Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

Testing for unreliable estimators and insignificant forecasts in combined forecasts

The reliability and precision of the weights used in combining individual forecasts, irrespective of the method of combination, is important in evaluating a combined forecast. The objective of this study is not to suggest the ‘best’ method of combining individual forecasts, but rather to propose exploratory procedures, that make use of all available sample information contained in the covariance matrix of individual forecast errors, to (1) detect if the weights used in combining forecasts are ‘reliable’ (and ‘stable’ if it is known that the covariance matrix of forecast errors is stationary over time) and (2) test for ‘insignificant’ individual forecasts used in forming a combined forecast. We present empirical applications using two-year sales and individual forecast data provided by a major consumer durables manufacturer to illustrate the feasibility of our proposed procedures.     

Plasma enteroglucagon,peptide YY and gastrin in rats deprived of luminal nutrition,and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p<0.001) of=" intravenously=" fed=" (tpn)=" rats.=" urogastrone-epidermal=" growth=" factor,=" (uro-egf),=" reversed=" these=" changes.=" although=" plasma=" enteroglucagon=" and=" gastrin=" levels=" showed=" a=" small=" increase=" with=" uro-egf,=" this=" was=" far=" less=" than=" the=" gut=" tissue=" weight=" change,=" suggesting=" that=" it=" was=" unlikely=" that=" they=" were=" involved=" in=" modulating=" the=" proliferative=" response=" of=" the=" intestine=" to=" uro-egf.=" peptide=" tyrosine=" tyrosine=" (pyy)=" levels=" were=" however=" significantly=" increased=" by=" uro-egf,=" indicating=" that=" pyy=" may=" possibly=" have=" a=" role=" in=" the=" modulation=" of=" intestinal=" cell=">We thank the Cancer Research Campaign for their financial assistance and acknowledge the technical assistance of Mr W. Lenton.     

A beautiful sea: P. A. M. Dirac's epistemology and ontology of the vacuum

This paper charts P.A.M. Dirac's development of his theory of the electron, and its radical picture of empty space as an almost-full plenum. Dirac's Quantum Electrodynamics famously accomplished more than the unification of special relativity and quantum mechanics. It also accounted for the ‘duplexity phenomena’ of spectral line splitting that we now attribute to electron spin. But the extra mathematical terms that allowed for spin were not alone, and this paper charts Dirac's struggle to ignore or account for them as a sea of strange, negative-energy, particles with positive ‘holes’. This work was not done in solitude, but rather in exchanges with Dirac's correspondence network. This social context for Dirac’s work contests his image as a lone genius, and documents a community wrestling with the ontological consequences of their work. Unification, consistency, causality, and community are common factors in explanations in the history of physics. This paper argues on the basis of materials in Dirac's archive that --- in addition --- mathematical beauty was an epistemological factor in the development of the electron and hole theory. In fact, if we believe that Dirac's beautiful mathematics captures something of the world, then there is both an epistemology and an ontology of mathematical beauty.     

Forecasting US inflation by Bayesian model averaging

Recent empirical work has considered the prediction of inflation by combining the information in a large number of time series. One such method that has been found to give consistently good results consists of simple equal‐weighted averaging of the forecasts from a large number of different models, each of which is a linear regression relating inflation to a single predictor and a lagged dependent variable. In this paper, I consider using Bayesian model averaging for pseudo out‐of‐sample prediction of US inflation, and find that it generally gives more accurate forecasts than simple equal‐weighted averaging. This superior performance is consistent across subsamples and a number of inflation measures. Copyright © 2008 John Wiley & Sons, Ltd.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.     

The modulus of elasticity of lobster aorta microfibrils

The presence of elastic fibres in the extracellular matrix (ECM) provides physiologically important elastic properties for many tissues. Until recently, microfibrils, one component of the ECM, were thought primarily to serve as a scaffolding on which elastin is deposited during development to form elaunin fibres [1]. The most prominent protein that forms mammalian microfibrils is fibrillin. It is known that mutations in the fibrillin gene cause a heterogenous connective tissue disease called marfan syndrome [2], so information on mechanical properties of microfibrils or their role in tissue function would be useful. Microfibrils are also found in the ECM of some invertebrate tissues, and there is growing evidence that the protein forming the structure is homologous to mammalian fibrillin [3, 4]. It has been shown that the microfibril-based arterial wall of the lobster has viscoelastic properties [5], and we have now utilized this primitive artery to measure the modulus of elasticity of microfibrils. It is similar to that of the rubber-like protein elastin.     

Population choice in mapping genes for complex diseases

The difficulty of identifying susceptibility genes for common diseases has polarized geneticists' views on what disease models are appropriate and how best to proceed once high-density genome maps become available. Different disease models have different implications for using linkage or linkage-disequilibrium-based approaches for mapping complex disease genes. We argue that the choice of study population is a critical factor when designing a study, and that genetically simplified isolates are more useful than diverse continental populations under most assumptions.