The role of stable nitroxyl radical precursors as antioxidants in polyolefins

Various 2,2,6,6-tetramethyl piperidines and their N-alkyl derivatives of stable nitroxyl radical precursors containing acrylic(s) and methacrylic(s) groups were reactively processed in the presence of a peroxide as bound-antioxidant masterbatches for polyolefin stabilisation. It was found that grafting of the antioxidant monomers onto the polymer backbone was inevitably in competition with homopolymerisation of the monomers as well as melt degradation of the polymer and other side reactions. As previously reported, binding efficiency of bisacrylic nitroxyl precursor was maximum due to formation of unextractable homopolymer of the antioxidant. On the other hand, the binding efficiency of monoacrylic derivatives was low and the homopolymers were found extractable, which suggests that the bound monoacrylic derivatives are entirely grafted onto the polyolefin backbone. Application of bis and tri-functional coagents gave improved binding efficiency of the monoacrylic monomers. This may be due to copolymerisation of the antioxidants with the coagents and grafting of the copolymers onto the polymer backbone. Comparison of photostabilising activity of the fully extracted bound antioxidants to those of the corresponding unbound analogous showed lower results for the former. However, thermal stabilising activity of the bound antioxidants was higher than that of the unbound analogous due to better substantivity. Analysis using physical techniques and GPC for molecular weight distribution of masterbatches containing the bound monoacrylic antioxidants showed formation of high molecular weight products. Model reaction of a secondary amine derivative in liquid hydrocarbon and analysis of the product using FTIR and NMR spectroscopy indicated a possibility of side reaction, i.e. involvement of the amine active group (>N-H) of the antioxidant in the binding process to form the high molecular weight product. Implementation of various N-alkylated derivatives did not inhibit the side reaction. The photostabilising activity of the bound-antioxidants can be improved when applied in conjunction with small amounts of a benzophenone uv-stabiliser. The synergistic stabilising activity, however, was diminished when the uv-stabiliser was removed from the system during the service time. Nitroxyl precursors containing methacrylic group(s) gave lower binding efficiency than the corresponding acrylic derivatives. Reversible deploymerisation of the grafted methacrylic antioxidants may be responsible for this. Bis and tris-acrylic coagents improved the binding efficiency, and the presence of methacrylic group improved stabilising activity of the antioxidants. N-methyl derivatives were found to exhibit better stabilising activity than their parent secondary amine derivatives.

Approximating differentiable relationships between delay embedded dynamical systems with radical basis functions

This thesis is about the study of relationships between experimental dynamical systems. The basic approach is to fit radial basis function maps between time delay embeddings of manifolds. We have shown that under certain conditions these maps are generically diffeomorphisms, and can be analysed to determine whether or not the manifolds in question are diffeomorphically related to each other. If not, a study of the distribution of errors may provide information about the lack of equivalence between the two. The method has applications wherever two or more sensors are used to measure a single system, or where a single sensor can respond on more than one time scale: their respective time series can be tested to determine whether or not they are coupled, and to what degree. One application which we have explored is the determination of a minimum embedding dimension for dynamical system reconstruction. In this special case the diffeomorphism in question is closely related to the predictor for the time series itself. Linear transformations of delay embedded manifolds can also be shown to have nonlinear inverses under the right conditions, and we have used radial basis functions to approximate these inverse maps in a variety of contexts. This method is particularly useful when the linear transformation corresponds to the delay embedding of a finite impulse response filtered time series. One application of fitting an inverse to this linear map is the detection of periodic orbits in chaotic attractors, using suitably tuned filters. This method has also been used to separate signals with known bandwidths from deterministic noise, by tuning a filter to stop the signal and then recovering the chaos with the nonlinear inverse. The method may have applications to the cancellation of noise generated by mechanical or electrical systems. In the course of this research a sophisticated piece of software has been developed. The program allows the construction of a hierarchy of delay embeddings from scalar and multi-valued time series. The embedded objects can be analysed graphically, and radial basis function maps can be fitted between them asynchronously, in parallel, on a multi-processor machine. In addition to a graphical user interface, the program can be driven by a batch mode command language, incorporating the concept of parallel and sequential instruction groups and enabling complex sequences of experiments to be performed in parallel in a resource-efficient manner.

