Towards a typology of experimental errors: An epistemological view

This paper is concerned with the problem of experimental error. The prevalent view that experimental errors can be dismissed as a tiresome but trivial blemish on the method of experimentation is criticized. It is stressed that the occurrence of errors in experiments constitutes a permanent feature of the attempt to test theories in the physical world, and this feature deserves proper attention. It is suggested that a classification of types of experimental error may be useful as a heuristic device in studying the nature of these errors. However, the standard classification of systematic and random errors is mathematically based does not focus on the causes of the errors, their origins, or the contexts in which they arise. A new typology of experimental errors is therefore proposed whose criterion is epistemological. This typology reflects the various stages that can be discerned in the execution of an experiment, each stage constituting a category of a certain type of experimental error. The proposed classification consists of four categories which are illustrated by historical cases.     

An examination of factors contributing to delphi accuracy

Three experiments examined the accuracy in the Delphi method. The first experiment assessed the accuracy of group predictions over 1-, 2- and 3- month time spans. Results indicated that predictions derived from the group were more accurate than those of 95 per cent of the individual panelists, but did not exceed in accuracy the best panelists. Experiment 2 evaluated the gross contributions of polling and feedback to Delphi accuracy. The manipulations did not improve the group's ability to forecast the probabilities of the occurrence of events, but did decrease the error in predicting when the events would occur. Experiment 3 separated the effects of polling and feedback as determinants of accuracy. Neither manipulation improved the accuracy of the group's predictions of whether an event would occur. The effect of iterated polling was to reduce the group's error in predicting the time course for those scenarios that did occur.     

Coffee and cola beverage consumption as heart disease risk factors in men

Summary The relationship of coffee drinking and cola beverage consumption to recognized heart disease risk factors was studied in 365 adult men. Cola beverage consumption was not positively related to any risk factor. Heavy coffee drinking seemed to reflect a life style characterized by infrequent eating, which was significantly correlated to all the heart disease risk factors studied.This investigation was supported in part by the Computer Science Center of the University of Maryland.An acknowledgment is due Michael W. Delaney and the Heart Association of Southern Maryland for providing the original data on which this analysis is based.     

A molecular view of cardiogenesis

Cardiac development involves a complex integration of subcellular processes into multicellular and, finally, whole organ effects. Until recently it has been difficult to investigate the genetic control of this organ level differentiation of the heart. The proliferation of molecular biology methodologies has provided mechanisms to directly investigate the control of these processes. This article focuses on molecular lines of research on two key areas in cardiac development: the regulation of expression of sarcomeric contractile and regulatory proteins, and atrial natriuretic factor. Molecular approaches are described which have allowed investigators to begin to determine the tissue and stage-specific expression of genes, to locate those genes in the genome, determine their sequences, and to directly investigate the mechanisms controlling their expression.     

An overview of factors influencing sex determination and gonadal development in birds

The morphological development of the embryonic gonads is very similar in birds and mammals, and recent evidence suggests that the genes involved in this process are conserved between these classes of vertebrates. The genetic mechanism by which sex is determined in birds remains to be elucidated, although recent studies have reinforced the contention that steroids may play an important role in the structural development of the testes and ovaries in birds. So far, few genes have been assigned to the avian sex chromosomes, but it is known that the Z and W chromosomes do not share significant homology with the mammalian X and Y chromosomes. The commercial importance of poultry breeding has motivated considerable investment in developing physical and genetic maps of the chicken genome. These efforts, in combination with modern molecular approaches to analyzing gene expression, should help to elucidate the sex-determining mechanism in birds in the near future.     

Structural view of cadherin-mediated cell-cell adhesion

Following the multiplication of biochemical, biophysical and structural studies describing cadherin molecules and their interactions, several ideas have emerged to explain the mechanisms of cadherin-mediated cell adhesion. Although different models were proposed for cadherin interactions, a consensus has come forth considering lateral dimerization of cadherins as being a central component of the cell-cell adhesion process. This review summarizes the recent development in structural studies of cadherins. Received 14 September 1998; received after revision 14 November 1998; accepted 16 November 1998     

A structural view of microtubule dynamics

The essential microtubule property of dynamic instability is based on the binding, hydrolysis and exchange of GTP in each tubulin dimer. The recent high-resolution structures of tubulin and the microtubule have given us the first view at atomic level of properties such as nucleotide exchangeability, the linkage between polymerization and nucleotide hydrolysis. and the origin of microtubule destabilization, as well as the mode of action of antimitotic agents such as taxol.     

A view on intramembraneous particles

Summary Intramembraneous particles of the outer membrane ofEscherichia coli show complementary pits on the opposite fracture face. This complementarity characteristic has been discussed in relation to the nature of the particle and the mode of fracturing.Acknowledgment. We thank Dr Lugtenberg for his active support and critical comments and Mrs J. Leunissen-Bijvelt for her technical assistance.     

