Timing jitter reduction of passively Q-switched solid-state lasers by coupling resonance between pumping and firing rates.

The coupling resonance between pumping and firing rates is originally proposed to achieve the timing jitter reduction of a Nd:YVO4 laser passively Q-switched with a saturable absorber. When the pumping rate is higher than the spontaneous emission rate, it is experimentally confirmed that the pulse firing rate can be fractionally locked with the pumping rate by controlling the pump power. The locking characteristics of the firing rate display a variety of complex plateaus that can be excellently manifested with the sine-circle map. From numerical analyses, the coupling strength can be verified to be effectively enhanced by reducing the duty cycle of the pumping rate.

Iatrogenic subcutaneous facial emphysema secondary to a Class V dental restoration: a case report.

Subcutaneous facial emphysema (SFE) following routine dental operative procedure is an uncommon but potentially life-threatening complication. The present case details a Class V restoration where air was introduced into the fascial tissue planes via the gingival sulcus from the use of an air-driven dental handpiece. Although the SFE is usually self-limiting within 3-10 days, such instances should be regarded as a medical emergency as in severe cases, the air may spread to the neck, mediastinum and thorax to result in cervicofacial emphysema with potential pneumomediastinum and pneumothorax.

Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP1 pathway.

In the classical signaling pathway, the estrogen receptor (ER) binds directly to estrogen response elements (EREs) to regulate gene transcription. To test the hypothesis that the nonclassical pathway involves ER interactions with other proteins rather than direct binding to DNA, mutations were introduced into the DNA binding domain (DBD) of the mouse ERalpha. The effects of these DBD mutations were examined in DNA binding assays using reporter constructs containing either EREs (classical) or AP1 (nonclassical) response elements. Using the AP1 reporter, there was a reversal of ER action relative to that seen with the ERE reporter. Estradiol induced suppression, and the antiestrogen ICI 182,780 stimulated transcription of the AP1 reporter. DBD mutations in the proximal (P-box) of the first zinc finger of the ER (E207A/G208A and E207G/G208S) eliminated ERE binding. These mutants were inactive using the ERE reporter but retained partial or full activity with the AP1 reporter. The DBD mutant ERs interacted with Jun when tested in mammalian cell two-hybrid assays. Two mutations (K366D and I362R) in the ER ligand binding domain known to alter coactivator interactions impaired transcriptional responses using either the ERE or AP1 reporters. We concluded that ER action through the AP1 response element involves interactions with other promoter-bound proteins instead of, or in addition to, direct binding to DNA. Interactions with coactivators were required for both pathways. These data supported a model in which ER-mediated transcriptional activation or repression is dependent on the ligand and the nature of the response element in the target gene.

Adenovirus-directed expression of dominant negative estrogen receptor induces apoptosis in breast cancer cells and regression of tumors in nude mice.

BACKGROUND: Estrogen receptors (ER) are expressed in about two thirds of human breast cancer, and are an important pharmacological target for treatment of these tumors. Dominant negative forms of the ER have been suggested as an alternative method to disrupt ER function. In this study, we examined the effect of dominant negative ER mutants (ER1-536 and L540Q) on ER-positive breast cancer cells in vitro and in vivo. MATERIALS AND METHODS: ER-positive T47D breast cancer cells were infected with adenoviral vectors expressing ER1-536 and L540Q to examine the effects of the mutants on gene expression and cell growth. Adenoviral vectors containing the wild type ER (AdwtER) and beta-galactosidase gene (AdGal) were used as controls. RESULTS: Ad1-536 or AdL540Q infection inhibited T47D cell growth and induced apoptosis, increasing Bax protein and phosphorylation of p38 mitogen-activated-protein kinase (MAPK). Consistent with the apoptotic effects in vitro, pre-infection of T47D cells with Ad1-536 or AdL540Q inhibited tumor formation when these cells were introduced into nude mice. In addition, injection of Ad1-536 and AdL540Q into pre-established T47D tumors induced tumor regression. Apoptosis, in conjunction with the activation of caspase-3 and phosphorylation of p38 MAPK, was detected in the shrinking tumors. Overexpression of wild-type ER by AdwtER infection also produced antiproliferative and apoptotic effects, but to a lesser extent than the ER1-536 and L540Q mutants. CONCLUSIONS: These results indicate that dominant negative ER mutants have the potential to induce apoptosis of T47D cells and regression of tumors. The delivery of dominant negative ERs by adenoviral vectors may provide a useful tool for targeted therapy of ER-positive breast cancer.

