Reversed dispersion slope photonic bandgap fibers for broadband dispersion control in femtosecond fiber lasers.

Higher-order-mode solid and hollow core photonic bandgap fibers exhibiting reversed or zero dispersion slope over tens or hundreds of nanometer bandwidths within the bandgap are presented. This attractive feature makes them well suited for broadband dispersion control in femtosecond pulse fiber lasers, amplifiers and optical parametric oscillators. The canonical form of the dispersion profile in photonic bandgap fibers is modified by a partial reflector layer/interface placed around the core forming a 2D cylindrical Gires-Tournois type interferometer. This small perturbation in the index profile induces a frequency dependent electric field distribution of the preferred propagating higher-order-mode resulting in a zero or reversed dispersion slope.

Design and simulation of 1310 nm and 1480 nm single-mode photonic crystal fiber Raman lasers.

We have numerically investigated the Raman lasing characteristics of a highly nonlinear photonic crystal fiber (HNPCF). HNPCF Raman lasers are designed to deliver outputs at 1.3 microm and 1.48 microm wavelengths through three and six cascades of Raman Stokes cavities when the pumps of 1117 nm and 1064 nm are injected into HNPCF module, respectively. A quantum efficiency of approximately 47% was achieved in a short length of HNPCF for 1.3 microm lasing wavelength. The HNPCF design is modified further to operate in single-mode fashion keeping intact its Raman lasing characteristics. The modified HNPCF design consists of two air-hole rings where the higher-order modes in the central core are suppressed by enhancing their leakage losses drastically, thus ceasing their propagation in the short length of HNPCF. On the other hand, the fundamental mode is well confined to the central core region, unaffecting its lasing performances. Further, the lasing characteristics of HNPCF at 1480 nm are compared with conventional highly nonlinear fiber Raman laser operating at 1480 nm. It is found that one can reduce the fiber length by five times in case of HNPCF with nearly similar conversion efficiency.

Bend-insensitive lasing characteristics of single-mode, large-mode-area ytterbium-doped photonic crystal fiber.

The bend-insensitive lasing characteristics of a newly designed ytterbium-doped photonic crystal fiber (YPCF) are evaluated numerically. The designed YPCF remains single-mode and possesses large-mode-area of 1400 microm(2) at 1064 nm wavelength with the beam quality factor (M(2)) of 1.15, suggesting a diffraction-limited and continuous-wave lasing operation. The doped-region size is optimized for maximum conversion efficiency and it is found through numerical simulations that the doped radius should be more than 21 microm. The "mode expansion", which is the self-expansion of the fundamental mode within the doped region with wavelength increments on bending the fiber, is the basic physical mechanism to give the bend-insensitive lasing performances of YPCF. It leads to an unusual variation of overlap factor when the wavelength is increased. A 41 cm long piece of YPCF demonstrates more than 83% of slope efficiency with 75% of conversion efficiency when pumped with a 975 nm laser source delivering an input power of 1 W.

Strategies for realizing photonic crystal fiber bandpass filters.

Numerical design strategies are presented to achieve efficient broad or narrow band-pass filters based on index-guiding, solid-core, and single-mode photonic crystal fibers (PCFs). The filtering characteristics have been verified through BPM solver. By scaling the pitch constant, the bandpass window can be shifted accordingly. The fiber design constitutes a fluorine-doped central core, enlarged air-holes surrounding the down-doped core, and small air-holes in the cladding. The proposed bandpass filter is based on controlling the leakage losses, so one can tune filter characteristics simply by changing its length. From numerical simulations we show that for large values of air-hole diameter in the first ring, the bandpass window is narrow, while for low doping concentration and small sized air-holes in the first ring, bandpass window is very broad. We also simulate how the hole-size and number of rings in the PCF cladding affects the device characteristics. We find that a 5-cm long PCF with down-doped core and eleven rings of air-holes can result in approximately 440 nm 3-dB bandwidth with more than 90% of transmission. The longer device has reduced transmission and smaller 3-dB bandwidth. Tolerance analysis has also been performed to check the impact of fiber tolerances on the performance of the PCF bandpass filter. It has been observed that the decrement in cladding hole-diameter by 1% reduces the transmission to 21% from its peak value of 93%, however +/-1% tolerance in the inner hole-diameter degrades the transmission to 75% from its peak.

