Stabilization of a Kerr frequency comb oscillator.

We study stability and spectral purity of a microresonator-based Kerr frequency comb oscillator experimentally and observe a correlation between the frequency of the continuous wave laser pumping the nonlinear resonator and the repetition frequency of the comb. This correlation is used in a proof-of-principle demonstration of a Kerr frequency comb stabilized with an optical transition of 87Rb.

Voltage-controlled photonic oscillator.

We report the development and demonstration of an X-band voltage-controlled photonic oscillator based on a whispering gallery mode resonator made of an electro-optic crystalline material. The oscillator has good spectral purity and wide, agile, linear tunability. We have modified the existing theoretical model of the opto-electronic oscillator to describe the performance of our tunable oscillator and have found a good agreement between the theoretical predictions and the measurement results. We show that the device is promising for higher-frequency applications where high-performance tunable oscillators with wide tunability do not exist.

Overproduction of protein p53 contributes to simian virus 40-mediated transformation.

The possible involvement of p53 overproduction in simian virus 40 (SV40)mediated transformation was studied by using the rat embryo fibroblast focus formation assay. Transformation by wild-type SV40 was enhanced two- to threefold by cotransfection of a plasmid overexpressing mouse p53. More significantly, such a plasmid could partially complement a transformation-defective deletion mutant of SV40. Hence, the ability of SV40 T antigen to induce high p53 levels may indeed be directly relevant to the viral transforming potential.

Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life.

The 11-4 p53 cDNA clone failed to transform primary rat fibroblasts when cotransfected with the ras oncogene. Two linker insertion mutations at amino acid 158 or 215 (of 390 amino acids) activated this p53 cDNA for transformation with ras. These mutant cDNAs produced a p53 protein that lacked an epitope, recognized by monoclonal antibody PAb246 (localized at amino acids 88 to 110 in the protein) and preferentially bound to a heat shock protein, hsc70. In rat cells transformed by a genomic p53 clone plus ras, two populations of p53 proteins were detected, PAb246+ and PAb246-, which did or did not bind to this monoclonal antibody, respectively. The PAb246- p53 preferentially associated with hsc70, and this protein had a half-life 4- to 20-fold longer than free p53 (PAb246+). These data suggest a possible functional role for hsc70 in the transformation process. cDNAs for p53 derived from methylcholanthrene-transformed cells transform rat cells in cooperation with the ras oncogene and produce a protein that bound with the heat shock proteins. Recombinant clones produced between a Meth A cDNA and 11-4 were tested for the ability to transform rat cells. A single amino acid substitution at residue 132 was sufficient to activate the 11-4 p53 cDNA for transformation. These studies have identified a region between amino acids 132 and 215 in the p53 protein which, when mutated, can activate the p53 cDNA. These results also call into question what the correct p53 wild-type sequence is and whether a wild-type p53 gene can transform cells in culture.

Meth A fibrosarcoma cells express two transforming mutant p53 species.

Expression plasmids directing the synthesis of various forms of the p53 cellular tumor antigen were compared with respect to their biological activities. All plasmids encoding wild type p53, derived from two different cDNA libraries, had absolutely no detectable activity when assayed for transformation of primary rat embryo fibroblasts in collaboration with Ha-ras. In contrast, p53 variants carrying point mutations in the protein coding region exhibited at least some transforming activity. Most notably, this was true for both types of mutant p53 cDNA clones isolated from Meth A cells. The data indicate that these cells, derived from a chemically-induced tumor, carry two independently mutated p53 alleles, each encoding a transformationally activated protein. This may imply that the mutations in the p53 gene played a role in the development of the Meth A tumor. Finally, cells overexpressing a transfected mutant p53 exhibit a physical complex between this exogenous p53 and its endogenous counterpart, possibly resulting in the stabilization of the latter.

High spectral purity Kerr frequency comb radio frequency photonic oscillator.

Femtosecond laser-based generation of radio frequency signals has produced astonishing improvements in achievable spectral purity, one of the basic features characterizing the performance of an radio frequency oscillator. Kerr frequency combs hold promise for transforming these lab-scale oscillators to chip-scale level. In this work we demonstrate a miniature 10 GHz radio frequency photonic oscillator characterized with phase noise better than -60 dBc Hz(-1) at 10 Hz, -90 dBc Hz(-1) at 100 Hz and -170 dBc Hz(-1) at 10 MHz. The frequency stability of this device, as represented by Allan deviation measurements, is at the level of 10(-10) at 1-100 s integration time-orders of magnitude better than existing radio frequency photonic devices of similar size, weight and power consumption.

Ultralow noise miniature external cavity semiconductor laser.

