Light scattering study of human serum albumin in pre-denaturation:relation to dynamic transition in water at 42°C

Protein functional motions are ultimately connected to water dynamics. The goal of this study is to link the conformational dynamics of albumin to a dynamic transition taking place at ∼ 42°C in water. We report the results of dynamic light scattering measurements of albumin aqueous solution in the temperature interval 20-65°C. The processing of the experimental data produced the temperature dependence of the macromolecular hydrodynamic radius. We demonstrate that the growth of the macromolecular size in this temperature range can be divided into two stages that are connected to the dynamical properties of water. © 2012 Elsevier B.V. All rights reserved.

The transition from severe to mild wear in law alloy steel

The wear rates of sliding surfaces are significantly reduced if mild oxidational wear can be encouraged. It is hence of prime importance in the interest of component life and material conservation to understand the factors necessary to promote mild, oxidational wear, The present work investigates the fundamental mechanism of the running-in wear of BS EN 31!EN 8 steel couples. under various conditions of load. speed and test duration. Unidirectional sliding experiments were carried out on a pin-on~disc wear machine where frictional force, wear rate, temperature and contact resistance were continuously monitored during each test. Physical methods of analysis (x-ray, scanning electron microscopy etc.) were used to examine the wear debris and worn samples. The wear rate versus load curves revealed mild wear transitions, which under long duration of running, categorized mild wear into four distinct regions.α-Fe20s. Fe304, FeO and an oxide mixture were the predominant oxides in four regions of oxidational wear which were identified above the Welsh T2 transition. The wear curves were strongly effected by the speed and test duration. A surface model was used to calculate the surface parameters, and the results were found to be comparable with the experimentally observed parameters. Oxidation was responsible for the transition from severe to mild wear at a load corresponding to the Welsh T2 transition. In the running-in period sufficient energy input and surface hardness enabled oxide growth rate to increase and eventually exceeded the rate of removal, where mild wear ensued. A model was developed to predict the wear volume up to the transition. Remarkable agreement was found between the theoretical prediction and the experimentally-measured values. The oxidational mechanjsm responsible for transitjon to mild wear under equilibrium conditions was related to the formation of thick homogenous oxide plateaux on subsurface hardened layers, FeO was the oxide formed initially at the onset of mild wear but oxide type changed.during the total running period to give an equilibrium oxide whose nature depended on the loads applied.

The challenges faced by reporting entities on their transition to international financial reporting standards:a qualitative study

This study explores the challenges of implementing International Financial Reporting Standards (IFRS) at the organisational level. Based on interviews with experts with aggregated experience relating to the transition projects of over 170 reporting entities, this paper highlights the main challenges in delivering a successful implementation of IFRS. The findings show that the problems faced in implementation include lack of education and training, securing executive-level support, identifying and responding to the wider business-related implications of the transition, and issues with capturing the necessary information for reporting under IFRS.This paper complements the existing literature and offers a qualitative alternative to considering the transition to IFRS, offering insight into the organisational context of IFRS implementation. These insights are useful not only from a historic perspective, but also for organisations and regulators in the many jurisdictions where IFRS is permitted but not required, where more reporting entities will voluntarily move to IFRS-based reporting in the future. More broadly, they are also applicable to the challenges faced in implementing new and significantly revised IFRSs.

Laminar-turbulent transition in Raman fiber lasers:a first passage statistics based analysis

Loss of coherence with increasing excitation amplitudes and spatial size modulation is a fundamental problem in designing Raman fiber lasers. While it is known that ramping up laser pump power increases the amplitude of stochastic excitations, such higher energy inputs can also lead to a transition from a linearly stable coherent laminar regime to a non-desirable disordered turbulent state. This report presents a new statistical methodology, based on first passage statistics, that classifies lasing regimes in Raman fiber lasers, thereby leading to a fast and highly accurate identification of a strong instability leading to a laminar-turbulent phase transition through a self-consistently defined order parameter. The results have been consistent across a wide range of pump power values, heralding a breakthrough in the non-invasive analysis of fiber laser dynamics.