Measurement of chromatic dispersion and Raman gain efficiency of a hole-assisted fiber: Influence of bend.

We have experimentally measured the Raman gain efficiency (RGE) and chromatic dispersion (CD) of a hole-assisted fiber (HAF). The RGE of a HAF was characterized using standard pump on/off technique while the CD of the fiber was measured using optical network analyzer. Theoretical simulations of the modal characteristics and the RGE of HAF were carried out using an accurate full-vectorial finite element method. Further, the bending effects on the CD and the RGE of a HAF with a smallest feasible bending radius are demonstrated. It was found that the CD increases while the RGE is decreased by bending HAF in a smallest bending radius of 5 mm. Numerical predictions from the theory are shown to be in good agreement with the experimental results.

A novel polymorphism of the SSA1 gene is associated with anti-SS-A/Ro52 autoantibody in Japanese patients with primary Sjögren's syndrome.

OBJECTIVE: To investigate the association of polymorphisms of the SSA1 gene (OMIM 109092) with primary Sjögren's syndrome (SS) and anti-SS-A/Ro52 antibody production. METHODS: Polymorphisms of SSA1 gene in 111 Japanese SS patients and in 97 healthy controls were analyzed with polymerase chain reaction and automated DNA sequencing. RESULTS: A new single-nucleotide polymorphism (SNP) was identified in intron 1 at position 7216. The allele frequency and genotype of 7216A/G were not significantly different between SS patients and control subjects. However, the allele frequency and genotype of 7216A/G were associated with the presence of anti-SS-A/Ro52 antibody among primary SS patients. The association was not found in patients with SLE, suggesting the limited role for the SNP in anti-SS-A/Ro52 antibody production. The 9571C/T polymorphism, which has been shown to associate with anti-SS-A/Ro52 antibody in Caucasian patients, was not associated with the presence of anti-SS-A/Ro52 antibody in Japanese patients. CONCLUSIONS: 7216A/G polymorphism of SSA1 gene may be one of the genetic factors that determine the presence of anti-SS-A/Ro52 antibody in patients with primary SS.

Modification of cytokine milieu by A2A adenosine receptor signaling--possible application for inflammatory diseases.

Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro lipopolysaccharide (LPS)-stimulated human peripheral blood CD14+ cells (PB-CD14) was inhibited by A2A adenosine receptor (AdoR) (A2AR) or beta2 adrenergic receptor (ADR) (beta2R) signaling in a concentration-dependent manner. These inhibitory effects were presumably mediated by the increase in intracellular cAMP. Furthermore A2AR agonist and beta2R agonist synergistically inhibited the TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the anti-inflammatory effect of extracellular adenosine is, at least in part, due to the modification of the cytokine milieu via A2A signaling, and that the targeting of both A2AR and beta2R may have strong therapeutic potential for the inflammatory diseases.

Air-core photonic band-gap fibers: the impact of surface modes.

We study the dispersion and leakage properties for the recently reported low-loss photonic band-gap fiber by Smith et al. [Nature 424, 657 (2003)]. We find that surface modes have a significant impact on both the dispersion and leakage properties of the fundamental mode. Our dispersion results are in qualitative agreement with the dispersion profile reported recently by Ouzounov et al. [Science 301, 1702 (2003)] though our results suggest that the observed long-wavelength anomalous dispersion is due to an avoided crossing (with surface modes) rather than band-bending caused by the photonic band-gap boundary of the cladding.

Polarization splitter in three-core photonic crystal fibers.

A novel design of polarization splitter in three-core photonic crystal fibers (PCFs) has been proposed. The three-core PCF consists of two given identical cores with two-fold symmetry separated by a core with high birefringence. The polarization splitter is based on the phenomenon of resonant tunneling. Numerical simulations with a full vectorial beam propagation method demonstrate that it is possible to obtain a 1.9-mm-long splitter with the extinction ratio better than -20 dB and a bandwidth of 37nm.

Association of the TAP2*Bky2 allele with presence of SS-A/Ro and other autoantibodies in Japanese patients with systemic lupus erythematosus.

