Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts.

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.

Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery

A bioactive and bioresorbable scaffold fabricated from medical grade poly (epsilon-caprolactone) and incorporating 20% beta-tricalcium phosphate (mPCL–TCP) was recently developed for bone regeneration at load bearing sites. In the present study, we aimed to evaluate bone ingrowth into mPCL–TCP in a large animal model of lumbar interbody fusion. Six pigs underwent a 2-level (L3/4; L5/6) anterior lumbar interbody fusion (ALIF) implanted with mPCL–TCP þ 0.6 mg rhBMP-2 as treatment group while four other pigs implanted with autogenous bone graft served as control. Computed tomographic scanning and histology revealed complete defect bridging in all (100%) specimen from the treatment group as early as 3 months. Histological evidence of continuing bone remodeling and maturation was observed at 6 months. In the control group, only partial bridging was observed at 3 months and only 50% of segments in this group showed complete defect bridging at 6 months. Furthermore, 25% of segments in the control group showed evidence of graft fracture, resorption and pseudoarthrosis. In contrast, no evidence of graft fractures, pseudoarthrosis or foreign body reaction was observed in the treatment group. These results reveal that mPCL–TCP scaffolds could act as bone graft substitutes by providing a suitable environment for bone regeneration in a dynamic load bearing setting such as in a porcine model of interbody spine fusion.

Plasma cytokine changes in relation to exercise intensity and muscle damage

The purpose of this study was to compare the effects of exercise intensity and exercise-induced muscle damage on changes in anti-inflammatory cytokines and other inflammatory mediators. Nine well-trained male runners completed three different exercise trials on separate occasions: (1) level treadmill running at 60% VO2max (moderate-intensity trial) for 60 min; (2) level treadmill running at 85% VO2max (high-intensity trial) for 60 min; (3) downhill treadmill running (-10% gradient) at 60% VO2max (downhill running trial) for 45 min. Blood was sampled before, immediately after and 1 h after exercise. Plasma was analyzed for interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-5, IL-10, IL-12p40, IL-13, monocyte chemotactic protein-1 (MCP-1), prostaglandin E(2), leukotriene B(4) and heat shock protein 70 (HSP70). The plasma concentrations of IL-1ra, IL-12p40, MCP-1 and HSP70 increased significantly (P<0.05) after all three trials. Plasma prostaglandin E(2) concentration increased significantly after the downhill running and high-intensity trials, while plasma IL-10 concentration increased significantly only after the high-intensity trial. IL-4 and leukotriene B(4) did not increase significantly after exercise. Plasma IL-1ra and IL-10 concentrations were significantly higher (P<0.05) after the high-intensity trial than after both the moderate-intensity and downhill running trials. Therefore, following exercise up to 1 h duration, exercise intensity appears to have a greater effect on anti-inflammatory cytokine production than exercise-induced muscle damage

Grid-side cascade inverter system as an interface for wind energy storage

Additional converters that are used to interface energy storage devices incur power losses as well as increased system cost and complexity. The need for additional converters can be eliminated if the grid side inverter can itself be effectively used as the interface for energy storage. This paper therefore proposes a technique whereby the grid side inverter can also be used as an interface to connect a supercapacitor energy storage for wind energy conversion systems. The proposed grid side inverter is formed by cascading a 3-level inverter and a 2-level inverter through a coupling transformer. The three-level inverter is the main inverter and it is powered by the rectified output of the wind turbine coupled AC generator while the 2-level auxiliary inverter is connected to the super capacitor bank that is used to compensate short term power fluctuations. Novel modulation and control techniques are proposed to address the problems associated with non-integer and dynamically-changing dc-link voltage ratio, which is caused by the random nature of wind. Simulation results are presented to verify the efficacy of the proposed system in suppressing short term wind power fluctuations.

A Battery Energy Storage interface for wind power systems with the use of grid side inverter

This paper presents a novel concept of Energy Storage System (ESS) interfacing with the grid side inverter in wind energy conversion systems. The inverter system used here is formed by cascading a 2-level inverter and a three level inverter through a coupling transformer. The constituent inverters are named as the “main inverter” and the “auxiliary inverter” respectively. The main inverter is connected with the rectified output of the wind generator while the auxiliary inverter is attached to a Battery Energy Storage System (BESS). The BESS ensures constant power dispatch to the grid irrespective of change in wind condition. Furthermore, this unique combination of BESS and inverter eliminates the need of additional dc-dc converters. Novel modulation and control techniques are proposed to address the problem of non-integer, dynamically-changing dc-link voltage ratio, which is due to random wind changes. Strategies used to handle auxiliary inverter dc-link voltage imbalances and controllers used to charge batteries at different rates are explained in detail. Simulation results are presented to verify the efficacy of the proposed modulation and control techniques in suppressing random wind power fluctuations.

