Forecasting recessions using the yield curve

We compare forecasts of recessions using four different specifications of the probit model: a time invariant conditionally independent version; a business cycle specific conditionally independent model; a time invariant probit with autocorrelated errors; and a business cycle specific probit with autocorrelated errors. The more sophisticated versions of the model take into account some of the potential underlying causes of the documented predictive instability of the yield curve. We find strong evidence in favour of the more sophisticated specification, which allows for multiple breakpoints across business cycles and autocorrelation. We also develop a new approach to the construction of real time forecasting of recession probabilities. Copyright © 2005 John Wiley & Sons, Ltd.     

Empirical factors and structure transference: Returning to the London account

We offer a framework to represent the roles of empirical and theoretical factors in theory construction, and examine a case study to illustrate how the framework can be used to illuminate central features of scientific reasoning. The case study provides an extension of French and Ladyman's (1997) analysis of Fritz and Heinz London's model of superconductivity to accommodate the role of the analogy between superconductivity and diamagnetic phenomena in the development of the model between 1935 and 1937. We focus on this case since it allows us to separate the roles of empirical and theoretical factors, and so provides an example of the utility of the approach that we have adopted. We conclude the paper by drawing on the particular framework here developed to address a range of concerns.     

Unitary inequivalence as a problem for structural realism

The existence of unitarily inequivalent representations in quantum field theory has been presented as a serious problem for structural realism. In this paper I explore two possible responses. The first involves adopting Wallace's ‘naïve Lagrangian’ interpretation of QFT and dismissing the generation of inequivalent representations as either a mathematical artefact or as non-pathological. The second takes up Ruetsche's ‘Swiss Army Knife’ approach and understands the relevant structure as spanning a range of possibilities. Both options present interesting implications for structural realism and I shall also consider related issues to do with underdetermination, the significance of spontaneous symmetry breaking and how we should understand superselection rules in the context of quantum statistics. Finally, I shall suggest a way in which these options might be combined.     

How People Use Rich Pictures to Help Them Think and Act

Groups of all kinds are complex organisations. To understand them and to facilitate them in process terms is a matter of rich and diverse discourse in varied fields from sustainable development to coastal ecology; from bandwidth in rural communities to health service provision. How to allow groups to discourse, problem solve and review their own issues and concerns? Diagrams in general and rich pictures in particular can be great means to allow groups to explore their subconscious, their occult sentiments and conflicted understandings. This paper explores and explains diverse use of pictures and shows how they can be applied and understood in group processes of all kinds.     

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF

Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.