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.     

Regulation of insulin receptor function

Resistance to the biological actions of insulin contributes to the development of type 2 diabetes and risk of cardiovascular disease. A reduced biological response to insulin by tissues results from an impairment in the cascade of phosphorylation events within cells that regulate the activity of enzymes comprising the insulin signaling pathway. In most models of insulin resistance, there is evidence that this decrement in insulin signaling begins with either the activation or substrate kinase activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action. Activation of the IR can be impaired by post-translational modifications of the protein involving serine phosphorylation, or by binding to inhibiting proteins such as PC-1 or members of the SOCS or Grb protein families. The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. Received 3 August 2006; received after revision 1 December 2006; accepted 8 January 2007     

Memory

The molecular mechanisms underlying the induction and maintenance of memory are highly dynamic and comprise distinct phases covering a time window from seconds to even a lifetime. Neuronal networks, which contribute to these processes, have been extensively characterized on various levels of analysis, and imaging techniques allow monitoring of both gross brain activity as well as functional changes in defined brain areas during the time course of memory formation. New techniques developed in honeybees and fruit flies even allow for manipulation of neuronal networks and molecular cascades in a short temporal domain while a living animal under observation acquires new associative memories. These advantages make honeybees and flies ideal organisms to study transient molecular events underlying dynamic memory processing in vivo. In this review we will focus on the temporal features of molecular processes in learning and memory formation, summarize recent knowledge and present an outlook on future developments.     

Lake Tanganyika as an evolutionary reservoir of old lineages of East African cichlid fishes: Inferences from allozyme data

Genetic differences between 20 species of cichlid fish, representing all the 12 tribes proposed for the cichlid fish fauna of Lake Tanganyika, were studied by allozyme electrophoresis. Most species were genetically very differentiated from each other. Phylogenetic analysis based on the allozyme data indicated that at least seven old, ancestral lineages have contributed to the present cichlid fauna of the lake. Lake Tanganyika, the oldest of the rift-valley lakes, can be recognized as an evolutionary reservoir of major lineages of cichlids in East Africa.     

Melatonin: presence and formation in invertebrates

In vertebrates, it is now clearly demonstrated that the pineal gland is implicated in conveying photoperiodic information via the daily pattern of melatonin secretion. Invertebrates, like vertebrates, use photoperiodic changes as a temporal cue to initiate physiological processes such as reproduction or diapause. How this information is integrated in invertebrates remains an unsolved question. Our review will be an attempt to evaluate the possible role of melatonin in conveying photoperiodic information in invertebrates. It is now well demonstrated in both vertebrates and invertebrates that melatonin as well as its precursors or synthesizing enzymes are present in various organs implicated in photoreceptive processes or in circadian pacemaking. Melatonin, serotonin or N-acetyltransferase have been found in the head, the eyes, the optic lobe and the brain of various invertebrate species. In some species it has also been shown that melatonin is produced rhythmically with high concentrations reached during the dark period. Moreover, the physiological effects of melatonin on various periodic processes such as rhythmic contractions in coelenterates, fissioning of asexual planarians or reproductive events in flies have been reported in the literature. All these results support the hypothesis (refs 36, 37) that melatonin is not solely a pineal hormone but that it may be an evolutionary conservative molecule principally involved in the transduction of photoperiodic information in all living organisms.     

Species concepts,process analysis,and the hierarchy of nature

Species figure prominently in all biological studies, but what a species actually is and how we recognize it in practice is still a much-debated issue. Present discussion revolves around five major species concepts: the biological, the evolutionary, the cladistic, the recognition and the phylogenetic concepts. Each of these species notions has its theoretical and practical problems. One important point that has emerged from recent discussions on the ontological status of species is that there is a tension between species concepts based on interbreeding and those based on genealogy, and that practical application of these two kinds of concept may give rise to incompatible results. Species recognized by one species concept appear to be essentially different entities compared with species demarcated by another. However, these different species may all represent real and objective entities in nature. What we perceive as a species depends on the evolutionary processes that we have made objects of our research. Some of these processes are between entities of the genealogical hierarchy of nature, while other processes relate to nature's ecological hierarchy. It is essential that our species concept should be adjusted to the focal level of our research program, thereby taking into full account the two process hierarchies of nature.     

