The Runx1 transcription factor controls CSF-1-dependent and -independent growth and survival of macrophages

Gene translocations that repress the function of the Runx1 transcription factor play a critical role in the development of myeloid leukemia. In this report, we demonstrate that Runx1 precisely regulates c-fms (CSF-1 receptor) gene expression. Runx1 controlled expression by binding to multiple sites within the mouse c-fms gene, allowing interaction between promoter and downstream enhancer elements. The runx1 and c-fms genes showed an identical pattern of expression in mature macrophages. Runx1 expression was repressed in CSF-1 stimulated, proliferating bone marrow-derived macrophages (BMM) and significantly increased in quiescent, CSF-1 starved cells. The RAW264.7 and Mono-Mac-6, macrophage-like cell lines expressed low levels of Runx1 and both showed growth arrest and cell death with ectopic expression of Runx1. The EM-3 cell line, which represents an early myeloid progenitor cell line, showed growth arrest with Runx1 expression in the absence of any detectable changes in cell differentiation. These findings suggest that Runx1 regulates growth and survival of myeloid cells and provide a novel insight into the role of Runx family gene translocations in leukemogenesis.

Adaptive responses of wild mungbean (Vigna radiata ssp sublobata) to photo-thermal environment. II. Growth, biomass, and seed yield

The leaf growth, dry matter production, and seed yield of 11 wild mungbean ( Vigna radiata ssp. sublobata) accessions of diverse geographic origin were observed under natural and artificial photoperiod temperature conditions, to determine the extent to which genotypic differences could be attributed to adaptive responses to photo-thermal environment. Environments included serial sowings in the field in SE Queensland, complemented by artificial photoperiod extension and controlled-environment growth rooms. Photo-thermal environment influenced leaf growth, total dry matter production ( TDM), and seed yield directly, through effects of ( mainly cool) temperature on growth, and indirectly, through effects on phenology. In terms of direct effects, leaf production, leaf expansion, and leaf area were all sensitive to temperature, with implied base temperatures higher than usually observed in cultivated mungbean ( V. radiata ssp. radiata). Genotypic sensitivity to temperature varied systematically with accession provenance and appeared to be of adaptive significance. In terms of the indirect effects of photo-thermal environment, genotypic and environmental effects on TDM were positively related to changes in total growth duration, and harvest index was negatively related to the period from sowing to flowering, similar to cultivated mungbean. However, seed yield was positively related to the duration of reproductive growth, reflecting the indeterminate growth habit of the wild accessions. As a consequence, the wild accessions are more responsive to favourable environments than typically observed in cultivated mungbean, which is determinate in habit. It is suggested that the introduction of the indeterminate trait into mungbean from the wild subspecies would increase the responsiveness of mungbean to favourable environments, analogous to that of black gram ( V. mungo). Although the wild subspecies appeared more sensitive to cool temperature than cultivated mungbean, it may provide a source of tolerance to the warmer temperatures experienced during the wet season in the tropics.

General discussion session of the 2004 Hume-Rothery Symposium on "The structure and diffusional growth mechanisms of irrational interphase boundaries"

Details on the general discussion session of the 2004 Hume-Rothery Symposium on "The Structure and Diffusional Growth Mechanisms of Irrational Interphase Boundaries" is presented. The symposium was held on Mar 17, 2004 at the Charlotte Convention Center in Charlotte NC.

Physical activity and strength of the femoral neck during the adolescent growth spurt: A longitudinal analysis

Loading of the femoral neck (FN) is dominated by bending and compressive stresses. We hypothesize that adaptation of the FN to physical activity would be manifested in the cross-sectional area (CSA) and section modulus (Z) of bone, indices of axial and bending strength, respectively. We investigated the influence of physical activity on bone strength during adolescence using 7 years of longitudinal data from 109 boys and 121 girls from the Saskatchewan Paediatric Bone and Mineral Accrual Study (PBMAS). Physical activity data (PAC-Q physical activity inventory) and anthropometric measurements were taken every 6 months and DXA bone scans were measured annually (Hologic QDR2000, array mode). We applied hip structural analysis to derive strength and geometric indices of the femoral neck using DXA scans. To control for maturation, we determined a biological maturity age defined as years from age at peak height velocity (APHV). To account for the repeated measures within individual nature of longitudinal data, multilevel random effects regression analyses were used to analyze the data. When biological maturity age and body size (height and weight) were controlled, in both boys and girls, physical activity was a significant positive independent predictor of CSA and Z of the narrow region of the femoral neck (P < 0.05). There was no independent effect of physical activity on the subperiosteal width of the femoral neck. When leg length and leg lean mass were introduced into the random effects models to control for size and muscle mass of the leg (instead of height and weight), all significant effects of physical activity disappeared. Even among adolescents engaged in normal levels of physical activity, the statistically significant relationship between physical activity and indices of bone strength demonstrate that modifiable lifestyle factors like exercise play an important role in optimizing bone strength during the growing years. Physical activity differences were explained by the interdependence between activity and lean mass considerations. Physical activity is important for optimal development of bone strength. (c) 2005 Elsevier Inc. All rights reserved.

