Suppression of Rayleigh-scattering-induced noise in OEOs.

Optoelectronic oscillators (OEOs) are hybrid RF-photonic devices that promise to be environmentally robust high-frequency RF sources with very low phase noise. Previously, we showed that Rayleigh-scattering-induced noise in optical fibers coupled with amplitude-to-phase noise conversion in photodetectors and amplifiers leads to fiber-length-dependent noise in OEOs. In this work, we report on two methods for the suppression of this fiber-length-dependent noise: altering the amplitude-dependent phase delay of the OEO loops and suppressing the Rayleigh-scattering-induced noise in optical fibers. We report a 20 dB reduction in the flicker phase noise of a 6 km OEO via these suppression techniques.

Spontaneous inelastic Rayleigh scattering in optical fibers.

Rayleigh scattering (RS) adds noise to signals that are transmitted over optical fibers and other optical waveguides. This noise can be the dominant noise source in a range between 10 Hz and 100 kHz from the carrier and can seriously degrade the performance of optical systems that require low close-in noise. Using heterodyne techniques, we demonstrate that the backscattered close-in noise spectrum in optical fibers is symmetric about the carrier and grows linearly with both input power and fiber length. These results indicate that the RS is spontaneous and is due to finite-lifetime thermal fluctuations in the glass.

Acute medical management of the non-ST-segment elevation acute coronary syndromes (NSTE-ACS) in older patients.

Older patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) represent many clinical challenges. For example diagnosis can be difficult, and comorbidities are common. Furthermore, NSTE-ACS is particularly common in older patients (>60% of acute myocardial infarctions occurring in patients aged 65 years or older) and the mortality associated with NSTE-ACS is particularly high. Despite these many concerns, evidence from clinical trials based on this group of patients is limited. Future prospective clinical trials should therefore more accurately reflect the NSTE-ACS patient population by including more elderly patients and including efficacy endpoints that are relevant for these patients. Furthermore, the lack of clear clinical evidence in this population means that the current treatment guidelines do not fully address the needs of elderly patients. Several recent clinical trials have highlighted some of the main considerations we should make when treating elderly patients with NSTE-ACS. Different therapy options in the pharmacological management of NSTE-ACS in this age group are also discussed.

Side-hole fiber sensor based on surface plasmon resonance.

Surface plasmon resonance (SPR) is demonstrated in a microstructured optical fiber sensor for the first time (to our knowledge). SPR features were observed at 560 and 620 nm when sample fluids of refractive indices n=1.38 and n=1.41, respectively, were applied to the sensor. This study also identifies a new approach to improve the resolution of fiber SPR sensors.

Antiresonant reflection and inhibited coupling in hollow-core square lattice optical fibres.

We propose a guidance mechanism in hollow-core optical fibres dominated by antiresonant reflection from struts of solid material in the cladding. Resonances with these struts determine the high loss bands of the fibres, and vector effects become important in determining the width of these bands through the non-degeneracy of the TE and TM polarised strut modes near cut-off. Away from resonances the light is confined through the inhibited coupling mechanism. This is demonstrated in a square lattice hollow-core microstructured polymer optical fibre.

ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23.

CD23, the low-affinity immunoglobulin E receptor, is an important modulator of the allergic response and of diseases such as rheumatoid arthritis. The proteolytic release of CD23 from cells is considered a key event in the allergic response. Here we used loss-of-function and gain-of-function experiments with cells lacking or overexpressing candidate CD23-releasing enzymes (ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19 and ADAM33), ADAM-knockout mice and a selective inhibitor to identify ADAM10 as the main CD23-releasing enzyme in vivo. Our findings provide a likely target for the treatment of allergic reactions and set the stage for further studies of the involvement of ADAM10 in CD23-dependent pathologies.

Asymptotic analysis of collision-induced timing shifts in return-to-zero quasi-linear systems with predispersion and postdispersion compensation.

An asymptotic method for calculating the collision-induced frequency and timing shifts for quasi-linear pulses in return-to-zero, wavelength-division multiplexed systems with predispersion and postdispersion compensation is developed. Predictions of the asymptotic theory agree well with quadrature and direct numerical simulations. Using this theory, computational savings of many orders of magnitude can be realized over direct numerical simulations.

Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical.

