Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells

The progression of renal disease correlates strongly with hypertension and the degree of proteinuria, suggesting a link between excessive Na+ reabsorption and exposure of the proximal tubule to protein. The present study investigated the effects of albumin on cell growth and Na+ uptake in primary cultures of human proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to 134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total Na-22(+) uptake to 119.1 &PLUSMN; 6.3% (P = 0.005) and 115.6 &PLUSMN; 5.3% (P < 0.006) of control levels, respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3) activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal microscopy with a novel antibody raised against the predicted extracellular NH2 terminus of human NHE3, we observed in nonpermeabilized cells that exposure of PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 &PLUSMN; 2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels, respectively. This effect was paralleled by significant increases in NHE3 in the subplasmalemmal region as measured in permeabilized cells. These albumin-induced increases in expression and activity of NHE3 in PTC suggest a possible mechanism for Na+ retention in response to proteinuria.

Skeletal muscle and nuclear hormone receptors: Implications for cardiovascular and metabolic disease

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of the total body mass and a major player in energy balance. It accounts for > 30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the pathophysiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidernia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease. (c) 2005 Published by Elsevier Ltd.

Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity

Although obesity and physical activity have been argued to predict back pain, these factors are also related to incontinence and breathing difficulties. Breathing and continence mechanisms may interfere with the physiology of spinal control, and may provide a link to back pain. The aim of this study was to establish the association between back pain and disorders of continence and respiration in women. We conducted a cross-sectional analysis of self-report, postal survey data from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression to model four levels of back pain in relation to both the traditional risk factors of body mass index and activity level, and the potential risk factors of incontinence, breathing difficulties, and allergy. A total of 38 050 women were included from three age-cohorts. When incontinence and breathing difficulties were considered, obesity and physical activity were not consistently associated with back pain. In contrast, odds ratios (OR) for often having back pain were higher for women often having incontinence compared to women without incontinence (OR were 2.5, 2.3 and 2.3 for young, mid-age! and older women, respectively). Similarly, mid-aged and older women had higher odds of having back pain often when they experienced breathing difficulties often compared to women with no breathing problems (OR of 2.0 and 1.9, respectively). Unlike obesity and physical activity, disorders of continence and respiration were strongly related to frequent back pain. This relationship may be explained by physiological limitations of co-ordination of postural, respiratory and continence functions of trunk muscles.

Website physical activity interventions: preferences of potential users

Information and communication technologies (particularly websites and e-mail) have the potential to deliver health behavior change programs to large numbers of adults at low cost. Controlled trials using these new media to promote physical activity have produced mixed results. User-centered development methods can assist in understanding the preferences of potential participants for website functions and content, and may lead to more effective programs. Eight focus group discussions were conducted with 40 adults after they had accessed a previously trialed physical activity website. The discussions were audio taped, transcribed and interpreted using a themed analysis method. Four key themes emerged: structure, interactivity, environmental context and content. Preferences were expressed for websites that include simple interactive features, together with information on local community activity opportunities. Particular suggestions included online community notice boards, personalized progress charts, e-mail access to expert advice and access to information on specific local physical activity facilities and services. Website physical activity interventions could usefully include personally relevant interactive and environmentally focused features and services identified through a user-centered development process.

Similarity in recognition processes used for bodies and faces: Bodies show caricature effects

Because faces and bodies share some abstract perceptual features, we hypothesised that similar recognition processes might be used for both. We investigated whether similar caricature effects to those found in facial identity and expression recognition could be found in the recognition of individual bodies and socially meaningful body positions. Participants were trained to name four body positions (anger, fear, disgust, sadness) and four individuals (in a neutral position). We then tested their recognition of extremely caricatured, moderately caricatured, anticaricatured, and undistorted images of each stimulus. Consistent with caricature effects found in face recognition, moderately caricatured representations of individuals' bodies were recognised more accurately than undistorted and extremely caricatured representations. No significant difference was found between participants' recognition of extremely caricatured, moderately caricatured, or undistorted body position line-drawings. AU anti-caricatured representations were named significandy less accurately than the veridical stimuli. Similar mental representations may be used for both bodies and faces.

