Allocating the weights in the linear opinion pool

A standard approach to the combination of probabilistic opinions involves taking a weighted linear average of the individuals distributions. This paper reviews some of the possible interpretations that have been proposed for these weights in the literature on expert use. Several paradigms for selecting weights are also considered. Special attention is devoted to the Bayesian mechanism used for updating expert weights in the face of new information. An asymptotic result is proved which highlights the importance of choosing the initial weights carefully.     

THE PERIODIC CAPACITATED ARC ROUTING PROBLEM LINEAR PROGRAMMING MODEL, METAHEURISTIC AND LOWER BOUNDS

1. Introduction The Capacitated Arc Routing Problem(CARP) is defined on an undirected network inwhich a fleet of identical vehicles with limitedcapacity is based at a depot node. Each edge hasa non-negative traversal cost and can betraversed any number…     

Probability distributions,trading strategies and leverage: an application of Gaussian mixture models

The purpose of this paper is twofold. Firstly, to assess the merit of estimating probability density functions rather than level or classification estimations on a one‐day‐ahead forecasting task of the EUR/USD time series. This is implemented using a Gaussian mixture model neural network, benchmarking the results against standard forecasting models, namely a naïve model, a moving average convergence divergence technical model (MACD), an autoregressive moving average model (ARMA), a logistic regression model (LOGIT) and a multi‐layer perceptron network (MLP). Secondly, to examine the possibilities of improving the trading performance of those models with confirmation filters and leverage. While the benchmark models perform best without confirmation filters and leverage, the Gaussian mixture model outperforms all of the benchmarks when taking advantage of the possibilities offered by a combination of more sophisticated trading strategies and leverage. This might be due to the ability of the Gaussian mixture model to identify successfully trades with a high Sharpe ratio. Copyright © 2004 John Wiley & Sons, Ltd.     

Nucleotide analogues as probes for DNA polymerases

Transmission of the genetic information from the parental DNA strand to the offspring is crucial for the survival of any living species. In nature, all DNA synthesis in DNA replication, recombination and repair is catalyzed by DNA polymerases and depends on their ability to select the canonical nucleobase pair from a pool of structurally similar building blocks. Recently, a wealth of valuable new insights into DNA polymerase mechanisms have been gained through application of carefully designed synthetic nucleotides and oligonucleotides in functional enzyme studies. The applied analogues exhibit features that differ in certain aspects from their natural counterparts and, thus, allow investigation of the involvement and efficacy of a chosen particular aspect on the entire complex enzyme mechanism. This review will focus on a depiction of the efforts that have been undertaken towards the development of nucleotide analogues with carefully altered properties. The different approaches will be discussed in the context of the motivation and the problem under investigation.Received 16 March 2005; received after revision 5 May 2005; accepted 8 June 2005     

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.     

Structure of the cross-beta spine of amyloid-like fibrils

Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross-beta spine. It is a double beta-sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.     

An extant cichlid fish radiation emerged in an extinct Pleistocene lake

The haplochromine cichlid fish of the East African Great Lakes represent some of the fastest and most species-rich adaptive radiations known, but rivers in most of Africa accommodate only a few morphologically similar species of haplochromine cichlid fish. This has been explained by the wealth of ecological opportunity in large lakes compared with rivers. It is therefore surprising that the rivers of southern Africa harbour many, ecologically diverse haplochromines. Here we present genetic, morphological and biogeographical evidence suggesting that these riverine cichlids are products of a recent adaptive radiation in a large lake that dried up in the Holocene. Haplochromine species richness peaks steeply in an area for which geological data reveal the historical existence of Lake palaeo-Makgadikgadi. The centre of this extinct lake is now a saltpan north of the Kalahari Desert, but it once hosted a rapidly evolving fish species radiation, comparable in morphological diversity to that in the extant African Great Lakes. Importantly, this lake seeded all major river systems of southern Africa with ecologically diverse cichlids. This discovery reveals how local evolutionary processes operating during a short window of ecological opportunity can have a major and lasting effect on biodiversity on a continental scale.