Matrix metalloproteinase (MMP)-2 and its hemopexin C domain autolytic fragment (also called PEX) have been proposed to be crucial for angiogenesis. Here, we have investigated the dependency of in vitro angiogenesis on MMP-mediated extracellular proteolysis and integrin alpha(v)beta3-mediated cell adhesion in a three-dimensional collagen I model. The hydroxamate-based synthetic inhibitors BB94, CT1399, and CT1847 inhibited endothelial cell invasion, as did neutralizing anti-membrane-type 1-MMP (MT1-MMP) antibodies and tissue inhibitor of MMP (TIMP)-2 and TIMP-3 but not TIMP-1. This confirmed the pivotal importance of MT1-MMP over other MMPs in this model. Invasion was also inhibited by a nonpeptidic antagonist of integrin alpha(v)beta3, EMD 361276. Although PEX strongly inhibited pro-MMP-2 activation, when contaminating lipopolysaccharide was neutralized, PEX neither affected angiogenesis nor bound integrin alpha(v)beta(3). Moreover, no specific binding of pro-MMP-2 to integrin alpha(v)beta3 was found, whereas only one out of four independently prepared enzymatically active MMP-2 preparations could bind integrin alpha(v)beta3 , and this in a PEX-independent manner. Likewise, integrin alpha(v)beta3 -expressing cells did not bind MMP-2-coated surfaces. Hence, these findings show that endothelial cell invasion of collagen I gels is MT1-MMP and alpha(v)beta3 - dependent but MMP-2 independent and does not support a role for PEX in alpha(v)beta3 integrin binding or in modulating angiogenesis in this system.

Calculation, characterization, and application of the time shift function in wavelength-division-multiplexed return-to-zero systems.

We calculate the time shift function for collisions of pairs of pulses in different channels in a prototypical return-to-zero wavelength-division-multiplexed system with dispersion management and precompensation and postcompensation. Once the time shift function is known, the impairments that are due to collision-induced timing jitter can be rapidly determined. We characterize the shape of this function and determine how it scales with the initial pulse separation in time and with channel separation in wavelength. Finally, we apply it to the calculation of the worst-case time shift.

Reduction of collision-induced timing shifts in dispersion-managed quasi-linear systems with periodic-group-delay dispersion compensation.

Periodic-group-delay (PGD) dispersion-compensation modules were recently proposed as mechanisms to alleviate collision-induced timing shifts in dispersion-managed (DM) systems. Frequency and timing shifts in quasi-linear DM systems with PGDs were obtained, and it is shown that significant reductions are achieved when even a small fraction of the total dispersion is compensated for by PGDs.

Incomplete collisions in strongly dispersion-managed return-to-zero communication systems.

Incomplete collisions in wavelength-division-multiplexed return-to-zero transmission systems are analyzed by asymptotic methods. Formulas for frequency and timing shifts are obtained. The results agree with direct numerical calculations.

Treatment of hypertensive patients with coexisting coronary arterial disease.

Despite clear guidelines and an array of available antihypertensive medications, patients with hypertension and coronary artery disease are often inadequately treated. New data from HOPE, LIFE, and ALLHAT underscores the importance of blood pressure reduction for patients with coronary artery disease. Despite our improved understanding of the mechanism by which the various classes of antihypertensive medications achieve their effect, it remains the case that blood pressure reduction remains more important than the medication used to achieve the reduction. For most patients with coronary artery disease, combination therapy will be required to achieve a target blood pressure of less than 140/80. When tolerated, this therapy should include a beta-blocker and ACE inhibitor, both of which are of prognostic benefit for patients with coronary artery disease. There are also attractions in choosing calcium antagonists because of their efficacy in controlling anginal symptoms (Dihydropyridine calcium channel blockers if already on a beta-blocking agent and rate-limiting calcium channel blockers if beta blockers are contraindicated). Thiazide diuretics have proven themselves effective again in the ALLHAT study and are likely to be an integral part of treatment for the great majority of patients with coronary artery disease.

The metalloprotease disintegrin ADAM8. Processing by autocatalysis is required for proteolytic activity and cell adhesion.

