Physiological detection of interaural phase differences

Auditory evoked cortical responses to changes in the interaural phase difference (IPD) were recorded using magnetoencephalography (MEG). Twelve normal-hearing young adults were tested with amplitude-modulated tones with carrier frequencies of 500, 1000, 1250, and 1500 Hz. The onset of the stimuli evoked P1m-N1m-P2m cortical responses, as did the changes in the interaural phase. Significant responses to IPD changes were identified at 500 and 1000 Hz in all subjects and at 1250 Hz in nine subjects, whereas responses were absent in all subjects at 1500 Hz, indicating a group mean threshold for detecting IPDs of 1250 Hz. Behavioral thresholds were found at 1200 Hz using an adaptive two alternative forced choice procedure. Because the physiological responses require phase information, through synchronous bilateral inputs at the level of the auditory brainstem, physiological "change" detection thresholds likely reflect the upper limit of phase synchronous activity in the brainstem. The procedure has potential applications in investigating impaired binaural processing because phase statistic applied to single epoch MEG data allowed individual thresholds to be obtained.     

Both core- and shell-cross-linked nanogels: photoinduced size change, intraparticle LCST, and interparticle UCST thermal behaviors

New thermal- and photoresponsive core-shell nanogel particles were obtained from self-assembly in aqueous solution of a double-hydrophilic block copolymer (DHBCP) of which the two blocks could be photo-cross-linked via the reversible photodimerization and photocleavage of coumarin moieties. The diblock copolymer, consisting of poly[N,N-dimethylacrylamide-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin] and poly[N-isopropylacrylamide-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin] (P(DMA-co-CMA)-b-P(NIPAM-co-CMA)), was synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization. At T > LCST of the P(NIPAM-co-CMA) block, core-shell micelles were formed and UV light irradiation at λ > 310 nm resulted in cross-linking of both the micelle core of P(NIPAM-co-CMA) and the micelle shell of P(DMA-co-CMA); subsequent cooling of the solution to T < LCST gave rise to water-soluble, swollen nanogel particles. Upon UV light irradiation at λ < 260 nm, the decrease of cross-linking density could increase the swelling of nanogel particles by ～23% in diameter. By alternating irradiation with the different wavelengths, the average hydrodynamic diameter of nanogel particles was tunable between ～58 and ～47 nm. Interestingly, upon further cooling of the solution, aggregation occurred for nanogel particles with a moderate cross-linking density (10%-40% dimerization of coumarin moieties). Therefore, such core- and shell-cross-linked nanogel could display both "intraparticle" LCST (solubility of polymer chains forming the core) and "interparticle" UCST (solubility of particles). The possible mechanism and the effect of dimerization degree on the UCST behavior were discussed.     

Evaluation of CO coordination energies from spectroscopic data: on the use of vibrational isotopic effects

For molecules containing a linearly coordinated carbonyl group, relationships linking 13C and 18O isotopic effects on the CO stretching vibration to the force constant of the M-C coordination bond are proposed. These relationships are rationalized by simple considerations involving the mechanical coupling of the CO and M-C oscillators, tested on model triatomic molecules, and generalized to larger systems. Previous theoretical considerations and several examples presented here show that the long-accepted relation between the shift in the stretching frequency of the coordinated CO with respect to that of isolated CO and the coordination strength has no general predictive power. In contrast, the force constant of the coordination bond can be correlated with the coordination binding energy, and a method for empirically estimating this important parameter from spectroscopic observations of the strongly absorbing CO stretching vibrations of molecular systems or adsorbates is proposed.     

