Reactions of Nickel(0)-Olefin Pincer Complexes with Terminal Alkynes: Cooperative C-H Bond Activation and Alkyne Coupling.

Metal-ligand cooperation can facilitate the activation of chemical bonds, opening reaction pathways of interest for catalyst development. In this context, olefins occupying the central position of a diphosphine pincer ligand (PC=CP) are emerging as reversible H atom acceptors, e.g., for H2 activation. Here, we report on the reactivity of nickel complexes of PC=CP ligands with a terminal alkyne, for which two competing pathways are observed. First, cooperative and reversible C-H bond activation generates a Ni(II) alkyl/alkynyl complex as the kinetic product. Second, in the absence of a bulky substituent on the olefin, two alkyne molecules are incorporated in the ligand structure to form a conjugated triene bound to Ni(0). The mechanisms of these processes are studied by density functional theory calculations supported by experimental observations.

Kernel adaptive filtering-based phase noise compensation for pilot-free optical phase conjugated coherent systems.

We propose a kernel-based adaptive filtering method to suppress the phase noise (PN) arising from small deviations from ideal counter-phasing in the dual-pump fibre-based optical phase conjugation (OPC) of pilot-free quadrature-amplitude modulation (QAM) signals. We demonstrate experimentally and numerically that the proposed scheme achieves signal-to-noise ratio improvement over conventional PN compensation under optimised pump dithering settings in the OPC device and features no performance penalty across a range of pump-phase mismatch values, when it is used with a 16-QAM signal in an optical back-to-back configuration. We also illustrate the applicability of the method to the 64-QAM modulation format, and evaluate its performance in a transmission setup with mid-link OPC by means of numerical simulations.

Assessing the carbonisation temperatures recorded by ancient charcoals for δ13C-based palaeoclimate reconstruction.

Ancient charcoal fragments, produced by the use of wood as fuel in archaeological contexts or during natural or anthropic forest fires, persist in soil and sediments over centuries to millennia. They thus offer a unique window to reconstruct past climate, especially palaeo-precipitation regimes thanks to their stable carbon isotope composition. However, the initial δ13C of wood is slightly modified as a function of the carbonisation temperature. Carbonisation-induced 13C fractionation is classically investigated through a transfer function between experimental carbonisation temperatures and the carbon content. This approach assumes that the carbon content is conservative through time in ancient charcoals and neglects the potential impact of post-depositional oxidation occurring in soils and sediments. In the present study, we first show that post-depositional oxidation can lead to a large underestimation of past carbonisation temperatures, thereby minimising the estimation of carbonisation-induced 13C fractionations and possibly biasing δ13C-based climate reconstructions. Secondly, by combining carbon content, Fourier-transform infrared and Raman spectroscopy, we propose a new framework to assess the carbonisation temperatures registered in ancient charcoals. This new framework paves the way to reassessing δ13C-based climate reconstruction.

Distributed Raman Amplification for Fiber Nonlinearity Compensation in a Mid-Link Optical Phase Conjugation System.

In this paper, we review different designs of distributed Raman amplifiers which have been proposed to minimize the signal power profile asymmetry in mid-link optical phase conjugation systems. We demonstrate how the symmetrical signal power profiles along the fiber can be achieved using various distributed Raman amplification techniques in the single-span and more realistic multi-span circumstances. In addition, we show the theoretically predicted results of the Kerr nonlinear product reduction with different Raman techniques in mid-link optical phase conjugator systems, and then in-line/long-haul transmission performance using numerical simulations.

Raman Amplification Optimization in Short-Reach High Data Rate Coherent Transmission Systems.

We compared the transmission performances of 600 Gbit/s PM-64QAM WDM signals over 75.6 km of single-mode fibre (SMF) using EDFA, discrete Raman, hybrid Raman/EDFA, and first-order or second-order (dual-order) distributed Raman amplifiers. Our numerical simulations and experimental results showed that the simple first-order distributed Raman scheme with backward pumping delivered the best transmission performance among all the schemes, notably better than the expected second-order Raman scheme, which gave a flatter signal power variation along the fibre. Using the first-order backward Raman pumping scheme demonstrated a better balance between the ASE noise and fibre nonlinearity and gave an optimal transmission performance over a relatively short distance of 75 km SMF.

Digital compensation of imperfect pump counter-phasing induced phase distortion in optical phase conjugation of high-order QAM.

We propose a new two-stage digital signal processing scheme to suppress the phase distortion that arises from imperfect pump counter-phasing in a dual-pump fibre-based optical phase conjugation system. We demonstrate experimentally and numerically a signal-to-noise ratio improvement of more than 4 dB relative to conventional phase noise compensation, when the proposed scheme is used with 16/64/256 quadrature-amplitude modulation signals at pump-phase mismatch values as large as 8°.