ADAMs (a disintegrin and metalloprotease domains) are metalloprotease and disintegrin domain-containing transmembrane glycoproteins with proteolytic, cell adhesion, cell fusion, and cell signaling properties. ADAM8 was originally cloned from monocytic cells, and its distinct expression pattern indicates possible roles in both immunology and neuropathology. Here we describe our analysis of its biochemical properties. In transfected COS-7 cells, ADAM8 is localized to the plasma membrane and processed into two forms derived either by prodomain removal or as remnant protein comprising the extracellular region with the disintegrin domain at the N terminus. Proteolytic removal of the ADAM8 propeptide was completely blocked in mutant ADAM8 with a Glu(330) to Gln exchange (EQ-A8) in the Zn(2+) binding motif (HE(330)LGHNLGMSHD), arguing for autocatalytic prodomain removal. In co-transfection experiments, the ectodomain but not the entire MP domain of ADAM8 was able to remove the prodomain from EQ-ADAM8. With cells expressing ADAM8, cell adhesion to a substrate-bound recombinant ADAM8 disintegrin/Cys-rich domain was observed in the absence of serum, blocked by an antibody directed against the ADAM8 disintegrin domain. Soluble ADAM8 protease, consisting of either the metalloprotease domain or the complete ectodomain, cleaved myelin basic protein and a fluorogenic peptide substrate, and was inhibited by batimastat (BB-94, IC(50) approximately 50 nm) but not by recombinant tissue inhibitor of matrix metalloproteinases 1, 2, 3, and 4. Our findings demonstrate that ADAM8 processing by autocatalysis leads to a potential sheddase and to a form of ADAM8 with a function in cell adhesion.

The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs.

The ADAM family of proteases are type I transmembrane proteins with both metalloproteinase and disintegrin containing extracellular domains. ADAMs are implicated in the proteolytic processing of membrane-bound precursors and involved in modulating cell-cell and cell-matrix interactions. ADAM8 (MS2, CD156) has been identified in myeloid and B cells. In this report we demonstrate that soluble ADAM8 is an active metalloprotease in vitro and is able to hydrolyse myelin basic protein and a variety of peptide substrates based on the cleavage sites of membrane-bound cytokines, growth factors and receptors which are known to be processed by metalloproteinases. Interestingly, although ADAM8 was inhibited by a number of peptide analogue hydroxamate inhibitors, it was not inhibited by the tissue inhibitors of metalloproteinases (TIMPs). We also demonstrate that the activity of recombinant soluble ADAM9 (meltrin-gamma, MDC9) lacks inhibition by the TIMPs, but can be inhibited by hydroxamate inhibitors. The lack of TIMP inhibition of ADAM8 and 9 contrasts with other membrane-associated metalloproteinases characterised to date in this respect (ADAM10, 12, 17, and the membrane-type metalloproteinases) which have been implicated in protein processing at the cell surface.

Pulmonary hypertension secondary to left ventricular dysfunction: the role of nitric oxide and endothelin-1 in the control of pulmonary vascular tone.

1. Using an in vivo model of pulmonary hypertension (PHT) secondary to left ventricular dysfunction (LVD), the pulmonary arterial response to the nitric oxide synthase (NOS) blocker L-NAME (30 micromol.min(-1) i.v.) and the subsequent responses to cumulatively administered endothelin-1 (ET-1) (0.001 -- 4 nmol.kg(-1) i.v.) or big ET-1 (0.1 -- 2.0 nmol.kg(-1) i.v.) were studied. Additionally, the effect of the non-selective ET-1 receptor antagonist, SB209670, was investigated. 2. Eight weeks after coronary artery ligation or sham operation, rabbits demonstrated increased mean pulmonary arterial pressure (PAP) accompanied by right ventricular hypertrophy. 3. Blockade of NOS caused a greater increase in basal PAP (increased by 7.7 +/- 1.1 mmHg c.f. 3.8 +/- 1.0 mmHg in controls, P<0.05) and uncovered a greater pulmonary pressor response to exogenous ET-1 in rabbits with PHT (increased by 10.2 +/- 2.3 mmHg c.f. 4.9 +/- 1.0 mmHg in controls, P<0.05). 4. Big ET-1 evoked a pulmonary pressor effect, in both groups of rabbits, that was increased following blockade of NOS and was more potent in rabbits with PHT. 5. The non-selective ET-1 receptor antagonist, SB209670, reduced basal PAP (from 16.9 mmHg to 15.9 mmHg, P < 0.05) in rabbits with PHT and blocked the response to ET-1 in the presence of L-NAME. 6. In conclusion, the results demonstrate that basal NO activity masks a pulmonary pressor response to exogenously administered ET-1. An increased responsiveness to ET-1 was shown in the pulmonary arterial bed of rabbits with PHT secondary to LVD, implicating a pathophysiological role for ET-1 in this model.

Collision-induced timing shifts in dispersion-managed soliton systems.

The frequency and timing shifts associated with dispersion-managed solitons in a wavelength-division multiplexed system are computed by the numerically efficient Poisson sum technique. Analytical formulas are attainable by use of this approach with a Gaussian approximation for the soliton. The results are favorably compared with known results for the frequency shift. The method also applies to quasi-linear return-to-zero transmission formats.