Effect of osmolytes on the interaction of flavin adenine dinucleotide with muscle glycogen phosphorylase b

The effect of three osmolytes, trimethylamine N-oxide (TMAO), betaine and proline, on the interaction of muscle glycogen phosphorylase b with allosteric inhibitor FAD has been examined. In the absence of osmolyte, the interaction is described by a single intrinsic dissociation constant (17.8 muM) for two equivalent and independent binding sites on the dimeric enzyme. However, the addition of osmolytes gives rise to sigmoidal dependencies of fractional enzyme-site saturation upon free inhibitor concentration. The source of this cooperativity has been shown by difference sedimentation velocity to be an osmolyte-mediated isomerization of phosphorylase b to a smaller dimeric state with decreased affinity for FAD. These results thus have substantiated a previous inference that the tendency for osmolyte-enhanced self-association of dimeric glycogen phosphorylase b in the presence of AMP was being countered by the corresponding effect of molecular crowding on an isomerization of dimer to a smaller, nonassociating state. (C) 2004 Elsevier Ltd. Inc. All rights reserved.

FT-Raman studies of a range of polyimides subjected to high-energy Radiations at room and elevated temperatures

A range of polyimides have been subjected to electron beam radiolysis at different temperatures. These polyimides were chemically designed to suit space applications, being either transparent or having groups which provide oxidation resistance. The structural changes that occur in the polyimides, when subjected to electron beam irradiation doses up to 18.5 MGy and up to temperatures close to their glass transition temperatures, were studied using FT-Raman spectroscopy. The range of polyimides studied included a series of perfluoropolyimides, a silicon-modified polyimide, and Ultem. The changes in the Raman peak intensities of the different groups indicated scission reactions involving the imide rings and ether linkages. (c) 2006 Wiley Periodicals, Inc.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

1 Hypoxic pulmonary hypertension in rats (10% O-2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 Perindopril (30 mg kg(-1) d(-1)) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5 We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

Data quality initiatives - striving for continuous improvements

Although managers consider accurate, timely, and relevant information as critical to the quality of their decisions, evidence of large variations in data quality abounds. Over a period of twelve months, the action research project reported herein attempted to investigate and track data quality initiatives undertaken by the participating organisation. The investigation focused on two types of errors: transaction input errors and processing errors. Whenever the action research initiative identified non-trivial errors, the participating organisation introduced actions to correct the errors and prevent similar errors in the future. Data quality metrics were taken quarterly to measure improvements resulting from the activities undertaken during the action research project. The action research project results indicated that for a mission-critical database to ensure and maintain data quality, commitment to continuous data quality improvement is necessary. Also, communication among all stakeholders is required to ensure common understanding of data quality improvement goals. The action research project found that to further substantially improve data quality, structural changes within the organisation and to the information systems are sometimes necessary. The major goal of the action research study is to increase the level of data quality awareness within all organisations and to motivate them to examine the importance of achieving and maintaining high-quality data.

