Scintillation proximity assays for the real-time detection and quantification of the progress of reactions upon solid supports

A scintillation proximity assay (SPA) has been used successfully to detect and quantify, in real-time, the kinetic progress of hydrolysis of [ H]acetate esters from scintillant-containing styrenic and poly(ethylene glycol) (PEG)-based polymer supports in both organic and aqueous media.

Mechanisms of chromium deposition and dissolution under direct and pulse reverse plating conditions

Baths containing sulphuric acid as catalyst and others with selected secondary catalysts (methane sulphonic acid - MSA, SeO2, a KBrO3/KIO3 mixture, indium, uranium and commercial high speed catalysts (HEEF-25 and HEEF-405)) were studied. The secondary catalysts influenced CCE, brightness and cracking. Chromium deposition mechanisms were studied in Part II using potentiostatic and potentiodynamic electroanalytical techniques under stationary and hydrodynamic conditions. Sulphuric acid as a primary catalyst and MSA, HEEF-25, HEEF-405 and sulphosalycilic acid as co-catalysts were explored for different rotation, speeds and scan rates. Maximum current was resolved into diffusion and kinetically limited components, and a contribution towards understanding the electrochemical mechanism is proposed. Reaction kinetics were further studied for H2SO4, MSA and methane disulphonic acid catalysed systems and their influence on reaction mechanisms elaborated. Charge transfer coefficient and electrochemical reaction rate orders for the first stage of the electrodeposition process were determined. A contribution was made toward understanding of H2SO4 and MSA influence on the evolution rate of hydrogen. Anodic dissolution of chromium in the chromic acid solution was studied with a number of techniques. An electrochemical dissolution mechanism is proposed, based on the results of rotating gold ring disc experiments and scanning electron microscopy. Finally, significant increases in chromium electrodeposition rates under non-stationary conditions (PRC mode) were studied and a deposition mechanisms is elaborated based on experimental data and theoretical considerations.

Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation

Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.

Governance of open content creation:a conceptualization and analysis of control and guiding mechanisms in the open content domain

The open content creation process has proven itself to be a powerful and influential way of developing text-based content, as demonstrated by the success of Wikipedia and related sites. Distributed individuals independently edit, revise, or refine content, thereby creating knowledge artifacts of considerable breadth and quality. Our study explores the mechanisms that control and guide the content creation process and develops an understanding of open content governance. The repertory grid method is employed to systematically capture the experiences of individuals involved in the open content creation process and to determine the relative importance of the diverse control and guiding mechanisms. Our findings illustrate the important control and guiding mechanisms and highlight the multifaceted nature of open content governance. A range of governance mechanisms is discussed with regard to the varied levels of formality, the different loci of authority, and the diverse interaction environments involved. Limitations and opportunities for future research are provided.

Identification and molecular mechanisms of the rapid tonicity-induced relocalization of the aquaporin 4 channel

The aquaporin family of integral membrane proteins is comprised of channels that mediate cellular water flow. Aquaporin 4 (AQP4) is highly expressed in the glial cells of the central nervous system and facilitates the osmotically-driven pathological brain swelling associated with stroke and traumatic brain injury. Here we show that AQP4 cell surface expression can be rapidly and reversibly regulated in response to changes of tonicity in primary cortical rat astrocytes and in transfected HEK293 cells. The translocation mechanism involves protein kinase A (PKA) activation, influx of extracellular calcium and activation of calmodulin. We identify five putative PKA phosphorylation sites and use site-directed mutagenesis to show that only phosphorylation at one of these sites, serine- 276, is necessary for the translocation response. We discuss our findings in the context of the identification of new therapeutic approaches to treating brain oedema.

Antecedents, mechanisms and processes of deinstitutionalization and institutional change:a case study approach to understanding enterprise under duress

Adopting a grounded theory methodology, the study describes how an event and pressure impact upon a process of deinstitutionalization and institutional change. Three case studies were theoretically sampled in relation to each other. They yielded mainly qualitative data from methods that included interviews, observations, participant observations, and document reviews. Each case consisted of a boundaried cluster of small enterprises that were not industry specific and were geographically dispersed. Overall findings describe how an event, i.e. a stimulus, causes disruption, which in turn may cause pressure. Pressure is then translated as a tension within the institutional environment, which is characterized by opposing forces that encourage institutional breakdown and institutional maintenance. Several contributions are made: Deinstitutionalization as a process is inextricable from the formation of institutions – both are needed to make sense of institutional change on a conceptual level but are also inseparable experientially in the field; stimuli are conceptually different to pressures; the historical basis of a stimulus may impact on whether pressure and institutional change occurs; pressure exists in a more dynamic capacity rather than only as a catalyst; institutional breakdown is a non-linear irregular process; ethical and survival pressures as new types were identified; institutional current, as an underpinning mechanism, influences how the tension between institutional breakdown and maintenance plays out.

