Aluminium and human breast diseases

The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268±28 g/l) compared with control healthy subjects (mean 131±10 g/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150g/l) compared with human serum (median 6g/l) or human milk (median 25g/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

UK planning controls and the market responsiveness of housing supply

There is growing international interest in the impact of regulatory controls on the supply of housing The UK has a particularly restrictive planning regime and a detailed and uncertain process of development control linked to it. This paper presents the findings of empirical research on the time taken to gain planning permission for selected recent major housing projects from a sample of local authorities in southern England. The scale of delay found was far greater than is indicated by average official data measuring the extent to which local authorities meet planning delay targets. Hedonic analysis indicated that there is considerable variation in time it takes local authorities to process planning applications, with the worst being four times slower than the best. Smaller builders and housing association developments are processed more quickly than those of large developers and small sites appear to be particularly time intensive. These results suggest that delays in development control may be a significant contributory factor to the low responsiveness of UK housing supply to upturns in market activity.

Planning delay and the responsiveness of English housing supply

There is growing international interest in the impact of regulatory controls on the supply of housing. Most research focuses on the supply impacts of prescribed limits on land use but housing supply may also be affected by the process of planning monitoring and approval but this is hard to measure in detail. The UK has a particularly restrictive planning regime and a detailed and uncertain process of development control linked to it, but does offer the opportunity of detailed site-based investigation of planning delay. This paper presents the findings of empirical research on the time taken to gain planning permission for selected recent major housing projects in southern England. The scale of delay found was far greater than is indicated by average official data measuring the extent to which local authorities meet planning delay targets. Hedonic modelling indicated that there is considerable variation in the time it takes local authorities to process planning applications. Housing association developments are processed more quickly than those of large developers and small sites appear to be particularly time-intensive. These results suggest that delays in development control may be a significant contributory factor to the low responsiveness of UK housing supply to upturns in market activity.

Influences of increasing temperature on Indian wheat: quantifying limits to predictability

As climate changes, temperatures will play an increasing role in determining crop yield. Both climate model error and lack of constrained physiological thresholds limit the predictability of yield. We used a perturbed-parameter climate model ensemble with two methods of bias-correction as input to a regional-scale wheat simulation model over India to examine future yields. This model configuration accounted for uncertainty in climate, planting date, optimization, temperature-induced changes in development rate and reproduction. It also accounts for lethal temperatures, which have been somewhat neglected to date. Using uncertainty decomposition, we found that fractional uncertainty due to temperature-driven processes in the crop model was on average larger than climate model uncertainty (0.56 versus 0.44), and that the crop model uncertainty is dominated by crop development. Simulations with the raw compared to the bias-corrected climate data did not agree on the impact on future wheat yield, nor its geographical distribution. However the method of bias-correction was not an important source of uncertainty. We conclude that bias-correction of climate model data and improved constraints on especially crop development are critical for robust impact predictions.

Artisanal mining's democratizing directions and deviations

Artisanal miners have tended to be portrayed in the literature and media as people who work hard and play hard, not infrequently depicted as ‘rough diamonds’ likely to cross the boundaries of appropriate behaviour through pursuit of wealth and flamboyant living, often at the cost of local environmental damage. A popular alternative image is that of marginalised labourers, driven by poverty to toil in harsh conditions and pursuing mining livelihoods in the face of national governments and large-scale mining companies’ subversion of their land and mineral rights. Both views reflect partial realities, but are inclined to exaggerate the position of miners as mischief-making rogues or victims. Through documentation of the multi-faceted nature of Tanzanian artisanal miners’ work and home lives during the country’s on-going economic mineralisation, we endeavour to convey a balanced rendering of their aspirations, occupational identity and social ties. Our emphasis is on their working lives as artisans, how they organise themselves and contend with the risks of their occupation, including their engagement with government policy and large-scale mining interests.