O PAPEL CONTRADITÓRIO DO PROFESSOR EVENTUAL DA REDE PÚBLICA DE ENSINO DO ESTADO DE SÃO PAULO NA ARTICULAÇÃO DAS RELAÇÕES DE TRABALHO E PROFISSÃO DOCENTE: LÚMPEN-PROFESSORADO ?

Esta pesquisa busca diagnosticar como ocorre a contratação e a atuação do professor eventual do EF II e EM na rede pública de ensino do estado de São Paulo e se essa forma de contratação e de atuação é a causa da quase inexistência desse professor nessa rede. Parte da hipótese de que a forma de contratação coloca esse professor em situação de lúmpen-professorado e que a pouca procura pelo professor eventual para o desempenho dessa função relaciona-se a esse fato, intimamente ligado ao não reconhecimento da importância de sua atuação, ao caráter contraditório do seu papel e às condições em que se dá seu exercício, levando-o a deixar de procurar esse tipo de atividade. Objetiva-se apresentar, discutir e promover uma reflexão a respeito desses temas e contribuir com estudos sobre o assunto, para uma possível análise e quiçá estruturação de uma política educacional adequada nesse âmbito. A carência de estudos sobre o tema justifica esta pesquisa. A partir da revisão bibliográfica, levantaram-se autores que abordaram o assunto, porém, sob outros pontos de vista. A metodologia abrangeu a leitura da bibliografia básica e complementar, a pesquisa documental (legislação federal e do estado de São Paulo), paralelamente a um estudo de caso e pesquisa qualitativa. Numa contextualização histórica geral, priorizaram-se as mudanças nas relações de trabalho e profissão docente, a construção e desconstrução de direitos adquiridos pelo professor, publicados em legislação específica, e, nesse ínterim, a figura do professor eventual. Abordou-se, então, numa perspectiva teórica, a situação precária da profissão docente e suas consequências, mostrando-se o panorama da deterioração do magistério público. O estudo de caso foi realizado por meio de observação sistemática numa escola estadual da periferia do Grande ABC (SP), além da coleta de depoimentos e/ou entrevistas junto a três professores eventuais, três gestores, um gerente de organização escolar e do secretário adjunto da Secretaria da Educação do estado de São Paulo, no intuito de valorar recortes dos diversos olhares. O estudo encerra-se com a discussão sobre a articulação entre os elementos de pesquisa. Os resultados contemplaram as questões propostas quanto à atuação e à contratação do professor eventual, confirmando assim as hipóteses levantadas para a pesquisa.

Accessibility indices and linked trips: a case study of the elderly

The confusion over the concept of accessibility in transport planning and the deficiencies of existing accessibility indices are examined by developing a conceptual framework of accessibility with a fundamental distinction being drawn between the, often conflicting, theoretical and practical dimensions. The theoretical validity of alternative indices is assessed with reference to the problems and assumptions implicit in defining, measuring, valuing and aggregating the variables and components comprising accessibility. The major deficiencies of existing indices are identified as the inability of indices to take account of the potential to link trips between more than one activity location and the level of assumptions implicit in valuing and aggregating accessibility information. In this context, it is argued that accessibility information is more appropriately expressed on a comparative basis in the form of a profile rather than as a composite single-unit index and that the present confines of accessibility measurement must be extended in line with current developments in disaggregate travel and activity modelling. The sensitivity of accessibility levels to the use of alternative value judgements, alternative forms and levels of aggregation and the inclusion of information on the potential to link trips is examined by undertaking a case study. Accessibility profiles are developed for 23 zones in the London Borough of Hammersmith and Fulham showing the accessibility of the elderly to post offices and grocers. In a practical context, the profiles assist in identifying areas and individuals with relatively poor accessibility. The incidence and nature of linked trip-making and its significance and implications for accessibility measurement are explored further by analysing the results of a survey of the elderly's travel patterns. It is concluded that future accessibility analysis should be undertaken at a disaggregate level, taking account of the potential opportunity available from nonhome as well as home origins.

Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle

Background - Cancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour-bearing cachectic mice. Methods - Superoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples. Results - Superoxide levels increased 1.4-fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40phox and p67phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity. Conclusion - Despite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40phox and p67phox, were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.

A strategic activity model of Enterprise System implementation and use:scaffolding fluidity

This paper builds on a Strategic Activity Framework (Jarzabkowski, 2005) and activity based theories of development (Vygotsky, 1978) to model how Enterprise Systems are used to support emerging strategy. It makes three contributions. Firstly, it links fluidity and extensiveness of system use to patterns of strategising. Fluidity - the ability to change system use as needs change - is supported by interactive strategising, where top managers communicate directly with the organisation. Extensiveness requires procedural strategising, embedding system use in structures and routines. Secondly, it relates interactive and procedural strategising to the importance of the system - procedural strategising is more likely to occur if the system is strategically important. Thirdly, using a scaffolding metaphor it identifies patterns in the activities of top managers and Enterprise System custodians, who identify process champions within the organisational community, orient them towards system goals, provide guided support, and encourage fluidity through pacing implementation with learning.© 2013 Published by Elsevier B.V. All rights reserved.

An empirical examination of the strategic decision-making process:the relationship between context, process, and outcomes

Despite concerted academic interest in the strategic decision-making process (SDMP) since the 1980s, a coherent body of theory capable of guiding practice has not materialised. This is because many prior studies focus only on a single process characteristic, often rationality or comprehensiveness, and have paid insufficient attention to context. To further develop theory, research is required which examines: (i) the influence of context from multiple theoretical perspectives (e.g. upper echelons, environmental determinism); (ii) different process characteristics from both synoptic formal (e.g. rationality) and political incremental (e.g. politics) perspectives, and; (iii) the effects of context and process characteristics on a range of SDMP outcomes. Using data from 30 interviews and 357 questionnaires, this thesis addresses several opportunities for theory development by testing an integrative model which incorporates: (i) five SDMP characteristics representing both synoptic formal (procedural rationality, comprehensiveness, and behavioural integration) and political incremental (intuition, and political behaviour) perspectives; (ii) four SDMP outcome variables—strategic decision (SD) quality, implementation success, commitment, and SD speed, and; (iii) contextual variables from the four theoretical perspectives—upper echelons, SD-specific characteristics, environmental determinism, and firm characteristics. The present study makes several substantial and original contributions to knowledge. First, it provides empirical evidence of the contextual boundary conditions under which intuition and political behaviour positively influence SDMP outcomes. Second, it establishes the predominance of the upper echelons perspective; with TMT variables explaining significantly more variance in SDMP characteristics than SD specific characteristics, the external environment, and firm characteristics. A newly developed measure of top management team expertise also demonstrates highly significant direct and indirect effects on the SDMP. Finally, it is evident that SDMP characteristics and contextual variables influence a number of SDMP outcomes, not just overall SD quality, but also implementation success, commitment, and SD speed.

Interdependent lateral interactions, hydrophobicity and acid strength and their influence on the catalytic activity of nanoporous sulfonic acid silicas

A series of propylsulfonic (MCM-SOH) and octyl co-functionalised propylsulfonic (MCM-Oc-SOH) catalysts have been prepared by post modification of MCM-41 with mercaptopropyltrimethoxysilane (MPTS) to achieve SOH surface coverages spanning the range 0.12-1 monolayer. Within the MCM-Oc-SOH series, samples with submonolayer MPTS coverages were further grafted with octyltrimethoxysilane to cap bare hydroxyl sites and tune the hydrophobicity of the support. For the MCM-SO H series NH calorimetry revealed acid strength increases as a function of sulfonic acid loading, with -ΔH(NH ) increasing from 87 to 118 kJ mol. In contrast, MCM-Oc-SOH exhibits a dramatic enhancement of acid strength for submonolayer SOH coverages, with -ΔH(NH ) found to increase to 103 kJ mol. In line with these acid strength measurements the per-site activity of the MCM-SOH series in the esterification of butanol with acetic acid was found to increase with SOH content. Incorporation of octyl groups further promotes esterification activity of all the samples within the MCM-Oc-SOH series, such that the turn over frequency of the sample with the lowest loading of SOH more than doubles. Molecular dynamic simulations indicate that the interaction of isolated sulfonic acid groups with the pore walls is the primary cause of the decrease in acid strength and activity of submonolayer samples within the MCM-SOH series. Incorporation of octyl groups results in a combination of increased hydrophobicity and lateral interactions between adjacent sulfonic acid head groups, resulting in a striking enhancement of acid strength and esterification activity. © 2010 The Royal Society of Chemistry.