Aging out of dependent coverage and the effects on the use of inpatient medical care.

We investigate the impact of losing health insurance coverage at age 26 due to aging out of the Affordable Care Act's dependent coverage on health insurance coverage rates and various indicators of inpatient medical care. We find that the probability of being covered under any type of health insurance plan decreases by 2.5-6.2 percentage points at age 26. However, the effects of this discrete change in health insurance coverage on inpatient medical care and related costs are insignificant.

Allelopathic Potential of Rice and Identification of Published Allelochemicals by Cloud-Based Metabolomics Platform.

The methanol extracts of nine popular cultivated Vietnamese rice cultivars (Oryza sativa L.cv. OM 2395, 5451, 6976, 380, 5930, 4498, 3536, N406, and 7347) were used to explore their allelopathic potential on barnyardgrass (Echinochola crus-galli L.). At 0.1 g mL-1, OM 5930, OM 4498, and OM 6976 correlatively possessed greatest phytotoxicity on barnyardgrass shoot (98.77%, 90.75%, and 87.17%) and root (99.39%, 92.83%, and 86.56%) growth. The following study aimed to detect previously-known allelochemicals in those rice using XCMS online cloud-based metabolomics platform. Twenty allelochemicals were semi-quantified and seven of them were detected predominantly and five was putatively confirmed in OM 5930 (mg/ 100g fresh rice) as salicylic acid (5.0076), vanillic acid (0.1246), p-coumaric acid (0.1590), 2,4-dimethoxybenzoic acid (0.1045), and cinnamic acid (3.3230). These compounds were active at concentrations greater than 0.5 mM and the average EC50 were 1.24 mM. The results indicated that OM 5930 may use as promising candidates in weed biological control for rice production.

Simpplified extended Kalman filter phase noise estimation for CO-OFDM transmissions.

We propose a flexible simplified extended Kalman filter (S-EKF) scheme that can be applied in both pilot-aided and blind modes for phase noise compensation in 16-QAM CO-OFDM transmission systems employing a small-to-moderate number of subcarriers. The performance of the proposed algorithm is evaluated and compared with conventional pilot-aided (PA) and blind phase search (BPS) methods via extensive an Monte Carlo simulation in a back-to-back configuration and with a dual polarization fiber transmission. For 64 subcarrier 32 Gbaud 16-QAM CO-OFDM systems with 200 kHz combined laser linewidths, an optical signal-to-noise ratio penalty as low as 1 dB can be achieved with the proposed S-EKF scheme using only 2 pilots in the pilot-aided mode and just 4 inputs in the blind mode, resulting in a spectrally efficient enhancement by a factor of 3 and a computational effort reduction by a factor of more than 50 in comparison with the conventional PA and the BPS methods, respectively.

The pharmacokinetics of PF-734200, a DPP-IV inhibitor, in subjects with renal insufficiency.

AIMS: PF-734200 is a potent, selective inhibitor of DPP-IV. This two-part study evaluated the pharmacokinetics (PK) of oral 20mg PF-734200 in subjects with varying degrees of renal insufficiency or with end-stage renal disease (ESRD) requiring chronic haemodialysis (HD). The study also assessed the HD clearance of PF-734200 in ESRD. METHODS: Part 1 included subjects with normal renal function or renal insufficiency but not on HD. Subjects received a single dose of 20mg PF-734200 while fasting and serum and urine samples were collected. In part 2, period 1, 1h after HD, a single 20-mg dose was given to subjects with ESRD and serum samples were collected. After a 7-day washout, subjects received another dose followed by collection of serum samples (period 2), during which HD was initiated 4h after dosing. Dialysate samples were collected to quantify amount of drug removed, from which HD clearance was calculated. The fraction of drug dialysed was calculated using an AUC-based method. RESULTS: Systemic exposures of PF-734200 increased approximately 1.5-, 2.2-, 2.1- and 2.8-fold in subjects with mild, moderate, or severe renal insufficiency or ESRD, respectively, compared with subjects with normal renal function. The terminal half-life increased from 16.2h in subjects with normal renal function to 36.6h in subjects with ESRD. Approximately, 29% of PF-734200 in the body after a single-dose administration was dialysed by 4h HD. CONCLUSIONS: Systemic exposure of PF-734200 increases with decreasing renal function. The effect of HD on drug removal is modest.

Potential implications of matrix metalloproteinase-9 in assessment and treatment of coronary artery disease.