A fusion protein of the estrogen receptor (ER) and nuclear receptor corepressor (NCoR) strongly inhibits estrogen-dependent responses in breast cancer cells.

Nuclear receptor corepressor (NCoR) mediates repression (silencing) of basal gene transcription by nuclear receptors for thyroid hormone and retinoic acid. The goal of this study was to create novel estrogen receptor (ER) mutants by fusing transferable repressor domains from the N-terminal region of NCoR to a functional ER fragment. Three chimeric NCoR-ER proteins were created and shown to lack transcriptional activity. These fusion proteins silenced basal transcription of the ERE2-tk-Luc reporter gene and inhibited the activity of co-transfected wild-type ER (wtER), indicating that they possess dominant negative activity. One of the fusion proteins (CDE-RD1), containing the ER DNA-binding and ligand-binding domains linked to the NCoR repressor domain (RD1), was selected for detailed examination. Its hormone affinity, intracellular localization, and level of expression in transfected cells were similar to wtER, and it bound to the estrogen response element (ERE) DNA in gel shift assays. Glutathione-S-transferase pull-down assays showed that CDE-RD1 retains the ability to bind to steroid receptor coactivator-1. Introduction of a DNA-binding domain mutation into the CDE-RD1 fusion protein eliminated silencing and dominant negative activity. Thus, the RD1 repressor domain prevents transcriptional activation despite the apparent ability of CDE-RD1 to bind DNA, ligand, and coactivators. Transcriptional silencing was incompletely reversed by trichostatin A, suggesting a histone deacetylase-independent mechanism for repression. CDE-RD1 inhibited ER-mediated transcription in T47D and MDA-MB-231 breast cancer cells and repressed the growth of T47D cells when delivered to the cells by a retroviral vector. These ER-NCoR fusion proteins provide a novel means for inhibiting ER-mediated cellular responses, and analogous strategies could be used to create dominant negative mutants of other transcription factors.

Measurement of absolute displacement by a double-modulation technique based on a Michelson interferometer.

A novel method is presented for of measuring absolute displacement with a synthesized wavelength interferometer. The optical phase of the interferometer is simultaneously modulated with a frequency-modulated laser diode and optical path-length difference. The error signal originating from the intensity modulation of the source is eliminated by a signal processing circuit. In addition, a lock-in technique is used to demodulate the envelope of the interferometric signal. The displacement signal is derived by the self-mixing technique.

Neurotensin and dopamine D2 activation oppositely regulate the same K+ conductance in rat midbrain dopaminergic neurons.

Midbrain dopaminergic neurons are excited by neurotensin (NT) and inhibited by dopamine. Interactions between these neurotransmitters have been reported, but no interaction has yet been identified at the level of ionic and signal transduction mechanisms. Using the whole-cell clamp technique, we examined the interaction of NT and quinpirole (QUIN) (a dopamine D2 agonist) on midbrain ventral tegmental area neurons cultured from the rat. We found that NT could inhibit the K+ conductance induced by QUIN. By interrupting normal signal transduction with the non-hydrolyzable GTP analogue GTPgammaS, we found that this interaction occurred downstream of the membrane neurotransmitter receptors. Similar interactions were observed between QUIN and tachykinin or metabotropic glutamate agonists.

Distance and velocity measurements by the use of an orthogonal Michelson interferometer.

