Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.

[1] An updated accumulation map for Greenland is presented on the basis of 39 new ice core estimates of accumulation, 256 ice sheet estimates from ice cores and snow pits used in previous maps, and reanalysis of time series data from 20 coastal weather stations. The period 1950-2000 is better represented by the data than are earlier periods. Ice-sheetwide accumulation was estimated based on kriging. The average accumulation (95% confidence interval, or ±2 times standard error) over the Greenland ice sheet is 30.0 ± 2.4 g cm À2 a À1 , with the average accumulation above 2000-m elevation being essentially the same, 29.9 ± 2.2 g cm À2 a À1 . At higher elevations the new accumulation map maintains the main features shown in previous maps. However, there are five coastal areas with obvious differences: southwest, northwest, and eastern regions, where the accumulation values are 20-50% lower than previously estimated, and southeast and northeast regions, where the accumulation values are 20-50% higher than previously estimated. These differences are almost entirely due to new coastal data. The much lower accumulation in the southwest and the much higher accumulation in the southeast indicated by the current map mean that long-term mass balance in both catchments is closer to steady state than previously estimated. However, uncertainty in these areas remains high owing to strong gradients in precipitation from the coast inland. A significant and sustained precipitation measurement program will be needed to resolve this uncertainty.

Hepatocellular carcinoma is a primary malignancy of hepatocytes which accounts for 80 % of all primary liver cancers. DFNA5 has been identified as a tumor suppressor gene with an important role in several frequent forms of cancers, while little is known about its role in hepatocellular carcinoma. Through comparison of the DFNA5 protein expression in hepatocellular carcinoma cells (HepG2) with human fetal lung fibroblast cells (MRC5), we found that the DFNA5 protein expression in hepatocellular carcinoma cells was significantly lower than that in normal cells. The transfection of DFNA5 gene into HepG2 cells could increase DFNA5 protein expression, which subsequently led to inhibition of cell proliferation. Underlying mechanism study revealed that decreased proliferation was due to increased apoptosis and cell cycle arrest. In view of the important role of DFNA5 gene in carcinogenesis, these findings are expected to provide new understanding on development and treatment of human hepatocellular carcinoma.

The delicate influence of minute structural difference, such as regiochemistry, on self-assembly and phase behaviors has been commonly observed in small molecules but rarely in synthetic polymers. Herein, we report the precision synthesis of a series of double-chain giant surfactant regioisomers and their distinct phase structures and phase behaviors. These giant surfactants possess a hydroxyl-functionalized cubic T8 polyhedral oligomeric silsesquioxane head and two polystyrene tails tethered at para-, meta-, and ortho-configurations and were prepared following the sequential “click” method. As revealed by temperature-dependent small-angle X-ray scattering and bright-field transmission electron microscopy, their order–disorder transition temperatures decrease in the order of ortho-, meta-, and para-isomers, while order–order transitions were observed in the meta-isomer from lamellae to double gyroids and in the ortho-isomer from double gyroids to hexagonal cylinders upon increasing temperature. The mechanisms are elucidated by the influence of the tethering positions on the different free energy contributions, i.e., the interfacial energy, the head-to-head interaction, and the entropic energy of the tails. The distinct assembly behaviors of the three regioisomers are unusual in macromolecules yet resemble small molecules. It opens an avenue to fine-tune the macromolecular assembly at the level of molecular precision.