RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis

Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.     

Magnitude and timing of temperature change in the Indo-Pacific warm pool during deglaciation

Ocean-atmosphere interactions in the tropical Pacific region have a strong influence on global heat and water vapour transport and thus constitute an important component of the climate system. Changes in sea surface temperatures and convection in the tropical Indo-Pacific region are thought to be responsible for the interannual to decadal climate variability observed in extra-tropical regions, but the role of the tropics in climate changes on millennial and orbital timescales is less clear. Here we analyse oxygen isotopes and Mg/Ca ratios of foraminiferal shells from the Makassar strait in the heart of the Indo-Pacific warm pool, to obtain synchronous estimates of sea surface temperatures and ice volume. We find that sea surface temperatures increased by 3.5-4.0 degrees C during the last two glacial-interglacial transitions, synchronous with the global increase in atmospheric CO2 and Antarctic warming, but the temperature increase occurred 2,000-3,000 years before the Northern Hemisphere ice sheets melted. Our observations suggest that the tropical Pacific region plays an important role in driving glacial-interglacial cycles, possibly through a system similar to how El Ni?o/Southern Oscillation regulates the poleward flux of heat and water vapour.     

Detection of human influence on sea-level pressure

Greenhouse gases and tropospheric sulphate aerosols--the main human influences on climate--have been shown to have had a detectable effect on surface air temperature, the temperature of the free troposphere and stratosphere and ocean temperature. Nevertheless, the question remains as to whether human influence is detectable in any variable other than temperature. Here we detect an influence of anthropogenic greenhouse gases and sulphate aerosols in observations of winter sea-level pressure (December to February), using combined simulations from four climate models. We find increases in sea-level pressure over the subtropical North Atlantic Ocean, southern Europe and North Africa, and decreases in the polar regions and the North Pacific Ocean, in response to human influence. Our analysis also indicates that the climate models substantially underestimate the magnitude of the sea-level pressure response. This discrepancy suggests that the upward trend in the North Atlantic Oscillation index (corresponding to strengthened westerlies in the North Atlantic region), as simulated in a number of global warming scenarios, may be too small, leading to an underestimation of the impacts of anthropogenic climate change on European climate.     

Detection of human influence on twentieth-century precipitation trends

Human influence on climate has been detected in surface air temperature, sea level pressure, free atmospheric temperature, tropopause height and ocean heat content. Human-induced changes have not, however, previously been detected in precipitation at the global scale, partly because changes in precipitation in different regions cancel each other out and thereby reduce the strength of the global average signal. Models suggest that anthropogenic forcing should have caused a small increase in global mean precipitation and a latitudinal redistribution of precipitation, increasing precipitation at high latitudes, decreasing precipitation at sub-tropical latitudes, and possibly changing the distribution of precipitation within the tropics by shifting the position of the Intertropical Convergence Zone. Here we compare observed changes in land precipitation during the twentieth century averaged over latitudinal bands with changes simulated by fourteen climate models. We show that anthropogenic forcing has had a detectable influence on observed changes in average precipitation within latitudinal bands, and that these changes cannot be explained by internal climate variability or natural forcing. We estimate that anthropogenic forcing contributed significantly to observed increases in precipitation in the Northern Hemisphere mid-latitudes, drying in the Northern Hemisphere subtropics and tropics, and moistening in the Southern Hemisphere subtropics and deep tropics. The observed changes, which are larger than estimated from model simulations, may have already had significant effects on ecosystems, agriculture and human health in regions that are sensitive to changes in precipitation, such as the Sahel.     

Human contribution to the European heatwave of 2003

The summer of 2003 was probably the hottest in Europe since at latest ad 1500, and unusually large numbers of heat-related deaths were reported in France, Germany and Italy. It is an ill-posed question whether the 2003 heatwave was caused, in a simple deterministic sense, by a modification of the external influences on climate--for example, increasing concentrations of greenhouse gases in the atmosphere--because almost any such weather event might have occurred by chance in an unmodified climate. However, it is possible to estimate by how much human activities may have increased the risk of the occurrence of such a heatwave. Here we use this conceptual framework to estimate the contribution of human-induced increases in atmospheric concentrations of greenhouse gases and other pollutants to the risk of the occurrence of unusually high mean summer temperatures throughout a large region of continental Europe. Using a threshold for mean summer temperature that was exceeded in 2003, but in no other year since the start of the instrumental record in 1851, we estimate it is very likely (confidence level >90%) that human influence has at least doubled the risk of a heatwave exceeding this threshold magnitude.     

浅谈用人之道

人才是提高综合国力的关键要素。为用好人才，一是要辨证地把握好识别人才、起用人才的标准，既要选拔出德才兼备的人才，又不可求全责备；二是用人要讲究方法。做到公平竞争、择优录用、知人善用，同时鼓励人才合理流动；三是用人要遵循讲正气、讲民主、讲大度的原则，大胆使用人才。     

研究型大学图书馆的人力资源管理

引入研究型大学及其图书馆的定义,阐述了研究型大学图书馆进行人力资源管理的重要意义。进而提出了研究型大学图书馆人力资源管理的策略,包括改变人力资源管理理念,建立以人为本的人才管理机制,注重人才的使用和培养,充分调动馆员的积极性等。     

Origins and estimates of uncertainty in predictions of twenty-first century temperature rise

Predictions of temperature rise over the twenty-first century are necessarily uncertain, both because the sensitivity of the climate system to changing atmospheric greenhouse-gas concentrations, as well as the rate of ocean heat uptake, is poorly quantified and because future influences on climate-of anthropogenic as well as natural origin-are difficult to predict. Past observations have been used to help constrain the range of uncertainties in future warming rates, but under the assumption of a particular scenario of future emissions. Here we investigate the relative importance of the uncertainty in climate response to a particular emissions scenario versus the uncertainty caused by the differences between future emissions scenarios for our estimates of future change. We present probabilistic forecasts of global-mean temperatures for four representative scenarios for future emissions, obtained with a comprehensive climate model. We find that, in the absence of policies to mitigate climate change, global-mean temperature rise is insensitive to the differences in the emissions scenarios over the next four decades. We also show that in the future, as the signal of climate change emerges further, the predictions will become better constrained.