Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11

The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.     

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.     

Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.     

Risk reduction in a project portfolio

The positive impacts of managing projects as a portfolio are quantified by comparing the value of the integrated risk of a project portfolio and the aggregation of single project risks implemented separately. Firstly, the integrated risk is defined by proposing risky events based on set theory. Secondly, as projects interact with each other in a project portfolio, the integrated risk is evaluated by using a Bayesian network structure learning algorithm to construct an interdependent network of risks. Finally, the integrated risk of a practical case is assessed using this method, and the results show that the proposed method is an effective tool for calculating the extent of risk reduction of implementing a project portfolio and identifying the most risky project, so as to assist companies in making comprehensive decisions in the phase of portfolio selection and portfolio controlling.     

A DEA-TOPSIS method for multiple criteria decision analysis in emergency management

A hybrid approach of DEA (data envelopment analysis) and TOPSIS (technique for order performance (preference) by similarity to ideal solution) is proposed for multiple criteria decision analysis in emergency management. Two DEA-based optimization models are constructed to facilitate identifying parameter information regarding criterion weights and quantifying qualitative criteria in TOPSIS. An emergency management case study utilizing data from the Emergency Management Australia (EMA) Disasters Database is provided to demonstrate the feasibility of the proposed analysis procedure.     

A Maturing of Systems Thinking? Evidence from Three Perspectives

This paper reviews trends in systems theory/thinking from the 1970s to the early 2000s. It proposes a maturation of the field based on certain conceptual and methodological advances that have sought to liberate systems thinking from earlier strictures. An edited dialogue among three prominent systems thinkers from different systems schools—Merrelyn Emery, Bob Flood, and Eric Wolstenholme—provides evidence. Similarities and differences are identified, complementarities among the schools are derived and analyzed, and trajectories for future research are indicated.     

A hierarchical multiple criteria model for eliciting relative preferences in conflict situations

A multiple criteria decision analysis(MCDA) approach is designed for capturing the relative preference information of a decision maker involved in a conflict.More specifically,an MCDA approach based on the outranking method,ELECTRE III,is employed for ranking states or possible scenarios in the conflict from most to least preferred,where ties are allowed,for a decision maker according to his or her value system.To demonstrate how this preference elicitation methodology can be conveniently implemented in practice within the framework of the Graph Model for Conflict Resolution,it is applied to a real world water supply crisis which occurred in the town of North Battleford,located in the Canadian province of Saskatchewan.