A dual inverter with integrated energy storage for wind power systems

This paper explores the possibility of using grid side inverter as an interface to connect energy storage systems. A dual inverter system, formed by cascading two 2-level inverters through a coupling transformer, is used as the testing model. The inverters are named as “main inverter” and “auxiliary inverter”. The main inverter is powered by the rectified output of the wind generator while the auxiliary inverter is attached to a Battery Energy Storage System (BESS). If there is a surplus of wind power compared to the demand, then that would be stored in BESS while if there is a deficit in wind power then the demand will be satisfied by supplying power from the BESS. This enables constant power dispatch to the grid irrespective of wind changes. Novel modulation and control techniques are proposed to address the problem of non-integer, dynamically-varying dc-link voltage ratio, which is due to random wind changes. Furthermore, a maximum power tracking controller for this unique system is explained in detail. Simulation results verify the efficacy of proposed modulation and control techniques in suppressing random power fluctuations.

A dual inverter based supercapacitor direct integration scheme for wind energy conversion systems

This paper presents a new direct integration scheme for supercapacitors that are used to mitigate short term power fluctuations in wind power systems. The proposed scheme uses the popular dual inverter topology for grid connection as well as interfacing a supercapacitor bank. The dual inverter system is formed by cascading two 2-level inverters named as the “main inverter” and the “auxiliary inverter”. The main inverter is powered by the rectified output of a wind turbine coupled permanent magnet synchronous generator. The auxiliary inverter is directly connected to a super capacitor bank. This approach eliminates the need for an interfacing dc-dc converter for the supercapacitor bank and thus improves the overall efficiency. A detailed analysis on the effects of non-integer dynamically changing voltage ratio is presented. The concept of integrated boost rectifier is used to carry out the Maximum Power Point Tracking (MPPT) of the wind turbine generator. Another novel feature of this paper is the power reference adjuster which effectively manages capacitor charging and discharging at extreme conditions. Simulation results are presented to verify the efficacy of the proposed system in suppressing short term wind power fluctuations.

Effect of mobile phone use and aggression on speed selection by young drivers : a driving simulator study

Aggressive driving has been associated with engagement in other risky driving behaviours, such as speeding; while drivers using their mobile phones have an increased crash risk, despite the tendency to reduce their speed. Research has amassed separately for mobile phone use and aggressive driving among younger drivers, however little is known about the extent to which these behaviours may function independently and in combination to influence speed selection behaviour. The main aim of the current study was to investigate the effect of driver aggression (measured by the Driving Anger Expression Inventory) and mobile phone use on speed selection by young drivers. The CARRS-Q advanced driving simulator was used to test the speed selection of drivers aged 18 to 26 years (N = 32) in a suburban (60kph zone) driving context. A 2 (level of driving anger expression: low, high) X 3 (mobile phone use condition: baseline, hands-free, hand-held) mixed factorial ANOVA was conducted with speed selection as the dependent variable. Results revealed a significant main effect for mobile phone use condition such that speed selection was lowest for the hand-held condition and highest for the baseline condition. Speed selection, however, was not significantly different across the levels of driving anger expression; nor was there a significant interaction effect between the mobile phone use and driving anger expression. As young drivers are over-represented in road crash statistics, future research should further investigate the combined impact of driver aggression and mobile phone use on speed selection.

Effect of mobile phone use and aggression on speed selection by young drivers : a driving simulator study

Aggressive driving has been associated with engagement in other risky driving behaviours, such as speeding; while drivers using their mobile phones have an increased crash risk, despite the tendency to reduce their speed. Research has amassed separately for mobile phone use and aggressive driving among younger drivers, however little is known about the extent to which these behaviours may function independently and in combination to influence speed selection behaviour. The main aim of the current study was to investigate the effect of driver aggression (measured by the Driving Anger Expression Inventory) and mobile phone use on speed selection by young drivers. The CARRS-Q advanced driving simulator was used to test the speed selection of drivers aged 18 to 26 years (N = 32) in a suburban (60kph zone) driving context. A 2 (level of driving anger expression: low, high) X 3 (mobile phone use condition: baseline, hands-free, hand-held) mixed factorial ANOVA was conducted with speed selection as the dependent variable. Results revealed a significant main effect for mobile phone use condition such that speed selection was lowest for the hand-held condition and highest for the baseline condition. Speed selection, however, was not significantly different across the levels of driving anger expression; nor was there a significant interaction effect between the mobile phone use and driving anger expression. As young drivers are over-represented in road crash statistics, future research should further investigate the combined impact of driver aggression and mobile phone use on speed selection.

Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution

A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 A˚, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced "leopard skin"-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism.

