Block copolymers consist of two or more chemically different polymers connected by covalent linkages. In solution, repulsion between the blocks leads to a variety of morphologies, which are thermodynamically driven. Polyferrocenyldimethylsilane block copolymers show an unusual propensity to forming cylindrical micelles in solution. We found that the micelle structure grows epitaxially through the addition of more polymer, producing micelles with a narrow size dispersity, in a process analogous to the growth of living polymer. By adding a different block copolymer, we could form co-micelles. We were also able to selectively functionalize different parts of the micelle. Potential applications for these materials include their use in lithographic etch resists, in redox-active templates, and as catalytically active metal nanoparticle precursors.

Speech recognition was measured as a function of spectral resolution (number of spectral channels) and speech-to-noise ratio in normal-hearing (NH) and cochlear-implant (CI) listeners. Vowel, consonant, word, and sentence recognition were measured in five normal-hearing listeners, ten listeners with the Nucleus-22 cochlear implant, and nine listeners with the Advanced Bionics Clarion cochlear implant. Recognition was measured as a function of the number of spectral channels (noise bands or electrodes) at signal-to-noise ratios of + 15, + 10, +5, 0 dB, and in quiet. Performance with three different speech processing strategies (SPEAK, CIS, and SAS) was similar across all conditions, and improved as the number of electrodes increased (up to seven or eight) for all conditions. For all noise levels, vowel and consonant recognition with the SPEAK speech processor did not improve with more than seven electrodes, while for normal-hearing listeners, performance continued to increase up to at least 20 channels. Speech recognition on more difficult speech materials (word and sentence recognition) showed a marginally significant increase in Nucleus-22 listeners from seven to ten electrodes. The average implant score on all processing strategies was poorer than scores of NH listeners with similar processing. However, the best CI scores were similar to the normal-hearing scores for that condition (up to seven channels). CI listeners with the highest performance level increased in performance as the number of electrodes increased up to seven, while CI listeners with low levels of speech recognition did not increase in performance as the number of electrodes was increased beyond four. These results quantify the effect of number of spectral channels on speech recognition in noise and demonstrate that most CI subjects are not able to fully utilize the spectral information provided by the number of electrodes used in their implant.

Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and that regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanisms that remain unclear. Here, we show that the expression and function of EZH2 in cancer cell lines is inhibited by microRNA-101 (miR-101). Analysis of human prostate tumors revealed that miR-101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in 37.5% of clinically localized prostate cancers (6/16) and 66.7% of metastatic disease (22/33). We propose that genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression.Polycomb Group Proteins, including EZH2, play a master regulatory role in controlling important cellular process such as maintaining stem cell pluripotency (1-3), cell proliferation (4,5), early embryogenesis (6), and X chromosome inactivation (7). EZH2 functions in a multiprotein complex called Polycomb Repressive Complex 2 (PRC2) which includes SUZ12 (Suppressor of Zeste 12) and EED (Embryonic Ectoderm Development) (8,9). The primary activity of the EZH2 protein complex is to tri-methylate histone H3 lysine 27 (H3K27) at target gene promoters, leading to epigenetic silencing (10,11). Mounting evidence suggests that #Address correspondence and requests for reprints to:

We have identified the lymphocyte semaphorin CD100/Sema4D as a CD40-inducible molecule by subtractive cDNA cloning. CD100 stimulation significantly enhanced the effects of CD40 on B cell responses. Administration of soluble CD100 markedly accelerated in vivo antigen-specific antibody responses. CD100 receptors with different binding affinities were detected on renal tubular cells (K(d) = approximately 1 x 10(-9)M) and lymphocytes (K(d) = approximately 3 x 10(-7)M). Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness. CD72 thus represents a novel class of semaphorin receptors. CD100 stimulation induced tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72. Our findings indicate that CD100 plays a critical role in immune responses by the novel mechanism of turning off negative signaling by CD72.

The class IV semaphorin CD100/Sema4D differentially utilizes two distinct receptors: plexin-B1 in nonlymphoid tissues, such as brain and kidney, and CD72 in lymphoid tissues. We have generated CD100-deficient mice and demonstrated that they have functional defects in their immune system, without apparent abnormalities in other tissues. The number of CD5(+) B-1 cells was considerably decreased in the mutant mice, whereas conventional B cells and T cells appeared to develop normally. In vitro proliferative responses and immunoglobulin production were reduced in CD100-deficient B cells. The humoral immune response against a T cell-dependent antigen and in vivo priming of T cells were also defective in the mutant mice. These results demonstrate nonredundant and essential roles of CD100-CD72 interactions in the immune system.