We previously reported that a new allele of transporter associated with antigen processing (TAP) 2 gene, TAP2*Bky2 (Val577), was significantly increased in Japanese patients with Sjögren's syndrome (SS) and had a strong association with SS-A/Ro antibody production. In the present study, it was investigated whether the association of TAP2*Bky2 with SS-A/Ro antibody production was also found in Japanese patients with systemic lupus erythematosus (SLE). Polymorphisms of the TAP1 and TAP2 genes were determined in 114 Japanese SLE patients by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) method. The allele frequencies of the TAP1 and TAP2 genes in SLE patients were not significantly different from those in controls, although the allele frequency of TAP2*Bky2 was slightly higher in SLE patients than in healthy control subjects (9.2% vs 5.5%, P = 0.126). The allele frequency of TAP2*Bky2 was significantly higher in SLE patients with oral ulcers than in those without. It was noteworthy that TAP2*Bky2 was significantly associated with the appearance of not only SS-A/Ro antibody but also SS-B/La, nRNP, and Sm antibodies in the patients. The association of TAP2*Bky2 was found with the antibody production to both 60 and 52kDa SS-A/Ro antigens. As TAP2*Bky2 had a strong linkage disequilibrium with DRB1*08032, TAP2*Bky2 or its haplotype with DRB1*08032 may be involved in SS-A/Ro antibody production not only in SS but also SLE patients, indicating that TAP2*Bky2 may be a susceptible gene not only to the disease of SS but also to the SS-A/Ro autoantibody production.

Chromatic dispersion control in photonic crystal fibers: application to ultra-flattened dispersion.

In order to control dispersion and dispersion slope of indexguiding photonic crystal fibers (PCFs), a new controlling technique of chromatic dispersion in PCF is reported. Moreover, our technique is applied to design PCF with both ultra-low dispersion and ultra-flattened dispersion in wide wavelength range. A full-vector finite element method with anisotropic perfectly matched layers is used to analyze the dispersion properties and the confinement losses in a PCF with finite number of air holes. It is shown from numerical results that it is possible to design a fourring PCF with flattened dispersion of 0 +/- 0.5 ps/(km.nm) from 1.19 m to 1.69 m wavelength range and a five-ring PCF with flattened dispersion of 0 +/- 0.4 ps/(km.nm) from 1.23 m to 1.72 m wavelength range.

Structural dependence of effective area and mode field diameter for holey fibers.

A rigorous full-vector finite element method is effectively applied to evaluating the effective area Aeff and the mode field diameter (MFD) of holey fibers (HFs) with finite cross sections. The effective modal spot size (a half of MFD), weff, is defined with the help of the second moment of the optical intensity distribution. The influence of hole diameter, hole pitch, operating wavelength, and number of rings of air holes on Aeff and weff is investigated in detail. As a result, it is shown that Aeff and weff are almost independent of the number of hole rings and that the relation Aeff = piweff 2, which is frequently utilized in the conventional optical fibers, does not always hold, especially in smaller air-filling fraction and/or longer wavelength regions. In addition, we find that for HFs with large air holes operating at longer wavelengths, the mode profiles of the two linearly polarized fundamental modes are significantly different from each other, even though they are degenerate. Using the values of Aeff and weff obtained here, the beam divergence and the nonlinear phase shift are calculated and are compared with the earlier experimental results.

Creatine kinase gene mutation in a patient with muscle creatine kinase deficiency.

BACKGROUND: We describe a 56-year-old woman admitted to the hospital with a diagnosis of acute myocardial infarction without an increase of serum creatine kinase (CK) activity during her clinical course. She died on the 11th hospital day, and the diagnosis was confirmed by autopsy. The patient had had no previous muscular symptoms. METHODS: Expression of the CK-muscle (CK-M) protein in cardiac tissue was examined by immunoblotting and immunochemical staining. CK-M mRNA expression was estimated by semiquantitative reverse transcription-PCR. Gene structure of CK-M was determined by Southern blotting and direct sequencing of 2251 bp. Existence of a point mutation in the CK-M gene was examined by restriction fragment length polymorphism analysis of PCR products (PCR-RFLP) in the patient and in 108 controls. RESULTS: CK-M protein in the myocardial tissue of the patient was substantially lower (103 +/- 7 ng/mg protein) than in control myocardial tissue (35 800 +/- 2860 ng/mg protein). Immunoreactive CK-M in the patient tissue sample was 0.3% of the value for the control sample. CK-M mRNA was 53-fold less in the patient sample compared with the control. This very low expression of CK-M mRNA was considered to be the primary reason for CK-M deficiency. Direct sequencing revealed a point mutation at residue 54 in exon 2, which was specific for the patient. No other abnormalities were found in the CK-M gene of the patient. CONCLUSIONS: This report identifies a molecular abnormality in human CK deficiency and discusses the physiologic relevance of CK-M.

