The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.     

Strategies for mitigating an influenza pandemic

Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures. Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options. Here we use a large-scale epidemic simulation to examine intervention options should initial containment of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2-3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40-50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics.     

A magnetically collimated jet from an evolved star

Planetary nebulae often have asymmetric shapes, even though their progenitor stars were symmetric; this structure could be the result of collimated jets from the evolved stars before they enter the planetary nebula phase. Theoretical models have shown that magnetic fields could be the dominant source of jet-collimation in evolved stars, just as these fields are thought to collimate outflows in other astrophysical sources, such as active galactic nuclei and proto-stars. But hitherto there have been no direct observations of both the magnetic field direction and strength in any collimated jet. Here we report measurements of the polarization of water vapour masers that trace the precessing jet emanating from the asymptotic giant branch star W43A (at a distance of 2.6 kpc from the Sun), which is undergoing rapid evolution into a planetary nebula. The masers occur in two clusters at opposing tips of the jets, approximately 1,000 au from the star. We conclude from the data that the magnetic field is indeed collimating the jet.     

Dietary overlap of snow leopard and other carnivores in the Pamirs of Northwestern China

Information about competition between carnivore species for food within high altitude regions is limited.Data collected from the Taxkorgan Nature Reserve,China revealed important interactions between snow leopard(Panthera uncia),grey wolf(Canis lupus),red fox(Vulpes vulpes)and their prey species,including domestic livestock.Sixty-four line transects were conducted in order to identify field signs of habitat occupancy and collect scats for diet analysis.High dietary overlap was observed between all three carnivore species:snow leopard and red fox(Pianka’s index=0.96),red fox and grey wolf(Pianka’s index=0.90),snow leopard and grey wolf(Pianka’s index=0.87).Snow leopard and grey wolf showed significant predation on livestock(36.8%for snow leopard and 29.4%for grey wolf in diet composition).As a pioneering exploration of the endangered snow leopard and its relationship with other species within the alpine ecosystem under livestock grazing pressure,this study contributes a greater understanding of the relationship within carnivore guild in the Pamirs whilst providing implications for conservation planning and project implementation activities in China.     

Geopolitical risk and global financial cycle: Some forecasting experiments

In this study, we investigate the connection between geopolitical risk (GPR) and global financial cycle (GFCy) as well as whether the former has predictive value for the out-of-sample predictability of the latter. We utilize both the historical and recent GPR data and their variants, namely, GPR act covering all “acts” that constitute GPR such as war, nuclear invasion and terrorism, and GPR threat, which represents threats of these acts. We construct a predictive model that accommodates the salient features of the predicted and predictor series while the forecast evaluation is conducted for both in-sample and out-of-sample periods. Our findings reveal that a rise in GPR discourages investments in risky assets and by implication worsens GFCy. The impact is more severe after the global financial crisis (gfc), and the GPR threat exerts more adverse effect on GFCy compared with GPR act regardless of whether historical GPR or recent GPR is used. Meanwhile, the predictive model of GFCy that accommodates the GPR data outperforms the benchmark model that ignores it both in the in-sample and out-of-sample estimates albeit with improved forecast performance during the post-gfc period and at a longer forecast horizon. However, the recent GPR data, which are broader in scope, offer better forecast accuracy than the historical GPR data. Additional analyses involving the vulnerability of global economic conditions reveal similar outcomes as GFCy.     

The impact of seasonal constants on forecasting seasonally cointegrated time series

In this paper we focus on the effect of (i) deleting, (ii) restricting or (iii) not restricting seasonal intercept terms on forecasting sets of seasonally cointegrated macroeconomic time series for Austria, Germany and the UK. A first empirical result is that the number of cointegrating vectors as well as the relevant estimated parameter values vary across the three models. A second result is that the quality of out-of-sample forecasts critically depends on the way seasonal constants are treated. In most cases, predictive performance can be improved by restricting the effects of seasonal constants. However, we find that the relative advantages and disadvantages of each of the three methods vary across the data sets and may depend on sample-specific features. © 1998 John Wiley & Sons, Ltd.     

Size-dependent optical properties of Au nanorods

In the fast evolving field of nanoscience and nanotechnology,where size and shape are crucial in deciding the optoelectronic properties of nanomaterials,the understanding of size and shape dependent behavior is of direct relevance to device applications.Present study reports the synthesis of Au nanorods with well controlled aspect ratios,and the influence of the aspect ratio on the surface enhanced Raman scattering(SERS) activity using crystal violet(CV) as the probe molecule.The influence of pH and the concentrations of reducing agent and Ag ions in controlling the aspect ratio of gold nanorods are also investigated.The structural and optical properties of the synthesized samples have been characterized by transmission electron microscopy(TEM) and UV-visible absorption spectroscopy.The nonlinear optical(NLO) transmission of the Au nanorods investigated using the open aperture Z-scan technique revealed the absorption saturation followed by an optical limiting behavior,which may find potential applications in optoelectronic nanodevices.