Styles of reasoning: A pluralist view

Styles of reasoning are important devices to understand scientific practice. As I use the concept, a style of reasoning is a pattern of inferential relations that are used to select, interpret, and support evidence for scientific results. In this paper, I defend the view that there is a plurality of styles of reasoning: different domains of science often invoke different styles. I argue that this plurality is an important source of disunity in scientific practice, and it provides additional arguments in support of the disunity claim. I also contrast Ian Hacking’s broad characterization of styles of reasoning with a narrow understanding that I favor. Drawing on examples from molecular biology, chemistry and mathematics, I argue that differences in style of reasoning lead to differences in the way the relevant results are obtained and interpreted. The result is a pluralist view about styles of reasoning that is sensitive to nuances of inferential relations in scientific activity.     

A unified view of statistical forecasting procedures

A large number of statistical forecasting procedures for univariate time series have been proposed in the literature. These range from simple methods, such as the exponentially weighted moving average, to more complex procedures such as Box–Jenkins ARIMA modelling and Harrison–Stevens Bayesian forecasting. This paper sets out to show the relationship between these various procedures by adopting a framework in which a time series model is viewed in terms of trend, seasonal and irregular components. The framework is then extended to cover models with explanatory variables. From the technical point of view the Kalman filter plays an important role in allowing an integrated treatment of these topics.     

A non representationalist view of model explanation

In this paper, I examine two idealized models in astrophysics, with the aim of showing that the idealizations in these models play an important explanatory role. I argue, against many representationalists, that it is because of the idealizations in these models, rather than in spite of them, that the models turn out to have explanatory power. In many cases, this claim can be extended to the use of idealized models in the sciences more generally, and thus it gives important insight into the nature of model explanation.     

Cystic fibrosis: a clinical view

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.     

A structural view of translation initiation in bacteria

The assembly of the protein synthesis machinery occurs during translation initiation. In bacteria, this process involves the binding of messenger RNA(mRNA) start site and fMet-tRNA^fMet to the ribosome, which results in the formation of the first codon-anticodon interaction and sets the reading frame for the decoding of the mRNA. This interaction takes place in the peptidyl site of the 30S ribosomal subunit and is controlled by the initiation factors IF1, IF2 and IF3 to form the 30S initiation complex. The binding of the 50S subunit and the ejection of the IFs mark the irreversible transition to the elongation phase. Visualization of these ligands on the ribosome has been achieved by cryo-electron microscopy and X-ray crystallography studies, which has helped to understand the mechanism of translation initiation at the molecular level. Conformational changes associated with different functional states provide a dynamic view of the initiation process and of its regulation. Received 16 July 2008; received after revision 31 August 2008; accepted 10 September 2008 A. Simonetti, S. Marzid: These authors contributed equally to this work.     

A dynamic view of peptides and proteins in membranes

Biological membranes are highly dynamic supramolecular arrangements of lipids and proteins, which fulfill key cellular functions. Relatively few high-resolution membrane protein structures are known to date, although during recent years the structural databases have expanded at an accelerated pace. In some instances the structures of reaction intermediates provide a stroboscopic view on the conformational changes involved in protein function. Other biophysical approaches add dynamic aspects and allow one to investigate the interactions with the lipid bilayers. Membrane-active peptides fulfill many important functions in nature as they act as antimicrobials, channels, transporters or hormones, and their studies have much increased our understanding of polypeptide-membrane interactions. Interestingly several proteins have been identified that interact with the membrane as loose arrays of domains. Such conformations easily escape classical high-resolution structural analysis and the lessons learned from peptides may therefore be instructive for our understanding of the functioning of such membrane proteins. Received 11 March 2008; received after revision 2 May 2008; accepted 5 May 2008     

Another view of the role of FMRP in translational regulation

No Abstract.  .     

A view of progress in the chemistry of indole alkaloids

Zusammenfassung Neuere Erkenntnisse der theoretischen Chemie, Entwicklungen der chemischen Experimentierkunst und neue und verbesserte physikalische Instrumentation haben die Entwicklung der Indolalkaloidchemie im letzten Dezennium entscheidend gefördert. Die erfolgreiche Konstitutionsermittlung einer Reihe längst bekannter Indolalkaloide wurde dadurch ermöglicht. Ihre Konstitution sowie die Strukturen unlängst isolierter Indolbasen lassen auf eine grosse Mannigfaltigkeit im strukturellen Bau der Indolalkaloide schliessen. Die Biosynthese der Indolalkaloide wird kurz diskutiert, zusammen mit Kommentaren über den Ursprung des Rings E und der Carboxylgruppe in den Yohimbinen.

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This essay reflects the authors' approach to this subject. Only the major theme is developed but certain ideas buried in text may act as catalysts for further thought.