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.     

Variation in complement factor 3 is associated with risk of age-related macular degeneration

The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.     

A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

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.     

FROM MANUFACTURING SCHEDULING TO SUPPLY CHAIN COORDINATION：THE CONTROL OF COMPLEXITY AND UNCERTAINTY

With time-based competition and rapid technology advancements, effective manufacturingscheduling and supply chain coordination are critical to quickly respond to changing marketconditions. These problems, however, are difficult in view of inherent complexity and variousuncertainties involved. Based on a series of results by the authors, decomposition and coordination byusing Lagrangian relaxation is identified in this paper as an effective way to control complexity anduncertainty.A manufacturing scheduling problem is first formulated within the job shop context withuncertain order arrivals, processing times, due dates, and part priorities as a separable optimizationproblem. A solution methodology that combines Lagrangian relaxation, stochastic dynamicprogramming, and heuristics is developed. Method improvements to effectively solve large problemsare also highlighted. To extend manufacturing scheduling within a factory to coordinate autonomicmembers across chains of suppliers, a decentralized supply chai     

Analysis of discrete-time queues with batch renewal input and multiple vacations

This paper analyzes a discrete-time multiple vacations finite-buffer queueing system with batch renewal input in which inter-arrival time of batches are arbitrarily distributed.Service and vacation times are mutually independent and geometrically distributed.The server takes vacations when the system does not have any waiting jobs at a service completion epoch or a vacation completion epoch.The system is analyzed under the assumptions of late arrival system with delayed access and early arrival system.Using the supplementary variable and the imbedded Markov chain techniques, the authors obtain the queue-length distributions at pre-arrival,arbitrary and outside observer’s observation epochs for partial-batch rejection policy.The blocking probability of the first-,an arbitrary-and the last-job in a batch have been discussed.The analysis of actual waiting-time distributions measured in slots of the first-,an arbitrary- and the last-job in an accepted batch,and other performance measures along with some numerical results have also been investigated.     

Suggestions for New Application Areas for Soft Systems Methodology in the Information Age

Soft systems methodology (SSM) is now 40?years old. Another decade has passed since Checkland??s thirty year retrospective on the methodology, published in 2000. It can now be described as an old methodology. But it has adapted and changed over the years and is still very much alive, although the days are long gone when it was mainly developed and practised by its founders at the University of Lancaster. Interestingly, considering that many applications of SSM over the years have been to information systems, it was developed before the age of personal computers and the Internet. The way SSM is viewed has changed over the years as it has been applied to various types of problem situation. Every use of SSM will potentially hold methodological lessons in addition to those about the situation of concern; these may include SSMs framework of ideas, processes and way of use. How is SSM going to change in the future? This will depend in part on the types of problem situation to which it is applied. This paper examines some problem situations associated with emerging technologies in the information age to which SSM has not yet been much applied. These include computer simulation and virtual reality, ubiquitous computing and the design of cities, Information Technology Service Management and the design of enterprise information architectures. Some of the different worldviews associated with these problem situations which could be explored using SSM are noted.     

An equivalency condition of nonsingularity in nonlinear semidefinite programming

<正> In this paper,an equivalency condition of nonsingularity in nonlinear semidefinite programming,which can be viewed as a generalization of the equivalency condition of nonsingularity for linearsemidefinite programming,is established under certain conditions of convexity.