Experimental realization of Fermi-Pasta-Ulam-Tsingou recurrence in a long-haul optical fiber transmission system.

The integrable nonlinear Schrödinger equation (NLSE) is a fundamental model of nonlinear science which also has important consequences in engineering. The powerful framework of the periodic inverse scattering transform (IST) provides a description of the nonlinear phenomena modulational instability and Fermi-Pasta-Ulam-Tsingou (FPUT) recurrence in terms of exact solutions. It associates the complex nonlinear dynamics with invariant nonlinear spectral degrees of freedom that may be used to encode information. While optical fiber is an ideal testing ground of its predictions, maintaining integrability over sufficiently long distances to observe recurrence, as well as synthesizing and measuring the field in both amplitude and phase on the picosecond timescales of typical experiments is challenging. Here we report on the experimental realization of FPUT recurrence in terms of an exact space-time-periodic solution of the integrable NLSE in a testbed for optical communication experiments. The complex-valued initial condition is constructed by means of the finite-gap integration method, modulated onto the optical carrier driven by an arbitrary waveform generator and launched into a recirculating fiber loop with periodic amplification. The measurement with an intradyne coherent receiver after a predetermined number of revolutions provides a non-invasive full-field characterization of the space-time dynamics. The recurrent space-time evolution is in close agreement with theoretical predictions over a distance of 9000 km. Nonlinear spectral analysis reveals an invariant nonlinear spectrum. The space-time scale exceeds that of previous experiments on FPUT recurrence in fiber by three orders of magnitude.

Polarization-division multiplexing based on the nonlinear Fourier transform.

Polarization-division multiplexed (PDM) transmission based on the nonlinear Fourier transform (NFT) is proposed for optical fiber communication. The NFT algorithms are generalized from the scalar nonlinear Schrödinger equation for one polarization to the Manakov system for two polarizations. The transmission performance of the PDM nonlinear frequency-division multiplexing (NFDM) and PDM orthogonal frequency-division multiplexing (OFDM) are determined. It is shown that the transmission performance in terms of Q-factor is approximately the same in PDM-NFDM and single polarization NFDM at twice the data rate and that the polarization-mode dispersion does not seriously degrade system performance. Compared with PDM-OFDM, PDM-NFDM achieves a Q-factor gain of 6.4 dB. The theory can be generalized to multi-mode fibers in the strong coupling regime, paving the way for the application of the NFT to address the nonlinear effects in space-division multiplexing.

Pharmacological profile of JNJ-27141491 [(S)-3-[3,4-difluorophenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxyl acid methyl ester], as a noncompetitive and orally active antagonist of the human chemokine receptor CCR2.

The interaction between CC chemokine receptor 2 (CCR2) with monocyte chemoattractant proteins, such as MCP-1, regulates the activation and recruitment of inflammatory leukocytes. In this study, we characterized (S)-3-[3,4-difluoro-phenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxyl acid methyl ester (JNJ-27141491) as a noncompetitive and orally active functional antagonist of human (h)CCR2. JNJ-27141491 strongly suppressed hCCR2-mediated in vitro functions, such as MCP-1-induced guanosine 5'-O-(3-[(35)S]thio)triphosphate binding; MCP-1, -3, and -4-induced Ca(2+) mobilization; and leukocyte chemotaxis toward MCP-1 (IC(50) = 7-97 nM), whereas it had little or no effect on the function of other chemokine receptors tested. The inhibition of CCR2 function was both insurmountable and reversible, consistent with a noncompetitive mode of action. JNJ-27141491 blocked the binding of (125)I-MCP-1 to human monocytes (IC(50) = 0.4 microM), but it failed to affect MCP-1 binding to mouse, rat, and dog cells (IC(50) > 10 microM). Therefore, transgenic mice, in which the mouse (m)CCR2 gene was replaced by the human counterpart, were generated for in vivo testing. In these mice, oral administration of JNJ-27141491 dose-dependently [5-40 mg/kg q.d. (once daily) or b.i.d.] inhibited monocyte and neutrophil recruitment to the alveolar space 48 h after intratracheal mMCP-1/lipopolysaccharide instillation. Furthermore, treatment with JNJ-27141491 (20 mg/kg q.d.) significantly delayed the onset and temporarily reduced neurological signs in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Taken together, these results identify JNJ-27141491 as a noncompetitive, functional antagonist of hCCR2, capable of exerting oral anti-inflammatory activity in transgenic hCCR2-expressing mice.

Synthesis and biological evaluation of 1,2,4-triazinylphenylalkylthiazolecarboxylic acid esters as cytokine-inhibiting antedrugs with strong bronchodilating effects in an animal model of asthma.

The influx of leukocytes (eosinophils, lymphocytes, and monocytes) into the airways and their production of proinflammatory cytokines contribute to the severity of allergic asthma. We describe here the synthesis and pharmacological evaluation of a series of triazinylphenylalkylthiazolecarboxylic acid esters that were designed to act as lung-specific antedrugs and inhibitors of the production of interleukin (IL)-5, a primary eosinophil-activating and proinflammatory cytokine. Closer examination of the hydroxypropyl ester, 15, indicated its high metabolic stability (t(1/2) > 240 min) in human lung S9 fraction but rapid conversion (t(1/2) = 15 min) into the pharmacologically inactive carboxylic acid by human liver preparations. In stimulated human whole blood cultures, 15 reduced not only the production of IL-5 (IC(50) = 78 nM) but also the biosynthesis of the monocyte chemotactic proteins MCP-1 (IC(50) = 220 nM), MCP-2 (IC(50) = 580 nM), and MCP-3 (IC(50) = 80 nM). In vivo, intratracheal administration of 15 (6 mg/animal) to allergic sheep, either before (-4 h) or after (+1.5 h) the pulmonary allergen challenge, completely abrogated the late-phase airway response and reduced the bronchial hyperreactivity to inhaled carbachol.

Dominant hemochromatosis due to N144H mutation of SLC11A3: clinical and biological characteristics.

Hereditary hemochromatosis is classically inherited as a recessive trait but is genetically heterogeneous. Mutations in the HFE and the TFR2 genes account for about 80% of patients and a third locus on chromosome 1q is responsible for juvenile hemochromatosis. We describe here the clinical and biological characteristics of autosomal dominant form of iron overload due to the N144H mutation of the SLC11A3 gene. Clinical signs of iron overload in patients include joint pains, cardiomyopathies, liver fibrosis and hormonal disorders including diabetes mellitus. The main and most common clinical symptoms in this family were joint complaints and early signs of arthrosis. Serum ferritin levels in iron overloaded subjects varied from 31 to 2179 ng/ml and the transferrin saturation from 13 to 88.6%. The iron overload is moderate compared to patients with type 1 hemochromatosis but the deferoxamine test was normal in all patients. The disease in this family segregated as a dominant trait. None of the patients was homozygous or compound heterozygous for any known mutation in the HFE or TFR2 genes. The disease in this family represents a non-classical form of iron overload caused by the N144H mutation in the SLC11A3 gene. The reports of other distinct mutations in SLC11A3 suggest that this gene may be of interest for further etiologic research.