Advanced applications in optical metrology demand improved lasers with high spectral purity, in form factors that are small and insensitive to environmental perturbations. While laboratory-scale lasers with extraordinarily high stability and low noise have been reported, all-integrated chip-scale devices with sub-100 Hz linewidth have not been previously demonstrated. Lasers integrated with optical microresonators as external cavities have the potential for substantial reduction of noise. However, stability and spectral purity improvements of these lasers have only been validated with rack-mounted support equipment, assembled with fibre lasers to marginally improve their noise performance. In this work we report on a realization of a heterogeneously integrated, chip-scale semiconductor laser featuring 30-Hz integral linewidth as well as sub-Hz instantaneous linewidth.

Modified composition of major ontogenetically regulated mRNAs and proteins in the cerebellum of old and of staggerer mice.

The macromolecular composition of the cerebellum was examined in young and old mice, and in staggerer mutant mice, as compared with their background control strain. We examined the in vitro translation products of cerebellum mRNA, which reflect the biosynthetic potential of cell bodies endogenous to the cerebellum. Simultaneously, we examined the composition of the major cerebellum proteins, which includes the contribution of incoming fibers, in addition to the proteins composing cerebellar cells. Changes in the concentrations of various major proteins and a significant reduction in the translational efficiency of RNA were observed in the cerebellum of old BALB/c mice. This reduction probably does not reflect a specific damage to interneurons, since RNA from the cerebellum of 5-month-old staggerer mice was as efficient in translation in vitro as RNA from the cerebellum of mice from C57B6J normal background strain. Several of the major cerebellar proteins were identified by 2-dimensional gel electrophoresis. Changes were observed at the level of and the microheterogeneity of tubulin from the cerebellum of old, as compared with young mice. The aging-related modifications in cerebellar tubulin may be regulated at the level of mRNA, since mRNA from the cerebellum of old mice appeared to produce lower amounts of a polypeptide band co-migrating with tubulin. When compared with translation products directed by mRNA from normal cerebellum, most of the major identified polypeptides produced by mRNA from staggerer cerebellum showed marked differences in their relative intensity. Thus, this mutation appears to change the composition of cerebellar mRNA. These differences were analyzed together with previously obtained data on the composition of translation products during development of normal and of irradiation-agranulated cerebellum. The combined analysis of cerebellar mRNA products permits us to tentatively assign defined protein markers to specific cerebellar cell types and periods in development.

Inhibition of pheromone biosynthesis in Helicoverpa armigera by pheromonostatic peptides.

Male insect accessory glands contain factors that are transferred during mating to the female, some inducing post-mating behavior, including the cessation of pheromone production, non-receptivity and the initiation of oviposition. One such factor is the Drosophila melanogaster sex-peptide (DrmSP). A pheromone suppression peptide, termed HezPSP, was identified in the moth Helicoverpa zea, isolated by HPLC and the active peak sequenced, but the activity of the synthesized peptide has not been reported to date. HezPSP bears no sequence homology to DrmSP. However, both peptides contain a disulfide bridge separated by an equal number, but dissimilar, amino acids. We herein report on the pheromonostatic activity of HezPSP partial peptides in the moth Helicoverpa armigera.

Degranulation of rat cerebellum induces selective variations in gene expression.

Selective variations in the composition of poly(A)-containing mRNA were found to be induced in the rat cerebellum by X-irradiation. mRNA populations prepared from normal and X-irradiated rat cerebella at different stages of their development displayed equal efficiencies when translated in vitro in reticulocyte lysates. Specific differences were revealed, however, when the labeled translation products of both mRNA preparations were subjected to two-dimensional gel electrophoresis followed by fluorography of the dried gels. Of more than 100 polypeptide products, several showed marked intensity differences, indicating changes in the abundance of their directing mRNA species. These differences appear both in developing and in mature cerebellar mRNA, and the extent of modification in mRNA is much higher than the consequent changes in the composition of proteins in the irradiated cerebellum. The degranulation-induced modifications in levels of specific cerebellar mRNA species can be used to identify proteins whose biosynthesis depends on the presence of interneurons.

Overproduction of p53 antigen makes established cells highly tumorigenic.

The p53 cellular tumour antigen, long known to be overproduced in a variety of neoplastically transformed cells, was recently shown to be directly involved in transformation. Thus, p53 can complement activated Ha-ras in transforming secondary rat embryo fibroblasts into grossly altered, tumorigenic cells. Moreover, p53 can also be shown to possess immortalizing activity. Our previous results indicated, however, that the contribution of p53 to the transformation was not synonymous with immortalization, suggesting that the two activities of the protein are probably separable. We demonstrate here that this is indeed the case, as overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential. Furthermore, the tumorigenic efficiency of such cell lines may be correlated with the extent of p53 over-production.

