Is there a stability problem for Bayesian noncommutative probabilities?

A stability condition for Bayesian statistical inference, which Redei [(1992). When can non-commutative statistical inference be Bayesian? International Studies in the Philosophy of Science, 6, 129–132; (1998). Quantum logic in algebraic approach. Dordrecht: Kluwer Academic Publishers] formulated as a rationality constraint holding in classical probability theory, is shown to fail in quantum mechanics. That allegedly challenges a Bayesian interpretation of quantum probabilities. In this paper we demonstrate that Redei's argument does not apply to quantum mechanics. Moreover, we provide a solution to the problem of Bayesian noncommutative statistical inference arising from the violation of stability condition in general probability spaces.     

Taking up statistical thermodynamics: Equilibrium fluctuations and irreversibility

The microscopic explanation of the physical phenomena represented by a macroscopic theory is often cast in terms of the reduction of the latter to a more fundamental theory, which represents the same phenomena at the microscopic level, albeit in an idealized way. In particular, the reduction of thermodynamics to statistical mechanics is a much discussed case-study in philosophy of physics. Based on the Generalized Nagel–Schaffner model, the alleged reductive explanation would be accomplished if one finds a corrected version of classical thermodynamics that can be strictly derived from statistical mechanics. That is the sense in which, according to Callender (1999, 2001), one should not take thermodynamics too seriously. Arguably, the sought-after revision is given by statistical thermodynamics, intended as a macroscopic theory equipped with a probabilistic law of equilibrium fluctuations. The present paper aims to evaluate this proposal. The upshot is that, while statistical thermodynamics enables one to re-define equilibrium so as to agree with Boltzmann entropy, it does not provide a definitive solution to the problem of explaining macroscopic irreversibility from a microscopic point of view.     

CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein. We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme. Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction.     

Adaptive-optics corrections available for the whole sky

Adaptive-optics systems can in principle allow a telescope to achieve performance at its theoretical maximum (limited only by diffraction), by correcting in real time for the distortion of starlight by atmospheric turbulence. For such a system installed on an 8-m-class telescope, the spatial resolution and sensitivity could be up to 100 times better than conventional imaging. Adaptive-optics corrections have hitherto been achieved only for regions of the sky within a few arcseconds of a bright reference source. But it has been proposed theoretically that by using multiple guide stars, the tomography of atmospheric turbulence could be probed and used to extend adaptive-optics corrections to the whole sky. Here we report the experimental verification of such tomographic corrections, using three off-axis reference stars approximately 15 arcsec from the central star. We used the observations of the off-axis stars to calculate the deformations of the wavefront of the central star, and then compare them with the real measured values. This tomographic approach is found to reduce variations in the wavefront by approximately 92%. Our result demonstrates that a serious barrier to achieving diffraction-limited seeing over the whole sky has been removed.     

Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome

Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies.     

Comparing the accuracy of density forecasts from competing models

A rapidly growing literature emphasizes the importance of evaluating the forecast accuracy of empirical models on the basis of density (as opposed to point) forecasting performance. We propose a test statistic for the null hypothesis that two competing models have equal density forecast accuracy. Monte Carlo simulations suggest that the test, which has a known limiting distribution, displays satisfactory size and power properties. The use of the test is illustrated with an application to exchange rate forecasting. Copyright © 2004 John Wiley & Sons, Ltd.     

An SCN9A channelopathy causes congenital inability to experience pain

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.     

Yeast as a sensor of factors affecting the accuracy of protein synthesis

The cell monitors and maintains the fidelity of translation during the three stages of protein synthesis: initiation, elongation and termination. Errors can arise by multiple mechanisms, such as altered start site selection, reading frame shifts, misincorporation or nonsense codon suppression. All of these events produce incorrect protein products. Translational accuracy is affected by both cis- and trans-acting elements that insure the proper peptide is synthesized by the protein synthetic machinery. Many cellular components are involved in the accuracy of translation, including RNAs (transfer RNAs, messenger RNAs and ribosomal RNAs) and proteins (ribosomal proteins and translation factors). The yeast Saccharomyces cerevisiae has proven an ideal system to study translational fidelity by integrating genetic approaches with biochemical analysis. This review focuses on the ways studies in yeast have contributed to our understanding of the roles translation factors and the ribosome play in assuring the accuracy of protein synthesis.Received 27 November 2002; received after revision 16 April 2003; accepted 25 April 2003