A novel signal processing scheme for detecting distance and velocity signals simultaneously is demonstrated. In this method, a frequency-modulated diode laser is used to illuminate a dual-channel Michelson interferometer with two orthogonal output signals. The distance and the velocity signals then exist on the beat frequencies of the output interferometric signal. Two interferometric output signals with a quadrature phase shift are used to adjust the gating time period of frequency counters for beat-frequency measurement. The distance and velocity signals can thus be obtained from the counting number within the gated-in time period.

Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor.

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen. At concentrations (approximately 3-10 microM) comparable to those required for its other biological effects, resveratrol inhibited the binding of labeled estradiol to the estrogen receptor and it activated transcription of estrogen-responsive reporter genes transfected into human breast cancer cells. This transcriptional activation was estrogen receptor-dependent, required an estrogen response element in the reporter gene, and was inhibited by specific estrogen antagonists. In some cell types (e.g., MCF-7 cells), resveratrol functioned as a superagonist (i.e., produced a greater maximal transcriptional response than estradiol) whereas in others it produced activation equal to or less than that of estradiol. Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. We conclude that resveratrol is a phytoestrogen and that it exhibits variable degrees of estrogen receptor agonism in different test systems. The estrogenic actions of resveratrol broaden the spectrum of its biological actions and may be relevant to the reported cardiovascular benefits of drinking wine.

Single-channel properties of the nonselective cation conductance induced by neurotensin in dopaminergic neurons.

Slow nonselective cation conductances play a central role in determining the excitability of many neurons, but heretofore this channel type has not been analyzed at the single-channel level. Neurotensin (NT) excites cultured dopaminergic neurons from the ventral tegmental area primarily by increasing such a cation conductance. Using the outside-out configuration of the patch clamp, we elicited single-channel activity of this NT-induced cation channel. Channel activity was blocked by the nonpeptide NT antagonist SR48692, indicating that the response was mediated by NT receptors. The channel opened in both solitary form and in bursts. The reversal potential was -4.2 +/- 1.7 mV, and the elementary conductance was 31 pS at -67 mV with [Na+]o = 140 mM, [Cs+]o = 5 mM, [Na+]i = 88 mM, and [Cs+]i = 74 mM. Thus, the channel was permeable to both Na+ and Cs+. From these characteristics, it is likely that this channel is responsible for the whole-cell current we studied previously. In guanosine 5'-[gamma-thio]triphosphate-loaded cells, NT irreversibly activated about half of the channel activity, suggesting that at least part of the response was mediated by a G protein. Similar channel activity could be induced occasionally in the cell-attached configuration by applying NT outside the patch region.

Properties of a slow nonselective cation conductance modulated by neurotensin and other neurotransmitters in midbrain dopaminergic neurons.

1. A widespread mechanism of slow excitation throughout the nervous system involves overlapping changes in nonselective ion conductance and K+ conductance. We used whole cell patch-clamp recording to characterize such a nonselective conductance induced by neurotensin (NT) and other neurotransmitters in immunocytochemically identified dopaminergic neurons cultured from the rat ventral tegmental area (VTA). 2. The NT-induced inward current consisted of an initial peak and later "hump." The response was blocked reversibly by the nonpeptide NT-receptor antagonist SR48692, suggesting that it resulted from activation of NT receptors. 3. The channel was almost equally permeable to Na+ and K+, as determined from the reversal potential shift upon switching from Na+- to K(+)-containing external solution. The permeability of Cs+ was similar to that of Na+, as determined from the zero-current equation and average reversal potential in the 75 mM Na+ solution. Cl- was not significantly permeable. 4. In Ca(2+)-free external solution, the NT-induced current showed a fourfold increase in amplitude, and in high Mg2+ (20 mM) external solution, the NT-induced current showed an 80% decrease in amplitude, suggesting that external Ca2+ and Mg2+ could block the nonselective conductance. 5. The NT response was unaffected by loading the neurons with either the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or with 1 mM ca2+. The nonselective conductance was therefore not Ca2+ activated. 6. Loading the neurons with cyclic GMP or cyclic AMP (each with the phosphodiesterase inhibitor isobutyl-methylxanthine) did not affect the NT response. The NT-induced nonselective conductance was therefore not cyclic nucleotide-activated. 7. The latency of the NT response was long (> or = 185 ms, average 406 ms, 30 degrees C), indicating that NT did not induce the conductance through ligand-gated channels. Thus, NT activated a slow nonselective cation conductance. 8. Neurokinin B, a metabotropic glutamate agonist, and muscarine elicited responses similar to the NT response. The NT response could be elicited after desensitizing the responses to these other neurotransmitters, indicating receptor specificity in the activation of the nonselective conductance.

