Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome

Individuals with congenital or acquired prolongation of the QT interval, or long QT syndrome (LQTS), are at risk of life-threatening ventricular arrhythmia. LQTS is commonly genetic in origin but can also be caused or exacerbated by environmental factors. A missense mutation in the L-type calcium channel Ca(V)1.2 leads to LQTS in patients with Timothy syndrome. To explore the effect of the Timothy syndrome mutation on the electrical activity and contraction of human cardiomyocytes, we reprogrammed human skin cells from Timothy syndrome patients to generate induced pluripotent stem cells, and differentiated these cells into cardiomyocytes. Electrophysiological recording and calcium (Ca(2+)) imaging studies of these cells revealed irregular contraction, excess Ca(2+) influx, prolonged action potentials, irregular electrical activity and abnormal calcium transients in ventricular-like cells. We found that roscovitine, a compound that increases the voltage-dependent inactivation of Ca(V)1.2 (refs 6-8), restored the electrical and Ca(2+) signalling properties of cardiomyocytes from Timothy syndrome patients. This study provides new opportunities for studying the molecular and cellular mechanisms of cardiac arrhythmias in humans, and provides a robust assay for developing new drugs to treat these diseases.     

Soft System Dynamics Methodology in Action: A study of the Problem of Citizen Insecurity in an Argentinean Province

This paper illustrates an application of soft system dynamics methodology (SSDM). SSDM arose as a fusion of two well-known methodologies in the systems movement: system dynamics (SD) and soft systems methodology (SSM). SSDM includes 10 steps to orchestrate and implant change in social systems, based on a multimethodological and multiparadigmatic approach as an outcome of the combination of the mentioned methodologies. After a brief introduction, the paper starts by briefly explaining SSM and SD, their stages and their problematical issues as systemic methodologies, then goes on to explain SSDM, its philosophical roots and stages, ending with a comparison among the three. It then introduces the citizen insecurity problem in Argentina, specifically in Mendoza Province, where SSDM was applied to analyze this issue. The paper concludes with an explanation of the learning points that arose from the use of SSDM in this study and suggestions for further research on citizen security and SSDM.     

South American SLR stations monitoring ground displacement caused by the M8.8 Chilean earthquake of 2010

The M8.8 Chilean earthquake of February 27, 2010 caused a large surface displacement near its epicenter. Satellite Laser Ranging (SLR) station 7405, cooperatively operated by Germany and Chile about 130 km from the epicenter was affected by the earthquake. Another SLR station, No. 7406, operated jointly by the National Astronomical Observatories of the Chinese Academy of Sciences and San Juan University of Argentina, was about 600 km from the epicenter. Combining the observations of these two SLR stations with global SLR station observations, we calculate the geocentric coordinates of the two stations based on ITRF2000. The results show that the coordinates of the two stations have changed by varying degrees. SLR-7405 moved substantially towards the southwest with displacements of about 3.11, 0.52 and 0.49 m in X, Y, Z directions; the corresponding displacements for SLR-7406 are about 0.02, 0.03 and 0.02 m. This solution, as an independent result derived from SLR observations, could provide an essential external check for other positioning techniques such as GPS.     

Estimation and Forecasting of Locally Stationary Processes

This paper develops a state space framework for the statistical analysis of a class of locally stationary processes. The proposed Kalman filter approach provides a numerically efficient methodology for estimating and predicting locally stationary models and allows for the handling of missing values. It provides both exact and approximate maximum likelihood estimates. Furthermore, as suggested by the Monte Carlo simulations reported in this work, the performance of the proposed methodology is very good, even for relatively small sample sizes. Copyright © 2011 John Wiley & Sons, Ltd.     

Capturing complex, non-linear team behaviours during competitive football performance

This study investigated changes in the complexity (magnitude and structure of variability) of the collective behaviours of association football teams during competitive performance. Raw positional data from an entire competitive match between two professional teams were obtained with the ProZone® tracking system. Five compound positional variables were used to investigate the collective patterns of performance of each team including: surface area, stretch index, team length, team width, and geometrical centre. Analyses involve the coefficient of variation (%CV) and approximate entropy (ApEn), as well as the linear association between both parameters. Collective measures successfully captured the idiosyncratic behaviours of each team and their variations across the six time periods of the match. Key events such as goals scored and game breaks (such as half time and full time) seemed to influence the collective patterns of performance. While ApEn values significantly decreased during each half, the %CV increased. Teams seem to become more regular and predictable, but with increased magnitudes of variation in their organisational shape over the natural course of a match.     

Modelling conservation in the Amazon basin

Expansion of the cattle and soy industries in the Amazon basin has increased deforestation rates and will soon push all-weather highways into the region's core. In the face of this growing pressure, a comprehensive conservation strategy for the Amazon basin should protect its watersheds, the full range of species and ecosystem diversity, and the stability of regional climates. Here we report that protected areas in the Amazon basin--the central feature of prevailing conservation approaches--are an important but insufficient component of this strategy, based on policy-sensitive simulations of future deforestation. By 2050, current trends in agricultural expansion will eliminate a total of 40% of Amazon forests, including at least two-thirds of the forest cover of six major watersheds and 12 ecoregions, releasing 32 +/- 8 Pg of carbon to the atmosphere. One-quarter of the 382 mammalian species examined will lose more than 40% of the forest within their Amazon ranges. Although an expanded and enforced network of protected areas could avoid as much as one-third of this projected forest loss, conservation on private lands is also essential. Expanding market pressures for sound land management and prevention of forest clearing on lands unsuitable for agriculture are critical ingredients of a strategy for comprehensive conservation.     

Experience in combining subjective and quantitative forecasts of open market rates

This paper presents a method of combining subjective information from open-market operators with results from a time-series forecasting model. Empirical results of forecasts for interest rates of bank reserves are presented.     

Ectopic human chorionic gonadotropin in breast carcinoma.

Immunoreactive human chorionic gonadotropin (hCG) was found in 9 of 65 surgically removed malignant breast tumors. Concentrations ranged from 5 to greater than 500 mIU hCG/g tumor. hCG was measured by a beta-chain specific readiommunoassay. In further study of these specimens, an immunoperoxidase staining technique was used to stain for hCG in formalin-fixed sections. The hCG was shown to be localized within the cytoplasm and on the surface of the malignant cells.