Vibrational dynamics and structure of natural feldspars

The present study gives a contribution to the knowledge on the Na-feldspar and plagioclases, extending the database of the Raman spectra of plagioclases with different chemical compositions and structural orders. This information may be used for the future planetary explorations by “rovers”, for the investigation of ceramics nanocrystal materials and for the mineralogical phase identification in sediments. Na-feldspar and plagioclase solid solution have been investigated by Raman spectroscopy in order to determine the relationships between the vibrational changes and the plagioclase crystal chemistry and structure. We focused on the Raman micro-spectroscopy technique, being a non-destructive method, suited for contactless analysis with high spatial resolution. Chemical and structural analyses have been performed on natural samples to test the usefulness of Raman spectroscopy as a tool in the study of the pressure-induced structural deformations, the disordering processes due to change in the Al-Si distribution in the tetrahedral sites and, finally, in the determination of the anorthitic content (Anx) in plagioclase minerals. All the predicted 39 Ag Raman active modes have been identified and assigned to specific patterns of atomic vibrational motion. A detailed comparison between experimental and computed Raman spectra has been performed and previous assignments have been revised, solving some discrepancies reported in recent literature. The ab initio calculation at the hybrid HF/DFT level with the WC1LYP Hamiltonian has proven to give excellent agreement between calculated and experimentally measured Raman wavenumbers and intensities in triclinic minerals. A short digression on the 36 infrared active modes of Na-feldspar has been done too. The identification of all 39 computed Raman modes in the experimentally measured spectra of the fully ordered Na-feldspar, known as low albite, along with the detailed description of each vibrational mode, has been essential to extend the comparative analysis to the high pressure and high temperature structural forms of albite, which reflect the physical–chemical conditions of the hosting rocks. The understanding of feldspar structure response to pressure and temperature is crucial in order to constrain crustal behaviour. The compressional behaviour of the Na-feldspar has been investigated for the first time by Raman spectroscopy. The absence of phase transitions and the occurrence of two secondary compression mechanisms acting at different pressures have been confirmed. Moreover, Raman data suggest that the internal structural changes are confined to a small pressure interval, localized around 6 GPa, not spread out from 4 to 8 GPa as suggested by previous X-rays studies on elasticity. The dominant compression mechanisms act via tetrahedral tilting, while the T-O bond lengths remain nearly constant at moderate compressional regimes. At the spectroscopic level, this leads to the strong pressure dependencies of T-O-T bending modes, as found for the four modes at 478, 508, 578 and 815 cm-1. The Al-Si distribution in the tetrahedral sites affects also the Raman spectrum of Na-feldspar. In particular, peak broadening is more sensitive than peak position to changes in the degree of order. Raman spectroscopy is found to be a good probe for local ordering, in particular being sensitive to the first annealing steps, when the macroscopic order parameter is still high. Even though Raman data are scattered and there are outliers in the estimated values of the degree of order, the average peak linewidths of the Na-feldspar characteristic doublet band, labelled here as υa and υb, as a function of the order parameter Qod show interesting trends: both peak linewidths linearly increase until saturation. From Qod values lower than 0.6, peak broadening is no more affected by the Al-Si distribution. Moreover, the disordering process is found to be heterogeneous. SC-XRD and Raman data have suggested an inter-crystalline inhomogeneity of the samples, i.e., the presence of regions with different defect density on the micrometric scale. Finally, the influence of Ca-Na substitution in the plagioclase Raman spectra has been investigated. Raman spectra have been collected on a series of well characterized natural, low structural plagioclases. The variations of the Raman modes as a function of the chemical composition and the structural order have been determined. The number of the observed Raman bands at each composition gives information about the unit-cell symmetry: moving away from the C1 structures, the number of the Raman bands enhances, as the number of formula units in the unit cell increases. The modification from an “albite-like” Raman spectrum to a more “anorthite-like” spectrum occurs from sample An78 onwards, which coincides with the appearance of c reflections in the diffraction patterns of the samples. The evolution of the Raman bands υa and υb displays two changes in slope at ~An45 and ~An75: the first one occurs between e2 and e1 plagioclases, the latter separates e1 and I1 plagioclases with only b reflections in their diffraction patterns from I1 and P1 samples having b and c reflections too. The first variation represents exactly the e2→e1 phase transitions, whereas the second one corresponds in good approximation to the C1→I1 transition, which has been determined at ~An70 by previous works. The I1→P1 phase transition in the anorthite-rich side of the solid solution is not highlighted in the collected Raman spectra. Variations in peak broadening provide insights into the behaviour of the order parameter on a local scale, suggesting an increase in the structural disorder within the solid solution, as the structures have to incorporate more Al atoms to balance the change from monovalent to divalent cations. All the information acquired on these natural plagioclases has been used to produce a protocol able to give a preliminary estimation of the chemical composition of an unknown plagioclase from its Raman spectrum. Two calibration curves, one for albite-rich plagioclases and the other one for the anorthite-rich plagioclases, have been proposed by relating the peak linewidth of the most intense Raman band υa and the An content. It has been pointed out that the dependence of the composition from the linewidth can be obtained only for low structural plagioclases with a degree of order not far away from the references. The proposed tool has been tested on three mineralogical samples, two of meteoric origin and one of volcanic origin. Chemical compositions by Raman spectroscopy compare well, within an error of about 10%, with those obtained by elemental techniques. Further analyses on plagioclases with unknown composition will be necessary to validate the suggested method and introduce it as routine tool for the determination of the chemical composition from Raman data in planetary missions.