A spectroscope study of some semiquinone radical ions

The effect of substituents on the value of the oxidation potential of quinones is reviewed and attempts to prepare substituted diphenoquinones with high oxidation potentials are reported. Attempts to characterise the mechanism of addition and substitution in diphenoquinones by identifying the products of the Thiele acetylation of diphenoquinone are reported. The reaction proved most efficient when the incoming acetylinium ion is directed by substituents in the diphenoquinone. A 1,8-addition to diphenoquinone is reported and characterised by isolating the products of the reaction between acetyl chloride and diphenoquinone, with perchloric acid as catalyst. The alternating linewidth effects observed in e.s.r.spectra are discussed and applied to account for such effects observed in the e.s.r.spectra of diphenosemiquinone anion and cation radicals. The spectra are analysed and the intramolecular processes producing these effects are discussed. A dianion diradical where intramolecular rotation about the 1 - 1' bond is restricted is produced by the oxidation of 2,2' ,4,4' -tetra hydroxybiphenyl. Previous studies of diphenosemiquinone anions are reviewed and alkylated diphenosemiquinone anion are produced by the reduction of the parent quinone with potassium hydroxide solution, the resulting radical being stabilised by the presence of pyridine. A qualitative interpretation of the solvent-ion effect in alkylated diphenosemiquinone anions is given. Diphanosemiquinone cation radicals are reviewed and previous studies are re-examined.

A sulphonate based hydrogel for nucleus pulposus repair

Introduction: Lower back pain treatment and compensation costs >$80 billion overall in the US. 75% of back pain is due to disc degeneration in the lumbar region of the spine. Current treatment comprises of painkillers and bed rest or as a more radical solution – interbody cage fusion. In the early stages of disc degeneration the patient would benefit from addition of an injectable gel which polymerises in situ to support the degenerated nucleus pulposus. This involves a material which is an analogue of the natural tissue capable of restoring the biomechanical properties of the natural disc. The nucleus pulposus of the intervertebral disc is an example of a natural proteoglycan consisting of a protein core with negatively charged keratin and chondroitin sulphate attached. As a result of the high fixed charge density of the proteoglycan, the matrix exerts an osmotic swelling pressure drawing sufficient water into support the spinal system. Materials and Methods: NaAMPs (sodium 2- acrylamido 2-methyl propane sulphonic acid) and KSPA (potassium 3- sulphopropyl acrylate) were selected as monomers, the sulphonate group being used to mimic the natural sulphate group. These are used in dermal applications involving chronic wounds and have acceptably low cytotoxicity. Other hydrophilic carboxyl, amide and hydroxyl monomers such as 2-hydroxyethyl acrylamide, ß-carboxyethyl acrylate, acryloyl morpholine, and polyethylene glycol (meth)acrylate were used as diluents together with polyethyleneglycol di(meth)acrylate and hydrophilic multifunctional macromers as cross-linker. Redox was the chosen method of polymerisation and a range of initiators were investigated. Components were packaged in two solutions each containing a redox pair. A dual syringe method of injection into the cavity was used, the required time for polymerisation is circa 3-7 minutes. The final materials were tested using a Bohlin CVO Rheometer cycling from 0.5-25Hz at 37oC to measure the modulus. An in-house compression testing method was developed, using dialysis tubing to mimic the cavity, the gels were swelled in solutions of various osmolarity and compressed to ~ 20%. The pre-gel has also been injected into sheep spinal segments for mechanical compression testing to demonstrate the restoration of properties upon use of the gel. Results and Discussion: Two systems resulted using similar monomer compositions but different initiation and crosslinking agents. NaAMPs and KSPA were used together at a ratio of ~1:1 in both systems with 0.25-2% crosslinking agent, diacrylate or methacrylate. The two initiation systems were ascorbic acid/oxone, and N,N,N,N - tetramethylethylenediamine (TEMED)/ potassium persulphate. These systems produced gelation within 3-7 and 3-5 minutes respectively. Storage of the two component systems was shown to be stable for approximately one month after mixing, in the dark, refrigerated at 1-4oC. The gelation was carried out at 37oC. Literature values for the natural disc give elastic constants ranging from 3-8kPa. The properties of the polymer can be tailored by altering crosslink density and monomer composition and are able to match those of the natural disc. It is possible to incorporate a radio-opaque (histodenz) to enable x-ray luminescence during and after injection. At an inclusion level of 5% the gel is clearly visible and polymerisation and mechanical properties are not altered. Conclusion: A two-pac injection system which will polymerise in situ, that can incorporate a radio-opaque, has been developed. This will reinforce the damaged nucleus pulposus in degenerative disc disease restoring adequate hydration and thus biomechanical properties. Tests on sheep spine segments are currently being carried out to demonstrate that a disc containing the gel has similar properties to an intact disc in comparison to one with a damaged nucleus.