Distance- and velocity-detection interferometer by using a frequency triangular-modulated laser diode.

A scheme for distance and velocity signal detection is implemented. This technique is based on a laser diode with its frequency modulated by a triangular waveform and followed by time gating.

Distance and velocity detection based on a deep sinusoidal phase-modulated interferometer.

A deep phase-modulation signal with a sinusoidal waveform is employed on a Michelson interferometer for detecting distance and velocity signals simultaneously. This approach is simple to implement and has a wide-dynamic-range capability with a linear scale factor.

Interferometric phase locking of two electronic oscillators with a cascade electro-optic modulator.

An optical-type electrical phase-locked-loop system based on a cascade electro-optic modulator has been demonstrated. By using this technique, a set of optical-type phase detectors, operating at any harmonic frequencies of two applied phase-modulation signals, has been implemented.

Scale-factor-stabilized fiber-optic gyroscope by deep phase modulation.

A scale-factor-stabilized fiber-optic gyroscope by deep phase modulation is demonstrated. There are two servo loops included in this system. The first servo loop is used for stabilization of the light intensity output of the fiber-optic gyroscope. The second loop is used to stabilize the phase-modulation index. The third-harmonic frequency of the phase-modulation signal is used for detection of the Sagnac phase shift by the lock-in technique.

Two-frequency fiber-optic sensor system using high-birefringence optical fiber.

A fiber sensor system based on high-birefringence optical fiber and a frequency-stabilized He-Ne Zeeman laser (lambda = 0.6328 microm) has been demonstrated. The small path-length changes of interest are extracted from the amplitude or phase of the laser beat frequency by using either the phase-sensitive detection or the phase-demodulation technique. A minimum detectable optical phase delay of 1.5 x 10(-6) rad/Hz((1/2)) or 17 x 10(-6) rad/Hz((1/2)) has been achieved.

Triangularly phase-modulated optical fiber ring resonator sensor.

An optical fiber ring resonatory sensor system has been demonstrated by applying a triangular phase modulation signal to a fiber loop. The dynamic range for detection of optical phase change is 2pi. The sensor is linear within this range. The minimum detectable optical phase change is 1.5 x10(-4) rad/Hz((1/2)).

Fiber-optic gyroscopes based on polarization scrambling.

A novel fiber-optic gyroscope with a single-mode diode laser as the light source and two polarization scramblers as time-varying depolarizers is demonstrated. This arrangement reduces the nonreciprocal phase noise induced by the cross coupling between polarization modes in single-mode fibers. The experimental results show that a phase-noise reduction factor of 18 can be achieved.

Scale-factor-stabilized fiber-optic gyroscope based on a spectrum-broadened laser-diode source.

A spectrum-broadened laser-diode source that uses the optical feedback and current-modulation effects has been adopted as the light source of a fiber-optic gyroscope to reduce the inherent phase noise. The scale factor of the gyroscope has also been stabilized.

Multiplexed fiber-optic sensors using a dual-slope frequency-modulated source.

We propose and demonstrate a multiplexed fiber-optic sensor system using a dual-slope (triangular) frequency-modulated laser source. The restrictions in the selection of beat frequencies of the multiplexed sensors in previous studies that employed ramp modulation wave forms are eliminated.