FORMAÇÃO DE PROFESSORES EM SERVIÇO: UMA EXPERIÊNCIA DA REDE MUNICIPAL DE EDUCAÇÃO DE SÃO PAULO INICIADA NO GOVERNO ERUNDINA

Este trabalho de pesquisa trata da política voltada para a formação continuada em serviço docente cujo período de implantação aconteceu entre 1989 e 1992 na cidade de São Paulo, durante a administração da prefeita Luíza Erundina, que teve à frente da Secretaria Municipal de Educação, nos anos iniciais de sua gestão, o professor Paulo Freire. Tal política marcou o início do processo de consolidação de conquistas, como resultado de longa luta de muitos educadores brasileiros por mudanças na educação. Erundina e Freire representaram a possibilidade da concretização de transformações estruturais na educação em um período de grande efervescência política da sociedade brasileira. A conquista de um espaço para formação na escola, de forma democrática e com a participação dos docentes representava uma das grandes bandeiras desta luta. Para melhor compreensão do processo de implantação desta política de formação docente em serviço, optamos por realizar uma pesquisa qualitativa a partir de documentos e estudo bibliográfico seguida de uma pesquisa de campo a partir de um pequeno roteiro de questões que serviram como ponto de partida para a realização de um círculo epistemológico, envolvendo educadores que de alguma forma participaram desta política; buscando compor, dessa maneira, um panorama das concepções que deram sustentação a esta política pública possibilitando uma análise das ações que foram desenvolvidas.

Autonomia de Gestão dos Agrupamentos dos Centros de Saúde

The National Health Service is one of the portuguese social progress pillars and as a key role in terms of health services, organized around a universal service, general and tend to free, provided for the Portuguese Republic Constitution, in order to promote people's access to health care,adequate and adaptively to their needs and expectations, seeking economic efficiency in a control context of public expenditure and budget. Primary Health Care are considered fundamental piece for the National Health Service, as they are the first users accessibility to health care, being the health center a unit to serve and providing the essential first treatments, preventive and/or curative, assuming important functions of promotion of health and prevention of disease, cooperating with other services for continuity of caring. The implementation of the Health Centers Groupings aims to decentralize the management and allow decision making on key resources to the provision of care, absorbing the district offices of the extinct Health Sub-Regions and having the task of ensuring the provision of health care primary the population of a given geographical area, based on a multidisciplinary team with organization and technical autonomy and is guaranteed intercooperation with other functional units. However, these district offices were attached to the Regional Health Administrations following the reverse path, causing dysfunctional positions and making health centers Groupings their dependents. Thus, before the reform of Primary Health Care, all the structural changes were made, except to check the Health Centers Groupings proper management autonomy, currently one of the biggest obstacles to the implementation of such reform. It is intended in this work through a inquiry by forms done at 21 Health Centers Groupings North Regional Health Authority, IP, evidence can the management autonomy in Health Centers Groupings provide greater efficiency in the provision of Primary health Care to citizens and ensure greater sustainability of the National health Service, better managing existing resources, human and financial, showing a growing responsibility in its management and ensuring appropriate practices, more quality in health care and better accessibility, providing the ability to apply more adjusted measures in providing health care to the population of their geographical área.

Exchange rate exposure : do size and foreign operations matter?

Purpose – The purpose of this paper is to examine the effect of firm size and foreign operations on the exchange rate exposure of UK non-financial companies from January 1981 to December 2001. Design/methodology/approach – The impact of the unexpected changes in exchange rates on firms’ stock returns is examined. In addition, the movements in bilateral, equally weighted (EQW) and trade-weighted and exchange rate indices are considered. The sample is classified according to firm size and the extent of firms’ foreign operations. In addition, structural changes on the relationship between exchange rate changes and individual firms’ stock returns are examined over three sub-periods: before joining the exchange rate mechanism (pre-ERM), during joining the ERM (in-ERM), and after departure from the ERM (post-ERM). Findings – The findings indicate that a higher percentage of UK firms are exposed to contemporaneous exchange rate changes than those reported in previous studies. UK firms’ stock returns are more affected by changes in the EQW, and US$ European currency unit exchange rate, and respond less significantly to the basket of 20 countries’ currencies relative to the UK pound exchange rate. It is found that exchange rate exposure has a more significant impact on stock returns of the large firms compared with the small and medium-sized companies. The evidence is consistent across all specifications using different exchange rate. The results provide evidence that the proportion of significant foreign exchange rate exposure is higher for firms which generate a higher percentage of revenues from abroad. The sensitivities of firms’ stock returns to exchange rate fluctuations are most evident in the pre-ERM and post-ERM periods. Practical implications – This study provides important implications for public policymakers, financial managers and investors on how common stock returns of various sectors react to exchange rate fluctuations. Originality/value – The empirical evidence supports the view that UK firms’ stock returns are affected by foreign exchange rate exposure.

