Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.     

利用Agro浮标估计南大洋混合的时空变化

海洋中的湍流跨等密度面混合(以下简称混合)控制着海洋中淡水、热量以及CO2等溶解物质的输运。南大洋是全球湍流混合最强烈的区域之一。理解南大洋湍流混合的时空分布特征对于模拟和预测全球大洋环流和气候变化起着至关重要的作用。目前,部分投放在南大洋的新型Argo浮标已经采用铱星通讯系统传送数据,可以返回垂向高分辨率的水文剖面,从而为研究南大洋的湍流混合提供了前所未有的机遇。本文作者在国际上首次利用这些新型浮标观测得到的高分辨率剖面对湍流混合进行了研究。结果表明,南大洋的混合存在明显的空间分布不均匀性,并且与地形变化密切相关。此外,在地形平坦处,湍流混合表现出明显的季节变化。这种变化主要是由风输入到海洋中的近惯性能量的季节性变化引起的。     

A Comparison of Box—Jenkins and objective methods for determining the order of a non-seasonal ARMA Model

This paper evaluates different procedures for selecting the order of a non-seasonal ARMA model. Specifically, it compares the forecasting accuracy of models developed by the personalized Box-Jenkins (BJ) methodology with models chosen by numerous automatic procedures. The study uses real series modelled by experts (textbook authors) in the BJ approach. Our results show that many objective selection criteria provide structures equal or superior to the time-consuming BJ method. For the sets of data used in this study, we also examine the influence of parsimony in time-series forecasting. Defining what models are too large or too small is sensitive to the forecast horizon. Automatic techniques that select the best models for forecasting are similar in size to BJ models although they often disagree on model order.     

A Theoretical Framework for Facilitating Methodological Choice

Total Systems Intervention, in a recent version, facilitates the intervention process via three modes: problem solving, critical reflection, and critical review. Of these modes, there has been relatively little attention paid to the critical review mode, the purpose of which is to assess the value of different methodologies within a given problem situation. This paper takes as its basis the only major work in this area and seeks to build on this in order to improve the mixing of methodologies within a single intervention.     

A Critical Assessment of Project Management Methods with Respect to Electronic Government Implementation Challenges

In taking forward both the Government Modernization and the Civil Service Reform agendas, renewed emphasis is being placed on project management approaches and techniques for achieving objectives more effectively and efficiently. After elaborating on specific electronic government project implementation challenges and giving an overview of state-of-the-art project management approaches, the paper examines the weaknesses of three commonly used methods in the light of the e-Government project challenges. The analysis identifies gaps in the methods, contributing to a better understanding of the factors that lead to success or failure. The resolution of such methodological limitations could lead to the enhancement of project management methods when applied to future projects.     

Microbiome–health interactions in older people

Alterations in the composition and function of the gut microbiome have been implicated in a range of conditions and diseases. Culture-dependent and culture-independent studies both showed that older people harbour a gut microbiome that differs in composition from that of younger adults. Detailed analyses have identified discrete microbiota subtypes that characterize intermediates between a high diversity microbiota found in healthy community-dwelling subjects and a low diversity microbiota typical for elderly living in long-term residential care. There are also alterations in the microbiome composition associated with biological age, independent of health status. Even after adjusting for confounding factors such as age and medication, trends in microbiota composition correlate with gradients in clinical metadata particularly frailty and inflammatory status. There are few known mechanisms by which these associations might be causative rather than consequential, and this is a subject of intensive research. The strongest candidate effectors are microbial metabolites that could impact host energy balance, act as signalling molecules to modulate host metabolism or inflammation, and potentially also impact on the gut–brain axis.     

Low melting point nanocrystalline Sn–Ag solder synthesized by a refined chemical reduction method

The commercial market of Sn-Pb solder is gradually decreasing due to its toxicity, calling for Pb-free substitute materials. Sn-Ag alloy is a potential candidate in terms of good mechanical property. The major problematic issue of using Sn-Ag is their high melting temperature, consequently this study is dedicated to lowering the melt- ing temperature of Sn3.5Ag （wt%） alloy by developing nanomaterials using a chemical reduction approach. The resultant nanocrystalline Sn3.5Ag is characterized by field emission scanning electron microscope. The size dependence of the melting temperature is discussed based on differential scanning calorimetry results. We have reduced the melting temperature to 209.8 ℃ in the nanocrystalline Sn3.5Ag of （32.4± 8.0） nm, compared to ～221 ℃ of the bulk alloy. The results are consistent with the prediction made by a relevant theoretical model, and it is possible to further lower the melting temperature using the chemical reduction approach developed by this study.     

Plant genetics: increased outcrossing in hothead mutants

Arising from: S. J. Lolle, J. L. Victor, J. M. Young & R. E. Pruitt 434, 505-509 (2005); Lolle et al. reply. Lolle et al. report that loss-of-function alleles of the HOTHEAD (HTH) gene in Arabidopsis thaliana are genetically unstable, giving rise to wild-type revertants. On the basis of the reversion of many other genetic markers in hth plants, they suggested a model in which a cache of extragenomic information could cause genes to revert to the genotype of previous generations. In our attempts to reproduce this phenomenon, we discovered that hth mutants show a marked tendency to outcross (unlike wild-type A. thaliana, which is almost exclusively self-fertilizing). Moreover, when hth plants are grown in isolation, their genetic inheritance is completely stable. These results may provide an alternative explanation for the genome wide non-mendelian inheritance reported by Lolle et al.