Evidence of altered prefrontal-thalamic circuitry in schizophrenia: An optimised diffusion MRI study

MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were non-linearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia. (c) 2006 Elsevier Inc. All rights reserved.

Growth of crystals in optical tweezers

We report here on the use of optical tweezers in the growth and manipulation of protein and inorganic crystals. Sodium chloride and hen egg-white lysozyme crystals were grown in a batch process, and then seeds from the solution were introduced into the optical tweezers. The regular and controllable shape and the known optical birefringence in these structures allowed a detailed study of the orientation effects in the beam due to both polarization and gradient forces. Additionally, we determined that the laser tweezers could be used to suspend a crystal for three-dimensional growth under varying conditions. Studies included increasing the protein concentration, thermal cycling, and a diffusion-induced increase in precipitant concentration. Preliminary studies on the use of the tweezers to create a localized seed for growth from polyethylene oxide solutions are also reported.

Modelling the growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of these PrP aggregates is important both in attempting to the elucidate of the pathogenesis of prion disease and in the development of treatments designed to prevent or inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein aggregates. Mathematical models suggest that if aggregation/disaggregation or surface diffusion is the predominant factor, the size frequency distribution of the resulting protein aggregates in the brain should be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different types of PrP deposit, viz., the diffuse and florid-type PrP deposits in patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse plaques were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of plaque deviated significantly from a log-normal model in all brain areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid plaques. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse plaques. These results may be useful in the design of treatments to inhibit the development of protein aggregates in vCJD.

Introduction: improving manufacturing performance through technology diffusion, implementation and management

The role of technology management in achieving improved manufacturing performance has been receiving increased attention as enterprises are becoming more exposed to competition from around the world. In the modern market for manufactured goods the demand is now for more product variety, better quality, shorter delivery and greater flexibility, while the financial and environmental cost of resources has become an urgent concern to manufacturing managers. This issue of the International Journal of Technology Management addresses the question of how the diffusion, implementation and management of technology can improve the performance of manufacturing industries. The authors come from a large number of different countries and their contributions cover a wide range of topics within this general theme. Some papers are conceptual, others report on research carried out in a range of different industries including steel production, iron founding, electronics, robotics, machinery, precision engineering, metal working and motor manufacture. In some cases they describe situations in specific countries. Several are based on presentations made at the UK Operations Management Association's Sixth International Conference held at Aston University at which the conference theme was 'Achieving Competitive Edge: Getting Ahead Through Technology and People'. The first two papers deal with questions of advanced manufacturing technology implementation and management. Firstly Beatty describes a three year longitudinal field study carried out in ten Canadian manufacturing companies using CADICAM and CIM systems. Her findings relate to speed of implementation, choice of system type, the role of individuals in implementation, organization and job design. This is followed by a paper by Bessant in which he argues that a more a strategic approach should be taken towards the management of technology in the 1990s and beyond. Also considered in this paper are the capabilities necessary in order to deploy advanced manufacturing technology as a strategic resource and the way such capabilities might be developed within the firm. These two papers, which deal largely with the implementation of hardware, are supplemented by Samson and Sohal's contribution in which they argue that a much wider perspective should be adopted based on a new approach to manufacturing strategy formulation. Technology transfer is the topic of the following two papers. Pohlen again takes the case of advanced manufacturing technology and reports on his research which considers the factors contributing to successful realisation of AMT transfer. The paper by Lee then provides a more detailed account of technology transfer in the foundry industry. Using a case study based on a firm which has implemented a number of transferred innovations a model is illustrated in which the 'performance gap' can be identified and closed. The diffusion of technology is addressed in the next two papers. In the first of these, by Lowe and Sim, the managerial technologies of 'Just in Time' and 'Manufacturing Resource Planning' (or MRP 11) are examined. A study is described from which a number of factors are found to influence the adoption process including, rate of diffusion and size. Dahlin then considers the case of a specific item of hardware technology, the industrial robot. Her paper reviews the history of robot diffusion since the early 1960s and then tries to predict how the industry will develop in the future. The following two papers deal with the future of manufacturing in a more general sense. The future implementation of advanced manufacturing technology is the subject explored by de Haan and Peters who describe the results of their Dutch Delphi forecasting study conducted among a panel of experts including scientists, consultants, users and suppliers of AMT. Busby and Fan then consider a type of organisational model, 'the extended manufacturing enterprise', which would represent a distinct alternative pure market-led and command structures by exploiting the shared knowledge of suppliers and customers. The three country-based papers consider some strategic issues relating manufacturing technology. In a paper based on investigations conducted in China He, Liff and Steward report their findings from strategy analyses carried out in the steel and watch industries with a view to assessing technology needs and organizational change requirements. This is followed by Tang and Nam's paper which examines the case of machinery industry in Korea and its emerging importance as a key sector in the Korean economy. In his paper which focuses on Venezuela, Ernst then considers the particular problem of how this country can address the problem of falling oil revenues. He sees manufacturing as being an important contributor to Venezuela's future economy and proposes a means whereby government and private enterprise can co-operate in development of the manufacturing sector. The last six papers all deal with specific topics relating to the management manufacturing. Firstly Youssef looks at the question of manufacturing flexibility, introducing and testing a conceptual model that relates computer based technologies flexibility. Dangerfield's paper which follows is based on research conducted in the steel industry. He considers the question of scale and proposes a modelling approach determining the plant configuration necessary to meet market demand. Engstrom presents the results of a detailed investigation into the need for reorganising material flow where group assembly of products has been adopted. Sherwood, Guerrier and Dale then report the findings of a study into the effectiveness of Quality Circle implementation. Stillwagon and Burns, consider how manufacturing competitiveness can be improved individual firms by describing how the application of 'human performance engineering' can be used to motivate individual performance as well as to integrate organizational goals. Finally Sohal, Lewis and Samson describe, using a case study example, how just-in-time control can be applied within the context of computer numerically controlled flexible machining lines. The papers in this issue of the International Journal of Technology Management cover a wide range of topics relating to the general question of improving manufacturing performance through the dissemination, implementation and management of technology. Although they differ markedly in content and approach, they have the collective aim addressing the concepts, principles and practices which provide a better understanding the technology of manufacturing and assist in achieving and maintaining a competitive edge.