Parenting a child with chronic illness as they transition into adulthood:a systematic review and thematic synthesis of parents’ experiences

Objective - To understand how parents view and experience their role as their child with a long-term physical health condition transitions to adulthood and adult healthcare services. Methods - Five databases were systematically searched for qualitative articles examining parents’ views and experiences of their child’s healthcare transition. Papers were quality assessed and thematically synthesised. Results - Thirty-two papers from six countries, spanning a 17-year period were included. Long-term conditions were diverse. Findings indicated that parents view their child’s progression toward self-care as an incremental process which they seek to facilitate through up-skilling them in self-management practices. Parental perceptions of their child’s readiness, wellness, competence and long-term condition impacted on the child’ progression to healthcare autonomy. A lack of transitional healthcare and differences between paediatric and adult services served as barriers to effective transition. Parents were required to adjust their role, responsibilities and behaviour to support their child’s growing independence. Conclusion - Parents can be key facilitators of their child’s healthcare transition, supporting them to become experts in their own condition and care. To do so, they require clarification on their role and support from service providers. Practice Implications - Interventions are needed which address the transitional care needs of parents as well as young people.

Investigating optical complexity of the phase transition in the intensity of a fibre laser radiation

Fibre lasers have been shown to manifest a laminar-to-turbulent transition when increasing its pump power. In order to study the dynamical complexity of this transition we use advanced statistical tools of time-series analysis. We apply ordinal analysis and the horizontal visibility graph to the experimentally measured laser output intensity. This reveal the presence of temporal correlations during the transition from the laminar to the turbulent lasing regimes. Both methods allow us to unveil coherent structures with well defined time-scales and strong correlations both, in the timing of the laser pulses and in their peak intensities.

Ireland and immigration: explaining the absence of the far right

Garner seeks to explain the absence of far-right political formations in the history of the Republic of Ireland, especially in relation to immigration. He argues that the ‘mainstream’ nationalist parties have implemented a racialized governance of Ireland via the issue of citizenship (in the referendum of 2004). While hegemonic ideas on the racial purity of indigenous populations and the highly ambivalent attitudes and policies on immigration pursued over the last decade are characteristic of a broader European trend, this has not, in the Republic, been accompanied by meaningful far-right political mobilization. Ireland has frequently been seen as sui generis in political terms, and indeed emerges in some ways as a counter-case: increasing hostility towards Others has been identified in the midst of rapid economic growth and political stability. A variety of issues related to the country’s political development have given rise to an especially small left-wing vote, a nationalist centre ground and longlasting domination by a single populist party, Fianna Fa´ il. This party has been partnered in government since 1997 by a free-market party, the Progressive Democrats, who have contributed to Ireland’s movement towards neo-liberal policies and a highly functional approach to immigration. The transition from country of emigration to country of immigration has thus taken place against an ideological backdrop in which the imperatives of labour demand and consolidating domestic support for reform have made an uneasy match, resulting in the racialization of Irishness. The state has, however, amended the Constitution in order to qualify jus soli citizenship entitlement in the case of particular categories of people: those whose parents are not Irish nationals. The significant stakes of these changes are analysed in the context of state responses to Eire’s transition to a country of immigration, and the role of nationalist-populism in the country’s political culture.

Minimizing unsatisfaction in colourful neighbourhoods

Colouring sparse graphs under various restrictions is a theoretical problem of significant practical relevance. Here we consider the problem of maximizing the number of different colours available at the nodes and their neighbourhoods, given a predetermined number of colours. In the analytical framework of a tree approximation, carried out at both zero and finite temperatures, solutions obtained by population dynamics give rise to estimates of the threshold connectivity for the incomplete to complete transition, which are consistent with those of existing algorithms. The nature of the transition as well as the validity of the tree approximation are investigated.

Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor ?B signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3ß (GSK3ß) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3ß inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ß-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

