Polymorphic CAG repeat length in the androgen receptor gene and association with neurodegeneration in a heterozygous female carrier of Kennedy's disease

Kennedy's disease (spinobulbar muscular atrophy) is an X-linked form of motor neuron disease affecting adult males carrying a CAG trinucleotide repeat expansion within the androgen receptor gene. While expression of Kennedy's disease is thought to be confined to males carrying the causative mutation, subclinical manifestations have been reported in a few female carriers of the disease. The reasons that females are protected from the disease are not clear, especially given that all other diseases caused by CAG expansions display dominant expression. In the current study, we report the identification of a heterozygote female carrying the Kennedy's disease mutation who was clinically diagnosed with motor neuron disease. We describe analysis of CAG repeat number in this individual as well as 33 relatives within the pedigree, including two male carriers of the Kennedy's mutation. The female heterozygote carried one expanded allele of the androgen receptor gene with CAG repeats numbering in the Kennedy's disease range (44 CAGs), with the normal allele numbering in the upper-normal range (28 CAGs). The subject has two sons, one of whom carries the mutant allele of the gene and has been clinically diagnosed with Kennedy's disease, whilst the other son carries the second allele of the gene with CAGs numbering in the upper normal range and displays a normal phenotype. This coexistence of motor neuron disease and the presence of one expanded allele and one allele at the upper limit of the normal range may be a coincidence. However, we hypothesize that the expression of the Kennedy's disease mutation combined with a second allele with a large but normal CAG repeat sequence may have contributed to the motor neuron degeneration displayed in the heterozygote female and discuss the possible reasons for phenotypic expression in particular individuals.

Accessing chain length dependent termination rate coefficients of methyl methacrylate (MMA) via the reversible addition fragmentation chain transfer (RAFT) process

The RAFT-CLD-T methodology is demonstrated to be not only applicable to 1-substituted monomers such as styrene and acrylates, but also to 1,1-disubstituted monomers such as MMA. The chain length of the terminating macromolecules is controlled by CPDB in MMA bulk free radical polymerization at 80 degrees C. The evolution of the chain length dependent termination rate coefficient, k(t)(i,i), was constructed in a step-wise fashion, since the MMA/CPDB system displays hybrid behavior (between conventional and living free radical polymerization) resulting in initial high molecular weight polymers formed at low RAFT agent concentrations. The obtained CLD of k(t) in MMA polymerizations is compatible with the composite model for chain length dependent termination. For the initial chain-length regime, up to a degree of polymerization of 100, k(t) decreases with alpha (in the expression k(t)(i,i) = k(t)(0) . i(-alpha)) being close to 0.65 at 80 degrees C. At chain lengths exceeding 100, the decrease is less pronounced (affording an alpha of 0.15 at 80 degrees C). However, the data are best represented by a continuously decreasing nonlinear functionality implying a chain length dependent alpha.

Referral patterns in a global store-and-forward telemedicine system

We examined the nature of the referral patterns in the email telemedicine network operated by the Swinfen Charitable Trust with a view to informing long-term resource planning. Over the first six years of operation, 62 hospitals from 19 countries registered with the Trust in order to be able to refer cases for specialist advice; 55 of these hospitals (89%) actually referred cases during this period. During the first six years of operation, nearly 1000 referrals were submitted and answered, from a wide range of specialty areas. Between July 2002 and March 2005 the referral rate rose from 127 to 318 cases per year. The median length of time required to provide a specialist's response was 2.3 days during the first 12 months and 1.8 days during the last 12 months. Five hospitals submitted cases for more than four years (together sending a total of 493 cases). Their activity data showed a trend to declining referral rates over the four-year period, which may represent successful knowledge transfer. There is some evidence that over the last three years the growth in demand has been exponential, while the growth in resources available (i.e. specialists) has been linear, a situation which cannot continue for very long before demand outstrips supply.

Efficiency, costs and trade-offs in marine reserve system design

With marine biodiversity conservation the primary goal for reserve planning initiatives, a site's conservation potential is typically evaluated on the basis of the biological and physical features it contains. By comparison, socio-economic information is seldom a formal consideration of the reserve system design problem and generally limited to an assessment of threats, vulnerability or compatibility with surrounding uses. This is perhaps surprising given broad recognition that the success of reserve establishment is highly dependent on widespread stakeholder and community support. Using information on the spatial distribution and intensity of commercial rock lobster catch in South Australia, we demonstrate the capacity of mathematical reserve selection procedures to integrate socio-economic and biophysical information for marine reserve system design. Analyses of trade-offs highlight the opportunities to design representative, efficient and practical marine reserve systems that minimise potential loss to commercial users. We found that the objective of minimising the areal extent of the reserve system was barely compromised by incorporating economic design constraints. With a small increase in area (< 3%) and boundary length (< 10%), the economic impact of marine reserves on the commercial rock lobster fishery was reduced by more than a third. We considered also how a reserve planner might prioritise conservation areas using information on a planning units selection frequency. We found that selection frequencies alone were not a reliable guide for the selection of marine reserve systems, but could be used with approaches such as summed irreplaceability to direct conservation effort for efficient marine reserve design.