Modelling growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of PrP aggregates is important both in attempting to elucidate the pathogenesis of prion disease and in the development of treatments designed to inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein deposits. Mathematical models suggest that if either aggregation/disaggregation or surface diffusion is the predominant factor, then the size frequency distribution of the resulting protein aggregates will be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different populations of PrP deposit, viz., the diffuse and florid-type PrP deposits characteristic of patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse deposits were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of aggregate deviated significantly from a log-normal model in all areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid deposits. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse deposits. These results may be useful in the design of treatments to inhibit the development of PrP aggregates in vCJD.

The mechanics of creep crack growth in a Magnox alloy

Magnox AL80 has been used for a study of creep crack propagation. A number of variables have been considered such as specimen geometry,notch root radius, material thickness, creep prestrain and stress level.The work has covered the material behaving under two values of the creep exponent, n=3.5 and n=7, according to the stress level. As well as observing initiation times and crack growth rates, scribed grids have been used to examine the near crack tip strain levels and distributions. It was shown that estimations of COD from notch flank opening can give misleading indications of material behaviour and that a more informative method was to monitor displacements in the material surrounding the crack tip. Strong evidence was found for crack advance being displacement controlled, however it was shown that the COD approach should be considered geometry dependant. The summation of ∈xx and ∈yy provided the most successful description of crack advance as it produced a single value that described propagation in all the cases concidered. The strain distributions indicates that σyy was related to distance from a point ahead of the crack tip by the exponent - (l/n+l) and that σxx is proportional to σyy. The constraint stresses arising in the DEN and CN specimens were evaluated. Initiation time was found to be principally affected by the stress level but was modified by the constraints arising from specimen geometry. Crack growth was found not to obey either the empirical K or σpett relationships but was reviewed in context of the observed strain behaviour.

The effects of substrate water availability on the isolation and growth of fungi

The work reported in this thesis was carried out to contribute to the knowledge of the effects of substrate water availability or water activity (a ) on fungal growth parameters and its implications in the preparationw of materials susceptible to biodeterioration. Fungi were isolated from soils of different ecological sites at a range of substrate aw levels controlled by sodium chloride (NaCl). Three groups of fungi were isolated : firstly, those isolated only at high a (aw about 0.997).secondly, those isolated at high and decreasing aw (aw 0.997 to 0.85) and finally, those isolated at only decreased aw (aw O.95 to 0.80). From these isolations, test fungi were selected to study the effects of pH, temperature, exo-enzyme production and biocide efficacy at decreased aw levels, with glycerol and NaCl as a controlling solutes. The linear extension rates of the fungi increased at all test pH values near optimum a of growth. Test fungi of the Aspergillus glaucus group were found to be most resistant to low aw. Growth and survival of vegetative and fruiting bodies at elevated temperatures were enhanced with the addition of a controlling solutes. A. flavus, A. fumigatus displayed high heat resistance and A. amstelodami, A. versicolor and Penicillium citrinum displayed low heat resistance at high aw levels and vice versa at low aw levels. Amylase, lipase and protease activities were studied at lowered aw , using modifications of the test tube method of Raute11a and Cowling. Amylase and protease production in most xerophilic fungi ceased around 0.80 aw , but lipase production in some xerophilic fungi, including A. glatlcus fungi, was up to and including 0.70 aw with g1ycero1.

