Femtosecond optical nonlinearities of CdSe quantum dots

Femtosecond differential absorption measurements of the quantum-confined transitions in CdSe microcrystallites are reported. Spectral hole burning is observed, which is accompanied by an induced absorption feature on the high-energy side. The spectral position of the burned hole depends on the excitation wavelength. For excitation on the low-energy side of the lowest quantum-confined transition, a slight shift of the hole towards the line center is observed. The hole width increases with pump intensity and the magnitude of the induced transparency saturates at the highest excitation level. The results are consistently explained by bleaching of one-pair states and induced absorption caused by the photoexcited two electron-hole pair states. It is concluded that the presence of one electron in the excited state prevents further absorption of photons at the pair-transition energy and accounts for the major portion of the bleaching of the transition     

Novel antitumor 2-cyanoaziridine-1-carboxamides

A set of 20 2-cyanoaziridine-1-carboxamides was synthesized from 2-cyanoaziridine and appropriate isocyanates. These compounds were active against a variety of solid and hematological tumor cells in culture, including strains resistant to doxorubicin and mitoxantrone. Their potencies in these assays correlated with the lipophilicity of substituents. The N-phenyl derivative was more potent and equally effective to imexon, a cyclized 2-cyanoaziridine-1-carboxamide of clinical interest, against cloned fresh human tumors.     

EEG evidence of stimulus-directed response dynamics in human somatosensory cortex

Dense multichannel recordings of scalp electroencephalogram (EEG) were obtained in the vicinity of primary somatosensory cortex, time-locked to repetitive vibrotactile stimulation of sites on the right index finger of a single human subject. Frequency-domain analysis of cross-trial averages revealed prominent 'driving' responses in the EEG at the frequency of stimulation, which under specific stimulus conditions displayed pronounced changes in amplitude and topographic organization over brief (4 s) durations of stimulus exposure. The changes were systematic and physiologically coherent, evolving toward driving-response topographies observed in the same subject in conjunction with periodic microstimulation of single mechanoreceptive afferents whose receptive fields occupied corresponding positions on the digit. This dynamic process was orderly and reproducible, and could be controlled by manipulating factors such as the amplitude, frequency, and temporal spacing of the stimuli. The results are tentatively interpreted in light of a previously proposed neurophysiological model of stimulus-driven response plasticity in mammalian somatosensory cortex.     

A structure-based approach to nicotinic receptor pharmacology

Infrared difference spectroscopy has been used to examine the structural effects of local anesthetic (LA) binding to the nicotinic acetylcholine receptor (nAChR). Several LAs induce subtle changes in the vibrational spectrum of the nAChR over a range of concentrations consistent with their reported nAChR-binding affinities. At concentrations of the desensitizing LAs prilocaine and lidocaine consistent with their binding to the ion channel pore, the vibrational changes suggest the stabilization of an intermediate conformation that shares structural features in common with both the resting and desensitized states. Higher concentrations of prilocaine and lidocaine, as well as the LA dibucaine, lead to additional binding to the neurotransmitter-binding site, the formation of physical interactions (most notably cation-tyrosine interactions) between LAs and neurotransmitter-binding-site residues, and the subsequent formation of a presumed desensitized nAChR. Although concentrations of the LA tetracaine consistent with binding to the ion channel pore elicit a reversed pattern of spectral changes suggestive of a resting state-like nAChR, higher concentrations also lead to neurotransmitter site binding and desensitization. Our results suggest that LAs stabilize multiple conformations of the nAChR by binding to at least two conformationally sensitive LA-binding sites. The spectra also reveal subtle differences in the strengths of the physical interactions that occur between LAs and binding-site residues. These differences correlate with LA potency at the nAChR.     

Comparison of methods to enumerate bacteria in dental unit water lines

Millipore HPC samplers are simple, self-contained test devices that can be used by personnel in dental offices who do not have microbiologic training to easily and economically monitor dental unit water quality without laboratory support. This study evaluated the correlation of HPC samplers to R2A agar for enumerating planktonic bacteria in dental unit treatment water. Eight different dental units were sampled. Five replicates were performed for each media at each dilution. The Pearson correlation coefficient between the R2A agar and HPC sampler is 0.89. These data suggest HPC samplers correlate with conventional laboratory-based R2A culture techniques for determining dental unit water line contamination.     

Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. RESULTS: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P <.001), but total REE did not change. CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS.     

Differential sensitivity of myosin-heavy-chain-typed fibers to distinct aggregates of nerve-mediated activation

We studied the regulatory effects of nerve-mediated activity on the early expression of embryonic and adult myosin heavy chains (MHC) within inactive though still innervated rat plantaris and soleus muscle fibers. To this end, we stimulated motor nerves that were quiescent following treatment with tetrodotoxin (TTX) with paradigms designed to partition the influence of neural activation frequency and assessed the selective expression and accumulation of MHCs within muscle fibers using an array of specific antibodies. We show rapid de novo expression of IIx MHC within select soleus fibers in response to high-frequency activation for more than 0.01% of daily time. High-frequency aggregates were also the most effective in preventing the TTX-induced reexpression of embryonic MHCs within specific fibers. Only configurations that included high-frequency trains for more than 0.01% of daily time or combined with 10 Hz stimulation preserved the size of select fibers, used as a measure of the net cellular content of MHC. The effectiveness of this preservation varied according to the muscle type and MHC expressed, and, in a subset of fibers, was influenced by contractile loading status. Our results demonstrate that distinct subsets of MHC-typed fibers are differentially sensitive to the neural activation cues mediating the cellular expression of these proteins.