Churchman's Hegelian Inquiring System and Perspectival Thinking

This paper focuses upon a critical aspect implicit in C West Churchman's Hegelian Inquiring System, namely its ability to provide all the necessary ingredients for the emergence of a learning culture. This focus is achieved by articulating certain phenomenological aspects of the Hegelian model. In particular the relationship between subject and object is explored. After its emergence the learning culture then requires a special kind of thinking, which results in certain capacities, to continue its evolvement. This kind of thinking has been defined as Perspectival Thinking and is elaborated in the context of an Information System as a social system bound to technology. In the absence of a learning culture no organization can sustain its learning capacities, yet how often are learning cultures taken for granted? This paper explores a number of ideas that provide the ground for developing and sustaining learning cultures.     

Effect of superalloy substrate and bond coating on TBC lifetime

Several different single-crystal superalloys were coated with different bond coatings to study the effect of composition on the cyclic oxidation lifetime of an yttria-stabilized zirconia (YSZ) top coating deposited by electron beam physical vapor deposition from a commercial source. Three different superalloys were coated with a 7 μm Pt layer that was diffused into the surface prior to YSZ deposition. One of the superalloys, N5, was coated with a low activity, Pt-modified aluminide coating and Pt-diffusion coatings with 3 and 7 μm of Pt. Three coatings of each type were furnace cycled to failure in 1 h cycles at 1150 °C to assess average coating lifetime. The 7 μm Pt diffusion coating on N5 had an average YSZ coating lifetime > 50% higher than a Pt-modified aluminide coating on N5. Without a YSZ coating, the Pt-modified aluminide coating on N5 showed the typical surface deformation during cycling, however, the deformation was greatly reduced when constrained by the YSZ coating. The 3 μm Pt diffusion coating had a similar average lifetime as the Pt-modified aluminide coating but a much wider scatter. The Pt diffusion bond coating on superalloy X4 containing Ti exhibited the shortest YSZ coating lifetime, this alloy-coating combination also showed the worst alumina scale adhesion without a YSZ coating. The third generation superalloy N6 exhibited the longest coating lifetime with a 7 μm Pt diffusion coating.     

Interactions between Artemisinins and other Antimalarial Drugs in Relation to the Cofactor Model—A Unifying Proposal for Drug Action

Artemisinins are proposed to act in the malaria parasite cytosol by oxidizing dihydroflavin cofactors of redox‐active flavoenzymes, and under aerobic conditions by inducing their autoxidation. Perturbation of redox homeostasis coupled with the generation of reactive oxygen species (ROS) ensues. Ascorbic acid–methylene blue (MB), N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–MB, BNAH–lumiflavine, BNAH–riboflavin (RF), and NADPH–FAD–E. coli flavin reductase (Fre) systems at pH 7.4 generate leucomethylene blue (LMB) and reduced flavins that are rapidly oxidized in situ by artemisinins. These oxidations are inhibited by the 4‐aminoquinolines piperaquine (PPQ), chloroquine (CQ), and others. In contrast, the arylmethanols lumefantrine, mefloquine (MFQ), and quinine (QN) have little or no effect. Inhibition correlates with the antagonism exerted by 4‐aminoquinolines on the antimalarial activities of MB, RF, and artemisinins. Lack of inhibition correlates with the additivity/synergism between the arylmethanols and artemisinins. We propose association via π complex formation between the 4‐aminoquinolines and LMB or the dihydroflavins; this hinders hydride transfer from the reduced conjugates to the artemisinins. The arylmethanols have a decreased tendency to form π complexes, and so exert no effect. The parallel between chemical reactivity and antagonism or additivity/synergism draws attention to the mechanism of action of all drugs described herein. CQ and QN inhibit the formation of hemozoin in the parasite digestive vacuole (DV). The buildup of heme–Fe^III results in an enhanced efflux from the DV into the cytosol. In addition, the lipophilic heme–Fe^III complexes of CQ and QN that form in the DV are proposed to diffuse across the DV membrane. At the higher pH of the cytosol, the complexes decompose to liberate heme–Fe^III. The quinoline or arylmethanol reenters the DV, and so transfers more heme–Fe^III out of the DV. In this way, the 4‐aminoquinolines and arylmethanols exert antimalarial activities by enhancing heme–Fe^III and thence free Fe^III concentrations in the cytosol. The iron species enter into redox cycles through reduction of Fe^III to Fe^II largely mediated by reduced flavin cofactors and likely also by NAD(P)H–Fre. Generation of ROS through oxidation of Fe^II by oxygen will also result. The cytotoxicities of artemisinins are thereby reinforced by the iron. Other aspects of drug action are emphasized. In the cytosol or DV, association by π complex formation between pairs of lipophilic drugs must adversely influence the pharmacokinetics of each drug. This explains the antagonism between PPQ and MFQ, for example. The basis for the antimalarial activity of RF mirrors that of MB, wherein it participates in redox cycling that involves flavoenzymes or Fre, resulting in attrition of NAD(P)H. The generation of ROS by artemisinins and ensuing Fenton chemistry accommodate the ability of artemisinins to induce membrane damage and to affect the parasite SERCA PfATP6 Ca²⁺ transporter. Thus, the effect exerted by artemisinins is more likely a downstream event involving ROS that will also be modulated by mutations in PfATP6. Such mutations attenuate, but cannot abrogate, antimalarial activities of artemisinins. Overall, parasite resistance to artemisinins arises through enhancement of antioxidant defense mechanisms.     

