assess the effect of the thermal susceptibility of PVC to dehydrochlorination. It was found that epoxidized rubber seed oil, the metal soaps of rubber seed oil, and epoxidized rubber seed oil markedly enhance the thermal stability of PVC. The order of increasing stabilizing influence was metal soaps of epoxidized rubber seed oil > metal soaps of rubber seed oil > epoxidized rubber seed oil > rubber seed oil. © 1993 John Wiley & Sons, Inc.     

Natural products as leads for anticancer drug discovery: discovery of new chemotypes of microtubule stabilizers through reengineering of the epothilone scaffold

Epothilones are bacterial macrolides with potent microtubule-stabilizing and antiproliferative activity, which have served as successful lead structures for the discovery of several clinical candidates for cancer treatment. Overall, seven epothilone-type agents have been advanced to clinical evaluation in humans so far and one of these has been approved by the FDA in 2007 for clinical use in breast cancer patients. Notwithstanding these impressive numbers, however, the structural diversity represented by the collection of epothilone analogs that have been (or still are) investigated clinically is rather limited and their individual structures show little divergence from the original natural product leads. In contrast, we have elaborated a series of epothilone-derived macro-lactones, whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of conformationally constrained side chains, the removal of the C(3)-hydroxyl group, and the replacement of C(12) with nitrogen. The latter modification leads to aza-macrolides that may be described as 'non-natural natural products'.     

Synthesis and biological activity of new functionalized epothilones for prodrug design and tumor targeting

Epothilones are potent antiproliferative agents, which have served as successful lead structures for anticancer drug discovery. However, their therapeutic efficacy would benefit greatly from an increase in their selectivity for tumor cells, which may be achieved through conjugation with a tumor-targeting moiety. Three novel epothilone analogs bearing variously functionalized benzimidazole side chains were synthesized using a strategy based on palladium-mediated coupling and macrolactonization. The synthesis of these compounds is described and their in vitro biological activity is discussed with respect to their interactions with the tubulin/microtubule system and the inhibition of human cancer cell proliferation. The additional functional groups may be used to synthesize conjugates of epothilone derivatives with a variety of tumor-targeting moieties.