Evaluation of the activity and stability of alkali-doped metal oxide catalysts for application to an intensified method of biodiesel production

A series of alkali-doped metal oxide catalysts were prepared and evaluated for activity in the transesterification of rapeseed oil to biodiesel. Of those evaluated, LiNO3/CaO, NaNO3/CaO, KNO3/CaO and LiNO3/MgO exhibited >90% conversion in a standard 3 h test. There was a clear correlation between base strength and activity. These catalysts appeared to be promising candidates to replace conventional homogeneous catalysts for biodiesel production as the reaction times are low enough to be practical in continuous processes and the preparations are neither prohibitively difficult nor costly. However, metal leaching from the catalyst was detected, and this resulted in some homogeneous activity. This would have to be resolved before these catalysts would be viable for large-scale biodiesel production facilities.

Latin Americans in London:language, integration and ethnic identity

This thesis studies the links between language, migration and integration in the context of the 'new migrant' group of Latin Americans in London. It reviews the many ways in which language impacts the integration processes of migrants by influencing people's access to jobs, services, social contacts and information. By focusing on migrants' experiences this research also investigates the ways in which language and identity articulate, as well as the affective variables that are at play in the acquisition of the local language. With a large sector trapped in a cycle of poor command of English and labour market disadvantage, many Latin Americans experience exclusion and poverty. In reaction to this, a sector of the community is campaigning for ethnic minority recognition. This work reviews the debates for recognition and the strategy of organising around ethnicity, paying special attention to the role language plays in the process. The study is based on over two and half years of qualitative research, which included interviews, surveys, and long-term participant observation within a community organisation and a recognition campaign. Its interdisciplinary perspective allows the recognition of both the intimate links between language and identity, as well as the social and structural forces that influence migrants' linguistic integration. It unveils the practical and symbolic value that the mother tongue has for Latin American migrants and provides a broader account of their experiences. This research calls attention to the need for a more comprehensive approach to the study of language and migration in order to acknowledge the affective and social factors involved in the linguistic practices of migrants. By studying the community's struggles for recognition, this work evidences both the importance of visibility for minority groups in London and the intrinsic methodological limitations of monitoring through ethnic categorisation.

Time for action? Elementary engineering education - Challenging teachers, policy makers and parents

Grounded in the findings of a three year exploratory student whereby teachers' and policy makers' perceptions of elementary level engineering education were analysed, this paper focuses upon three strands of engineering education activity: Pedagogy: Practice, and: Policy. Taking into account the challenges associated with introducing engineering education at an elementary level across the UK, the paper critiques the role played by the 'competition model' in promoting engineering to children and 4 to 11 years. In considering the 'added value' that appropriately developed engineering education activities can offer in the classroom the discussion argues that elementary level engineering has the potential to reach across the curriculum, offering context and depth in many different areas. The paper concludes by arguing that by introducing the discipline to children at a foundational level, switching on their 'Engineering Imaginations' and getting them to experience the value and excitement of engineering, maths and applied science a new "Educational Frontier" will be forged. © American Society for Engineering Education, 2014.

The Knowledge: Its Presentation and Role in Recognition Systems

The concept of knowledge is the central one used when solving the various problems of data mining and pattern recognition in finite spaces of Boolean or multi-valued attributes. A special form of knowledge representation, called implicative regularities, is proposed for applying in two powerful tools of modern logic: the inductive inference and the deductive inference. The first one is used for extracting the knowledge from the data. The second is applied when the knowledge is used for calculation of the goal attribute values. A set of efficient algorithms was developed for that, dealing with Boolean functions and finite predicates represented by logical vectors and matrices.