Tailored laminin-332 alpha3 sequence is tethered through an enzymatic linker to a collagen scaffold to promote cellular adhesion

Surface modification techniques have been used to develop biomimetic scaffolds by incorporating cell adhesion peptides, which facilitates cell adhesion, migration and proliferation. In this study, we evaluated the cell adhesion properties of a tailored laminin-332 alpha3 chain tethered to a type I collagen scaffold using microbial transglutaminase (mTGase) by incorporating transglutaminase substrate peptide sequences containing either glutamine (peptide A: PPFLMLLKGSTREAQQIVM) or lysine (peptide B: PPFLMLLKGSTRKKKKG). The degree of cross-linking was studied by amino acid analysis following proteolytic digestion and the structural changes in the modified scaffold further investigated using Fourier transform infrared spectroscopy and atomic force microscopy. Fibroblasts were used to evaluate the cellular behaviour of the functionalized collagen scaffold. mTGase supports cell growth but tethering of peptide A and peptide B to the mTGase cross-linked collagen scaffold caused a significant increase in cell proliferation when compared with native and mTGase cross-linked collagen scaffolds. Both peptides enabled cell-spreading, attachment and normal actin cytoskeleton organization with slight increase in the cell proliferation was observed in peptide A when compared with the peptide B and mTGase cross-linked scaffold. An increase in the amount of epsilon(gamma-glutamyl) lysine isopeptide was observed in peptide A conjugated scaffolds when compared with peptide B conjugated scaffolds, mTGase cross-linked scaffold without peptide. Changes in D-spacing were observed in the cross-linked scaffolds with tethered peptides. These results demonstrate that mTGase can play a bifunctional role in both conjugation of the glutamine and lysine containing peptide sequences and also in the cross-linking of the collagen scaffold, thus providing a suitable substrate for cell growth.

Effect of sample preparation on the thermal degradation of metal-added biomass

The present study investigates the effect of different sample preparation methods on the pyrolysis behaviour of metal-added biomass; Willow samples were compared in the presence of two salts of zinc and lead containing sulphate and nitrate anions which were added to the wood samples with three different techniques as dry-mixing, impregnation and ion-exchange. The effect of acid and water wash as common demineralisation pre-treatments were also analysed to evaluate their roles in the thermal degradation of the biomass. Results from thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and pyrolysis-mass spectrometry (Py-MS) measurements indicated that these pre-treatments change the matrix and the physical-chemical properties of wood. Results suggested that these structural changes increase the thermal stability of cellulose during pyrolysis. Sample preparation was also found to be a crucial factor during pyrolysis; different anions of metal salts changed the weight loss rate curves of wood material, which indicates changes in the primary degradation process of the biomass. Results also showed that dry-mixing, impregnation or ion-exchange influence the thermal behaviour of wood in different ways when a chosen metal salt was and added to the wood material. © 2011 Elsevier B.V. All rights reserved.

Strategic innovation networks

This thesis draws on two key areas of the innovation literature, the strategic management of technology (SMOT) and innovation networks. The aim is to integrate these two areas of the management of innovation literature to develop a framework which I describe as the Strategic Innovation Network (SIN). The key proposition that the revised framework (SIN) aims to address is based on the work of Chandler (1962). Chandler's (1962) conclusion that 'structure follows strategy' is examined in relation to the interaction between corporate/technology strategy and network structure. The SIN is intended to address weaknesses in both the SMOT and network literature. The research data is based on five detailed longitudinal case studies. The organisations are defined as mid-corporate firms operating in traditional manufacturing sectors. Each organisation was chosen on the basis that it was aiming to develop its innovative capacity through product or process innovation projects. The research was carried out over an 18 month period with interviews being held regularly to develop the longitudinal aspect of the study analysis. The data for each individual case study is examined using the SIN framework. The longitudinal approach addresses the objective to provide a dynamic model of the innovation processes by mapping the changes in network structure during the course of individual projects. The network structural changes are examined in relation to each organisation's strategy and five key dynamic network stages are identified in relation to the innovation process. These network stages show the influence strategy has on the structures adopted by the five case studies.