Evolution of the arginase fold and functional diversity

Novel structural superfamilies can be identified among the large number of protein structures deposited in the Protein Data Bank based on conservation of fold in addition to conservation of amino acid sequence. Since sequence diverges more rapidly than fold in protein Evolution, proteins with little or no significant sequence identity are occasionally observed to adopt similar folds, thereby reflecting unanticipated evolutionary relationships. Here, we review the unique alpha/beta fold first observed in the manganese metalloenzyme rat liver arginase, consisting of a parallel eight-stranded beta-sheet surrounded by several helices, and its evolutionary relationship with the zinc-requiring and/or iron-requiring histone deacetylases and acetylpolyamine amidohydrolases. Structural comparisons reveal key features of the core alpha/beta fold that contribute to the divergent metal ion specificity and stoichiometry required for the chemical and biological functions of these enzymes.     

Biological teleology: Questions and explanations

This paper gives an account of evolutionary explanations in biology. Briefly, the explanations I am primarily concerned with are explanations of adaptations. (‘Adaptation’ is a technical term and defining it requires a fairly lengthy digression.) These explanations are contrasted with other nonteleological evolutionary explanations. The distinction is made by distinguishing the different kinds of questions these different explanations serve to answer. The sense in which explanations of adaptations are teleological is spelled out.     

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase (NMNAT) has long been known as the master enzyme in NAD biosynthesis in living organisms. A burst of investigations on NMNAT, going beyond enzymology, have paralleled increasing discoveries of key roles played by NAD homeostasis in a number or patho-physiological conditions. The availability of in-depth kinetics and structural enzymology analyses carried out on NMNATs from different organisms offer a powerful tool for uncovering fascinating evolutionary relationships. On the other hand, additional functions featuring NMNAT have emerged from investigations aimed at unraveling the molecular mechanisms responsible for complex biological phenomena such as neurodegeneration. NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at a crossroads of multiple cellular processes. The resultant wealth of biochemical data has built a robust framework upon which design of NMNAT activators, inhibitors or enzyme variants of potential medical interest can be based.     

Testing weak rationality of forecasts with different time horizons

Starting with conventional tests for weak rationality, we show how additional tests can be performed if predictions with different time horizons are commonly used in them. Next, we show that most of these tests can still be applied if the structure of the economic system changes but only some of them if the true system is unknown. Finally, these tests are applied to the semi-annual one-and two-step predictions of the group of five leading economic research institutes in the Federal Republic of Germany. For the two-step predictions we find more evidence against the rational expectations hypothesis than for the one-step predictions.     

Modelling of microbial degradation processes: The behaviour ofmicroorganisms in a waste repository

Summary In a repository for radioactive disposal the waste material is kept in place by several shells and boundaries to prevent a long term recycling of the material into the environment. Present investigations on various chemical and biological processes can be extrapolated into future centuries only with great uncertainty. Models may therefore be a good tool to forecast processes which may occur within the repository and to estimate whether the barriers present will prevent the leaching of waste material within a given time span. A mathematical model is described based on an experimental laboratory setup, a microcosm described by West et al.^19–22 simulating in a laboratory system repository conditions for a Swiss L/ILW repository. It includes microbial as well as physico-chemical processes. These simulations indicate that biological processes such as gas formation or proton release should also be included into the safety assessment of the repositories.     

Judgmental extrapolation and the salience of change

People may often forecast using cognitive procedures that resemble formal time-series extrapolation models. A model of judgmental extrapolation based on exponential smoothing is proposed in which the setting of the trend parameter is hypothesized to depend upon the relative salience of the successive changes. The salience hypothesis was first tested with exponential series by the use of a framing manipulation. As predicted, focusing the subjects' attention on the changes led to more accurate forecasts. In two investment simulation studies, the salience hypothesis was further examined by varying the statistical properties of the price changes. As predicted, subjects were more likely to sell as prices fell and to buy as prices rose (1) as the sample size of similar changes increased; (2) when the variance of the changes was low; and (3) when the absolute value of the mean change was high. Conditions that may influence judgmental forecasting processes are discussed.     