Selective excitation of coupled CO vibrations on a dissipative Cu(100) surface by shaped infrared laser pulses

In a previous paper [Beyvers et al., J. Chem. Phys. 124, 234706 (2006)], the possibility to mode and state selectively excite various vibrational modes of a CO molecule adsorbed on a dissipative Cu(100) surface by shaped IR pulses was examined. Reduced-dimensionality models with stretching-only coordinates were employed to do so. This model is now extended with the goal to include rotational modes. First, we present an analysis of the bound states of the adsorbed CO molecule in full dimension; i.e., six-dimensional eigenstates are obtained by diagonalizing the six-dimensional Hamiltonian containing the semiempirical potential of Tully et al. [J. Vac. Sci. Technol. A 11, 1914 (1993)]. This is achieved by using a contracted iterative eigensolver based on the coupled two-term Lanczos algorithm with full reorthogonalization. Reduced-dimension subsystem eigenvectors are also computed and then used to study the selective excitation of the molecule in the presence of dissipation within the density matrix formalism for open systems. In the density matrix propagations, up to four degrees of freedom were included, namely, r (the C-O distance), Z (the molecule-surface distance), and phi and theta (the azimuthal and polar angles of the molecular axis with respect to the surface). Short, intense laser pulses are rationally engineered and further refined with optimal control theory, again with the goal for mode and state selective excitation. Also, IR-laser induced desorption is studied. For the calculations, the previous two-mode (r,Z) dipole surface is extended to include the angular dependence and the model for the coupling of the molecule to the surface electronic degrees of freedom is refined.     

Sterically biased 3,3-sigmatropic rearrangement of chiral allylic azides: application to the total syntheses of alkaloids

We describe a tandem Mitsunobu/3,3-sigmatropic rearrangement of allylic azides on a chiral auxiliary system that favors one regioisomer thanks to its exceptional steric bias. The sequence may be completed by the oxidative cleavage of the auxiliary or by a ring-closing metathesis reaction that produces a carbo- or heterocycle directly and a recyclable form of the chiral auxiliary. Applications of the methodology to the total synthesis of (+)-coniine, (+)-lentiginosin, and (+)-pumiliotoxin C are reported.     

A versatile protocol for Stille-Migita cross coupling reactions

The combination of catalytic amounts of [Pd(PPh3)4], copper thiophene-2-carboxylate (CuTC) and [Ph2PO2][NBu4] allowed a series of exigent Stille-Migita reactions to be performed with high yields; as the protocol is fluoride free, a variety of O-silyl and C-silyl groups remained intact.     

In vitro enzymatic oxidation of a fluorine-tagged sulfido substrate analogue: a 19F NMR investigation

1H-decoupled 19F NMR has been used to monitor the highly regioselective oxidation of a fluorine-tagged thia-fatty acid derivative by castor stearoyl-ACP delta9 desaturase. The major enzymatic product, after reductive work-up, was identified as 9-fluoro-1-nonanol. This compound could be easily distinguished from substrate and a 9-sulfoxy by-product on the basis of its 19F NMR chemical shift and spiking experiments using authentic standards. Structural assignment of the cleavage product was confirmed by GC-MS analysis of the enzymatic products.     

A small-molecule probe for hepatitis C virus replication that blocks protein folding

The hepatitis C virus (HCV) is a growing global health problem. Small molecules that interfere with host-viral interactions can serve as powerful tools for elucidating the molecular mechanisms of pathogenesis and defining new strategies for therapeutic development. Using a cell-based screen involving subgenomic HCV replicons, we identified the ability of 18 different abscisic acid (ABA) analogs, originally developed as plant growth regulators, to inhibit HCV replication. Three of these were further studied. One compound, here named origamicin, showed antiviral activity through the inhibition of host proteins involved in protein folding. Origamicin could therefore be an important tool for studying the maturation of both host and viral proteins. Herein we demonstrate an application for molecular scaffolds based on ABA for mammalian cell targets involved in protein folding.     

Transferring self-assembled, nanoscale cables into electrical devices

This study details a new derivative of the contorted HBCs that self-organizes into one-dimensional, single-crystalline fibers. X-ray diffraction, transmission electron microscopy, and electron diffraction studies show that they have an orthorhombic unit cell with dimensions of 5.8 nm x 4.5 nm x 0.45 nm. Each fiber is composed of a few thousands columns. A method is put forth that utilizes elastomer stamps to manipulate and position isolated fibers in organic field effect transistors.