The impact of NC machinery upon manufacturing industry

The changing face of industry due to the adoption of `New Technology' is briefly discussed, as are the corresponding structural changes in the workforce. The adoption of NC machinery is identified as one of the major innovations affecting the structure of industry. The development of NC machinery, and of relevant programming techniques are reviewed, and the problems arising from its initial sponsorship by the aerospace industry are highlighted. The process of its subsequent diffusion into industry is reviewed. Skill levels adopted for NC use in Britain and Germany are discussed, and analysed to create a structural pattern. These classifications of skill levels are then used to examine the organisational structures adopted by companies utilising NC machines. The greater use made of higher level shop floor skills by German companies is discussed. The results of two surveys of the use made of NC by companies in the North East of England are presented. Effective company organisation for NC use is described, and lack of foresight is shown to lead to vulnerability problems where skills can become concentrated in a few key people. This led to closure of a company in one instance. It is shown that small sub-contract companies have adopted a highly skilled shop floor workforce, and that they have survived in the present hostile economic environment, whilst companies who have used NC to de-skill the shop floor contracted dramatically in the same period. The lack of awareness of the potential for reviewing the product design in relation to the flexibility of NC, so leading to reductions in work in progress levels, is highlighted. Recommendations for skill structures appropriate to various sized companies and suitable training programs are presented to ensure that the full potential of NC machinery is achieved.

An appraisal of employment problems and policies at the micro-economic level

This study has concentrated on the development of an impact simulation model for use at the sub-national level. The necessity for the development of this model was demonstrated by the growth of local economic initiatives during the 1970's, and the lack of monitoring and evaluation exercise to assess their success and cost-effectiveness. The first stage of research involved the confirmation that the potential for micro-economic and spatial initiatives existed. This was done by identifying the existence of involuntary structural unemployment. The second stage examined the range of employment policy options from the macroeconomic, micro-economic and spatial perspectives, and focused on the need for evaluation of those policies. The need for spatial impact evaluation exercise in respect of other exogenous shocks, and structural changes was also recognised. The final stage involved the investigation of current techniques of evaluation and their adaptation for the purpose in hand. This led to a recognition of a gap in the armoury of techniques. The employment-dependency model has been developed to fill that gap, providing a low-budget model, capable of implementation at the small area level and generating a vast array of industrially disaggregate data, in terms of employment, employment-income, profits, value-added and gross income, related to levels of United Kingdom final demand. Thus providing scope for a variety of impact simulation exercises.

Biometric and physiological factors in human ocular perfusion

By addressing the vascular features that characterise myopia, this thesis aims to provide an understanding of the early structural changes associated with human myopia and the progression to co-morbidity with age. This thesis addresses three main areas of study: 1. Ocular perfusion features and autoregulatory mechanisms in human myopia; 2. Choroidal thickness at the macular area of myopic eyes; 3. Effect of chronic smoking on the ocular haemodynamics and autoregulation. This thesis demonstrated a reduced resting ocular pulse amplitude and retrobulbar blood flow in human myopia, associated with an apparent oversensitivity to the vasodilatory effects of hypercapnia, which may be due to anatomical differences in the volume of the vessel beds. In young smokers, normal resting state vascular characteristics were present; however there also appeared to be increased reactivity to hypercapnia, possibly due to relative chronic hypoxia. The systemic circulation in myopes and smokers over-reacted similarly to hypercapnia suggesting that physiologic differences are not confined to the eye. Age also showed a negative effect on autoregulatory capacity in otherwise normal eyes. Collectively, these findings suggest that myopes and smokers require greater autoregulatory capacity to maintain appropriate oxygenation of retinal tissue, and since the capacity for such regulation reduces with age, these groups are at greater risk of insufficient autoregulation and relative hypoxia with age.