Methodological foundations of systems methodologies

In social systems science generally, and in management science particularly, recent developments in the variety of types of specific problem-solving methodologies (under the rubric of hard and soft systems approaches) have given an impetus to a line of inquiry, as well as debate on the nature of those methodologies. On the one hand, there has been the view that what we are witnessing is a form of Kuhnian crisis. On the other hand, a complementarist view of developments has been argued and a contingency approach proposed. But one thing has been common among the competing views: a belief that the prospects for further advances in the design and application of those methodologies, and in resolving the current controversies, lie in serious attempts to reconsider and clarify the underlying metatheoretical assumptions and concerns. This paper is an attempt to contribute to such an endeavor. A brief exposition of three methodological foundations (namely, empiricism, hermeneutics, and critique) is made, not only with the purpose of highlighting the nature as well as the limits of their epistemological and ethical claims, but also as a basis for illuminating both the nature of contemporary work on systems inquiry, design, and problem solving and the ongoing debate on what constitutes appropriate criteria for choice of specific methodologies.     

Misuses of biology in the context of the paranormal

Summary Public suspicion of science stems from science's challenging of perceptions and myths about reality, and a public fear of new technology. The result is a susceptibility to pseudoscience. In claiming that creation science is as valid as evolution the creationists misquote scientists and seek to spread their own scientific myths concerning a young age for the earth, an act of creation based on a particular literalist interpretation of the Christian Bible and a single worldwide flood. They use methods of debate and politics, rather than scientific research. A selection of their arguments is examined and the nature of the evidence for evolution is discussed. Problems with the creation science model are noted. In the myth of the hundredth monkey phenomenon, original research is misquoted to denigrate scientific research and support sentimental ideas of paranormal events. The misuse of science is seen as damaging to society because it reduces the effective gathering and application of scientific information. However, pseudoscience provides a valuable guide to gaps in public scientific education.     

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

Summary The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF₁ and TxB₂ was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5×10^–3 to 5×10^–7 g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.     

Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation

We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation.     

Definition of a consensus binding site for p53.

Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.     

C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.     

A frameshift mutation in the gamma E-crystallin gene of the Elo mouse.

The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype.     

Identification of a new predaceous stink bug pheromone and its attractiveness to the eastern yellowjacket

Summary Males ofPodisus fretus (Hemiptera: Pentatomidae) release a long-range attractant pheromone containing linalool (49.0%), (E)-2-hexenal (34.5%), benzyl alcohol (12.0%), nerolidol (2.0%),-terpineol (1.1%), and traces of several other compounds. The eastern yellowjacket,Vespula maculifrons (Hymenoptera: Vespidae), is attracted to artificial pheromones forP. fretus and for the sympatric species,Podisus maculiventris.The authors thank Mr T.J. Henry of the USDA Systematic Entomology Laboratory and Dr J.E. McPherson, Southern Illinois University, for examining the pentatomid species and Dr A.S. Menke, USDA-SEL, for determining the yellowjacket species. We also thank S. Wilzer for technical assistance. Mention of a company name does not imply endorsement by the US Department of Agriculture.     

Determination of erythrocyte pyrimidine 5′-nucleotidase activity by31P nuclear magnetic resonance: Comparison of normal controls and multiple sclerosis patients

Summary A technique to assay erythrocyte pyrimidine 5-nucleotidase activity in situ using³¹P nuclear magnetic resonance spectroscopy is presented. The assay is chemically specific, simple and applicable to untreated lysates. A comparison of enzyme levels in normal controls and in multiple sclerosis patients employing the assay yielded no significant differences between both groups. Difficulties encountered in the quantitative analysis of the assay using¹H-NMR spectroscopy are briefly discussed.     

Molt-induced muscle atrophy decreases the zinc content of the pectoralis of the Giant Canada Goose (Branta canadensis maxima)

Summary During molt-induced atrophy of the pectoralis muscle of the Giant Canada Goose (Branta canadensis maxima), the zinc content of the muscle was significantly reduced (p0.0139), though the concentration of zinc per unit weight of muscle appeared higher (p0.0232). Zinc lost from the muscle during molt could be utilized for growth of the new flight feathers.Acknowledgments. Funds for this study were obtained from an operating grant awarded to J. C. G. by the Natural Sciences and Engineering Research Council of Canada.