Sources of variability in distortion product otoacoustic emissions

The goal of this study was to determine the extent to which the variability seen in distortion product otoacoustic emissions (DPOAEs), among ears with normal hearing, could be accounted for. Several factors were selected for investigation, including behavioral threshold, differences in middle-ear transmission characteristics either in the forward or the reverse direction, and differences in contributions from the distortion and reflection sources. These variables were assessed after optimizing stimulus parameters for individual ears at each frequency. A multiple-linear regression was performed to identify whether the selected variables, either individually or in combination, explained significant portions of variability in DPOAE responses. Behavioral threshold at the f(2) frequency and behavioral threshold squared at that same frequency explained the largest amount of variability in DPOAE level, compared to the other variables. The combined model explained a small, but significant, amount of variance in DPOAE level at five frequencies. A large amount of residual variability remained, even at frequencies where the model accounted for significant amounts of variance.     

Sentence recognition in noise promoting or suppressing masking release by normal-hearing and cochlear-implant listeners

Normal-hearing (NH) listeners maintain robust speech understanding in modulated noise by "glimpsing" portions of speech from a partially masked waveform--a phenomenon known as masking release (MR). Cochlear implant (CI) users, however, generally lack such resiliency. In previous studies, temporal masking of speech by noise occurred randomly, obscuring to what degree MR is attributable to the temporal overlap of speech and masker. In the present study, masker conditions were constructed to either promote (+MR) or suppress (-MR) masking release by controlling the degree of temporal overlap. Sentence recognition was measured in 14 CI subjects and 22 young-adult NH subjects. Normal-hearing subjects showed large amounts of masking release in the +MR condition and a marked difference between +MR and -MR conditions. In contrast, CI subjects demonstrated less effect of MR overall, and some displayed modulation interference as reflected by poorer performance in modulated maskers. These results suggest that the poor performance of typical CI users in noise might be accounted for by factors that extend beyond peripheral masking, such as reduced segmental boundaries between syllables or words. Encouragingly, the best CI users tested here could take advantage of masker fluctuations to better segregate the speech from the background.     

Influence of primary-level and primary-frequency ratios on human distortion product otoacoustic emissions

The combined influence of primary-level differences (L1-L2) and primary-frequency ratio (f2/f1) on distortion product otoacoustic emission (DPOAE) level was investigated in 20 normal-hearing subjects. DPOAEs were recorded with continuously varying stimulus levels [Neely et al. J. Acoust. Soc. Am. 117, 1248-1259 (2005)] for the following stimulus conditions: f2= 1, 2, 4, and 8 kHz and f2/f1=1.05 to 1.4; various L1-L2, including one individually optimized to produce the largest DPOAE. For broadly spaced primary frequencies at low L2 levels, the largest DPOAEs were recorded when L1 was much higher than L2, with L1 remaining relatively constant as L2 increased. As f2/fl decreased, the largest DPOAEs were observed when L1 was closer to L2 and increased as L2 increased. Optimal values for L1-L2 and f2 f1 were derived from these data. In general, average DPOAE levels for the new L1-L2 and f2/f1 were equivalent to or larger than those observed for other stimulus combinations, including the L1-L2 described by Kummer et al. [J. Acoust. Soc. Am. 103, 3431-3444 (1998)] and those defined by Neely et al. in which L1-L2 was evaluated, but f2/f1 was fixed at 1.2.     

Synthesis and evaluation of some variants of the Nefkens’ reagent

A series of N-substituted phthalimides have been prepared in an effort to explore synthetic variants of the Nefkens’ reagent. Three N-acylphthalimides [R = –CH₃, –CH₂CH₃, and –C(CH₃)₃] were prepared and employed for the protection of a series of representative amines. In addition, an N-methanesulfonylphthalimide and N-(diethylphosphoryl)phthalimide were also prepared. It was determined that among the phthalimides that were prepared N-propanoylphthalimide was the most effective reagent for the protection reaction.     