The development and diffusion of industrial robots

This thesis describes the history of robots and explains the reasons for the international differences in robot diffusion, and the differences in the diffusion of various robot applications with reference to the UK. As opposed to most of the literature, diffusion is examined with an integrated and interdisciplinary perspective. Robot technology evolves from the interaction of development, supply and manufacture, adoption, and promotion. activities. Emphasis is given to the analysis of adoption, at present the most important limiting factor of robot advancement in the UK. Technical development is inferred from a comparison of surveys on equipment, and from the topics of ten years of symposia papers. This classification of papers is also used to highlight the international and institutional differences in robot development. Analysis of the growth in robot supply, manufacture, and use is made from statistics compiled. A series of interviews with users and potential users serves to illustrate the factors and implications of the adoption of different robot systems in the UK. Adoption pioneering takes place when several conditions exist: when the technology is compatible with the firm, when its advantages outweigh its disadvantages, and particularly when a climate exists which encourages the managerial involvement and the labour acceptance. The degree of compatibility (technical, methodological, organisational, and economic) and the consequences (profitability, labour impacts, and managerial effects) of different robot systems (transfer, manipulative, processing, and assembly) are determined by various aspects of manufacturing operations (complexity, automation, integration, labour tasks, and working conditions). The climate for adoption pioneering is basically determined by the performance of firms. The firms' policies on capital investment have as decisive a role in determining the profitability of robots as their total labour costs. The performance of the motor car industry and its machine builders explains, more than any other factor, the present state of robot advancement in the UK.

The development and stability analysis of a nonlinear growth model for microorganisms

A nonlinear dynamic model of microbial growth is established based on the theories of the diffusion response of thermodynamics and the chemotactic response of biology. Except for the two traditional variables, i.e. the density of bacteria and the concentration of attractant, the pH value, a crucial influencing factor to the microbial growth, is also considered in this model. The pH effect on the microbial growth is taken as a Gaussian function G0e-(f- fc)2/G1, where G0, G1 and fc are constants, f represents the pH value and fc represents the critical pH value that best fits for microbial growth. To study the effects of the reproduction rate of the bacteria and the pH value on the stability of the system, three parameters a, G0 and G1 are studied in detail, where a denotes the reproduction rate of the bacteria, G0 denotes the impacting intensity of the pH value to microbial growth and G1 denotes the bacterial adaptability to the pH value. When the effect of the pH value of the solution which microorganisms live in is ignored in the governing equations of the model, the microbial system is more stable with larger a. When the effect of the bacterial chemotaxis is ignored, the microbial system is more stable with the larger G1 and more unstable with the larger G0 for f0 > fc. However, the stability of the microbial system is almost unaffected by the variation G0 and G1 and it is always stable for f0 < fc under the assumed conditions in this paper. In the whole system model, it is more unstable with larger G1 and more stable with larger G0 for f0 < fc. The system is more stable with larger G1 and more unstable with larger G0 for f0 > fc. However, the system is more unstable with larger a for f0 < fc and the stability of the system is almost unaffected by a for f0 > fc. The results obtained in this study provide a biophysical insight into the understanding of the growth and stability behavior of microorganisms.

Precipitation casting of drug-loaded microporous PCL matrices:incorporation of progesterone by co-dissolution

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37°C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 μg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37°C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.

Delivery of the antibiotic gentamicin sulphate from precipitation cast matrices of polycaprolactone

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with the aminoglycoside antibiotic, gentamicin sulphate (GS) using the precipitation casting technique by suspension of powder in the PCL solution prior to casting. Improvements in drug loading from 1.8% to 6.7% w/w and distribution in the matrices were obtained by pre-cooling the suspension to 4°C. Gradual release of approximately 80% of the GS content occurred over 11 weeks in PBS at 37°C and low amounts of antibiotic were measured up to 20 weeks. The kinetics of release could be described effectively by the Higuchi model with the diffusion rate constant (D) increasing from of 1.7 to 5.1 μg/mg matrix/day0.5 as the drug loading increased from 1.4% to 8.3% w/w. GS-loaded PCL matrices retained anti-bacterial activity after immersion in PBS at 37°C over 14 days as demonstrated by inhibition of growth of S. epidermidis in culture. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of hydrophilic molecules such as anti-bacterial agents from implanted, inserted or topical devices. © 2005 Elsevier B.V. All rights reserved.