Extraction of all coefficients of coupled-mode equations for natural, single-phase, unidirectional SAW transducers from dispersion characteristics computed by hybrid finite element method.

A numerical method is presented for determining all of the coefficients of coupled-mode equations for natural, single-phase, unidirectional SAW transducers (NSP-UDTs). Substituting numerical results computed by the hybrid finite element method for infinite NSPUDTs with shorted and open electric ports into several relations derived from the coupled-mode theory, we can determine all of the coefficients. Specifically, the edge frequencies of a stop-band and the static capacitances yield the self-coupling coefficients and the amplitudes of mutual-coupling and transduction coefficients, and the electric potential standing wave on the substrate surface, which can be derived from the projection of the standing wave distributions of particle displacements and electric potential in the whole substrate onto the set of those predicted by the coupled-mode theory, yields the phases of mutual-coupling and transduction coefficients. NSPUDTs on ST-25 degrees X quartz, Y-51.25 degrees Z LiTaO3, and 50 degrees Y-25 degrees X La3Ga5SiO14 substrates are investigated. Our results agree well with the earlier experimental ones.

Detection of antinuclear antibodies by use of an enzyme immunoassay with nuclear HEp-2 cell extract and recombinant antigens: comparison with immunofluorescence assay in 307 patients.

BACKGROUND: A new enzyme immunoassay (EIA) for automated detection of antinuclear antibodies (ANAs) uses a mixture of HEp-2 cell extracts and multiple recombinant nuclear antigens immobilized on beads. We compared this EIA and an immunofluorescence (IF) assay in a large group of patients and controls. METHODS: We studied 492 healthy individuals and 307 patients with connective tissue diseases (CTDs). Sera were tested by an automated EIA (COBAS Core HEp2 ANA EIA; Roche Diagnostics) and IF. Samples were also tested for eight disease-specific antibodies, including antibodies against U1RNP, Sm, SSA/Ro, SSB/La, Scl-70, Jo-1, dsDNA, and centromere. RESULTS: Areas under ROC curves for the EIA were greater than (P = 0.008-0.012) or numerically identical to areas for the IF method for each of six CTDs studied. ROC areas for EIA were 0.98 (95% confidence interval, 0.95-0.99), 0.99 (0.96-1.00), and 0.99 (0.98-1.00) in systemic lupus erythematosus (n = 111), systemic sclerosis (n = 39), and mixed connective tissue disease (n = 33), respectively. For all 258 CTD patients with conditions other than rheumatoid arthritis (RA), the sensitivity and specificity of the IF method at a cutoff dilution of 1:40 were 92% and 65%, respectively, vs 93% and 79% for the EIA at a cutoff of 0.6. For the IF method at a cutoff dilution of 1:160, sensitivity and specificity were 81% and 87%, respectively, vs 84% and 94%, respectively, for the EIA at a cutoff of 0.9. For 207 sera containing at least one of eight disease-specific ANAs, positivities for the EIA and the IF method were 97.1% and 97.6%, respectively, at cutoffs of 0.6 and 1:40 (P = 0.76). CONCLUSIONS: An EIA that can be performed by a fully automated instrument distinguishes CTDs (except RA) from healthy individuals with both higher sensitivity and specificity than the IF method when the cutoff index was set at 0.9. Moreover, it can be used to exclude the presence of disease-specific ANAs by setting the cutoff index at 0.6 with almost the same efficacy as the IF method.

Hole-assisted lightguide fiber for large anomalous dispersion and low optical loss.

