Correction of the copper transport defect of Menkes patient fibroblasts by expression of two forms of the sheep Wilson ATPase

The Wilson disease (WD) protein (ATP7B) is a copper-transporting P-type ATPase that is responsible for the efflux of hepatic copper into the bile, a process that is essential for copper homeostasis in mammals. Compared with other mammals, sheep have a variant copper phenotype and do not efficiently excrete copper via the bile, often resulting in excessive copper accumulation in the liver. To investigate the function of sheep ATP7B and its potential role in the copper-accumulation phenotype, cDNAs encoding the two forms of ovine ATP7B were transfected into immortalised fibroblast cell lines derived from a Menkes disease patient and a normal control. Both forms of ATP7B were able to correct the copper-retention phenotype of the Menkes cell line, demonstrating each to be functional copper-transporting molecules and suggesting that the accumulation of copper in the sheep liver is not due to a defect in the copper transport function of either form of sATP7B.

Correction of a mouse model of Menkes disease by the human Menkes gene

The brindled mouse is an accurate model of the fatal human X-linked copper deficiency disorder, Menkes disease. Males carrying the mutant allele of the Menkes gene orthologue Atp7a die in the second week of life. To determine whether the genetic defect in the brindled mice could be corrected by expression of the human Menkes gene, male transgenic mice expressing ATP7A from the chicken β-actin composite promoter (CAG) were mated with female carriers of the brindled mutation (Atp7aMo-br). Mutant males carrying the transgene survived and were fertile but the copper defect was not completely corrected. Unexpectedly males corrected with one transgenic line (T25#5) were mottled and resembled carrier females, this effect appeared to be caused by mosaic expression of the transgene. In contrast, males corrected with another line (T22#2) had agouti coats. Copper concentrations in tissues of the rescued mutants also resembled those of the heterozygous females, with high levels in kidney (84.6 ± 4.9 μg/g in corrected males vs. 137.0 ± 44.3 μg/g in heterozygotes) and small intestine (15.6 ± 2.5 μg/g in corrected males vs. 15.7 ± 2.8 μg/g in heterozygotes). The results show that the Menkes defect in mice is corrected by the human Menkes gene and that adequate correction is obtained even when the transgene expression does not match that of the endogenous gene.

What explains dissent on the High Court of Australia? An empirical assessment using a cointegration and error correction approach

This article examines the factors influencing the annual dissent rate on the High Court of Australia from its first full year of operation in 1904 up to 2001 within a cointegration and error correction framework. We hypothesize that institutional factors, socioeconomic complexity, and leadership style explain variations in the dissent rate on the High Court of Australia over time. The institutional factors that we consider are the Court's caseload, whether it had discretion to select the cases it hears, and whether it was a final court of appeal. To measure socioeconomic complexity we use the divorce rate, urbanization rate, and real GDP per capita. Our main finding is that in the long run and short run, caseload and real income are the main factors influencing dissent. We find that a 1 percent increase in caseload and real income reduce the dissent rate on the High Court of Australia by 0.3 percent and 0.6 percent, respectively, holding other factors constant.

Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease

Background and Aim: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.

Methods: Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.

Results: Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non-repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.

Conclusion: Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.

Multilabel classification using error correction codes

This paper presents a multilabel classification method that employs an error correction code together with a base ensemble learner to deal with multilabel data. It explores two different error correction codes: convolutional code and BCH code. A random forest learner is used as its based learner. The performance of the proposed method is evaluated experimentally. The popular multilabel yeast dataset is used for benchmarking. The results are compared against those of several exiting approaches. The proposed method performs well against its counterparts.

Forecasting construction demand : a vector error correction model with dummy variables

Modelling the level of demand for construction is vital in policy formulation and implementation as the construction industry plays an important role in a country’s economic development process. In construction economics, research efforts on construction demand modelling and forecasting are various, but few researchers have considered the impact of global economy events in construction demand modelling. An advanced multivariate modelling technique, namely the vector error correction (VEC) model with dummy variables, was adopted to predict demand in the Australian construction market. The results of prediction accuracy tests suggest that the general VEC model and the VEC model with dummy variables are both acceptable for forecasting construction economic indicators. However, the VEC model that considers external impacts achieves higher prediction accuracy than the general VEC model. The model estimates indicate that the growth in population, changes in national income, fluctuations in interest rates and changes in householder expenditure all play significant roles when explaining variations in construction demand. The VEC model with disturbances developed can serve as an experimentation using an advanced econometrical method which can be used to analyse the effect of specific events or factors on the construction market growth.

Early symptomatic presbyopes - what correction modality works best?