Asymmetric reactions of organosilicon compounds and properties of novel optically active organosilanes

Partial reduction of racemic methoxysilanes by 1:1 complexes of lithium aluminium hydride with optically active cinchona and ephedra alkaloids give optically active silanes and methoxysilanes. Optical yields depend on the groups attached to silicon and the alkaloid used but in some cases approach 50%, The method has been used to prepare novel optically active organosilanes, possessing an asymmetric silicon centre, which are either inaccessible by any of the other available routes or would require a time consuming preparation. Such compounds are of use in the study of the mechanism of substitutions at silicon. Attempts have been made to rationalize the results of the asymmetric reductions in terms of differences in sterio and electronic interactions in diastereoisomeric transition states. Circular dichroism and optical rotatory dispersion spectra have been obtained for the optically active products in an attempt to elucidate the absolute configurations of the novel asymmetric organosilanes. The results from these studies provide a useful addition to the data so far accumulated for asymmetrically perturbed aromatic chromophores. Nuclear magnetic resonanoe studies of diastereoisomaric (-)-menthoxysilanes show that these compounds possess resonances extremely useful in the determination of optical purities for asymmetric organosilanes which possess an aromatic group. The effect of variable temperature on the spectra has revealed evidence for the conformational preferences in these compounds. Other diastereoisomeric alkoxysilanes have been prepared and their n.m.r.spectra studied in the hope of establishing trends. Exploratory studies for other asymmetric reactions proceeding at silicon have proved unfruitful.

Structure and reactivity of sol-gel sulphonic acid silicas

A range of mesoporous solid sulphonic acid catalysts have been prepared from a mercaptopropyl-trimethoxysilane (MPTS) precursor by sol-gel synthesis. The creation of surface sulphonic acid functionality via thiol oxidation has been followed by XPS and Raman spectroscopy. It is possible to continuously vary the sulphonic acid loading from 1 to 12wt.% while maintaining pore volume and mesostructure. The resulting materials exhibit high thermal stability and acid strength across the composition range and show good activity and selectivity in esterification and condensation reactions. © 2002 Elsevier Science B.V. All rights reserved.

Unravelling the photodegradation mechanisms of a low bandgap polymer by combining experimental and modeling approaches

Large-scale introduction of Organic Solar Cells (OSCs) onto the market is currently limited by their poor stability in light and air, factors present in normal working conditions for these devices. Thus, great efforts have to be undertaken to understand the photodegradation mechanisms of their organic materials in order to find solutions that mitigate these effects. This study reports on the elucidation of the photodegradation mechanisms occurring in a low bandgap polymer, namely, Si-PCPDTBT (poly[(4,4′-bis(2-ethylhexyl)dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-(4,7-bis(2-thienyl)-2,1,3-benzothiadiazole)-5,5′-diyl]). Complementary analytical techniques (AFM, HS-SPME-GC-MS, UV-vis and IR spectroscopy) have been employed to monitor the modification of the chemical structure of the polymer upon photooxidative aging and the subsequent consequences on its architecture and nanomechanical properties. Furthermore, these different characterization techniques have been combined with a theoretical approach based on quantum chemistry to elucidate the evolution of the polymer alkyl side chains and backbone throughout exposure. Si-PCPDTBT is shown to be more stable against photooxidation than the commonly studied p-type polymers P3HT and PCDTBT, while modeling demonstrated the benefits of using silicon as a bridging atom in terms of photostability. (Figure Presented).

Exploring oxidative modifications of tyrosine:an update on mechanisms of formation, advances in analysis and biological consequences

Protein oxidation is increasingly recognised as an important modulator of biochemical pathways controlling both physiological and pathological processes. While much attention has focused on cysteine modifications in reversible redox signalling, there is increasing evidence that other protein residues are oxidised in vivo with impact on cellular homeostasis and redox signalling pathways. A notable example is tyrosine, which can undergo a number of oxidative post-translational modifications to form 3-hydroxy-tyrosine, tyrosine crosslinks, 3-nitrotyrosine and halogenated tyrosine, with different effects on cellular functions. Tyrosine oxidation has been studied extensively in vitro, and this has generated detailed information about the molecular mechanisms that may occur in vivo. An important aspect of studying tyrosine oxidation both in vitro and in biological systems is the ability to monitor the formation of oxidised derivatives, which depends on a variety of analytical techniques. While antibody-dependent techniques such as ELISAs are commonly used, these have limitations, and more specific assays based on spectroscopic or spectrometric techniques are required to provide information on the exact residues modified and the nature of the modification. These approaches have helped understanding of the consequences of tyrosine oxidation in biological systems, especially its effects on cell signalling and cell dysfunction, linking to roles in disease. There is mounting evidence that tyrosine oxidation processes are important in vivo and can contribute to cellular pathology.