Racing for radical innovation:how motorsport companies harness network diversity for discontinuous innovation

The motorsport industry is a significant part of the UK economy. According to industry estimates approximately 4,500 companies are involved in the UK Motorsport and Performance Engineering Industry and its wide-ranging support activities. The industry has an annual turnover of £6.0 billion, and contributes £3.6 billion worth of exports. The Motorsport Industry Association estimates that the support side of the sector alone "involving events management, public relations, marketing, sponsorship and a host of other support functions" accounts for approximately £1.7 billion of the yearly industry total. And in terms of employment, UK Motorsport supports 38,500 full and part-time jobs, including 25,000 engineers.

When cost-efficient technologies meet politics:a case study of radical wireless network implementation

Cost efficiency has been a dominant perspective in the traditional IT literature. However, in complex technology and business environment, the widely recognized cost efficient assumption of information technology has been increasingly challenged. Drawing from a case study of wireless network implementation situated in a politically sensitive workplace, this paper provided practice insights for IT managers in today’s networked economy. More specifically, stories experienced in the case study illustrated that despite well-calculated cost efficiency of wireless network infrastructure, the radical implementation process in the case organization encountered enormous challenges and opposition due to the fact that administrators failed to consider various stakeholders’ positions and interests. Eventually, the implementation objectives and outcome were considerably undermined. Implications from this empirical case research reemphasized the significance of understanding political forces situated in any business environment where different stakeholders hold conflicting interests. Lessons learned from the case story further encouraged IT managers and policy makers to better strategize emerging information technology in general and wireless networks in particular as the whole global society and business environment are increasingly facing an emerging wireless world.

Detection of phosphatidylserine with a modified polar head group in human keratinocytes exposed to the radical generator AAPH

Phosphatidylserine (PS) is preferentially located in the inner leaflet of the cell membrane, and translocation of PS oxidized in fatty acyl chains to the outside of membrane has been reported as signaling to macrophage receptors to clear apoptotic cells. It was recently shown that PS can be oxidized in serine moiety of polar head-group. In the present work, a targeted lipidomic approach was applied to detecting OxPS modified at the polar head-group in keratinocytes that were exposed to the radical generator AAPH. Glycerophosphoacetic acid derivatives (GPAA) were found to be the major oxidation products of OxPS modified at the polar head-group during oxidation induced by AAPH-generated radicals, similarly to previous observations for the oxidation induced by OH radical. The neutral loss scan of 58Da and a novel precursor ion scan of m/z 137.1 (HOPO3CH2COOH) allowed the recognition of GPAA derivatives in the total lipid extracts obtained from HaCaT cells treated with AAPH. The positive identification of serine head group oxidation products in cells under controlled oxidative conditions opens new perspectives and justifies further studies in other cellular environments in order to understand fully the role of PS polar head-group oxidation in cell homeostasis and disease.