BACKGROUND: Matrix metalloproteinase (MMP)-9, a member of the MMP superfamily is consistently implicated in the pathophysiology of atherosclerosis and plaque rupture, the most common mechanism responsible for acute coronary syndrome (ACS). AIM: To summarize the role of MMP-9 in atherosclerosis and its potential implications in assessment and treatment of coronary artery disease (CAD). METHODS: We reviewed the PubMed database for relevant data regarding the role of MMP-9 in the pathophysiology of atherosclerosis. In the light of these data, we postulate potential implications of MMP-9 in the management and treatment of CAD. RESULTS AND CONCLUSIONS: Existing data strongly support the role of MMP-9 in plaque destabilization and rupture. Based on the current knowledge, MMP-9 can potentially serve as a diagnostic biomarker in ACS and a prognostic biomarker in ACS and chronic CAD patients. MMP-9 is reduced by therapies that are associated with favourable outcome in atherosclerosis and thus may serve as a surrogate biomarker of treatment efficacy. However, large morbidity and mortality trials are still required to confirm that MMP-9 reduction is associated with improved outcome independent of the traditional risk factors (i.e. low-density lipoprotein cholesterol). Given its role in plaque rupture, inhibition of MMP-9 may promote plaque stabilization and consequently reduce cardiovascular events. Yet, the efficacy and safety of MMPs inhibitors should be first studied in preclinical models of atherosclerosis.

Efficacy and safety of a potent and selective peroxisome proliferator activated receptor alpha agonist in subjects with dyslipidemia and type 2 diabetes mellitus.

The weak peroxisome proliferator activated receptor-alpha (PPAR-alpha) agonists gemfibrozil and fenofibrate achieve only small increases in high-density lipoprotein (HDL) cholesterol. CP-778,875 is a more potent PPAR-alpha agonist developed to produce greater HDL cholesterol increases. This randomized, multicenter, double-blinded, placebo-controlled study evaluated the efficacy and safety of CP-778,875 in subjects with mixed dyslipidemia and type 2 diabetes. Eight-six subjects with low HDL cholesterol (< or =45 mg/dl for men and < or =55 mg/dl for women) and increased triglycerides (150 to 500 mg/dl) who had coexisting type 2 diabetes were randomized. Subjects received CP-778,875 doses of 0.5, 2, or 6 mg/day or placebo for 6 weeks. Any other lipid-altering therapy was stopped at screening. The primary end point was percent change in HDL cholesterol from baseline. The 2-mg/day dose of CP-778,875 significantly increased HDL cholesterol by 14%. The 2-mg dose also increased concentrations of apolipoprotein (apo) A-I, HDL(2) cholesterol, and HDL(3) cholesterol by 13%, 12%, and 19%, respectively. An unusual dose-response pattern was observed in that at 6 mg/day CP-778,875 only increased HDL cholesterol by 3% and decreased HDL(2) cholesterol by 24%. Fasting triglyceride levels were significantly decreased to a similar extent (26%) by all 3 doses of CP-778,875. CP-778,875 significantly increased homocysteine levels. There was no significant relation between change in homocysteine and change in apoA-I or HDL cholesterol. No subjects developed myopathy. In conclusion, CP-778,875 2 mg/day significantly increased HDL cholesterol, significantly lowered fasting triglycerides, and increased apoA-I and HDL subfractions. The clinical relevance of the increase in homocysteine levels is unknown.

Non-traditional biomarkers of atherosclerosis in stable and unstable coronary artery disease, do they differ?

BACKGROUND: Biomarkers of atherosclerosis are emerging as a potential tool for assessment of coronary artery disease (CAD) patients. As acute coronary syndrome (ACS), and stable CAD are distinguished in their pathophysiology it is conceivable that they are also characterized by different biomarkers of atherosclerosis. METHODS: We systematically reviewed the literature for clinical studies of several non-traditional biomarkers of atherosclerosis reflecting various pathophysiological processes, namely macrophage-activity, oxidative-stress, tissue remodeling, and thrombosis in ACS and stable CAD to determine whether circulating biomarkers are differently expressed/predict outcome in these two clinical conditions. RESULTS: Macrophage-activity (monocyte chemoattractant protein-1, neopterin), tissue-remodeling (matrix metalloproteinase-9) and thrombosis (tissue-factor) related biomarkers were consistently elevated in ACS compared to stable CAD, in accordance with the pathophysiological role of these mediators in plaque rupture, characterizing ACS. Thus, these biomarkers may be applicable for diagnosis of ACS. Additionally, neopterin was consistently shown to predict outcome in both stable and ACS patients and myeloperoxidase was strongly shown to predict outcome in ACS, implying for their potential role in risk stratification of these patients. CONCLUSIONS: As ACS and stable CAD are characterized by different pathophysiological processes, it appears that the biomarkers that are associated with them are differently expressed in these two clinical conditions