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Using a genetic algorithm combined with density functional theory calculations, we perform a global search for the lowest-energy structures of B clusters with n = 46, 48, 50. Competition among different structural motifs including a hollow cage, core-shell, bilayer, and quasi-planar, is investigated. For B, a core-shell B@B structure resembling the larger B clusters with n ≥ 68 is found to compete with a quasi-planar structure with a central hexagonal hole. A quasi-planar configuration with two connected hexagonal holes is most favorable for B. More interestingly, an unprecedented bilayer structure is unveiled at B, which can be extended to a two-dimensional bilayer phase exhibiting appreciable stability. Our results suggest alternatives to the cage motif as lower-energy B cluster structures with n > 50.

Detachment of non-malignant epithelial cells from the extracellular matrix causes their growth arrest and, ultimately, death. By contrast, cells composing carcinomas, cancers of epithelial origin, can survive and proliferate without being attached to the extracellular matrix. These properties of tumor cells represent hallmarks of malignant transformation and are critical for cancer progression. Previously we identified several mechanisms by which ras, a major oncogene, blocks detachment-induced apoptosis of intestinal epithelial cells, but mechanisms by which Ras promotes proliferation of those cells that remain viable following detachment are unknown. We show here that detachment of non-malignant intestinal epithelial cells promotes formation of autophagosomes, vacuole-like structures that mediate autophagy (a process of cellular self-cannibalization), and that oncogenic ras prevents this autophagosome formation. We also found that ras activates a GTPase RhoA, that RhoA promotes activation of a protease calpain, and that calpain triggers degradation of Beclin-1, a critical mediator of autophagy, in these cells. The reversal of the effect of ras on Beclin-1 (achieved by expression of exogenous Beclin-1) promoted autophagosome formation following cell detachment, significantly reduced the fraction of detached cells in the S phase of the cell cycle and their rate of proliferation without affecting their viability. Furthermore, RNA interference-induced Beclin-1 down-regulation in non-malignant intestinal epithelial cells prevented detachmentdependent reduction of the fraction of these cells in the S phase of the cell cycle. Thus, ras oncogene promotes proliferation of those malignant intestinal epithelial cells that remain viable following detachment via a distinct novel mechanism that involves Ras-induced down-regulation of Beclin-1.The ability of cells that form carcinomas, cancers of epithelial origins, to survive and proliferate in the absence of adhesion to the extracellular matrix (ECM) 3 is thought to represent a critical prerequisite for carcinoma progression (1, 2). This concept is based on observations indicating that many types of normal epithelia grow in vivo as cellular monolayers in contact with a form of the ECM called basement membrane. Detachment from the ECM causes growth arrest (3) and apoptosis (4) of non-malignant epithelial cells (the latter type of death is referred to as anoikis (5)). By contrast, carcinomas typically represent three-dimensional disorganized multicellular masses in which the cells tend to be deprived of normal contacts with the basement membrane. It is known in this regard that carcinoma cells often secrete basement membrane degrading enzymes, and this allows tumors formed by these cells to invade adjacent tissues (6). Furthermore, at advanced stages of the disease cancer cells detach from the primary tumor and migrate toward ectopic locations, where they reattach and give rise to metastases (7,8). Despite the fact that carcinoma cells are frequently deprived of normal con...

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