The mirror neuron system as revealed through neonatal imitation: presence from birth, predictive power, and evidence of plasticity

There is strong evidence that neonates imitate previously unseen behaviors. These behaviors are predominantly used in social interactions, demonstrating neonates’ ability and motivation to engage with others. Research on neonatal imitation can provide a wealth of information about the early mirror neuron system (MNS): namely, its functional characteristics, its plasticity from birth, and its relation to skills later in development. Though numerous studies document the existence of neonatal imitation in the laboratory, little is known about its natural occurrence during parent-infant interactions and its plasticity as a consequence of experience. We review these critical aspects of imitation, which we argue are necessary for understanding the early action-perception system. We address common criticisms and misunderstandings about neonatal imitation and discuss methodological differences among studies. Recent work reveals that individual differences in neonatal imitation positively correlate with later social, cognitive, and motor development. We propose that such variation in neonatal imitation could reflect important individual differences of the MNS. Although postnatal experience is not necessary for imitation, we present evidence that neonatal imitation is influenced by experience in the first week of life.

Can perceptual differences account for managerial success?: the case of Japanese aid workers

Purpose – There is a wealth of studies which suggest that managers' positive perceptions/expectations can considerably influence the organisational performance; unfortunately, little empirical evidence has been obtained from development studies. This research aims to focus on the perceptual and behavioural trait differences of successful and unsuccessful aid workers, and their relationship with organisational performance. Design/methodology/approach – Through web-based survey, 244 valid responses were obtained from the Japan International Cooperation Agency (JICA)-aid managers worldwide. Five perception related factors were extracted and used for cluster analysis to group the respondents. Each cluster's perception/behaviour-related factors and organisational performance variables were compared by ANOVA. Findings – It was discovered that Japanese's positive perception/expectation about work and their local colleagues was related to higher organisational performance, and conversely, the negative perception on their part was generally associated with negative behaviour and lower organisational performance. Moreover, in a development context, lower work-related stress and feelings of resignation toward work were strongly associated with the acceptability of cross-cultural work environment. Practical implications – The differences in perceptual tendencies suggest that cautious consideration is advised since these findings may mainly apply to Japanese aid managers. However, as human nature is universal, positive perception and behaviour would bring out positive output in most organisations. Originality/value – This study extended the contextualised “Pygmalion effect” and has clarified the influence of perception/expectation on counter-part behaviour and organisational performance in development aid context, where people-related issues have often been ignored. This first-time research provides imperial data on the significant role of positive perception on the incumbent role holder.

Impacts of climate changes on crop physiology and food quality

Carbon emissions related to human activities have been significantly contributing to the elevation of atmospheric [CO(2)] and temperature. More recently, carbon emissions have greatly accelerated, thus much stronger effects on crops are expected. Here, we revise literature data concerning the physiological effects of CO(2) enrichment and temperature rise on crop species. We discuss the main advantages and limitations of the most used CO(2)-enrichment technologies, the Open-Top Chambers (OTCs) and the Free-Air Carbon Enrichment (FACE). Within the conditions expected for the next few years, the physiological responses of crops suggest that they will grow faster, with slight changes in development, such as flowering and fruiting, depending on the species. There is growing evidence suggesting that C(3) crops are likely to produce more harvestable products and that both C(3) and C(4) crops are likely to use less water with rising atmospheric [CO(2)] in the absence of stressful conditions. However, the beneficial direct impact of elevated [CO(2)] on crop yield can be offset by other effects of climate change, such as elevated temperatures and altered patterns of precipitation. Changes in food quality in a warmer, high-CO(2) world are to be expected, e.g., decreased protein and mineral nutrient concentrations, as well as altered lipid composition. We point out that studies related to changes in crop yield and food quality as a consequence of global climatic changes should be priority areas for further studies, particularly because they will be increasingly associated with food security. (c) 2009 Elsevier Ltd. All rights reserved.