Protein arginine methylation: a prominent modification and its demethylation

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.     

Representing with imaginary models: Formats matter

Models such as the simple pendulum, isolated populations, and perfectly rational agents, play a central role in theorising. It is now widely acknowledged that a study of scientific representation should focus on the role of such imaginary entities in scientists’ reasoning. However, the question is most of the time cast as follows: How can fictional or abstract entities represent the phenomena? In this paper, I show that this question is not well posed. First, I clarify the notion of representation, and I emphasise the importance of what I call the “format” of a representation for the inferences agents can draw from it. Then, I show that the very same model can be presented under different formats, which do not enable scientists to perform the same inferences. Assuming that the main function of a representation is to allow one to draw predictions and explanations of the phenomena by reasoning with it, I conclude that imaginary models in abstracto are not used as representations: scientists always reason with formatted representations. Therefore, the problem of scientific representation does not lie in the relationship of imaginary entities with real systems. One should rather focus on the variety of the formats that are used in scientific practice.     

Sexual responses of female canaries at the onset of song stimuli

The salience of a short conspecific song phrase versus a long one or a short heterospecific song phrase was tested in females of the common domesticated canary (Serinus canaria). All phrases were computer-edited. The copulation solicitation displays (CSD) served as an index of female responses. The results support the hypothesis that female canaries are able at the onset of a song phrase stimulus: 1) to respond to a conspecific one by displaying high levels of CSD and 2) to discriminate a conspecific from a heterospecific one. Proximal explanations examine the link between perceptual processes and phonology in the canary. Functional explanations investigate the relations between female responsiveness and the process of pair formation.     

Study of molecular events in cells by fluorescence correlation spectroscopy

To understand processes in a living cell, sophisticated and creative approaches are required that can be used for gathering quantitative information about large number of components interacting across temporal and spatial scales without major disruption of the integral network of processes. A physical method of analysis that can meet these requirements is fluorescence correlation spectroscopy (FCS), which is an ultrasensitive and non-invasive detection method capable of single-molecule and real-time resolution. Since its introduction about 3 decades ago, this until recently emerging technology has reached maturity. As commercially built equipment is now available, FCS is extensively applied for extracting biological information from living cells unattainable by other methods, and new biological concepts are formulated based on findings by FCS. In this review, we focus on examples in the field of molecular cellular biology. The versatility of the technique in this field is illustrated in studies of single-molecule dynamics and conformational flexibility of proteins, and the relevance of conformational flexibility for biological functions regarding the multispecificity of antibodies, modulation of activity of C5a receptors in clathrin-mediated endocytosis and multiplicity of functional responses mediated by the p53 tumor suppressor protein; quantitative characterization of physicochemical properties of the cellular interior; protein trafficking; and ligand-receptor interactions. FCS can also be used to study cell-to-cell communication, here exemplified by clustering of apoptotic cells via bystander killing by hydrogen peroxide.Received 15 July 2004; received after revision 13 October 2004; accepted 12 November 2004     

The accuracy of individual and group forecasts from business outlook surveys

This paper reports on the accuracy of quarterly multiperiod predictions of inflation, real growth, unemployment and percentage changes in nominal GNP and two of its more volatile components. The survey data are highly differentiated; they cover 79 professional forecasters (mostly economists, analysts and corporate executives). Combining corresponding predictions from different sources can result in significant gains; thus the group mean forecasts are on the average over time more accurate than most of the corresponding sets of individual forecasts. But there is also a moderate degree of consistency in the relative performance of a sufficient number of the survey members, as evidenced in positive rank correlations among ratios of the individual to group root mean square errors.