A partial convergence in action of methylene blue and artemisinins: antagonism with chloroquine, a reversal with verapamil, and an insight into the antimalarial activity of chloroquine

Artemisinins rapidly oxidize leucomethylene blue (LMB) to methylene blue (MB); they also oxidize dihydroflavins such as the reduced conjugates RFH₂ of riboflavin (RF), and FADH₂ of the cofactor flavin adenine dinucleotide (FAD), to the corresponding flavins. Like the artemisinins, MB oxidizes FADH₂, but unlike artemisinins, it also oxidizes NAD(P)H. Like MB, artemisinins are implicated in the perturbation of redox balance in the malaria parasite by interfering with parasite flavoenzyme disulfide reductases. The oxidation of LMB by artemisinin is inhibited by chloroquine (CQ), an inhibition that is abruptly reversed by verapamil (VP). CQ also inhibits artemisinin‐mediated oxidation of RFH₂ generated from N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–RF, or FADH₂ generated from NADPH or NADPH–Fre, an effect that is also modulated by verapamil. The inhibition likely proceeds by the association of LMB or dihydroflavin with CQ, possibly involving donor–acceptor or π complexes that hinder oxidation by artemisinin. VP competitively associates with CQ, liberating LMB or dihydroflavin from their respective CQ complexes. The observations explain the antagonism between CQ–MB and CQ–artemisinins in vitro, and are reconcilable with CQ perturbing intraparasitic redox homeostasis. They further suggest that a VP–CQ complex is a means by which VP reverses CQ resistance, wherein such a complex is not accessible to the putative CQ‐resistance transporter (PfCRT).     

At the edge: media constructions of a stigmatised Irish housing estate

By triangulating analyses of content and reception with a focus on production, this article attempts to understand the dynamics of and underlying reasons for the media stigmatisation of place. The research described contributes to a body of work examining how mass media and other social forces factor in the creation of negative stereotypes that damage the reputations of the places in which the poor reside. The overarching framework of understanding, provided by Goffman’s theory of stigma, is complemented by two further inter-related theoretical approaches, namely Social Exclusion and Political Economy. Combining analyses of media production (practices), media content (discourses) and audience reception (beliefs, attitudes), we analyse the representation of one of Ireland’s most deprived public housing estates in the print and broadcast media. Having established the stigmatising character and impact of national and local media content via this tripartite methodology, we focus on identifying and explaining the media practices that serve to (re)produce the estate’s ‘spoiled identity’. Our analysis of journalists’ explanations for these practices identifies the commercial realities, which progressively influence media production, as directly impacting media producers’ relationships with, and depictions of, poor places. We conclude by examining debates regarding the potential for rehabilitating a spoiled identity.     

Improving the Capability of Organizations

The intention of this paper is to provide some guidance on developing organizational capability. It is written with practitioners in mind. It focuses on an approach which draws on systems thinking and which has been found helpful in improving the effectiveness of complex organizations. One particular case study is used to illustrate the methodologies involved. The material is taken from the study of an “environmental” organization, Ecochemical, described in some detail in the text.