Dielectric and electro-optical properties of some cyanobiphenyl liquid-crystals

A variety of methods have been reviewed for obtaining parallel or perpendicular alignment in liquid-crystal cells. Some of these methods have been selected and developed and were used in polarised spectroscopy, dielectric and electro-optic studies. Also, novel dielectric and electro-optic cells were constructed for use over a range of temperature. Dielectric response of thin layers of E7 and E8 (eutectic mixture liquid-crystals) have been measured in the frequency range (12 Hz-100 kHz) and over a range of temperature (183-337K). Dielectric spectra were also obtained for supercooled E7 and E8 in the Hz and kHz range. When the measuring electric field was parallel to the nematic director, one loss peak (low-frequency relaxation process) was observed for E7 and for E8, that exhibits a Debye-type behaviour in the supercooled systems. When the measuring electric field was perpendicular to the nematic director, two resolved dielectric processes have been observed. The phase transitions, effective molecular polarisabilities, anisotropy of polarisabilities and order parameters of three liquid crystal homologs (5CB, 6CB, and 7CB), 60CB and three eutectic nematic mixtures E7, E8, and E607 were calculated using optical and density data measured at several temperatures. The order parameters calculated using the different methods of Vuks, Neugebauer, Saupe-Maier, and Palffy-Muhoray are nearly the same for the liquid crystals considered in the present study. Also, the interrelationship between density and refractive index and the molecular structure of these liquid crystals were established. Accurate dielectric and dipole results of a range of liquid-crystal forming molecules at several temperatures have reported. The role of the cyano-end group, biphenyl core, and flexible tail in molecular association, were investigated using the dielectric method for some molecules which have a structural relationship to the nematogens. Analysis of the dielectric data for solution of the liquid-crystals indicated a high molecular association, comparable to that observed in the nematic or isotropic phases. Electro-optic Kerr effect were investigated for some alkyl cyanobiphenyls, their nematic mixtures and the eutectic mixture liquid-crystals E7 and E8 in the isotropic phase and solution. The Kerr constant of these liquid crystals found to be very high at the nematic-isotropic transition temperatures as the molecules are expected to be highly ordered close to phase transition temperatures. Dynamic Kerr effect behaviour and transient molecular reorientation were also observed in thin layers of some alkyl cyanobiphenyls. Dichroic ratio R and order parameters of solutions containing some azo and anthraquinone dyes in the nematic solvent (E7 and E8), were investigated by the measurement of the intensity of the absorption bands in the visible region of parallel aligned samples. The effective factors on the dichroic ratio of the dyes dissolved in the nematic solvents were determined and discussed.

The effect of flow regimes in the distillation of systems containing two liquid phases

Single phase solutions containing three components have been observed to exhibit foaminess near a single to two liquid phase boundary. It was seen, in a sintered plate column under mass transfer conditions, that distillation systems where the liquid appeared as one phase in one part of a column and two phases in another part, exhibited foaminess when the liquid concentration was near the one phase to two phase boundary. Various ternary systems have been studied in a 50 plate. 30mm i.d. Oldershaw column and it was observed that severe foaming occurred in the middle section of the column near the one liquid phase to two liquid phase boundary and no foaming occurred at the end of the column where liquid was either one phase or two phase. This is known as Ross type foam. Mass transfer experiments with Ross type ternary systems have been carried out in a perspex simulator with small and large hole diameter trays. It was observed that by removal of the more volatile component, Ross type foam did not build up on the tray. Severe entrainment of liquid was observed in all cases leading to a 'dry' tray, even with a low free area small diameter hole tray which was expected to produce a bubbly mixture. Entrainment was more severe for high gas superficial velocities and large hole diameters. This behaviour is quite different from the build up of foam observed when one liquid phase/two liquid phase Ross systems were contacted with air above a small sintered disc or with vapour in an Oldershaw distillation column. This observation explains why distillation columns processing mixtures which change from one liquid phase to two liquid phases (or vice versa) must be severely derated to avoid flooding. Single liquid phase holdups at the spray to bubbly transition were measured using a perspex simulator similar to that of Porter & Wong (17). i.e. with no liquid cross flow. A light transmission technique was used to measure the transition from spray regime to bubbly regime. The effect of tray thickness and the ratio of hole diameter to tray thickness on the transition was evaluated using trays of the same hole diameter and free area but having thickness of 2.38 mm, 4 mm, and 6.35 mm. The liquid holdup at the transition was less with the thin metal trays. This result may be interpreted by the theory of Lockett (101), which predicts the transition liquid holdup in terms of the angle of the gas iet leaving the holes in the sieve plate. All the existing correlations have been compared and none were found to be satisfactory and these correlations have been modified in view of the experimental results obtained. A new correlation has been proposed which takes into account the effect of the hole diameter to tray thickness ratio on the transition and good agreement was obtained between the experimental results and the correlated values of the liquid holdup at the transition. Results have been obtained for two immiscible liquids [kerosene and water] on trays to determine whether foaming can be eliminated by operating in the spray regime. Kerosene was added to a fixed volume of water or water was added to a fixed volume of kerosene. In both cases, there was a transition from spray to bubbly. In the water fixed system. the liquid holdup at the transition was slightly less than the pure kerosene system. Whilst for the kerosene fixed system, the transition occurred at much lower liquid holdups. Trends In the results were similar to those for single liquid phase. New correlations have been proposed for the two cases. It has been found that Ross type foams, observed in a sintered plate column and in the Oldershaw column can be eliminated by either carrying out the separation in a packed column or by the addition of defoaming additives.

