High quality zinc blende ZnSe and ZnSe/ZnS core/shell nanocrystals have been synthesized by two converse injection methods (i.e. zinc precursor injection or selenium precursor injection) when Se-ODE complex was chosen as the phosphine-free selenium precursor. Absorption spectroscopy, fluorescence spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM) were used to characterize the as-synthesized ZnSe and ZnSe/ZnS nanocrystals. The quality of the as-prepared ZnSe nanocrystals reached the same high level compared with the method using phosphine selenium precursors since the quantum yields were between 40 and 60% and photoluminescence (PL) full width at half-maximum (FWHM) was well controlled between 14 and 17 nm. The parameter window for the growth of high quality ZnSe nanocrystals was found to be much broader and monodisperse ZnSe nanocrystals were synthesized successfully even when the reaction temperature was set as low as 240 degrees C. As cores, such zinc blende ZnSe nanocrystals were also used to synthesize ZnSe/ZnS core/shell nanocrystals with high fluorescence quantum yields of 70%. Cu(2+) or Mn(2+) doped ZnSe nanocrystals were also synthesized by simply modifying this phosphine-free method. The emission range has been extended to 500 and 600 nm with the use of Cu(2+) and Mn(2+) dopants compared with the emission coverage of ZnSe at around 400 nm. This is the first totally "green approach" (i.e. phosphine-free synthesis) for the synthesis of high quality ZnSe, ZnSe/ZnS, and Cu(2+) or Mn(2+) doped ZnSe nanocrystals.

A number of novel amidine containing heterocycles were designed to reproduce the unique interaction pattern, revealed by X-ray crystallography, between the BACE-1 catalytic diad and a weak NMR screening hit (3), with special attention paid to maintaining the appropriate basicity and limiting the number of H-bonding donors of these scaffolds. The iminohydantoin cores (10 and 23) were examined first and found to interact with the catalytic diad in one of two binding modes (A and B), each with the iminohydantoin core flipped 180 degrees in relation to the other. The amidine structural motif within each core forms a bidentate interaction with a different aspartic acid of the catalytic diad. Both modes reproduced a highly conserved interaction pattern between the inhibitors and the catalytic aspartates, as revealed by 3. Potent iminohydantoin BACE-1 inhibitors have been obtained, validating the molecular design as aspartyl protease catalytic site inhibitors. Brain penetrant small molecule BACE inhibitors with high ligand efficiencies have been discovered, enabling multiple strategies for further development of these inhibitors into highly potent, selective and in vivo efficacious BACE inhibitors.

Tissue regeneration of the vocal fold lamina propria extracellular matrix (ECM) will be facilitated by the use of suitable vocal fold fibroblast (VFF) cell lines in appropriate model systems. Primary human VFFs (hVFFs) were steadily transduced by a retroviral vector containing human telomerase reverse transcriptase (hTERT) gene; immortalized cells grew and divided vigorously for more than 120 days. Biochemical characterization of the six transduced lines included, at different time points, expression of hTERT, telomerase activity, telomere lengths, and transcript levels of ECM constituents. Telomere lengths of the transfected lines were elongated and stable. Gene expression levels of collagen Ialpha1, collagen Ialpha2, collagen VIalpha3, elastin, and fibronectin were measured between the transduced cell clones and the primary hVFFs to verify transcription. Absence of inter- and intraspecies contamination was confirmed with DNA fingerprinting and karyotype analysis. Cell morphology, growth, and transcription expression were examined on 2D scaffolds-collagen, fibronectin, and hyaluronic acid. Immortalized hVFFs demonstrated normal attachment and spread on 2D scaffolds. Collagen Ialpha1, collagen Ialpha2, collagen VIalpha3, elastin, and fibronectin transcript expression was measured from immortalized hVFFs, for all surfaces. This is the first report of immortalization and biochemical characterization of hVFFs, providing a novel and invaluable tool for tissue regeneration applications in the larynx.

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