Auditing as the Dissolution of Corruption

This paper develops a new discourse of control. The new discourse rejects the view that control is achieved through inspections and information alone, and supports the view that effective control means self-control and effective communications, both being necessary conditions to enable organizations to perform well. In this discourse, corruption is taken to be, among other things, the outcome of fragmentation in communications. Therefore, a movement toward a recursive organization of the State is offered as a way to countering corruption. This discourse was developed during a project for Institutional Change and Strengthening implemented at the Contraloría General de la República (CGR), in Colombia from 1995 to 1998. As part of the discourse we offer a distinction among traditional auditing practices, second-order auditing, and integrated systemic auditing practices.     

Probing the chemistry of thioredoxin catalysis with force

Thioredoxins are enzymes that catalyse disulphide bond reduction in all living organisms. Although catalysis is thought to proceed through a substitution nucleophilic bimolecular (S(N)2) reaction, the role of the enzyme in modulating this chemical reaction is unknown. Here, using single-molecule force-clamp spectroscopy, we investigate the catalytic mechanism of Escherichia coli thioredoxin (Trx). We applied mechanical force in the range of 25-600 pN to a disulphide bond substrate and monitored the reduction of these bonds by individual enzymes. We detected two alternative forms of the catalytic reaction, the first requiring a reorientation of the substrate disulphide bond, causing a shortening of the substrate polypeptide by 0.79 +/- 0.09 A (+/- s.e.m.), and the second elongating the substrate disulphide bond by 0.17 +/- 0.02 A (+/- s.e.m.). These results support the view that the Trx active site regulates the geometry of the participating sulphur atoms with sub-?ngstr?m precision to achieve efficient catalysis. Our results indicate that substrate conformational changes may be important in the regulation of Trx activity under conditions of oxidative stress and mechanical injury, such as those experienced in cardiovascular disease. Furthermore, single-molecule atomic force microscopy techniques, as shown here, can probe dynamic rearrangements within an enzyme's active site during catalysis that cannot be resolved with any other current structural biological technique.     

Metallothionein expression in the central nervous system of multiple sclerosis patients

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.     

Complexity and change: Reflections upon the cybernetic intervention in Chile, 1970–1973

Social change depends on communications. The more effective the communication mechanisms between the participants in a situation are, the more likely it is that they will contribute, to the best of their abilities, to the discovery and production of desirable change. Hence the relevance of studying, and improving, the cybernetics of problem situations. Effectiveness in this case is defined by the degree to which the complexity of the situation is matched by the complexity of the regulatory mechanisms in use. However, if this proposition is going to be useful, it is necessary to have approaches to work out the matching. This paper discusses a cybernetic methodology, relying on Beer's Viable System Model, which enables a deeper understanding of, and capacity to deal with, situational and regulatory complexities. Finally, these ideas are used to reflect upon the cybernetic intervention in the Chile of the early 1970's.     

Significant primordial star formation at redshifts z approximately 3-4

Four recent observational results have challenged our understanding of high-redshift galaxies, as they require the presence of far more ultraviolet photons than should be emitted by normal stellar populations. First, there is significant ultraviolet emission from Lyman break galaxies (LBGs) at wavelengths shorter than 912 A. Second, there is strong Lyman alpha emission from extended 'blobs' with little or no associated apparent ionizing continuum. Third, there is a population of galaxies with unusually strong Lyman alpha emission lines. And fourth, there is a strong He II (1,640 A) emission line in a composite of LBGs. The proposed explanations for the first three observations are internally inconsistent, and the fourth puzzle has remained hitherto unexplained. Here we show that all four problems are resolved simultaneously if 10-30 per cent of the stars in many galaxies at z approximately 3-4 are mainly primordial--unenriched by elements heavier than helium ('metals'). Most models of hierarchical galaxy formation assume efficient intragalactic metal mixing, and therefore do not predict metal-free star formation at redshifts significantly below z approximately 5. Our results imply that micromixing of metals within galaxies is inefficient on an approximately gigayear timescale, a conclusion that can be verified with higher-resolution simulations, and future observations of the He ii emission line.