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Biomedical subjects

J R Taylor

Publications and source records attributed to J R Taylor.

At least 19 recordsLinked to original sources

Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography.

Noncontact, depth-resolved, optical probing of retinal response to visual stimulation with a <10-microm spatial resolution, achieved by using functional ultrahigh-resolution optical coherence tomography (fUHROCT), is demonstrated in isolated rabbit retinas. The method takes advantage of the fact that physiological changes in dark-adapted retinas caused by light stimulation can result in local variation of the tissue reflectivity. fUHROCT scans were acquired from isolated retinas synchronously with electrical recordings before, during, and after light stimulation. Pronounced stimulus-related changes in the retinal reflectivity profile were observed in the inner/outer segments of the photoreceptor layer and the plexiform layers. Control experiments (e.g., dark adaptation vs. light stimulation), pharmacological inhibition of photoreceptor function, and synaptic transmission to the inner retina confirmed that the origin of the observed optical changes is the altered physiological state of the retina evoked by the light stimulus. We have demonstrated that fUHROCT allows for simultaneous, noninvasive probing of both retinal morphology and function, which could significantly improve the early diagnosis of various ophthalmic pathologies and could lead to better understanding of pathogenesis.

Animals↗

Ytterbium gain band self-induced modulation instability laser.

We demonstrate an ytterbium gain band self-induced modulation instability laser. A highly nonlinear holey fiber is used to provide the anomalous dispersion required for bright soliton generation at 1 microm. The all-fiber integrated source yields a 40 GHz train of 4 ps pulses at a wavelength of 1064 nm.

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FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance.

The kinase inhibitor imatinib is used in the treatment of chronic myeloid leukaemia, where it targets the intracellular Bcr-Abl tyrosine kinase, and gastrointestinal stromal tumours, where it targets either the KIT or PDGF tyrosine kinase receptors. Here, we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance. Imatinib readily reverted the transformed phenotype of haemopoietic and fibroblast cell lines that express the oncogene v-fms and also inhibited the growth of the Bacl.2F5 macrophage cell line. The cellular IC50 value of imatinib for FMS was similar to those for Bcr-Abl and KIT. Consequently, imatinib may also prove effective for the treatment of diseases whose progression is dependent upon macrophage-colony stimulating factor, this includes certain aspects of cancer and inflammation.

Animals↗

Extended blue supercontinuum generation in cascaded holey fibers.

By combining multiple photonic crystal fibers with sequentially decreasing zero-dispersion wavelengths we have produced a 1.2 W average-power white-light continuum, covering the visible-near-infrared spectrum from 0.44 to 1.89 microm (10 dB width), with an all-fiber picosecond ytterbium pump laser. Wavelengths as short as the ultraviolet (0.35 microm), and spectral power densities of more than 2 mW/nm in the blue spectral region, have been generated. The process is understood in terms of optimizing four-wave mixing phase matching to enhance short-wavelength generation.

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Wavelength-versatile subpicosecond pulsed lasers using Raman gain in figure-of-eight fiber geometries.

A family of compact pulsed fiber lasers is described that employs broadband, wavelength-flexible Raman scattering in passively mode-locked figure-of-eight fiber laser geometries. Specifically, sources at 1.57, 1.33, and 1.41 microm with respective soliton durations of 440, 500, and 860 fs are reported. Operation is possible at other wavelengths with a suitable pump source, gain fiber, and components.

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Red picosecond pulses generated by frequency doubling a Raman amplified widely tunable 1.3 microm fiber ring laser.

We generated 0.66 microm picosecond pulses by second-harmonic generation of the Raman amplified output of a 1.3 microm actively mode-locked fiber ring laser in a periodically poled potassium titanyl phosphate (PPKTP) waveguide. The ring laser produced 9 ps pulses at a 20 GHz repetition frequency, was tunable over 1284-1330 nm, and was based on a semiconductor optical amplifier and a Mach-Zehnder amplitude modulator. The Raman amplifier served both to amplify the ring laser and to compress the pulses as solitons. The spectral flexibility of the amplifiers and the modulator should enable similar configurations to be made at other wavelengths and facilitate efficient frequency doubling in waveguides to other visible wavelengths.

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Extended continuous-wave supercontinuum generation in a low-water-loss holey fiber.

We report on the development of a 2.5 microm core photonic crystal fiber with a substantially reduced water-peak loss around 1.38 microm, which allows extended Raman-soliton supercontinuum generation up to 1.55 microm with a cw ytterbium fiber laser pump source. The resulting broadband, high-spectral-power-density, low-coherence light source can be employed for advanced, submicrometer resolution optical coherence tomography.

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20-kW peak power all-fiber 1.57-microm source based on compression in air-core photonic bandgap fiber, its frequency doubling, and broadband generation from 430 to 1450 nm.

We demonstrate an ultrashort all-fiber-integrated chirped-pulse amplification system yielding 1-ps pulses with 20 kW of peak power. 40-ps initial pulses generated by an externally modulated laser diode are chirped by self-phase modulation in a conventional fiber, amplified, and compressed in 110 m of air-core photonic bandgap fiber. The compressed pulses are frequency doubled in a periodically poled KTP crystal with up to 48% efficiency and applied to supercontinuum generation in a holey fiber, resulting in a high-power uniform continuum that stretches from 430 to 1450 nm.

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Persistent changes in motivation to self-administer cocaine following modulation of cyclic AMP-dependent protein kinase A (PKA) activity in the nucleus accumbens.