Thermal decomposition behavior of 1,2-bis-(2,4,6-tribromophenoxy)ethane

The thermal decomposition behavior of 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE) widely used as flame retardant plastics additive was studied by HRTG and differential scanning calorimetries. It was pyrolysed in inert atmosphere at 240 and 340 °C in isothermal conditions, the decomposition products were collected and investigated by means of IR and GC-MS, most of them are identified. It was found that BTBPE mostly evaporates at 240 °C. The decomposition products at 340°C depend on rate of their removal from the hot reaction zone. Main primary decomposition products found in case of rapid removal are tribromophenol and vinyl tribromophenyl ether. Whereas, prolonged contact with heating zone also produces hydrogen bromide, ethylene bromide, polybrominated vinyl phenyl ethers and diphenyl ethers, and dibenzodioxins. The nature of the identified compounds are in accordance with a molecular and radical pyrolysis reaction pathway. © 2002 Elsevier Science B.V. All rights reserved.

25-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages

Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not I?B degradation or tumour necrosis factor- release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling.

CuII chain compound showing a ferromagnetic coupling through triple N1,N2-1,2,4-triazole bridges

[Cu(hyetrz)3](CF3SO3)2·H2O [hyetrz = 4-(2′-hydroxyethyl)-1,2,4-triazole] represents the first structurally characterised ferromagnetically coupled CuII chain compound containing triple N1,N2-1,2,4-triazole bridges. catena-[μ-Tris{4-(2′-hydroxyethyl)-1,2,4-triazole-N1,N2}copper(II)] bis(trifluoromethanesulfonate) hydrate (C14H23F6S2O10CuN9) crystallises in the triclinic space group Pl, a = 13.54(3), b = 14.37(3), c = 15.61(4) Å, α = 95.9(1), β = 104.9(1), γ = 106.5(1)°, V = 2763(11) Å3, Z = 4 (CuII units). The CuII ions are linked by triple N1,N2-1,2,4-triazole bridges yielding an alternating chain with Cu1−Cu2 = 3.8842(4) Å and Cu2−Cu3 = 3.9354(4) Å. Analysis of the magnetic data according to a high-temperature series expansion gives a J value of +1.45(3) cm−1. The nature and the magnitude of the ferromagnetic exchange have been discussed on the basis of the structural features. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Luminescent techniques for studying free radical production and cell viability in relation to cardiovascular disease and HRT

Epidemiological studies have suggested that hormone replacement therapy (HRT) offers protection from atherosclerosis, a precursor of cardiovascular disease (CVD), in postmenopausal women. There is good evidence that oxidation of low-density lipoprotein (LDL) by leucocyte-derived reactive oxygen species plays a key role in development of an atherosclerotic plaque. Therefore we have investigated whether the possible protection against CVD by HRT could be due to immunomodulation, specifically of free radical production. The study involves 2 approaches: I) analysing the production of free radicals by leucocytes from women on HRT, 2) investigating the effect of I7p-oestradiol and progesterone on cultured myeloid cells (HL60 and U937). Free radical production by leucocytes was determined using a recently developed bioluminescent assay. In the assay, Pholasin® emits light in the presence of free radicals produced by the NADPH oxidase system of leucocytes stimulated with PMA or fMLP. Cell viability was also investigated using a bioluminescent assay (Cell Titer-Glo®) in which cytosolic ATP levels were measured by the production of luminescence in the presence of Luciferin/Luciferase reagent. Studies of leucocytes from HRT patients showed considerable variation in free radical production, which appeared to be dependent on HRT regime. Studies on the cultured cells showed that there was no cell proliferation at low hormone concentrations, while high concentrations caused cytotoxicity. The effect of hormones on free radical production in this in vitro model system is currently being investigated. The results show that the effects of the hormones on cells of the immune system are very dose dependent, and that both beneficial and adverse effects may occur. In conclusion, luminescent techniques offer a valuable and sensitive approach to studying inflammatory and oxidative processes both in vivo and in vitro.

Conformational analysis of the natural iron chelator myo-inositol 1,2,3-trisphosphate using a pyrene-based fluorescent mimic

myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.