A study of the calcium-induced morphological transistions of human erythrocytes

An examination was made of the morphological transitions induced in human erythrocytes by the elevation of cytosolic calcium, and of the biochemical mechanisms responsible. The loss of the discocyte morphology and the sequential progression of cells through the echinocyte stages 1, 2, 3 and sphereo-echinocyte was found to occur in both a calcium concentration- and a time-dependent manner. SDS-PAGE analysis of cytoskeletal proteins prepared from intact cells loaded with 150uM or 1mM calcium revealed the partial proteolytic loss of proteins 2.1, 2.2 and 4.1. The rate of proteolysis was not paralleled by that of echinocytosis, making a causative relationship unlikely. Cytoskeletal integrity did appear to influence shape reversal from the echinocyte to the discocyte morphology after removal of the calcium and ionophore A23187. The loss of 80% protein 4.1, 40% 2.1 and 30% 2.2 was associated with, although not necessarily the sole cause, of irreversible sphereo-echinocytosis. Pre-treatment of cells with wheat germ agglutinin preserved the discocyte morphology despite continued cytoskeletal proteolysis during calcium-loading. All observations were made on cells incubated either in the presence or absence of glycolytic substrates, effectively altering cell metabolic status. This influenced the rate of progression of cells through the echinocyte stages, the rate of proteolysis of cytoskeletal proteins, and the extent and kinetics of shape reversal from cells transformed to the sphereo-echinocyte morphology. The stage 1 to discocyte transition was the rate limiting step of this shape recovery. In contrast the rate of loss of the discocyte morphology was independent of cell metabolic status during exposure to calcium, as was the extent of restoration of the discocyte morphology from cells transformed to stage 1 echinocytes. An hypothesis is presented that echinocytosis is a discontinuous process with discrete steps initiated by different biochemical mechanisms varying in their dependence on metabolic energy.

Theoretical modelling of the sulcated spring

Replacement of the traditional coil spring with one of more fibre-reinforced plastic sulcated springs is a future possibility. Spring designers of metallic coil springs have design formulae readily available, and software packages specific to coil spring design exist. However, the sulcated spring is at the prototype stage of development, so literature on these springs is very sparse. The thesis contains information on the market for sulcated springs, and their advantages and disadvantages. Literature on other types of fibre reinforced plastic springs has also been reviewed. Design software has been developed for the sulcated spring along similar lines to coil spring design software. In order to develop the software, a theoretical model had to be developed which formed the mathematical basis for the software. The theoretical model is based on a choice of four methods for calculating the flexural rigidity; beam theory, plate theory, and lamination theory assuming isotropic and orthoropic material properties. Experimental results for strain and spring stiffness have been compared with the theoretical model, and were in good agreement. Included in the design software are the results of experimental work on fatigue, and design limiting factors to prevent or warn against impractical designs. Finite element analysis has been used to verify the theoretical model developed, and to find the better approximation to the experimental results. Applications and types of assemblies for the sulcated spring were discussed. Sulcated spring designs for the automotive applications of a suspension, clutch and engine valve spring were found using the design computer software. These sulcated spring designs were within or close to the space of the existing coil spring and yield the same performance. Finally the commercial feasibility of manufacturing the sulcated spring was assessed and compared with the coil spring, to evaluate the plausibility of the sulcated spring replacing the coil spring eventually.