Drug-induced neuroadaptations within the nucleus accumbens, including activation of cAMP-dependent protein kinase A (PKA), may contribute to the synaptic plasticity and behavioural changes that underlie drug addiction. As a direct test of this hypothesis, we examined the effects in rats of PKA activation (Sp-cAMPS infusions of 10 and 20 nmol/side) and inhibition (Rp-cAMPS infusions of 10 and 20 nmol/side) in the nucleus accumbens on motivation to obtain cocaine as measured by responding under the progressive-ratio schedule. Bilateral infusions of Sp-cAMPS (20 nmol/side) resulted in an increase in progressive-ratio responding for cocaine and this effect persisted for several days. In contrast, Rp-cAMPS (20 nmol/side) produced persistent decreases in progressive-ratio responding for cocaine beginning on the day of administration and lasting for several days. These data suggest that alternations in PKA activity within the nucleus accumbens as a consequence of repeated cocaine exposure may contribute to addiction by producing persistent increases in motivation to obtain cocaine.

Anesthetics, Local↗

All-fiber format compression of frequency chirped pulses in air-guiding photonic crystal fibers.

Air-cored, photonic band-gap crystal fibers exhibiting low nonlinearity and anomalous chromatic dispersion in spectral ranges inaccessible to conventional fibers can be used in the realization of all-fiber-format pulse compressors with unprecedented peak powers and wavelength diversity. Linear compression of inherently chirped and prestretched pulses by factors ranging from 20 to 80 around 1.0 and 1.5 microm have allowed generation of pulses as short as 163 fs. The results show that totally integrated femtosecond fiber laser sources can be realized throughout the visible and near-infrared and point to the possibility of megawatt peak and tens of watt average in-fiber power levels.

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Continuous-wave, totally fiber integrated optical parametric oscillator using holey fiber.

We present, for the first time to our knowledge, a cw, all-fiber optical parametric oscillator that uses a holey fiber. The oscillator operates at 1.55 microns and can yield an oscillating parametric signal that consists of a single line with a 30-dB extinction ratio and a 10-pm linewidth or that consists of multiple lines. In addition to the signal and the idler, five other pairs of spectral lines can be observed that are due to multiple parametric interactions. The source reaches threshold for a pump power of 1.28 W and saturates for pump powers in excess of approximately 1.6 W.

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Soliton self-frequency shift in highly nonlinear fiber with extension by external Raman pumping.

A completely fiber-integrated, wavelength-tunable subpicosecond pulse source is demonstrated using the soliton self-frequency shift in highly nonlinear dispersion-shifted fiber from a 1.56-microm 10-GHz 400-fs signal. Solitons as short as 100 fs are obtained at tunable wavelengths as high as 1.72 microm. Raman gain from an external pump is used to extend the soliton self-frequency shift to longer wavelengths.

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Gain-flattened fiber Raman amplifiers with nonlinearity-broadened pumps.

Gain flattening of an E-band (1360-1460-nm) fiber Raman amplifier was achieved by pump spectral broadening to a 16.3-nm linewidth by use of nonlinearity in a 6.2-km standard fiber. With the broadened pump, the characteristic Raman gain ripple was removed and the 3-dB gain bandwidth was increased by 10.6 nm relative to the nonbroadened pump case. The experimental results agreed well with a gain profile simulation. The use of a 100-m holey fiber for pump broadening was also investigated near 1.56 microm for U-band (1625-1675-nm) Raman amplifiers. Much less broadening was observed, which is believed to be a result of less four-wave mixing.

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Short-pulse, all-fiber, Raman laser with dispersion compensation in a holey fiber.

The use of Raman gain in conventional fiber followed by dispersion compensation in a holey fiber in a synchronously pumped laser configuration allowed compression by a factor of 8.5 of output pulses at a selected wavelength with respect to the pump pulses. We obtained 2-ps output pulses at 1.14 microm from a totally fiber-integrated laser pumped with 17-ps pulses at 1 microm. Higher pulse compression should be possible with nonlinear chirp compensation. Ultrashort-pulse, all-fiber Raman lasers at wavelengths shorter than 1.3 microm are feasible.

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Continuous-wave, high-power, Raman continuum generation in holey fibers.

The possibility of using low pump power for cw Raman continuum generation is demonstrated by optimization of the pump peak power and by accounting for the loss-related reduction of the effective length of Raman interaction in holey fibers. A 3.8-W, 324-nm-wide cw Raman continuum with a spectral power density higher than 10 mW/nm is generated in a completely fiber-integrated, single-mode format.

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Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5.

Repeated exposure to cocaine produces an enduring increase in dendritic spine density in adult rat nucleus accumbens. It has been shown previously that chronic cocaine administration increases the expression of cyclin-dependent kinase-5 in this brain region and that this neuronal protein kinase regulates cocaine-induced locomotor activity. Moreover, cyclin-dependent kinase-5 has been implicated in neuronal function and synaptic plasticity. Therefore, we studied the involvement of this enzyme in cocaine's effect on dendritic spine density. Adult male rats, receiving intra-accumbens infusion of the cyclin-dependent kinase-5 inhibitor roscovitine or saline, were administered a 28-day cocaine treatment regimen. Animals were killed 24-48 h after the final cocaine injection and their brains removed and processed for Golgi-Cox impregnation. Our findings demonstrate that roscovitine attenuates cocaine-induced dendritic spine outgrowth in nucleus accumbens core and shell and such inhibition reduces spine density in nucleus accumbens shell of control animals. These data indicate that cyclin-dependent kinase-5 is involved in regulation of, as well as cocaine-induced changes in, dendritic spine density.

Animals↗

Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

BACKGROUND: Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. METHODS: Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. RESULTS: Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. CONCLUSIONS: These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

Animals↗