CO-stabilisation mechanisms of nanoparticles and surfactants in Pickering emulsions produced by membrane emulsification

Two different membrane emulsification methods were used to study mechanisms for co-stabilisation of emulsions, by either electrostatic or steric stabilised nanoparticles with anionic, cationic or non-ionic surfactants. The experimental results demonstrated the existence of two distinct co-stabilisation mechanisms that arise from interactions of the nanoparticles and surfactant molecules. When significant interaction is not involved, independent competitive adsorption of nanoparticles and surfactant molecules occurs spontaneously to stabilise droplets in formation. The adsorption/desorption equilibrium between surfactant molecules determines the longevity of the droplet stability. When the surfactant molecule reacts with the nanoparticle surface, the resultant surface modification appears to generate faster wetting kinetics for nanoparticles at the oil/water interface and yields enhanced stabilisation. The paper discusses the implications of controlling these interactions for emulsion production membrane systems.

Identification of the degradation mechanisms of organic solar cells:active layer and interfacial layers

Organic Solar Cells (OSCs) represent a photovoltaic technology with multiple interesting application properties. However, the establishment of this technology into the market is subject to the achievement of operational lifetimes appropriate to their application purposes. Thus, comprehensive understanding of the degradation mechanisms occurring in OSCs is mandatory in both selecting more intrinsically stable components and/or device architectures and implementing strategies that mitigate the encountered stability issues. Inverted devices can suffer from mechanical stress and delamination at the interface between the active layer, e.g. poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM), and the hole transport layer, e.g. poly(3,4-ethylenedioxythiophene):poly(p-styrene sulfonate) (PEDOT:PSS). This work proposes the incorporation of a thin adhesive interlayer, consisting of a diblock copolymer composed of a P3HT block and a thermally-triggerable, alkyl-protected PSS block. In this context, the synthesis of poly(neopentyl p-styrene sulfonate) (PNSS) with controlled molar mass and low dispersity (Ð ≤ 1.50) via Reversible Addition-Fragmentation chain Transfer (RAFT) polymerisation has been extensively studied. Subsequently, Atomic Force Microscopy (AFM) was explored to characterise the thermal deprotection of P3HT-b-PNSS thin layers to yield amphiphilic P3HT-b-PSS, indicating that surface deprotection prior to thermal treatment could occur. Finally, structural variation of the alkyl protecting group in PSS allowed reducing the thermal treatment duration from 3 hours (P3HT-b-PNSS) to 45 minutes for the poly(isobutyl p-styrene sulfonate) (PiBSS) analogous copolymer. Another critical issue regarding the stability of OSCs is the sunlight-driven chemical degradation of the active layer. In the study herein, the combination of experimental techniques and theoretical calculations has allowed identification of the structural weaknesses of poly[(4,4’- bis(2-ethylhexyl) dithieno [3,2-b:2’,3’-d]silole)-2,6-diyl-alt-(4,7-bis(2-thienyl)-2,1,3-benzothiadiazole)-5,5’-diyl], Si-PCPDTBT, upon photochemical treatment in air. Additionally, the study of the relative photodegradation rates in air of a series of polymers with systematically modified backbones and/or alkyl side chains has shown no direct correlation between chemical structure and stability. It is proposed instead that photostability is highly dependent on the crystalline character of the deposited films. Furthermore, it was verified that photostability of blends based on these polymers is dictated by the (de)stabilising effect that [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) has over each polymer. Finally, a multiscale analysis on the degradation of solar cells based on poly[4,4' bis(2- ethylhexyl) dithieno[3,2-b:2',3'-d]silole)-2,6-diyl-alt-[2,5 bis(3 tetradecylthiophen 2-yl)thiazole[5,4-d]thiazole)-1,8-diyl] and PCBM, indicated that by judicious selection of device layers, architectures, and encapsulation materials, operational lifetimes up to 3.3 years with no efficiency losses can be successfully achieved.