Broader, flatter optical spectra of passively mode-locked semiconductor lasers for a wavelength-division multiplexing source.

Using the time domain master equation for a complex electric-field pulse envelope, we find analytical results for the optical spectra of passively mode-locked semiconductor lasers. The analysis includes the effect of optical nonlinearity of semiconductor lasers, which is characterized by a slow saturable amplifier and absorber. Group velocity dispersion, bandwidth limiting, and self-phase modulation were considered as well. The FWHM of the spectrum profile was found to have a strong dependence on group velocity dispersion and self-phase modulation. For large absolute values of the chirp parameter, the optical spectra result in equispaced continuous wave frequencies, a large fraction of which have equal power.

Infrared thermographic imaging in the detection of sympathetic dysfunction in patients with patellofemoral pain syndrome.

OBJECTIVE: This study investigates the clinical utility of infrared thermography in the detection of sympathetic dysautonomia in patients with patellofemoral pain syndrome. The patients exhibited anterior knee pain, radiographic evidence of patella alta and the clinical signs and symptoms of patellofemoral pain syndrome. DESIGN: A case control study was carried out with two groups of patients: patients with anterior knee pain, and patients with no knee pain as a control SETTING: Private practice. PATIENTS: Group 1 consisted of 30 patients with patellofemoral pain syndrome. Group 2 consisted of 40 control patients with no history or presence of knee pain. Control patients were consecutively selected, and the knee pain patients were consecutively selected from a population-based sample. OUTCOME MEASURE: Infrared thermography scans were obtained on the knee pain patients and control patients to determine the sensitivity and specificity of infrared thermography for detecting patellofemoral pain syndrome. RESULTS: Twenty-nine of the 30 knee pain patients in group 1 had patellar thermal asymmetry from right to left sides (sensitivity 97%). Thirty-six of the 40 control patients exhibited thermal symmetry from right to left sides (specificity 90%). The incidence of patellar thermal asymmetry was found to be statistically significant when tested by chi 2 analysis (p less than .001). CONCLUSION: Infrared thermography appears to be a useful, noninvasive diagnostic test in the diagnosis and management of patellofemoral pain syndrome. The high incidence of patellar thermal asymmetry and dysautonomia at the patella in patients with patellofemoral pain syndrome implicates somatosympathetic mediation in this disorder. This may be helpful in understanding the evolution of patellofemoral disorders.

Thermographic imaging of pathoneurophysiology due to cervical disc herniation.

A patient suffering from cervical disc herniation as noted by magnetic resonance imaging was tested for presence of nerve irritation using infrared telethermography. The thermal findings and asymmetries observed followed a dermatomal pattern of hypothermia and decreased thermal emission. The neurophysiological information derived from the thermographic examination may be helpful in the diagnosis and management of cervical disc herniations encountered in clinical practice.

Retardation and reduction of pulse distortion by group-velocity dispersion through pulse shaping.

We show that a reduction in the pulse distortion caused by chromatic dispersion can be achieved through pulse shaping. We argue that a simple binary phase mask in the Fourier plane of the laser spectrum can improve the transmission of short pulses in a dispersive channel through reduced broadening. The argument was tested experimentally, and a good agreement was found with the theory.

Wild-type p53 can inhibit oncogene-mediated focus formation.

Mutant forms of the p53 cellular tumor antigen elicit neoplastic transformation in vitro. Recent evidence indicated that loss of normal p53 expression is a frequent event in certain types of tumors, raising the possibility that such loss provides transformed cells with a selective growth advantage. Thus, it was conceivable that the mutants might contribute to transformation by abrogating normal p53 function. We therefore studied the effect of plasmids encoding wild-type (wt) p53 on the ability of primary rat embryo fibroblasts to be transformed by a combination of mutant p53 and ras. It was found that wt p53 plasmids indeed caused a marked reduction in the number of transformed foci. Furthermore, wt p53 plasmids also suppressed the induction of transformed foci by combinations of bona fide oncogenes, such as myc plus ras or adenovirus E1A plus ras. On the other hand, plasmids carrying mutations in the p53 coding region totally failed to inhibit oncogene-mediated focus induction and often even slightly stimulated it. Hence, such mutations completely abolished the activity of wt p53 that is responsible for the "suppressor" effect. The latter fact is of special interest, since similar mutations in p53 are often observed in human and rodent tumors. The inhibitory effect of p53 was most pronounced when early-passage cells were used as targets, whereas established cell lines were less sensitive. These data support the notions that wt p53 expression may be restrictive to neoplastic progression and that p53 inactivation may play a crucial role in tumorigenesis.