Functionally conserved cis-regulatory elements of COL18A1 identified through zebrafish transgenesis

Type XVIII collagen is a component of basement membranes, and expressed prominently in the eye, blood vessels, liver, and the central nervous system. Homozygous mutations in COL18A1 lead to Knobloch Syndrome, characterized by ocular defects and occipital encephalocele. However, relatively little has been described on the role of type XVIII collagen in development, and nothing is known about the regulation of its tissue-specific expression pattern. We have used zebrafish transgenesis to identify and characterize cis-regulatory sequences controlling expression of the human gene. Candidate enhancers were selected from non-coding sequence associated with COL18A1 based on sequence conservation among mammals. Although these displayed no overt conservation with orthologous zebrafish sequences, four regions nonetheless acted as tissue-specific transcriptional enhancers in the zebrafish embryo, and together recapitulated the major aspects of col18a1 expression. Additional post-hoc computational analysis on positive enhancer sequences revealed alignments between mammalian and teleost sequences, which we hypothesize predict the corresponding zebrafish enhancers; for one of these, we demonstrate functional overlap with the orthologous human enhancer sequence. Our results provide important insight into the biological function and regulation of COL18A1, and point to additional sequences that may contribute to complex diseases involving COL18A1. More generally, we show that combining functional data with targeted analyses for phylogenetic conservation can reveal conserved cis-regulatory elements in the large number of cases where computational alignment alone falls short. (C) 2009 Elsevier Inc. All rights reserved.

Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T(3)) or antagonist (NH(3)). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, C-terminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T(3), but not NH(3), increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T(3) but not NH(3.) We present data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011)

En analys av testprocesser med TMap som testmetod

Today there are many system development projects that break both budget and time plan. Often this depends on defects in the information systems that could have been prevented. The cost of test can in some cases be as high as 50 % of the projects total cost and it's at the same time an important part of development. Test as such has moved its focus from the software it self and its faults to a wider perspective on whole infrastructures of information systems where assure a good quality is important. Sogeti in the Netherlands have developed a test method called TMap (Test Management approach) that can be used for structured testing of information systems. TMap haven't been used as much as desired in the office in Borlänge. Because Microsoft is releasing a new version of their platform Visual Studio Team System (VSTS 2010) some colleges at Sogeti in the Netherlands are about to develop a template that can support the use of TMap in VSTS 2010. When we write this the template is still in development. The goal for Sogeti was to find out the differences between the test functionality in VSTS 2008 and 2010. By using the purpose with this essay, which was to analyze the test process in VSTS 2008 with TMap against the test process in VSTS 2010 together with the template we got much help to achieve the goal. The analysis was done with four different aspects: The TPI and TMMi models, problem and strength analyses and a few question formulations. The TPI and TMMi models where used to analyses and evaluate the test process. The analysis showed that there were differences between the both test processes. VSTS 2010 together with the template gave a better support to use TMap and perform test. In VSTS 2010 the test tool Camano is connected to TFS and the tool is also to make the execution and logging of tests easier. This leads to a test process that is easier to handle and has a better support for TMap.

The attractiveness of the work is affected when production of handcrafted log houses moves indoors

Viewed from a historical perspective, a shift has occurred within the forestry and wood sector towards indoor work. In Sweden, the production of handcrafted log houses has now also begun to move indoors. With a point of departure in development processes within the log house sector involving working indoors, education, work attractiveness, between 2001-2005, the aim of this study was to compare indoor work with outdoor work, based on log house builders' experience of working on handcrafted log houses. Methods used in the interactive development project involving apprentices, experienced log house builders and researchers, were participation with continuous documentation of experiences and opinions; questions; interviews; and measurement of the work environment. The Attractive Work Model has been used in order to analyse perceptions and values. The changes, 15 out of 22 areas, were perceived both negatively and positively. Therefore, it can not be said that working on traditional, handcrafted log houses becomes more attractive if it is moved indoors. The majority wanted to work both outdoors and indoors, while most of the others only wanted to work outdoors. The results indicate that there is scope for developing more attractive work indoors by utilising experiences from log house builders and closely related activities such as the forestry and wood sector. Changes made within one area of work attractiveness affect other areas. Further research is needed both with regard to comparisons between indoor and outdoor work and regarding the interaction between the areas that are identified in the Attractive Work Model.