Vector Error-Correction Models in a consumer packaged goods category forecasting decision support system

A framework for developing marketing category management decision support systems (DSS) based upon the Bayesian Vector Autoregressive (BVAR) model is extended. Since the BVAR model is vulnerable to permanent and temporary shifts in purchasing patterns over time, a form that can correct for the shifts and still provide the other advantages of the BVAR is a Bayesian Vector Error-Correction Model (BVECM). We present the mechanics of extending the DSS to move from a BVAR model to the BVECM model for the category management problem. Several additional iterative steps are required in the DSS to allow the decision maker to arrive at the best forecast possible. The revised marketing DSS framework and model fitting procedures are described. Validation is conducted on a sample problem.

The effect of copper toxicity on the growth and root morphology of Rhodes grass (Chloris gayana Knuth.) in resin buffered solution culture

A solution culture experiment was conducted to examine the effect of Cu toxicity on Rhodes grass (Chloris gayana Knuth.), a pasture species used in mine-site rehabilitation. The experiment used dilute, solution culture to achieve external nutrient concentrations, which were representative of the soil solution, and an ion exchange resin to maintain stable concentrations of Cu in solution. Copper toxicity was damaging to plant roots, with symptoms ranging from disruption of the root cuticle and reduced root hair proliferation, to severe deformation of root structure. A reduction in root growth was observed at an external Cu concentration of < 1 mu M, with damage evident from an external concentration of 0.2 mu M. Critical to the success of this experiment, in quantitatively examining the relationship between external Cu concentration and plant response, was the use of ion exchange resin to buffer the concentration of Cu in solution. After some initial difficulty with pH control, stable concentrations of Cu in solution were maintained for the major period of plant growth. The development of this technique will facilitate future investigations of the effect of heavy metals on plants.

Pore size distribution analysis of activated carbons: Application of density functional theory using nongraphitized carbon black as a reference system

The application of nonlocal density functional theory (NLDFT) to determine pore size distribution (PSD) of activated carbons using a nongraphitized carbon black, instead of graphitized thermal carbon black, as a reference system is explored. We show that in this case nitrogen and argon adsorption isotherms in activated carbons are precisely correlated by the theory, and such an excellent correlation would never be possible if the pore wall surface was assumed to be identical to that of graphitized carbon black. It suggests that pore wall surfaces of activated carbon are closer to that of amorphous solids because of defects of crystalline lattice, finite pore length, and the presence of active centers.. etc. Application of the NLDFT adapted to amorphous solids resulted in quantitative description of N-2 and Ar adsorption isotherms on nongraphitized carbon black BP280 at their respective boiling points. In the present paper we determined solid-fluid potentials from experimental adsorption isotherms on nongraphitized carbon black and subsequently used those potentials to model adsorption in slit pores and generate a corresponding set of local isotherms, which we used to determine the PSD functions of different activated carbons. (c) 2005 Elsevier Ltd. All rights reserved.

Tracking the states of a nonlinear and nonstationary system in the weight-space of artificial neural networks

We propose a novel interpretation and usage of Neural Network (NN) in modeling physiological signals, which are allowed to be nonlinear and/or nonstationary. The method consists of training a NN for the k-step prediction of a physiological signal, and then examining the connection-weight-space (CWS) of the NN to extract information about the signal generator mechanism. We de. ne a novel feature, Normalized Vector Separation (gamma(ij)), to measure the separation of two arbitrary states i and j in the CWS and use it to track the state changes of the generating system. The performance of the method is examined via synthetic signals and clinical EEG. Synthetic data indicates that gamma(ij) can track the system down to a SNR of 3.5 dB. Clinical data obtained from three patients undergoing carotid endarterectomy of the brain showed that EEG could be modeled (within a root-means-squared-error of 0.01) by the proposed method, and the blood perfusion state of the brain could be monitored via gamma(ij), with small NNs having no more than 21 connection weight altogether.