Theoretical study of two states reactivity of methane activation on iron atom and iron dimer

Density functional theory (DFT) calculations have been carried out to explore the catalytic activation of C–H bonds in methane by the iron atom, Fe, and the iron dimer, Fe2. For methane activation on an Fe atom, the calculations suggest that the activation of the first C–H bond is mediated via the triplet excited-state potential energy surface (PES), with initial excitation of Fe to the triplet state being necessary for the reaction to be energetically feasible. Compared with the breaking of the first C–H bond, the cleavage of the second C–H bond is predicted to involve a significantly higher barrier, which could explain experimental observations of the HFeCH3 complex rather than CH2FeH2 in the activation of methane by an Fe atom. For methane activation on an iron dimer, the cleavage of the first C–H bond is quite facile with a barrier only 11.2, 15.8 and 8.4 kcal/mol on the septet state energy surface at the B3LYP/6-311+G(2df,2dp), BPW91/6-311+G(2df,2dp) and M06/B3LYP level, respectively. Cleavage of the second C–H bond from HFe2CH3 involves a barrier calculated respectively as 18.0, 10.7 and 12.4 kcal/mol at the three levels. The results suggest that the elimination of hydrogen from the dihydrogen complex is a rate-determining step. Overall, our results indicate that the iron dimer Fe2 has a stronger catalytic effect on the activation of methane than the iron atom.

Gas-phase reactions of aryl radicals with 2-butyne : an experimental and theoretical investigation employing the N-methyl-pyridinium-4-yl radical cation

Aromatic radicals form in a variety of reacting gas-phase systems, where their molecular weight growth reactions with unsaturated hydrocarbons are of considerable importance. We have investigated the ion-molecule reaction of the aromatic distonic N-methyl-pyridinium-4-yl (NMP) radical cation with 2-butyne (CH3C CCH3) using ion trap mass spectrometry. Comparison is made to high-level ab initio energy surfaces for the reaction of NMP and for the neutral phenyl radical system. The NMP radical cation reacts rapidly with 2-butyne at ambient temperature, due to the apparent absence of any barrier. The activated vinyl radical adduct predominantly dissociates via loss of a H atom, with lesser amounts of CH3 loss. High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry allows us to identify small quantities of the collisionally deactivated reaction adduct. Statistical reaction rate theory calculations (master equation/RRKM theory) on the NMP + 2-butyne system support our experimental findings, and indicate a mechanism that predominantly involves an allylic resonance-stabilized radical formed via H atom shuttling between the aromatic ring and the C-4 side-chain, followed by cyclization and/or low-energy H atom beta-scission reactions. A similar mechanism is demonstrated for the neutral phenyl radical (Ph center dot)+2-butyne reaction, forming products that include 3-methylindene. The collisionally deactivated reaction adduct is predicted to be quenched in the form of a resonance-stabilized methylphenylallyl radical. Experiments using a 2,5-dichloro substituted methyl-pyridiniumyl radical cation revealed that in this case CH3 loss from the 2-butyne adduct is favoured over H atom loss, verifying the key role of ortho H atoms, and the shuttling mechanism, in the reactions of aromatic radicals with alkynes. As well as being useful phenyl radical analogues, pyridiniumyl radical cations may form in the ionosphere of Titan, where they could undergo rapid molecular weight growth reactions to yield polycyclic aromatic nitrogen hydrocarbons (PANHs).

In vitro demonstration of the heavy-atom effect for photodynamic therapy

Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursuit of new PDT agents that can be optimized for the unique set of photophysical characteristics that are required for a successful clinical agent. We now describe a totally new class of PDT agent, the BF2-chelated 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-2-ylideneamines (tetraarylazadipyrromethenes). Optimized synthetic procedures have been developed to facilitate the generation of an array of specifically substituted derivatives to demonstrate how control of key therapeutic parameters such as wavelength of maximum absorbance and singlet-oxygen generation can be achieved. Photosensitizer absorption maxima can be varied within the body's therapeutic window between 650 and 700 nm, with high extinction coefficients ranging from 75,000 to 85,000 M(-1) cm(-1). Photosensitizer singlet-oxygen generation level was modulated by the exploitation of the heavy-atom effect. An array of photosensitizers with and without bromine atom substituents gave rise to a series of compounds with varying singlet-oxygen generation profiles. X-ray structural evidence indicates that the substitution of the bromine atoms has not caused a planarity distortion of the photosensitizer. Comparative singlet-oxygen production levels of each photosensitizer versus two standards demonstrated a modulating effect on singlet-oxygen generation depending upon substituent patterns about the photosensitizer. Confocal laser scanning microscopy imaging of 18a in HeLa cervical carcinoma cells proved that the photosensitizer was exclusively localized to the cellular cytoplasm. In vitro light-induced toxicity assays in HeLa cervical carcinoma and MRC5-SV40 transformed fibroblast cancer cell lines confirmed that the heavy-atom effect is viable in a live cellular system and that it can be exploited to modulate assay efficacy. Direct comparison of the efficacy of the photosensitizers 18b and 19b, which only differ in molecular structure by the presence of two bromine atoms, illustrated an increase in efficacy of more than a 1000-fold in both cell lines. All photosensitizers have very low to nondeterminable dark toxicity in our assay system.