David M. Tanenbaum

Nanoelectromechanical systems were fabricated from single- and multilayer graphene sheets by mechanically exfoliating thin sheets from graphite over trenches in silicon oxide. Vibrations with fundamental resonant frequencies in the megahertz range are actuated either optically or electrically and detected optically by interferometry. We demonstrate room-temperature charge sensitivities down to 8 x 10(-4) electrons per root hertz. The thinnest resonator consists of a single suspended layer of atoms and represents the ultimate limit of two-dimensional nanoelectromechanical systems.

Using an atomic force microscope, we measured effective spring constants of stacks of graphene sheets (less than 5) suspended over photolithographically defined trenches in silicon dioxide. Measurements were made on layered graphene sheets of thicknesses between 2 and 8nm, with measured spring constants scaling as expected with the dimensions of the suspended section, ranging from 1to5N∕m. When our data are fitted to a model for doubly clamped beams under tension, we extract a Young’s modulus of 0.5TPa, compared to 1TPa for bulk graphite along the basal plane, and tensions on the order of 10−7N.

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

The 2.8-A crystal structure of the complex formed by estradiol and the human estrogen receptor-alpha ligand binding domain (hERalphaLBD) is described and compared with the recently reported structure of the progesterone complex of the human progesterone receptor ligand binding domain, as well as with similar structures of steroid/nuclear receptor LBDs solved elsewhere. The hormone-bound hERalphaLBD forms a distinctly different and probably more physiologically important dimer interface than its progesterone counterpart. A comparison of the specificity determinants of hormone binding reveals a common structural theme of mutually supported van der Waals and hydrogen-bonded interactions involving highly conserved residues. The previously suggested mechanism by which the estrogen receptor distinguishes estradiol's unique 3-hydroxy group from the 3-keto function of most other steroids is now described in atomic detail. Mapping of mutagenesis results points to a coactivator-binding surface that includes the region around the "signature sequence" as well as helix 12, where the ligand-dependent conformation of the activation function 2 core is similar in all previously solved steroid/nuclear receptor LBDs. A peculiar crystal packing event displaces helix 12 in the hERalphaLBD reported here, suggesting a higher degree of dynamic variability than expected for this critical substructure.