Conjugation of arginine–glycine–aspartic acid peptides to thermoreversible N‐isopropylacrylamide polymers

Thermoreversible polymeric biomaterials are finding increased acceptance in tissue engineering applications. One drawback of the polymers is their synthetic nature, which does not allow direct interaction of mammalian cells with the polymers. This limitation may be alleviated by grafting arginine–glycine–aspartic acid (RGD) containing peptides onto the polymer backbone to facilitate interactions with cell‐surface integrins. Toward this goal, N‐isopropylacrylamide (NiPAM)‐based thermoreversible polymers containing amine‐reactive N‐acryloxysuccinimide (NASI) groups were synthesized. Conjugation of RGD‐containing peptides to polymers was demonstrated with ¹H NMR spectroscopy and reverse‐phase high‐pressure liquid chromatography. The conjugation reaction was optimal at 4 °C and pH of 8.0, and increased with the increasing NASI content of polymers. With a peptide grafting ratio of 0.25 mol %, there was no significant change in the lower critical solution temperature of the polymers. Finally, the NASI‐containing polymers, cast as films, on tissue culture polystyrene, were shown to conjugate to RGD‐containing peptides and support C2C12 cell attachment. We conclude that NASI‐containing thermoreversible polymers are amenable for grafting biomimetic peptides to impart cell adhesiveness to the polymers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3989–4000, 2003     

The alpha-effect in methyl transfers from S-methyldibenzothiophenium fluoroborate to substituted N-methylbenzohydroxamates

Studies of the alpha-effect show increased reactivity of nucleophiles having lone pairs of electrons on atoms neighboring the lone pair involved in reactivity when compared to the basicity of the nucleophiles. Hammett-type plots and Br?nsted-type plots of substituted methylphenyl sulfates vs hydrogen peroxide anions and substituted N-methylbenzohydroxanates (NMBH) with substituted methylarenesulfonates or substituted arenedimethylsulfonium ions have large rho or beta(nuc) values, indicating a putative tightening of the usual S(N)2 transition states (anti-Hammond effect). Electrochemical studies of S(N)2-SET or reactivity indicate that SET character occurs in looser transition states, whereas S(N)2 transition states are associated with greater tightness. The alpha-effects for the series of sulfonium salts in completion reactions for 3-ClNMBH anions and 3-nitrophenolate anions are (log k(alpha)/k(normal)) 1.124 for dimethylphenyl sulfonium, 1.512 for dimethyl-1-naphthyl sulfonium, 1.835 for dimethyl-9-anthracenyl sulfonium, and 1.137 for S-methyldibenzylthiophenium. Correlations of the sizes of alpha-effects with typical SET (or ET) experimental parameters and the inverse dependence of the size of the alpha-effect on electron demand indicate inclusion of SET character in these S(N)2 transition states, vs no (or at least diminished) SET character in normal transition states. This dichotomy of tighter S(N)2 transition states, but looser SET transition states indicated in the alpha-effect, is examined in the present work.     

syn-Diastereoselective glycolate aldol addition reactions of an N(3)-(p-methoxyphenoxy)acetyloxazolidine-2-thione

An N₃-(p-methoxyphenoxy)acetyloxazolidine-2-thione has been synthesized and employed in glycolate asymmetric aldol addition reactions with aromatic and aliphatic aldehydes. It was determined that the titanium tetrachloride medicated aldol reaction afforded diastereoselectivities that ranged from 75:25 to 94:6 when the reaction was conducted at ?78 °C. The absolute stereochemistry of the aldol adducts was determined by ¹H NMR spectroscopy and X-ray crystallography. The ¹H NMR spectra of the aldol adducts contained a signal (the α-proton of the glycolate position of the aldol side chain) that was highly deshielded due to conformational restriction about the N(3)-(p-methoxyphenoxy)acetyl side chain and the oxazolidine-2-thione auxiliary.     

A Photoaffinity Displacement Assay and Probes to Study the Cyclin‐Dependent Kinase Family

The CDK family plays a crucial role in the control of the cell cycle. Dysregulation and mutation of the CDKs has been implicated in cancer and the CDKs have been investigated extensively as potential therapeutic targets. Selective inhibition of specific isoforms of the CDKs is crucial to achieve therapeutic effect while minimising toxicity. We present a group of photoaffinity probes designed to bind to the family of CDKs. The site of crosslinking of the optimised probe, as well as its ability to enrich members of the CDK family from cell lysates, was investigated. In a proof of concept study, we subsequently developed a photoaffinity probe‐based competition assay to profile CDK inhibitors. We anticipate that this approach will be widely applicable to the study of small molecule binding to protein families of interest.     

A stable cardinality distance for topological classification

Advances in Data Analysis and Classification - This work incorporates topological features via persistence diagrams to classify point cloud data arising from materials science. Persistence diagrams...