A method for the in-situ determination of the hydraulic conductivity of gravels as used in constructed wetlands for wastewater treatment

A new instrument and method are described that allow the hydraulic conductivities of highly permeable porous materials, such as gravels in constructed wetlands, to be determined in the field. The instrument consists of a Mariotte siphon and a submersible permeameter cell with manometer take-off tubes, to recreate in-situ the constant head permeameter test typically used with excavated samples. It allows permeability to be measured at different depths and positions over the wetland. Repeatability obtained at fixed positions was good (normalised standard deviation of 1–4%), and results obtained for highly homogenous silica sand compared well when the sand was retested in a lab permeameter (0.32 mm.s–1 and 0.31 mm.s–1 respectively). Practical results have a ±30% associated degree of uncertainty because of the mixed effect of natural variation in gravel core profiles, and interstitial clogging disruption during insertion of the tube into the gravel. This error is small, however, compared to the orders of magnitude spatial variations detected. The technique was used to survey the hydraulic conductivity profile of two constructed wetlands in the UK, aged 1 and 15 years respectively. Measured values were high (up to 900 mm.s –1) and varied by three orders of magnitude, reflecting the immaturity of the wetland. Detailed profiling of the younger system suggested the existence of preferential flow paths at a depth of 200 mm, corresponding to the transition between more coarse and less coarse gravel layers (6–12 mm and 3–6 mm respectively), and transverse drift towards the outlet.

Understanding the link between transglutaminase and the induction of fibrosis in cystic fibrosis (CF)

The emerging role of the multifunctional enzyme, Transglutaminase 2 (TG2) in Cystic Fibrosis (CF) has been linked to its increased expression and intracellular transamidating activity. However, a full understanding of the molecular mechanisms involved still remains unclear despite numerous studies that have attempted to delineate this process. These mechanisms include the NFκB and TGFβ1 pathway amongst others. This study reveals for the first time that the development of fibrosis in CF is due to a TG2-driven epithelial to mesenchymal transition (EMT) via a mechanism involving the activation of the pro-fibrotic cytokine TGFβ1. Using a human ΔF508/W1282X CFTR CF mutant bronchial cell (IB3-1), its CFTR corrected “add-back” cell (C38) as well as a primary human bronchial epithelial cell (HBEC), elevated TG2 levels in the CFTR mutant IB3 cell were shown to activate latent TGFβ1 leading to increased levels found in the culture medium. This activation process was blocked by the presence of cell-permeable and impermeable TG2 inhibitors while inhibition of TGFβ1 receptors blocked TG2 expression. This demonstrates the direct link between TG2 and TGFβ1 in CF. The presence of active cell surface TG2 correlated with an increase in the expression of EMT markers, associated with the CF mutant cells, which could be blocked by the presence of TG2 inhibitors. This was mimicked using the “addback” C38 cell and the primary human bronchial epithelial cell, HBEC, where an increase in TG2 expression and activity in the presence of TGFβ1 concurred with a change in cell morphology and an elevation in EMT marker expression. Conversely, a knockdown of TG2 in the CF mutant IB3 cells illustrated that an inhibition of TG2 blocks the increase in EMT marker expression as well as causing an increase in TEER measurement. This together with an increase in the migration profile of the CF mutant IB3 cell against the “add-back” C38 cell suggests that TG2 drives a mesenchymal phenotype in CF. The involvement of TG2 activated TGFβ1 in CF was further demonstrated with an elevation/inhibition of p- SMAD 2 and 3 activation in the presence of TGFβ1/TG2 cell-permeable/impermeable inhibitors respectively. The use of a comparative airway cell model where bronchial epithelial cells were cultured at the air liquid interface (ALI) confirmed the observations in submerged culture depicting the robustness of the model and reiterated the importance of TG2 in CF. Using a CFTR corrector combined with TG2 inhibitors, this study showed that the correction and stabilisation of the ΔF508 CFTR mutation in the mutant cell forged an increase in matured CFTR copies trafficking to the apical surface by circumventing proteosomal degradation. Thus the results presented here suggests that TG2 expression is elevated in the CFTR mutant bronchial cell via a TGFβ1 driven positive feedback cycle whereby activation of latent TGFβ1 by TG2 leads in turn to an elevation in its own expression by TGFβ1. This vicious cycle then drives EMT in CF ultimately leading to lung remodelling and fibrosis. Importantly, TG2 inhibition blocks TGFβ1 activation leading to an inhibition of EMT and further blocks the emerging fibrosis, thus stabilizing and supporting the maturation, trafficking and conductance of CFTR channels at the apical surface.