Hole-assisted lightguide fiber (HALF) is a microstructured fiber comprising a material index profile for waveguiding and air holes for modifying optical properties. Anomalous dispersion larger than those of the conventional fibers can be realized without severe degradation in optical loss, because of low power fraction in the holes and structural simplicity. We investigate into the causes of the loss of the fabricated HALFs, and show that a GeO2-doped core, in addition to the low power fraction, is desirable for low loss. The fabricated HALF exhibits a loss as low as 0.41 dB/km and a large anomalous dispersion of +35 ps/nm/km at 1550 nm.

Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies.

Signaling through A2A adenosine receptors (A2AR) regulates T lymphocyte expansion and modulates T cell receptor (TCR)-mediated effector functions in vitro. To understand the role of A2ARs in the regulation of immune response, we investigated the expression levels of this receptor in different functional lymphocyte subsets. Monoclonal anti-A2AR antibody was used to develop a flow cytometric assay to quantify the expression A2ARs on lymphocytes. We report that detectable levels of expression of A2ARs are much higher among T cells than B cells. More CD4(+) than CD8(+) T cells express A2ARs, but activation of T cells increases A2AR expression, predominantly in CD8(+) T cells. No significant differences were found in the proportion of A2AR+ cells between CD8(low) and CD8(high) T cells or between TCR/CD3(low) and TCR/CD3(high) T cells. Studies of T helper cell subsets (TH1 and TH2) reveal that lymphokine-producing cells are much more likely to express A2ARs than are cells that do not produce lymphokines. These results suggest that A2ARs are variably expressed on T cell subsets and may regulate cytokine production in activated T lymphocytes.

Association of the glutathione S-transferase M1 homozygous null genotype with susceptibility to Sjögren's syndrome in Japanese individuals.

OBJECTIVE: To investigate the role of polymorphisms of the glutathione S-transferase M1 (GSTM1) and GSTT1 genes in determining susceptibility to Sjögren's syndrome (SS) and autoantibody production. METHODS: Polymorphisms of the GSTM1 and GSTT1 genes in 106 Japanese patients with primary SS and in 143 healthy controls were analyzed by polymerase chain reaction. RESULTS: Frequency of the GSTM1 homozygous null genotype was significantly increased in SS patients compared with controls (57.5% versus 44.1%; P = 0.035). Moreover, a significantly greater frequency of SSA antibodies was found among SS patients with the GSTM1 null genotype than among those with the GSTM1 non-null genotype (P = 0.0013). Frequency of the GSTT1 polymorphism was not different between SS patients and controls. CONCLUSION: The GSTM1 homozygous null genotype could be a genetic factor that determines susceptibility to SS and may be involved in SSA antibody production.

Memory of extracellular adenosine A2A purinergic receptor-mediated signaling in murine T cells.

Accumulation of extracellular and intracellular adenosine (Ado) under hypoxic conditions or in the absence of adenosine deaminase results in lymphocyte depletion and in severe combined immunodeficiency, which are currently explained by direct intracellular lymphotoxicity of Ado metabolites. In support of the alternative, "signaling" mechanism, we show that extracellular Ado (extAdo) suppresses all tested T cell receptor (TCR)-triggered effector functions of T lymphocytes including the TCR-triggered FasL mRNA up-regulation in cytotoxic T lymphocytes. Strong evidence against the intracellular lymphotoxicity of Ado (and in support of the signaling model) is provided by abrogation of TCR-triggered growth inhibition in Ado-exposed T cells. The brief exposure to Ado was sufficient to observe inhibition of TCR-triggered effector functions. The "memory" of T cells to exposure to extAdo is best explained by sustained increases in cAMP. Selective agonist (CGS21680) and antagonist (ZM241385) of A2A adenosine receptor were used in functional assays and cDNA probes for different sybtypes of adenosine receptors were used in Northern blot studies. A2A receptors are identified as the predominantly expressed subtype of Gs-coupled Ado receptors in T cells. The demonstration of cross-talk between the A2A receptors and TCR in both directions support the possible role of A2A receptors in mechanisms of extAdo-mediated immunosuppression in vivo under adenosine deaminase deficiency and hypoxic conditions in, e.g., solid tumors.