Purpose: To compare the performance of a low-addition silicone hydrogel multifocal soft lens with other soft lens correction options in a group of habitual soft lens wearers of distance correction who are symptomatic of early presbyopia.

Method: This clinical study was designed as a prospective, double-masked, randomized, crossover, dispensing trial consisting of four 1-week phases, one for each of the correction modalities: a low-addition silicone hydrogel multifocal soft lens, monovision, habitual correction, and optimized distance visual correction. The prescriptions of all modalities were finalized at a single fitting visit, and the lenses were worn according to a randomized schedule. All lenses were made from lotrafilcon B material. A series of objective vision tests were conducted: high- and low-contrast LogMAR under high- and low-room lighting conditions, stereopsis, and critical print size. A number of other data collection methods used were novel: some data were collected under controlled laboratory-based conditions and others under real-world conditions, some of which were completed on a BlackBerry hand-held communication device.

Results: All participants were able to be fit with all four correction modalities. Objective vision tests showed no statistical difference between the lens modalities except in the case of low-contrast near LogMAR acuity under low-lighting levels where monovision (+0.29 ± 0.10) performed better than the multifocal (+0.33 ± 0.11, P=0.027) and the habitual (+0.37 ± 0.12, P<0.001) modalities. Subjective ratings indicated a statistically better performance provided by the multifocal correction compared with monovision, particularly for the vision associated with driving tasks such as driving during the daytime (93.3 ± 8.8 vs. 84.2 ± 23.7, P=0.05), at nighttime (88.8 ± 11.7 vs. 74.9 ± 23.6, P=0.001), any associated haloes or glare (92.0 ± 10.6 vs. 78.0 ± 22.8, P=0.003), and observing road signs (90.1 ± 11.8 vs. 79.4 ± 20.2, P=0.027). Preference for the multifocal compared with monovision was also reported when watching television (95.0 ± 6.4 vs. 82.6 ± 20.1, P=0.001) and when changing focus from distance to near (87.0 ± 13.4 vs. 66.1 ± 32.2, P<0.001).

Conclusions: For this group of early presbyopes, the AIR OPTIX AQUA MULTIFOCAL-Low Add provided a successful option for visual correction, which was supported by the results of subjective ratings, many of which were made during or immediately after performing such activities as reading, using a computer, watching television, and driving. These results suggest that making a prediction of success or not based on consulting room acuity tests alone is probably unwise.

Correction of presbyopia with GP contact lenses

Presbyopia can be safely and effectively corrected with gas permeable (GP) multifocal (bifocal) contact lenses, but statistics indicate that they remain the most underutilized contact lenses on the market. We believe that practitioners have been “turned off of” GP multifocals due to their experiences with older generations of these lenses, which tended to be difficult to fit, with poor visual results.

Fortunately, GP multifocals have come a long way, and practitioners who avoid fitting them are missing out on an important niche market. With this booklet, we hope to show you just how far GP multifocals have come and demonstrate the ease with which they can now be fit and managed.

A panel error correction approach to explore spatial correlation patterns of the dominant housing market in Australian capital cities

Purpose - A panel error correction model has been developed to investigate the spatial correlation patterns among house prices. This paper aims to identify a dominant housing market in the ripple down process. Design/methodology/approach - Seemingly unrelated regression estimators are adapted to deal with the contemporary correlations and heterogeneity across cities. Impulse response functions are subsequently implemented to simulate the spatial correlation patterns. The newly developed approach is then applied to the Australian capital city house price indices. Findings - The results suggest that Melbourne should be recognised as the dominant housing market. Four levels were classified within the Australian house price interconnections, namely: Melbourne; Adelaide, Canberra, Perth and Sydney; Brisbane and Hobart; and Darwin. Originality/value - This research develops a panel regression framework in addressing the spatial correlation patterns of house prices across cities. The ripple-down process of house price dynamics across cities was explored by capturing both the contemporary correlations and heterogeneity, and by identifying the dominant housing market.

Does implicit motor imagery ability predict reaching correction efficiency? A test of recent models of human motor control

Neurocomputational models of reaching indicate that efficient purposive correction of movement midflight (e.g., online control) depends on one's ability to generate and monitor an accurate internal (neural) movement representation. In the first study to test this empirically, the authors investigated the relationship between healthy young adults’ implicit motor imagery performance and their capacity to correct their reaching trajectory. As expected, after controlling for general reaching speed, hierarchical regression demonstrated that imagery ability was a significant predictor of hand correction speed; that is, faster and more accurate imagery performance associated with faster corrections to reaching following target displacement at movement onset. They argue that these findings provide preliminary support for the view that a link exists between an individual's ability to represent movement mentally and correct movement online efficiently.